Structure, expression and promoter activity of two polyubiquitin genes from rice (Oryza sativa L.).
We have isolated two rice polyubiquitin genes designated as RUBQ1 and RUBQ2 by screening a Bacterial Artificial Chromosome (BAC) genomic library with a 32P-labeled ubiquitin cDNA probe. DNA sequence data revealed that both genes contained an open reading frame encoding a hexameric precursor ubiquitin and an intron immediate upstream of the initiation codon. The deduced amino acid sequences of both genes were identical to each other and to other plant ubiquitin sequences. Several putative regulatory elements such as enhancer core and heat shock consensus sequences were found in the 5'-upstream regions of both genes. Northern blot analyses using the 3'-untranslated region as gene specific probes showed that both genes were actively expressed in all rice plant tissues tested. Differential expression was observed in roots where RUBQ2 appeared to be predominantly expressed. Chimeric genes containing the 5'-upstream region including the intron of RUBQ1 or RUBQ2 and the beta-glucuronidase (GUS) coding region were constructed and transferred into rice suspension cells via particle bombardment. GUS activity from constructs containing RUBQ1 and RUBQ2 promoters in rice suspension cells was ten to 15-fold greater than those using the Cauliflower Mosaic Virus 35S (CaMV 35S) promoter, and two to threefold greater than constructs with the maize polyubiquitin Ubi1 promoter. The results demonstrate the potential usefulness of the two rice polyubiquitin promoters in rice or other monocot transformation systems.


Angiopoietin 2 displays a vascular endothelial growth factor dependent synergistic effect in hepatocellular carcinoma development in mice.
Orchestration of two major classes of angiogenic factors-namely, vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2)-has been shown to play a pivotal role in tumour angiogenesis, including hepatocellular carcinoma (HCC). However, few studies have focused on the direct interaction of these factors on in vivo tumour development and angiogenesis. To examine the interaction between both factors in murine HCC. We examined the combination effect of VEGF and Ang-2 overexpression by means of a combination of a retroviral tetracycline (tet) regulated gene manipulating system in vivo, by providing tet in the drinking water, and a conventional plasmid gene expression system. Neither Ang-2 nor VEGF overexpression induced proliferation of HCC cells in vitro. In vivo, although overexpression of Ang-2 did not increase tumour development, simultaneous expression of Ang-2 and VEGF synergistically augmented tumour growth and angiogenesis in murine HCC. Ang-2 plus VEGF induced tumour development was markedly attenuated by treatment with neutralising monoclonal antibodies against VEGF receptors. Ang-2 plus VEGF overexpression significantly increased the activities of matrix metalloproteinase (MMP)-2 and MMP-9 in the tumour. Suppression of intratumoral VEGF almost completely abolished this augmentation of MMPs. These results suggest that Ang-2 synergistically augments VEGF mediated HCC development and angiogenesis. This proangiogenic activity was exerted only in the presence of VEGF, at least partly mediated via induction of MMP-2 and MMP-9 in the tumour.


Sense of coherence mediates perceived social support and depressive and anxiety symptoms in cervical cancer patients: a cross-sectional study.
Depression and anxiety symptoms are two common psychological disturbances in cervical cancer patients. We tested whether sense of coherence (SOC) mediates the association of perceived social support (PSS) with depression and anxiety symptoms among cervical cancer patients in China. We conducted a survey involving 294 cervical cancer patients aged ≥ 18 years from July to December 2020 at three hospitals in Liaoning Province, China; 269 patients completed the survey. We included a demographic questionnaire, the Multidimensional Scale of Perceived Social Support (MSPSS), Antonovsky's Sense of Coherence Scale, the Hamilton Depression Rating Scale, and the Zung Self-Rating Anxiety Scale (SAS) in this study. We used hierarchical regression analysis to examine the relationship among PSS, SOC, and symptoms of depression and anxiety. We used asymptotic and resampling strategies to explore the mediating effect of SOC. PSS was negatively associated with depressive symptoms (r = - 0.439, P < 0.01) and anxiety symptoms (r = - 0.325, P < 0.01). SOC was negatively related to depressive symptoms (r = - 0.627, P < 0.01) and anxiety symptoms (r = - 0.411, P < 0.01). SOC partially mediated the association between PSS and depressive symptoms (a*b = - 0.23, BCa95% CI: [- 0.31, - 0.14]) and anxiety symptoms (a*b = - 0.15, BCa95% CI: [- 0.23, - 0.08]). The proportions of the mediating effect accounting for SOC were 49.78% and 41.73% for depressive symptoms and anxiety symptoms, respectively. The study showed that SOC could mediate the association between PSS and symptoms of depression and anxiety. This suggests that SOC might serve as a potential target for intervention in symptoms of depression and anxiety that accompany cervical cancer.


Hip Magnetic Resonance Arthrography Using Normal Saline Is Less Accurate Than Using a Gadolinium-Based Contrast Agent.
To evaluate the diagnostic performance of hip magnetic resonance (MR) arthrography with a gadolinium-based contrast agent (GBCA) or normal saline (NS) for intra-articular pathologies. This retrospective study was approved by the institutional review board of our hospital, and the requirement for informed consent was waived. The study included 37 consecutive patients (38 hips; 21 right hips; 24 males; mean age, 33 years) who underwent GBCA-hip MR arthrography from July 2011 to January 2020 and 30 consecutive patients (30 hips; 20 right hips; 21 males; mean age, 40 years) who underwent NS-hip MR arthrography from January 2018 to June 2020. All images were evaluated twice independently by two radiologists blinded to the arthroscopic findings for the presence of labral tears, cartilage abnormalities, or ligamentum teres tears. Intrareader and interreader reliabilities were determined by kappa values (k) using the chi-squared test, and diagnostic performance was evaluated based on the arthroscopic findings. A P value less than .05 was considered to indicate statistical significance. Intra-reader reliability in the detection of intra-articular pathologies ranged from moderate to almost perfect (k = 0.510-0.840) and inter-reader reliability ranged from moderate to substantial (k = 0.441-0.695) for GBCA- and NS-hip MR arthrography. The diagnostic accuracy of GBCA- and NS-hip MR arthrography was as follows: 81.6-92.1% and 66.7-73.3% for labral tears, respectively; 68.4-86.8% and 63.3-70.0% for cartilage abnormality, respectively; and 68.4-76.3% and 50.0-56.7% for ligamentum teres tears, respectively. NS-hip MR arthrography may be less accurate than GBCA-hip MR arthrography. LEVEL OF EVIDENCE: Level II of development of diagnostic criteria (consecutive patients with consistently applied reference standard and blinding).


Chondrosarcoma: a case report with left atrial involvement and systemic embolization.
A 26-year-old white man underwent amputation of the right lower extremity for a chondrosarcoma of the distal femur. Eleven years later, after a long symptom-free interval, he was hospitalized for rapidly progressive dyspnea, pleuritic chest pain, and hemoptysis resulting from a large pulmonary metastasis that had extended directly to the left atrium via the pulmonary vein. Within 24 hours of hospitalization, obstruction of the left commom iliac artery by tumor embolus necessitated embolectomy. This represents the second report of a metastatic chondrosarcoma involving the left atrium. The case presented clinically as an atrial myxoma and disseminated via the systemic circulation with a rapidly downhill course therafter.


Can iron overload in patients with lower-risk myelodysplastic syndromes be reduced using erythropoiesis-stimulating agents?
Iron overload (IOL) portends inferior outcome in myelodysplastic syndromes (MDS). Erythropoiesis-stimulating agents (ESA) may reduce red blood cell transfusion requirements. MDS patients receiving ESA were reviewed for characteristics, response to ESA by International Working Group 2006 criteria and ferritin levels. Forty-nine patients received an ESA, had ferritin levels available, and were not receiving iron chelation therapy. Baseline characteristics were not significantly different between ESA responders (ER) and non-responders (ENR; P = NS). The median ESA treatment duration was 6.7 (1.5-85.9) months. Twenty-one (43 %) patients had an ESA response. Median ferritin level in ER was pre-ESA, 473 (range 91-2727) and post-ESA, 801 (130-11,164) ng/mL (P = 0.01), and in ENR pre-ESA, 672 (76-3285) and post-ESA, 1423 (431-6593) ng/mL (P < 0.0001). There was a significant association between ESA response, post-ESA hemoglobin ≥100 g/L, and post-ESA ferritin <1000 ng/mL (P = 0.0003 and 0.03, respectively). At a median follow-up of 28 months, the 2-year overall survival for ER and ENR, respectively, were 80 % and 86 % (P = NS). In lower-risk MDS patients responding to ESA, although an expected decrease in ferritin levels over treatment was not seen, ferritin levels increased less than in non-responders. Whether IOL may be reduced by ESA over a longer treatment duration may require analysis of larger numbers of patients.


[A full screen waveform fast scrolling method based on DirectX technology under WindowsXP].
The microsoft DirectX technique is utilized to achieve the display of fast moving waveforms with high resolution and full screen in the environment of WindowsXP. The waveforms can move fluently under the resolution of 1280 x 1024 with the fastest speed of 1 m/s without any dither.


Increasing access to single-visit contraception in urban health care settings: Findings from a multi-site learning collaborative.
Multiple barriers limit access to the full range of contraceptive options. The purpose of this quality improvement initiative was to increase single-visit access to the full range of contraceptive methods in primary care, postabortion, and immediate postpartum settings in New York City (NYC). From 2015 to 2018 we convened 2 learning collaboratives, named the Quality Improvement Network for Contraceptive Access, with 17 teams (representing 40 sites) from New York City-based hospitals and health centers using an adaptation of the Institute for Healthcare Improvement's Breakthrough Series Learning Collaborative model. Participating teams sought to implement evidence-informed recommendations to increase access. The goal was to increase the patient-centeredness of services by reducing barriers. In the absence of a way to directly measure access, we measured progress toward implementation of the 4 recommendations and contraceptive care utilization measures as proxies for access, and asked teams to describe facilitating factors. Learning collaborative teams successfully implemented all 4 of the recommendations in 95% of the participating sites. Patients who chose and received a most or moderately effective method increased from 22% to 38% in primary care, and from 0% to 17% in the immediate postpartum period. Patients who chose and received a long-acting-reversible contraceptive increased from 5% to 11% in primary care, and from 0% to 3% in immediate postpartum. Facilitating factors included the involvement of interdisciplinary teams, consideration of costs, utilization of peers to demonstrate change, and champions to drive change. The application of evidence-informed recommendations using a structured quality improvement initiative increases contraceptive access. This paper identifies key facilitators and factors that influenced the successful implementation of evidence-based recommendations for access to the full range of contraceptive methods in primary care, postabortion, and immediate postpartum settings. Findings can inform future initiatives that seek to increase contraceptive access at the service delivery level, as a component of reproductive autonomy, and contraceptive equity.


Time-lapse electrical impedance spectroscopy for monitoring the cell cycle of single immobilized S. pombe cells.
As a complement and alternative to optical methods, wide-band electrical impedance spectroscopy (EIS) enables multi-parameter, label-free and real-time detection of cellular and subcellular features. We report on a microfluidics-based system designed to reliably capture single rod-shaped Schizosaccharomyces pombe cells by applying suction through orifices in a channel wall. The system enables subsequent culturing of immobilized cells in an upright position, while dynamic changes in cell-cycle state and morphology were continuously monitored through EIS over a broad frequency range. Besides measuring cell growth, clear impedance signals for nuclear division have been obtained. The EIS system has been characterized with respect to sensitivity and detection limits. The spatial resolution in measuring cell length was 0.25 μm, which corresponds to approximately a 5-min interval of cell growth under standard conditions. The comprehensive impedance data sets were also used to determine the occurrence of nuclear division and cytokinesis. The obtained results have been validated through concurrent confocal imaging and plausibilized through comparison with finite-element modeling data. The possibility to monitor cellular and intracellular features of single S. pombe cells during the cell cycle at high spatiotemporal resolution renders the presented microfluidics-based EIS system a suitable tool for dynamic single-cell investigations.


Biosorption of arsenic through bacteria isolated from Pakistan.
The aim of this study was to isolate arsenic-resistant bacteria and to further exploit it for remediation purposes. In the present study, we have isolated arsenic-resistant strain from ground water of Pakistan AT-01. The strain was cultivated at 37 °C in Luria Bertani broth supplemented with different concentrations of arsenate and arsenite. The minimum inhibitory concentration of arsenic against the bacterial isolate was 7 g/L (7000 mg/L) for arsenate and 1.4 g/L (1400 mg/L) for arsenite salt. The bacterial isolate was also characterized both on molecular and biochemical basis. The isolated strain belonged to the Pseudomonas aeruginosa. The high resistance against arsenic offered by the bacteria was exploited further for bioremediation purposes. The bacterial biomass generated from AT-01 strain was able to efficiently remove arsenic with 98% efficiency. Arsenic contamination of ground water is a widespread worldwide problem. The present study shows the potential of high arsenic-resistant bacteria for efficient arsenic removal.


[The ubiquitin system--structure and function].
Current opinions connected with the role and significance of ubiquitous proteins--ubiquitins (Ub) were discussed. Genetic determination of ubiquitins and their expression in nature were considered. Thymic ubiquitin complex, as an extract from calf thymus gland (TFX) was also presented. Very important biological activities in some experimental models and usefulness of TFX in medical practice were presented.


The prospective association between illicit drug use and nonprescription opioid use among vulnerable adolescents.
In recent years, more than half of all drug overdose deaths in United States involved an opioid. To address this epidemic, antecedents to opioid misuse must be identified and empirically validated. The objective of the current investigation was to examine whether illicit drug use was prospectively associated with nonprescription opioid use among adolescents from a vulnerable population with a greater prevalence of substance abuse. A population-based cohort study of 1060 adolescents from 29 alternative high schools in southern California was conducted over a two-year period. A total of 929 adolescents (mean age 17.5 years, 49.9% female, 76.4% Hispanic) who had not experimented with nonprescription opioids at the baseline assessment were included in the analytic sample. The outcome was self-reported use of nonprescription opioids within two years. The predictors tested were illicit drug use, illicit drug use excluding marijuana, and the use of nonmedical marijuana. Covariates included age, sex, ethnicity, socioeconomic status, parental education, weekly income, sensation seeking, stress, anxiety, depression, and the use of alcohol and nicotine products. Multilevel, covariate-adjusted logistic regression models indicated that the odds of experimentation with nonprescription opioids was greater among adolescents who had used illicit drugs or illicit drugs excluding marijuana. Nonmedical marijuana use alone was a statistically significant predictor in unadjusted but not covariate-adjusted models. While prior studies have examined the progression from nicotine, alcohol, and marijuana use to nonprescription opioid use, the present findings emphasize the importance of illicit drug use as a detectable and empirically supported risk factor for future opioid misuse.


Rapid measurement of phytosterols in fortified food using gas chromatography with flame ionization detection.
A novel method for the measurement of total phytosterols in fortified food was developed and tested using gas chromatography with flame ionization detection. Unlike existing methods, this technique is capable of simultaneously extracting sterols during saponification thus significantly reducing extraction time and cost. The rapid method is suitable for sterol determination in a range of complex fortified foods including milk, cheese, fat spreads, oils and meat. The main enhancements of this new method include accuracy and precision, robustness, cost effectiveness and labour/time efficiencies. To achieve these advantages, quantification and the critical aspects of saponification were investigated and optimised. The final method demonstrated spiked recoveries in multiple matrices at 85-110% with a relative standard deviation of 1.9% and measurement uncertainty value of 10%.


Feeding rate may affect dispersal in the orb-web spider Nephila clavata.
Population parameters of the orb-web spider Nephila clavata were estimated at two sites with different spider densities (for 2 successive years at the high density site and 1 year at the low density site), and the relationship between survival rate and feeding conditions was examined. The rate of decrease of population density was almost constant over time and nearly the same at the two sites. Daily survival rate (sum of the effects of mortality and emigration) was low during August to early September and increased markedly thereafter. Daily immigration rate (number of immigrants/number of residents) was high during August to early September. Since there were strong negative correlations between survival and immigration rates, low survival rate seems to be caused by a high rate of emigration. Strong positive correlations were found between survival rate and feeding frequency (mean percent observed feeding). Analysis of covariance revealed that the parameters of the regression between survival rate and feeding frequency did not differ significantly among three occasions. These results suggest that feeding condition has a significant influence on dispersal activity of populations in this spider.


Tumor-derived extracellular vesicles: Regulators of tumor microenvironment and the enlightenment in tumor therapy.
In recent decades, extracellular vesicles (EVs) have been proven to establish an important bridge of communication between cells or cells and their microenvironment. It is well known that EVs play crucial roles in many human diseases, especially in tumors. Tumor-derived EVs (TEVs) are not only involved in epithelial-mesenchymal transition and extracellular matrix remodeling to promote the invasion and metastasis, but also contribute to the suppression of antitumor immune responses by carrying different inhibitory molecules. In this review, we mainly discuss the effects of TEVs on the remodeling of tumor microenvironment through immune and non-immune associated mechanisms. We summarize the latest studies about utilizing EVs in clinical diagnosis and therapeutic drug delivery as well. In addition, the perspective of tumor therapy by targeting EVs is discussed in this review.


Terrien's marginal degeneration: clinicopathologic case reports.
We report the clinicopathologic features of seven cases of Terrien's marginal degeneration. Three specimens studied were lamellar resections and four were full-thickness corneal segments. Of the four full-thickness specimens, three were semilunar and one was an annular ("doughnut-shaped") specimen. All cases had stromal thinning, vascularization, lipid keratopathy and local absence of Bowman's membrane. Descemet's membrane was markedly thickened and the endothelium was intact. Three of the four full-thickness corneal specimens showed healed ruptures of Descemet's membrane. One specimen had four healed successive ruptures in Descemet's membrane in the same area. The corneal endothelium in that area had produced a basement membrane that totalled 35 micron in thickness. The clinical and histopathologic features of pellucid and Terrien's marginal degeneration are similar. When idiopathic peripheral corneal thinning remains clear, it is regarded as pellucid degeneration; vascularization, scarring, and lipid keratopathy are regarded as Terrien's marginal degeneration. Breaks in Descemet's membrane contribute to these latter changes.


Results of an international survey on the status of prehospital care.
Prehospital care including recognition of stroke symptoms by the public and professionals combined with an efficient and effective emergency medical service (EMS) is essential to increase access to effective acute stroke care. We undertook a survey to document the status of stroke prehospital care globally. A survey was distributed via email to the World Stroke Organization (WSO) members. Information was sought on the current status of stroke prehospital delay globally, including (1) ambulance availability and whether payment for use is required, (2) ambulance response times and the proportion of patients arriving at hospital by ambulance, (3) the proportion of patients arriving within 3 h and more than 24 h after symptom, (4) whether stroke care training of paramedics, call handlers, and primary care staff, (5) availability of specialist centers, and (6) the proportion of patients taken to specialist centers. Respondents were also asked to identify the top three changes in prehospital care that would benefit their population. Data were analyzed descriptively at both country and continent level. Responses were received from 116 individuals in 43 countries, with a response rate of 4.7%. Most respondents (90%) reported access to ambulances, but 40% of respondents reported payment was required by the patient. Where an ambulance service was available (105 respondents) 37% of respondents reported that less than 50% of patients used an ambulance and 12% less than 20% of patients used an ambulance. Large variations in ambulance response times were reported both within and between countries. Most of the participating high-income countries (HIC) offered a service used by patients, but this was rarely the case for the low- and middle-income countries (LMIC). Time to admission was often much longer in LMIC, and there was less access to stroke training for EMS and primary care staff. Significant deficiencies in stroke prehospital care exist globally especially in LMIC. In all countries, there are opportunities to improve the quality of the service in ways that would likely result in improved outcomes after acute stroke.


Physical performance and maximum tongue pressure associated with oral intake independence: a retrospective study on hospitalized patients with heart failure.
Dysphagia in patients with heart failure leads to poorer outcomes during hospitalization and after discharge. Therefore, addressing dysphagia is critical for improving patient prognosis. This retrospective observational study aimed to evaluate associations between improvements in swallowing dysfunction at the time of hospital discharge and the physical function, cognitive function, nutritional status, and maximum tongue pressure (MTP). Overall, 111 patients who underwent cardiac rehabilitation and were deemed to have oral intake impairment were included. The exclusion criteria comprised the following: pre-admission diagnosis of dysphagia, in-hospital death, and missing data. Patients were categorized based on whether they did (n = 65) or did not (n = 46) exhibit improvements in oral intake impairment, which were determined from the functional oral intake scale (FOIS) score at discharge. Associations between potential explanatory variables and the FOIS score at discharge were assessed using a linear regression model. After adjusting for covariates, such as age, sex, heart failure severity, short physical performance battery score, Mini-Mental State Examination score, transthyretin level, and provision of swallowing therapy, the FOIS score at discharge was significantly associated with the MTP (P = 0.024, confidence interval: 0.006-0.046). In conclusion, the MTP was independently associated with improvements in FOIS in patients with heart failure.


Does whole body vibration therapy assist in reducing fat mass or treating obesity in healthy overweight and obese adults? A systematic review and meta-analyses.
This review describes the effects of Whole Body Vibration therapy (WBV) for reducing fat mass (%/kg) among healthy (no comorbid disease) overweight and obese adults. Systematic literature search was conducted using Medline, Embase, Cochrane, CINAHL, and PubMed databases up to 27th March 2019. Studies evaluating the effects of WBV therapy on fat mass as a primary or secondary outcome among healthy (no comorbid disease), overweight or obese adults (Body Mass Index ≥25) were included. Following the search, 2,420 studies were reviewed and 1,603 studies were selected for title and abstract screening. Of 153 studies considered for full-text review, 13 controlled trials were included in the systematic review. Two meta-analyses were performed for five studies. The first random effects (I2 = 70%, p-value = 0.02) meta-analysis, revealed a statistically significant mean change for percent fat mass (-2.56, 95% CI: -3.81, -1.31). The second fixed effects meta-analysis, revealed a significant mean change (-1.91, 95% CI: -2.64, -1.18) for fat mass/kg. This systematic review and meta-analyses indicate a positive effect of Whole Body Vibration therapy on reducing fat mass (%/kg), especially when combined with conventional weight loss interventions specifically, diet and exercise.IMPLICATIONS FOR REHABILITATIONWhole Body Vibration therapy may assist obese and bariatric clients with weight loss.Whole Body Vibration therapy with conventional weight loss strategies may augment reductions in fat mass among obese clients in rehabilitation setting.


A critical overview of the current myofascial pain literature - October 2020.
With this edition, we welcome Dr. Orlando Mayoral from Toledo, Spain as a new contributor to this quarterly myofascial literature review. Dr. Mayoral has been studying myofascial pain since the early 1990-ies. He translated the Travell and Simons Trigger Point Manuals into Spanish (Simons et al., 2004), and contributed to many scientific studies, case reports, book chapters, and books (Mayoral del Moral and Salvat Salvat, 2017). In the current review, we included several trigger point (TrP) prevalence studies as well as the usual high volume of dry needling (DN) studies. But of particular interest are the basic research studies that increasingly support multiple aspects of the integrated TrP hypothesis.


Promoting soluble expression of hybrid mussel foot proteins by SUMO-TrxA tags for production of mussel glue.
Mussel foot proteins (Mfps) display application potential with strong adhesion, enabling mussels to adhere firmly to various surfaces. Mytilus galloprovincialis foot protein 3B (Mgfp-3B) exhibits this characteristic remarkably. However, it remains a challenge for further research due to the low soluble expression of heterologous production. In this study, a small ubiquitin-related modifier (SUMO) and thioredoxin A (TrxA), which catalyzed the proper folding of disulfide bridges, were selected to increase the soluble expression of mfps. An additional ribosome binding site was introduced between the molecular chaperones and Mgfp-3B (fp-3) to form a bicistronic translation-coupled expression vector for co-expression. The results revealed that the combination of SUMO-TrxA increased the soluble expression of fp-3 by 18.07 %. Furthermore, the SUMO-TrxA also boosted the soluble expression of hybrid mfps Mgfp-3B-Mfp-1 (fp-3-1) by 11.29 %, Mgfp-3B-Mgfp-3B (fp-3-3) by 19.91 %, and Mgfp-3B-Mgfp-5 (fp-3-5) by 14.03 %. Ultimately, by high cell density cultivation in a 5 L bioreactor, the yields of fp-3, fp-3-3, and fp-3-5 co-expressed with SUMO-TrxA reached 217.75 mg/L, 127.2 mg/L, and 97.28 mg/L, respectively. Consequently, soluble production of mfps holds great potential for the sustainable supply of protein adhesive materials.


Comparative Pharmacokinetics and Safety Studies of Dexibuprofen Injection and a Branded Product Ibuprofen Injection in Healthy Chinese Volunteers.
Ibuprofen, a nonsteroidal anti-inflammatory drug, is considered a safe and effective analgesic for treating different types of pain and joint disorders. Dexibuprofen, S-(+)-ibuprofen, is the single pharmacologically active enantiomer of ibuprofen. It is more potent than the racemic formulation of ibuprofen in terms of analgesic and anti-inflammatory properties and causes less acute gastric damage. For the first time, in the present single-dose, randomized, open-label, 2-period crossover study, the safety and pharmacokinetic (PK) characteristics of a single-dose dexibuprofen injection (0.2 g) were evaluated in healthy Chinese subjects and compared with the PK characteristics of a 0.2-g ibuprofen injection. Five consecutive men and women were randomly administered a single dose of the 0.2-g ibuprofen or 0.2-g dexibuprofen injection after fasting in every period during the 5-day interval. Then, plasma samples were collected for liquid chromatography-tandem mass spectrometric analysis. WinNonlin software was used for calculating the PK parameters. The geometric mean ratios of the 0.2-g dexibuprofen injection/ibuprofen injection for maximal plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable time point, and AUC from time 0 to infinity were 184.6%, 136.9%, and 134.4%, respectively. The dexibuprofen plasma exposure of the 0.15-g dexibuprofen injection was comparable to that of the 0.2-g ibuprofen injection, calculated using AUC from time 0 to infinity.


Association of Echocardiographic Parameter E/e' With Cardiovascular Events in a Diverse Population of Inpatients and Outpatients With and Without Cardiac Diseases and Risk Factors.
The echocardiographic parameter E/e' has been associated with cardiovascular (CV) events. However, few studies have analyzed multiple associated CV outcomes using E/e' in a diverse population of both inpatients and outpatients with and without cardiac diseases and risk factors. Medical records of 75,393 patients without atrial fibrillation (AF) with first available E/e' were retrieved from our hospital database. Patients with mitral valve disease were excluded, and the remainder were studied in protocol 1 (70,819 patients). Patients with hypertension, diabetes mellitus, hyperlipidemia, CV diseases, prior CV events, CV surgeries, and left ventricular ejection fraction <50% or missing left ventricular ejection fraction were further excluded, and the remaining patients were studied in protocol 2 (14,665 patients). The study outcomes are major adverse CV events (MACE), which included myocardial infarction (MI), AF, ischemic and hemorrhagic stroke (IHS), hospitalization for heart failure (HHF), and cardiac death. The primary outcomes were MACE and each of the MACE components. At the end of maximal 5-year follow-up (median 22.18 months with interquartile range 7.20-49.08 months for MACE in protocol 1 and 23.46 months with interquartile range 8.15-49.02 months for MACE in protocol 2), compared with an E/e' value of <8, an intermediate value of E/e' 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and cardiac death in protocol 1 (all P < .0001). In protocol 2, an intermediate E/e' value of 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and CV death (all P < .05), except an intermediate value E/e' 8 to 15 was not associated with AF. In a diverse population of inpatients and outpatients with and without cardiac diseases and risk factors, the echocardiographic parameter E/e' was associated with CV events and is a useful marker of risk.


Benzyladenine induces the appearance of LHCP-mRNA and of the relevant protein in dark-grown excised watermelon cotyledons.
Cotyledons were excised from imbibed watermelon seeds, grown for 4 days in darkness on water or 10 microM benzyladenine (BA) and then tested for the presence of the light-harvesting chlorophyll a/b protein (LHCP) and its mRNA. LHCP was assayed immunologically by western blotting of SDS gels: the protein was present in plastids, but it was not recovered with the thylakoid fraction. Antibodies directed against LHCP precipitated a 32 kDa polypeptide from translation products of poly(A) RNA of cotyledons only if these had been grown on BA. Taken together the data suggest that in absence of light cytokinins are necessary for the maintenance of a detectable level of LHCP-mRNA as well as for synthesis of the protein.


The magic wand: a new stereokinetic anomalous surface.
When a disc with two dots stuck on it a few centimetres apart is set in slow rotatory motion, the two dots appear displaced in depth and rigidly connected to form the two extremities of a rod. The rod appears as a diaphanous transparent object, slightly tinted to the same colour as the dots. Experimental analysis of the phenomenon shows that it is different from previously observed 'moving phantoms', 'motion-induced contours', and 'stereokinetic induced phantoms'. But it shows similarities with all three phenomena: the colour spreading along the apparent rod is facilitated by low illumination and is clearly visible under high illumination with bright colours only; it is seen only when the two dots appear to move with apparent displacement in depth and not when they appear to lie on the plane of the disc. When line-drawn circles instead of full colour dots are used, the anomalous surface of the rod appears to have colourless vitreous transparency. With half-line circles it is clearly visible as an opaque rod of the same colour as the background. When squares or diamonds are used instead of dots, a three-dimensional prism can be observed which has similar appearance to the rod.


The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM.
Interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD), is a major poor prognostic factor in patients with DM. We investigated the association of anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) with clinical characteristics and mortality in Japanese patients with DM. Seventy-nine DM patients, comprising 58 classic DM and 21 clinically amyopathic DM (CADM) patients, were enrolled. Serum Abs were screened by immunoprecipitation assays, and an immunosorbent assay (ELISA) was used for MDA5. The relationships of clinical characteristics and mortality with each Ab were investigated. Anti-MDA5 Ab was detected in 17 patients. Anti-clinically amyopathic DM 140 kDa polypeptide Abs (anti-CADM-140 Abs) were found in 16 of the 17 anti-MDA5 Ab(+) patients. Skin ulcers, palmar papules, CADM, RPILD and mediastinal emphysema were widely distributed in anti-MDA5 Ab(+) patients. Mortality at 6 months as well as 5 years was also significantly higher in anti-MDA5 Ab(+) patients than in anti-MDA5 Ab(-) patients. In a multivariable Cox regression analysis, mortality was independently associated with anti-MDA5 Ab (relative hazard 6.33; 95% CI 1.43, 28.0). All of the deaths in anti-MDA5 Ab(+) patients were attributed to respiratory failure of RPILD; however, RPILD did not worsen in any of the anti-MDA5 Ab(+) patients who survived the first 6 months. The presence of anti-MDA5 Ab identifies the characteristic skin, musculoskeletal, pulmonary and prognostic features in patients with DM. In addition, anti-MDA5 Ab seems to predict a group of patients with CADM-complicated fatal RPILD.


Stage (Ia) cervical cancer recurring 13 years after hysterectomy and causing small intestinal perforation. A case report with a review of the literature.
A rare case of recurrent cervical cancer presenting multiple metastases to the small intestine is reported. A 69-year-old Japanese woman with a past history of early-stage (Ia) cervical cancer 13 years previously suffered sudden onset of panperitonitis caused by perforation of the small intestine. In the perforated lesion, squamous cell carcinoma, which was histologically similar to that of the primary lesion, was observed, and was diagnosed as a late recurrence of the cervical cancer. Perforation of the small intestine caused by tumor metastasis, especially metastasis from cervical cancer, rerely occurs. Furthermore, recurrence of an early cervical cancer presenting 13 years after hysterectomy is extremely rare. The present case draws attention to the possibility of late recurrence of cervical cancer, even in cases treated at the early-stage.


Comparison of techniques to determine continence zone.
The urethral pressure profiles for 36 patients were analyzed specifically for continence zone by 3 techniques: 1) triangle, 2) planimeter and 3) weight. Graphically, the best agreement was between the weight and planimetry methods but, statistically, there was a significant difference among techniques except for the subgroup that had the smallest continence area.


Conjunctival ganglioglioma as a feature of basal cell nevus syndrome.
Basal cell nevus syndrome (MIM #109400), also known as Gorlin syndrome, is a rare, autosomal-dominant disorder with complete penetrance and variable expressivity. The syndrome is characterized by odontogenic keratocysts of the mandible, postnatal tumors, and multiple basal cell carcinomas. Mutations in the PTCH1 gene (a tumor suppressor gene) or, more rarely, the NBCCS or the TRPC1 genes are responsible for the development of many postnatal tumors. We present a case of Gorlin syndrome presenting as a conjunctival ganglioglioma in a 13-year-old girl. While cases of cerebral ganglioglioma have been described in association with Gorlin syndrome, conjunctival ganglioglioma has not, to the best of our knowledge, been reported.


Home Visiting Start-Up: Lessons Learned From Program Replication in New Mexico.
Growth in federal, state, and private funding is fueling the initiation of home visiting programs around the country. As communities expand home visiting programs, they need information to help them successfully start up new sites. This paper documents lessons learned about home visiting installation and initial implementation from the replication of the First Born(®) Program in six counties in New Mexico. Specifically, we examine how well sites met staffing, family referral and enrollment, program model fidelity, and financing goals in the first year of providing services. Data come from semi-structured interviews with program staff and document review. The findings are likely to be valuable to a wide spectrum of communities starting or expanding home visiting services, as well as to public and private funders of programs.


Expression of matrix metalloproteinase 12 is highly specific for non-proliferating invasive trophoblasts in the first trimester and temporally regulated by oxygen-dependent mechanisms including HIF-1A.
During first trimester pregnancy, trophoblast cells invade from the placenta into the maternal decidua where they anchor the placenta and remodel luminal structures like spiral arteries. This process depends on proteases secreted by invading trophoblasts, which degrade extracellular matrix (ECM). We here aimed to identify proteases particularly important for trophoblast invasion. We generated a list of proteases capable of degrading decidual ECM and trophoblast integrins using MEROPS database and compared expression of these proteases between primary trophoblasts isolated from first trimester placenta (FT, n = 3), representing an invasive phenotype, vs trophoblasts isolated from term pregnancy (TT, n = 3), representing a non-invasive trophoblast phenotype. Matrix metalloproteinase 12 (MMP12) revealed highest expression levels in FT, with absent expression in TT. In situ hybridisation and immunofluorescence localised MMP12 specifically to extravillous trophoblasts (evCT) whilst Ki67 co-staining revealed that proliferating trophoblasts of the cell columns were almost negative for MMP12. Quantification revealed a decline in MMP12 positive evCT at the end of first trimester, when oxygen levels start rising. MMP12 promoter analysis identified potential binding sites for hypoxia-inducible factor (HIF-1) and other oxygen-sensitive transcription factors. Moreover, MMP12 protein was increased by low oxygen in FT in vitro and by addition of a HIF-1α activator. Collectively, MMP12 is a highly expressed protease specific for invasive evCT during the first trimester. MMP12 down regulation by increasing oxygen concentration enables temporal expression control of MMP12 and involves several mechanisms including HIF-1α. These findings suggest MMP12 involved in trophoblast invasion during the first trimester.


MiR-222-3p inhibits formation of medulloblastoma stem-like cells by targeting Notch2/c-myc signaling pathway.
Medulloblastoma (MB) is an embryonal tumor of the cerebellum, which commonly occurs in childhood. Herein, we investigated the effects of miR-222-3p on the formation of MB stem-like cells via the Notch2/c-myc pathway. Quantitative real-time PCR (qRT-PCR) or western blotting was performed to determine the expression of miR-222-3p and Notch2, c-myc, proliferating cell nuclear antigen (PCNA), and caspase-3. Luciferase reporter gene, RNA immunoprecipitation (RIP), and RNA pull-down assay were applied to confirm the interaction between miR-222-3p and Notch2. Cell growth was examined by Cell Counting Kit-8. Cell cycle distribution and the number of stem cell marker CD133+ cells were examined using flow cytometry. The sphere formation assay was performed. miR-222-3p expression was decreased and Notch2 expression was increased in human medulloblastoma cells. miR-222-3p overexpression inhibited cell viability and the sphere formation, induced cell cycle arrest, decreased the number of CD133+ cells, and up-regulated caspase-3 expression and down-regulated PCNA, Notch2, and c-myc expression. However, Notch2 overexpression counteracted these effects of miR-222-3p overexpression. Simultaneous overexpression of Notch2 and miR-222-3p increased the c-myc promoter-luciferase activity which was decreased by miR-222-3p overexpression. Luciferase reporter gene, RIP, and RNA pull-down assay revealed that miR-222-3p targeted Notch2. MiR-222-3p suppressed cell viability, altered cell cycle distribution, and inhibited the formation of MB stem-like cells via the Notch2/c-myc pathway.


Effects of oral β- glucan on liver ischemia/reperfusion injury in rats.
Ischemia/reperfusion (IR) injury (IRI) in liver transplant patients may negatively affect graft function. Although β-glucan protects kidneys against IRI, its effect on the liver is unknown. This study sought to investigate β-glucan effects on oxidative damage to the liver after IRI in rats. Thirty-two rats were randomly divided into 4 experimental groups n = 8 in each group: sham, IR, β-glucan and IR + β-glucan. β-Glucan (50 mg.kg(-1) . day(-1)) was orally administered for 10 days to rats in the β-glucan and IR + β-glucan groups. The rats in the IR and IR + β-glucan groups were subjected to ischemia and reperfusion (IR) for 60 minutes each. All rats were killed on day 11 to evaluate histological changes as well as tissue levels of oxidants and antioxidants. Malondialdehyde (MDA) levels were significantly higher in the IR than the sham group (P = .001). MDA level was significantly higher in the IR group than in the IR + β-glucan group (P = .001). The levels of tissue antioxidant markers (superoxide dismutase [SOD], glutathione-peroxidase [GPx], and catalase [CAT]) were significantly lower in the IR group than in the sham group (P < .05). SOD and GPx levels did not differ significantly between the IR and IR + β-glucan groups. CAT activity was significantly higher in the IR than the IR + β-glucan group (P = .001). Histological tissue damage was reduced in the IR + β-glucan than the IR group. Liver IRI is an inevitable problem during liver surgery. Our results suggested that β-glucan pretreatment suppressed oxidative stress and increased antioxidant levels in an rat model of liver IRI.


Pharmacodynamic study of disulfiram in men with non-metastatic recurrent prostate cancer.
Preclinical drug screens identified disulfiram as a potent in vitro inhibitor of prostate cancer (PCa) cell growth. Although many mechanisms for its anticancer activity have been proposed, tumor suppressor gene re-expression through promoter demethylation emerged as one of the more plausible. We conducted an open-label, dose escalation trial of disulfiram in men with non-metastatic recurrent PCa after local therapy. Dose escalation occurred if a demethylating 'response' (that is, 10% decrease in peripheral blood mononuclear cell (PBMC) global 5-methyl cytosine (5(me)C) content) was observed in <3 patients in cohort 1. Cohorts 1 and 2 received disulfiram 250 mg and 500 mg daily, respectively. The primary end point was the proportion of subjects with a demethylation response. Secondary end points included the rate of PSA progression at 6 months, changes in PSA doubling time and safety/tolerability. Changes in global 5(me)C content were observed in two of nine patients (22.2%) in cohort 1 and 3 of 10 (30.0%) in cohort 2. Only five subjects were on trial for 6 months, all were in cohort 1 and all had PSA progression by 6 months. No changes in PSA kinetics were observed in either cohort. Disulfiram was poorly tolerated with six patients experiencing grade 3 adverse events (three per cohort). Three of the responders displayed pretreatment instability in their 5(me)C content. A minority of patients had transient global PBMC demethylation changes. Instability in 5(me)C may limit the reproducibility of these findings, limiting our ability to confirm our hypothesis. Given the toxicities and no clinical benefits, further development of disulfiram should not be pursued in this population.


Allelic loss of 10q23.3, the PTEN gene locus in cervical carcinoma from Northern Indian population.
Cervical cancer is one of the most common malignant diseases affecting women worldwide. Studies on loss of heterozygosity have been made for PTEN gene specific microsatellite markers in malignancies like breast, ovary and lungs and the results have shown a significant association. However the role of this gene is not clearly understood in cervical cancer from Indian population. A total of 135 cervical carcinoma tissues samples were analyzed for loss of heterozygosity. DNA was isolated from the samples and their matched control specimens. Polymerase chain reaction was performed using primer specific for two intragenic markers (D10S198 & D10S192) and one marker (D10S541) in flanking region and further electrophoresed on 8% denaturing polyacrylamide gel. Overall, 31 out of 133(23%) informative cases showed loss of heterozygosity in at least one locus in the region examined. The percentage of loss of heterozygosity for these markers ranged from 8% (D10S192) to 13% (D10S198). Loss of heterozygosity was more frequently detected in intragenic region (D10S198 & D10S192) than in flanking region, D10S541 (21% versus 9%). These data argue that PTEN is a tumor suppressor gene whose inactivation may play an important role in the carcinoma of uterine cervix.


What knowledge do ICU nurses have with regard to the effects of noise exposure in the Intensive Care Unit?
This small-scale study was undertaken to assess what knowledge nursing staff from a General Intensive Care Unit held with regard to noise exposure. To assess knowledge a self-administered multiple-choice questionnaire was used. Rigorous peer-review insured content validity. This study produced poor results in terms of the knowledge nurses held with regard to noise related issues in particular the psychophysiological effects and current legislation concerning its safe exposure. Non-parametric testing, using Kruskal-Wallis found no significant difference between nursing grades, however, descriptive analysis demonstrated that the staff nurse grade (D and E) performed better overall. Whilst the results of this study may seem self-evident in some respects, it is the problems of exposure to excessive noise levels for both patients and hospital personnel, which are clearly not understood. The effects noise exposure has on individuals for example decreased wound healing; sleep deprivation and cardiovascular stimulation must be of concern especially in terms of patient care but more so for nursing staff especially the effects noise levels can have on cognitive task performance.


Age, Sex and Overall Health, Measured As Frailty, Modify Myofilament Proteins in Hearts From Naturally Aging Mice.
We investigated effects of age, sex and frailty on contractions, calcium transients and myofilament proteins to determine if maladaptive changes associated with aging were sex-specific and modified by frailty. Ventricular myocytes and myofilaments were isolated from middle-aged (~12 mos) and older (~24 mos) mice. Frailty was assessed with a non-invasive frailty index. Calcium transients declined and slowed with age in both sexes, but contractions were largely unaffected. Actomyosin Mg-ATPase activity increased with age in females but not males; this could maintain contractions with smaller calcium transients in females. Phosphorylation of myosin-binding protein C (MyBP-C), desmin, tropomyosin and myosin light chain-1 (MLC-1) increased with age in males, but only MyBP-C and troponin-T increased in females. Enhanced phosphorylation of MyBP-C and MLC-1 could preserve contractions in aging. Interestingly, the age-related decline in Hill coefficients (r = -0.816; p = 0.002) and increase in phosphorylation of desmin (r = 0.735; p = 0.010), tropomyosin (r = 0.779; p = 0.005) and MLC-1 (r = 0.817; p = 0.022) were graded by the level of frailty in males but not females. In these ways, cardiac remodeling at cellular and subcellular levels is graded by overall health in aging males. Such changes may contribute to heart diseases in frail older males, whereas females may be resistant to these effects of frailty.


Atrial electromechanical delay in post-COVID-19 postural orthostatic tachycardia: Innocent bystander or pathologic factor.
Post-COVID-19 syndrome represents a wide range of ongoing symptoms that persist beyond weeks or even months, after recovery from the acute phase. Postural orthostatic tachycardia (POT) is one of these symptoms with a poorly recognized underlying pathophysiology. We aimed to investigate atrial electromechanical delay (AEMD), demonstrated by electrocardiographic P wave dispersion (PWD) and tissue Doppler echocardiography (TDE) in patients with POST-COVID-19 POT (PCPOT). 94 post-COVID-19 patients were enrolled and classified into two groups; PCPOT group, 34 (36.1%) patients, and normal heart rate (NR group), 60 (63.9%) patients. 31.9% of them were males and 68.1% were females, with a mean age of 35 ± 9 years. Both groups were compared in terms of PWD and AEMD. As compared to the NR group, the PCPOT group showed a significant increase in PWD (49 ± 6 versus 25.6 ± 7.8, p < 0.001), higher CRP (37 ± 9 versus 30 ± 6, p = 0.04), prolonged left-atrial EMD, right-atrial EMD and inter-atrial EMD at (p = 0.006, 0.001, 0.002 respectively). Multivariate logistic regression analysis revealed that P wave dispersion (β 0.505, CI (0.224-1.138), p = 0.023), PA lateral (β 0.357, CI (0.214-0.697), p = 0.005), PA septal (β 0.651, CI. (0.325-0.861), p = 0.021), and intra-left atrial EMD (β 0.535, CI (0.353-1.346) p < 0.012) were independent predictors of PCPOT. Atrial heterogenicity in the form of prolonged AEMD and PWD seems to be a reasonable underlying pathophysiology of PCPOT. This could provide a new concern during the management and novel pharmacological approaches in these patients.


[Radio-ulnar and radio-scaphoid-lunate arthrodesis in chronic polyarthritis. Clinical and radiologic follow-up of 32 cases].
In 75% of all cases of rheumatoid arthritis the wrist is affected and in 12% is the region of initial manifestation of this chronic inflammatory joint disease. To prevent destruction of the wrist through carpal dislocation, radiolunate and radioscapholunate arthrodeses have increased in importance. During a 6.5-year period, 28 radiolunate and 4 radioscapholunate arthrodeses were performed in 30 patients. The indication for operation was progressive carpal translation and increasing subluxation of the wrist in which existent radiological damage had not reached more than grade III according to the classification of Larsen and co-workers. The results obtained during the follow-up study (median: 17.3 months) showed in most treated patients after partial arthrodesis of the wrist no or fewer complaints concerning swelling and pain and an acceptable remaining range of motion of the wrist in everyday life. In patients with preoperatively existing ulnar deviation less than 15 degrees progressive carpal collapse and dislocation could be mostly prevented. All told radiolunate and radioscapholunate arthrodeses successfully stabilized the wrist in patients suffering from rheumatoid arthritis.


Status of carotenoids in elite and landrace maize genotypes: Implications for provitamin A biofortification in Tanzania.
Maize is among the crops containing carotenoids that are easily converted to vitamin A and have an enormous influence on consumers' health. Principally maize has high calories and proteins but has less number of other micronutrients such as vitamin A. Societies that use maize as their main and sole staple food are likely to be affected by vitamin A deficiency. Thus, development and production of maize varieties rich in micronutrients and vitamin A are important for improved health. This study characterized 5 carotenoid components in maize genotypes grown in Tanzania as a strategy for improving vitamin A content in maize. The study involved maize landraces, commercial or elite varieties, and inbred lines in determining their potential for provitamin A breeding programs for nutrition improvement. The study found that mean concentration of important carotenoid components, i.e., alpha carotene (AC), beta-carotene (BC), beta-cryptoxanthin (BCX), lutein (LU), zeaxanthin (ZX), provitamin A (ProVA), non-provitamin A (Non-ProVA), and total carotenoids (TC) varied significantly (P < 0.001) among maize genotypes. The 3 maize groups studied (landraces, commercial varieties, and breeding materials (BMs) varied significantly. For maize landraces, the concentration (µg/g) of studied carotenoids were AC (0.13-2.67), BC (0.60-3.72), BCX (0.36-1.01), ProVA (0.89-5.29), Retinol (0.25-0.87), LU (2.37-16.97). ZX (0.16-4.41), Non-ProVA (2.4-19.01), and TC (3.68-25.27); in commercial or elite maize varieties were (in µg/g): AC (0.31-3.84), BC (0.56-6.5), BCX (0.46-2.58), ProVA (0.92-11.80), Retinol (0.15-1.82), LU (3.28-22.39). ZX (0.05-11.31), Non-ProVA (2.56-28.81), and TC (4.23-37.84); and for maize BMs AC (0.53-6.64), BC (1.92-13.87), BCX (0.65-6.51), ProVA (2.69-18.62), Retinol (0.5-3.1), LU (4.86-34.99), ZX (0.06-18.58), Non-ProVA (4.8-53.57), and TC (9.86-76.94). Furthermore, the study found that the concentration of studied carotenoids was higher in pigmented (yellow or red) maize genotypes than in white maize genotypes. The current study found an appreciable amount of ProVA in studied materials, including maize landraces, commercial yellow varieties, and CIMMYT lines. The concentration of ProVA and retinol determined in studied maize genotypes were below 15 µg/g a daily vitamin A requirement, thus based on the current ProVA and retinol status it is difficult to meet Vitamin A requirement. Therefore, these maize genotypes with promising levels of carotenoid components are potential breeding materials that can be used in maize provitamin A biofortification program for improved food nutrition and livelihoods in Tanzania.


[Ultrastructural informational analysis of the dynamics of liver cell recovery after performance of a biliodigestive anastomosis in mechanical jaundice].
Hepatic ultrastructure has been studied in dogs at the level of cholestasis and at different time after cholecystenteroanastomosis. Owing to theoretico-informative approach applied in the investigation, it was possible to reveal certain essential disorganization in hepatic ultrastructures on the 7th day after the operation. This phenomenon seems to explain the occurrence of acute hepatic insufficiency at early postoperative stages not infrequently observed in clinic. Changes produced by 30-days' cholestasis are demonstrated to be reversible.


Glucagon-like peptide-1 receptor agonist Exendin-4 improves neurological outcomes by attenuating TBI- induced inflammatory responses and MAPK activation in rats.
Traumatic brain injury (TBI) can be exacerbated and prolonged for months or even years by chronic inflammatory processes with long-term consequences on neurodegeneration and neurological impairment. However, there are no clear pharmacological therapies of benefit to manage neurological dysfunctions, which, relating to the molecular mechanisms underlying the behavioral deficits after TBI, have yet to be fully identified. Recently, a glucagon-like peptide 1 (GLP-1) agonist, Exendin-4, was approved not only for the treatment of type 2 diabetes mellitus, but it also played a neurotrophic role in various CNS neurological diseases. In this study, we evaluated the neuroprotective effects of Exendin-4 on neurological outcome, cerebral blood flow, neurodegeneration, and inflammatory responses by utilizing a cortical contusion impact injury (CCI) model in rats. We found that TBI rats displayed neurological impairments, neurodegeneration, reduction of cerebral blood flow, and inflammatory responses, while Exendin-4 promoted neurological, cognitive, and cerebral blood flow recovery and attenuated neural degeneration and inflammatory cytokines after TBI. Furthermore, Exendin-4 treatment significantly diminished the TBI-induced overexpression of TNFα and IL-1β, as well as phosphorylation of p38 and ERK1/2. These data suggest a strong beneficial action of the glucagon-like peptide-1 receptor agonist Exendin-4 in improving neurological outcomes by attenuating inflammatory responses induced by traumatic brain injury, which is of therapeutic potential for TBI.


Fertilization and early seed formation.
The double fertilization of flowering plants is a complex process, encompassing multiple steps. From its discovery more than a century ago, many useful descriptive approaches have been employed to better unveil specific steps/mechanisms. More recently, the development of an in vitro assay developed in our laboratory, has allowed a better understanding of this phenomenon. However, in vitro methods may show some limitations. The search for complementary strategies, especially with the search of mutants affected in the fertilization step allowed one to elucidate this critical and unique phenomenon in living organisms. Genes involved in pollen tube guidance or pollen discharge in synergids have been identified, as well as genes exhibiting differential expression in sperm, egg and central cells before and after fertilization. A calcium wave proved to correspond to the first cellular event seen after cytoplasmic fusion in the fertilized egg cell or zygote, which develops into a multi-cellular organism with an elaborate body plan. The development of the fertilized central cell into a nourishing tissue (endosperm) starts with the formation of the coenocyte, a multinuclear single cell unique in the plant kingdom, cellularization occurring later on. The balance of the paternal and maternal genomes, which is under the control of the FIS polycomb group complex, was found to be of the utmost importance for the successful development of the seed.


Confronting Structural Racism in the Prevention and Control of Tuberculosis in the United States.
Tuberculosis incidence in the United States is declining, yet projections indicate that we will not eliminate tuberculosis in the 21st century. Incidence rates in regions serving the rural and urban poor, including recent immigrants, are well above the national average. People experiencing incarceration and homelessness represent additional key populations. Better engagement of marginalized populations will not succeed without first addressing the structural racism that fuels continued transmission. Examples include:(1)systematic underfunding of contact tracing in health departments serving regions where Black, Indigenous, and People of Color (BIPOC) live;(2) poor access to affordable care in state governments that refuse to expand insurance coverage to low-income workers through the Affordable Care Act;(3) disproportionate incarceration of BIPOC into crowded prisons with low tuberculosis screening rates; and(4) fear-mongering among immigrants that discourages them from accessing preventive health services. To eliminate tuberculosis, we must first eliminate racist policies that limit essential health services in vulnerable communities.


Treatment and survival of primary intracranial germ cell tumors: a population-based study using SEER database.
Primary intracranial germ cell tumors are rare neoplasms derived from gonadal cells. They are categorized as germinoma, non-germinomatous germ cell tumor (NGCCT), or teratoma, with the latter two sparking controversy regarding the role of different treatment strategies. We provide the largest multicenter analysis of treatment outcomes for iGCTs to date. The Surveillance, Epidemiology, and End Result (SEER) database were used to record patient demographics, tumor, and treatment characteristics. Cox proportional hazards model and multiple comparisons for the Logrank test with Sidak correction was applied to compare the different treatment regimens and survival. 1043 iGCT cases were divided into three cohorts of Germinoma, Malignant Teratoma (MT), and NGGCT. The mean age was 17.7 years for germinoma, 9.5 years for MT, and 14.4 years for NGGCT groups. Males comprised 77% of overall patient population. For Germinomas, both biopsy (hazard ratio [HR] = 4.6) and resection (HR = 14.1) had significantly worse survival outcomes compared to solo radiation therapy, with no difference between radiation and chemotherapy. For MT, no treatment combination had significantly different survival outcomes compared to resection alone. For NGGCTs, resection + chemotherapy + radiotherapy (HR = 0.012) and resection + chemotherapy (HR = 0.0049) had significantly better survival compared to resection alone. In germinomas, radiotherapy alone had superior survival outcomes compared to biopsy and resection, but no change in survival when compared to chemotherapy alone. Addition of radiotherapy or chemotherapy did not improve survival in MTs when compared to resection alone. Adding chemotherapy in NGGCT patients undergoing resection improved survival compared to resection alone.


Isolation of a natural cytotoxic IgM "antibody" in human serum sensitizing L cells to complement.
An IgM fraction of human serum was isolated and purified. A portion of this fraction firmly attaches to L cells' surfaces, which sensitizes these cells to the lytic action of low concentrations of serum C. It contains the natural cytotoxic "antibody" to L cells.


The sexual differentiation of social play.
Sex differences in social play are quantitative and not qualitative, referring to frequency and not the form of the behaviors. Whereas increased perinatal exposure to exogenous testosterone masculinizes social play, experimental manipulations of androgen levels after this period (i.e. following critical periods for neuronal differentiation) apparently have no effect on the expression of social play. This effect appears to involve, at least in part, androgen receptor occupancy in the amygdala. In the rat, there is a prominent sex difference in nuclear-bound androgen receptors in the amygdala during the sensitive period for the masculinization of play-fighting. Moreover, testosterone implants directly into the amygdala during this period masculinize social play in females. Progesterone exposure reduces play-fighting in male rats, as does corticosterone. This latter effect may be mediated by corticosteroid receptors in the limibic brain. Perinatal androgen exposure may also be important in humans, since girls born with congenital adrenal hyperplasia diagnosed and treated at birth still show male-like patterns of play. Theories concerning the function of sex differences in social play emphasize either the social or motor learning functions. Juvenile male primate social rank correlates with number of peer social interactions, which predominantly take the form of play-fighting. Females on the other hand appear to spend less time play-fighting and spend more time waiting and competing for interactions with infants, i.e. play-mothering, whereby they acquire the motor skills necessary for handling infants. Such differences may reflect socio-biological and developmental cascades that are, in some way, initiated by perinatal hormonal events.


Intra-observer and Device-Dependent Inter-observer Reliability of Contrast-Enhanced Ultrasound for Muscle Perfusion Quantification.
Muscle perfusion quantification by contrast-enhanced ultrasound (CEUS) may facilitate treatment decisions in musculoskeletal disorders. Translation into clinical routine relies on high intra-observer and inter-observer reliability and transferability between ultrasound devices to enable validation and multicenter studies. This study evaluates these aspects for deltoid muscle perfusion quantification, including possible multicenter study setups. One hundred sixty-six CEUS quantifications were conducted on 42 shoulders. Intra-observer reliability revealed a high intra-class correlation coefficient (ICC, r = 0.91) and low coefficient of variation (CV, 10.28%). Inter-observer reliability revealed an ICC of .84 and a CV of 17.1%, but these values decreased when different ultrasound devices were used (ICC = .60, CV = 18.6%). Re-evaluating subgroups with high sectional plane concordance significantly increased reliability (intra-observer: ICC = .97, CV = 5.49%, inter-observer/same device: ICC = .98, CV = 5.83%, varying devices: ICC = .78, CV = 9.8%). CEUS perfusion quantification of the deltoid seems applicable for multicenter studies, yet pooling different ultrasound devices remains critical. Sectional plane concordance appears to be crucial for reliability and transferability of CEUS muscle perfusion quantifications.


Long-lasting inhibition of neuron R15 of Aplysia: role of the interneuron II network.
Stimulation of the branchial or either connective nerve of the abdominal ganglion of Aplysia californica evokes simultaneous responses in cells R15, L8, L9, and L11 which are indistinguishable from those arising from spontaneous interneuron II (INT II) activity. Threshold for the INT II-like response in all cells is identical, suggesting that the response is mediated by INT II activity. The magnitude of the response in each cell increases with stimulus intensity and is subject to both temporal and spatial summation, implying the existence of multiple fibres in each nerve which converge on INT II. Repetitive stimulation evokes long-lasting inhibition in R15. The onset of this phenomenon is always accompanied by an INT II burst in the other follower cells. Long-lasting inhibition in R15 is not accompanied by prolonged INT II activity, suggesting an endogenous mechanism of inhibition. The phosphodiesterase inhibitor, IBMX, potentiates the response of R15 to nerve stimulation without affecting threshold for the response. This is consistent with inhibition by a mechanism endogenous to R15.


"We Need Other Human Beings in Order to be Human": Examining the Indigenous Philosophy of Umunthu and Strengthening Mental Health Interventions.
This paper examines how cultural, historical and contemporary perspectives of mental health continue to inform ways of understanding and responding to mental distress even under the biomedical gaze of the Movement for Global Mental Health (MGMH). Based on experiences in Malawi, the authors explore three prominent interventions (practical support, counselling and support groups) employed by village health workers within a mental health task-shifting initiative and reveal how the ancient philosophy of Umunthu with its values of interconnectedness, inclusion and inter-relationships informs and shapes the direction of these interventions. Practical support is marshalled through traditional village structures, counselling provides advice and an encouragement to hope, and support groups provide a place for emotional exchange and a forum for the enactment of values, reflection and reinforcement of Umunthu. What are pronounced as biomedical psychosocial interventions are in fact the delivery of culturally embedded therapeutic approaches. Historical and socio-political evidence is offered to explain the dominance of biomedical perspectives and the HSAs' responses and a call is made for a transformation of MGMH to embrace rich philosophies such as Umunthu and enact respectful, inclusive and democratic values to enlist collaborations between equals to develop relevant and effective knowledge and local responses to mental distress.


Bedside quantification of atherosclerosis severity for cardiovascular risk stratification: a prospective cohort study.
We sought to assess the ability of a new noninvasive method to quantify atherosclerosis severity and to examine its power to predict cardiovascular events. Drug prevention of cardiovascular events is effective but costly, leading to a debate about who should receive this treatment. Patient selection is often based on surrogate markers, but quantification of atherosclerosis severity is desirable. Atherosclerosis severity was quantified by determination of specific aortic wall elastance in transthoracic echocardiography, applying the biomechanics of pulse wave propagation. After validating the method in 52 patients by measuring aortic plaque burden in transesophageal echo directly, another 336 patients were prospectively studied by monitoring atherosclerotic events at one year and comparing the results with conventional risk stratification. Specific aortic elastance was well correlated with plaque burden (p < 0.0001) and largely independent of confounding variables. Specific aortic elastance predicted the primary end point of "atherosclerotic death, myocardial infarction or stroke" at one year (p < 0.0002). Event rate at one year in the lowest specific elastance tertile was 1.8% (CI 0.0% to 4.3%), in the middle tertile 5.4% (CI 1.1% to 9.7%) and in the highest tertile 12.7% (CI 6.3% to 19%). Secondary end points supported these findings. Stepwise multivariate analysis identified specific aortic elastance, prior atherosclerotic events and left ventricular ejection fraction as independent risk predictors. Specific elastance was of incremental value to clinically identified variables. Bedside measurement of specific aortic elastance allows assessment of atherosclerosis severity. It predicts the risk for future atherosclerotic events beyond conventional risk factors, promising better targeting of pharmacologic prevention and improved cost effectiveness.


The Home Program Advantage in the Otolaryngology Residency Match.
To evaluate the effect of home residency programs on outcomes in the otolaryngology residency match DESIGN: A retrospective online survey study during the 2015, 2018, 2019, 2020, and 2021 match cycles was conducted. All available otolaryngology residency positions listed by the National Resident Matching Program were compared with publicly available spreadsheets containing the following information: matriculated applicant name, medical school, whether the final match institution was the matriculated applicant's home program (HP), whether the matriculated applicant had completed an away rotation at their final matched institution (designated away institution, AI), or neither (designated Other Institution, OI). Nonclinical survey study using publicly available spreadsheets containing The Match data from 2015 to 2021 located online at Otomatch.com. Newly matched United States otolaryngology-head and neck surgery residents completing the Otomatch.com survey RESULTS: A total of 1771 matched OHNS applicants were identified. Fifty-one percent of students were affiliated with their matched institution, with 25% of students matching at HPs, and 26% matching at AIs. Students with home programs had an increased likelihood of remaining in the same geographic region compared to students without home programs (OR 1.742 95% CI [1.21-2.506], p = 0.003). Applicants with HPs matched at significantly larger residency programs (p < 0.001). This study found that a majority of residents match at an institution with which they were affiliated, either their home program or away institution. Applicants with HPs are more likely to remain in the same geographic region as their medical school, and to match into larger residency programs compared to applicants without HPs.


Purification and characterization of different types of exfoliative toxin from Staphylococcus aureus.
Exfoliative toxin was isolated from strain DI of Staphylococcus aureus using carboxymethyl cellulose and hydroxylapatite chromatography. This purified toxin was compared with that produced by strain TA. The specific biological activity of the two toxins was the same, but they were serologically distinct. These strains have different loci (plasmid or chromosomal) for toxin production; differences were seen in molecular weight and amino acid composition. N-terminal amino acid sequences from the two strains showed significant homology using a single unit alignment shift.


Arterial stiffness and physical fitness on cognitive function in community-dwelling middle-aged and older adults.
This study examined whether decline in cognitive function is related to arterial stiffness and reduction in physical fitness in middle-aged and older adults. A total of 1554 healthy middle-aged and older adults participated in this study. The trail making test parts-A (TMT-A) and B (TMT-B), brachial-ankle pulse wave velocity (baPWV), grip strength, the 30-s chair stand (CS-30) test, the 6-min walk (6MW) test, the 8-foot up-and-go (8UG) test and gait assessment were performed. Participants were classified into a middle-aged group (40-64 years; mean, 50.4 ± 0.2 years) or an older group (≥ 65 years; mean, 73.1 ± 0.5 years), as well as into three cognition (COG) groups (high, moderate, and low) based on median TMT-A and -B scores (high scores on both, either, or neither TMT-A and -B, respectively). The results revealed that baPWV was significantly lower in the high-than in the moderate- and low-COG groups in both middle-aged and older adults (P < 0.05). In addition, except for a few parameters (e.g., 6MW test in middle-aged adults), physical fitness was significantly higher in the high-than in the moderate- and low-COG groups in both middle-aged and older adults (P < 0.05). Multivariate regression analysis revealed that baPWV (P < 0.05) and some physical fitness indicators (grip strength, CS-30, and 8UG) were significantly independently associated with both TMT-A and -B in the middle-aged and older groups (P < 0.05). These results suggest that increased arterial stiffness and reduced physical fitness are associated with impaired cognitive function in middle-aged and older adults.


New technique for airway correction in neonates with severe Pierre Robin sequence.
To avoid tracheostomy in 11 neonates with severe Pierre Robin sequence, we used a technique of progressive elongation of the mandible (distraction osteogenesis) to correct tongue ptosis, increase pharyngeal airway, and correct micrognathia. All 11 patients were extubated within 3 to 6 days after beginning distraction. At 1 month 54.5% were oral feeders and at 1 year, 100%. Sleep studies were obtained on 7 patients and were normal 1 week to 1 month after operation. Growth was observed to be above the 50th percentile in all patients with no comorbidities. A 5-year clinical follow-up showed the operated mandible to maintain a normal shape and produce an undisturbed tooth eruption sequence. We conclude that distraction osteogenesis to increase the length of the short mandible is an effective alternative to tracheostomy in carefully selected patients.


Bayesian evaluation of the effect of non-genetic factors on the phenomics for quality-related milk nutrients and yield in Murciano-Granadina goats.
The aim of this study was to evaluate the effect of non-genetic factors on the variability of milk production and composition using Bayesian linear regression. We analyzed 2594 milk records from 159 dairy goats from the breeding nucleus of the Murciano-Granadina breed. Bayesian linear regression was used to determine the effects of non-genetic factors on the phenomics for quality-related milk nutrients and yield. Multivariate regression model significantly explained 21.5%, 40.0%, 41.5%, 44.3%, 44.6%, and 47.5% of the variability in somatic cell count (SCC, sc/mL), lactose (%), protein (%), milk yield (kg), fat (%), and dry matter (%), respectively. Although the aforementioned factor combination significantly conditions milk production and composition, SCC may be particularly affected by collateral factors. Milking routine and drying period factors are reference predictors to be considered in the evaluation of milk production and composition progression. Drying period extensions positively repercussed on milk yield and lactose content, but negatively affected fat, protein, dry matter contents, and somatic cell count. Variability across drying years may depend on the drying season rather than the drying month course, except for milk yield, for which an increasing trend was reported from winter to summer. Including drying period-related non-genetic factors in genetic evaluations improves the accuracy of the regression models and permits to boost the commercial possibilities and profitability of local breeds.


Late Axillary Recurrence After Negative Sentinel Lymph Node Biopsy is Uncommon.
This study was designed to determine the incidence of late axillary recurrence (AR) in patients with negative sentinel lymph node biopsy (SLNB) and provide a comparison with SLNB positive patients who underwent axillary lymph node dissection (ALND). Retrospective analysis of prospectively collected data on all breast cancer patients with negative SLNB from January 1997 to December 2000 was performed on a large, institutional database. Primary outcome was cumulative incidence of AR as a first event with/without concurrent local recurrence. SLNB positive patients who went on to ALND during the same timeframe were comparatively analyzed. A total of 1529 eligible patients were identified (median age 58 years, median tumor size 1.0 cm): 1297 (85 %) underwent lumpectomy; 1099 (75 %) received adjuvant radiation; and 874 (80 %) were estrogen receptor-positive. At 10.8 (range 0-16) years median follow-up, overall incidence of AR as a first event was low (n = 13). Cumulative incidence was 0.6 % [95 % confidence interval (CI) 0.2-0.9] 5 years after SLNB, and 0.9 % (95 % CI 0.4-1.4, 95 % CI 0.5-1.6) at 10 and 15 years. Late AR (>5 years after surgery) occurred in five patients. Median overall survival after AR was 4.6 years; median distant disease-free survival after AR was 3.8 years. Late AR was also low in a contemporaneous group of SLNB positive patients undergoing ALND. In this group, cumulative incidence of AR was 0.7 % (95 % CI 0.1-1.3) 5 years after surgery, and 0.8 % (95 % CI 0.2-1.5) at 10 and 15 years. Late AR after negative SLNB is rare; the majority of ARs are in the first 5 years after surgery. Prognosis after these events is poor. SLNB remains a safe and effective procedure for axillary evaluation in breast cancer.


Misoprostol provides a colonic mucosal protective effect during acetic acid-induced colitis in rats.
This study determined if intracolonically applied prostaglandin E1 analogue (misoprostol) had a mucosal protective effect in rats with 4% acetic acid-induced colitis. The effects of misoprostol were compared with those of 5-aminosalicylic acid and betamethasone. A single application of 4% acetic acid induced an experimental colitis which was maximal at 2 days and showed spontaneous macroscopic and histologic healing by 12 days. Misoprostol (100 micrograms/kg), but not 5-aminosalicylic acid or betamethasone, administered 30 min before induction of colitis, provided macroscopic and histologic colonic mucosal protection but not protection of in vivo fluid absorption. The mucosal protective effect of misoprostol was time, dose, and diluent volume dependent. In the presence of misoprostol-induced colonic morphologic but not functional absorptive mucosal protection, in vitro unidirectional sodium and chloride flux measurements showed protection of theophylline-stimulated chloride secretion but not sodium absorption. Protection of in vivo colonic fluid absorption, in addition to morphologic protection, could be achieved when misoprostol was administered between 2 and 16 min before induction of colitis or when the highest dose (1000 micrograms/kg) of misoprostol was examined. We conclude that intracolonic misoprostol administration provides unique mucosal protective effects in experimental colitis.


Decreased tumorigenesis and mortality from bladder cancer in mice lacking urothelial androgen receptor.
Much fewer mice lacking androgen receptor (AR) in the entire body develop bladder cancer (BCa). However, the role of urothelial AR (Uro-AR) in BCa development remains unclear. In the present study, we generated mice that lacked only Uro-AR (Uro-AR(-/y)) to develop BCa by using the carcinogen BBN [N-butyl-N-(4-hydroxybutyl)-nitrosamine] and found that Uro-AR(-/y) mice had a lower incidence of BCa and a higher survival rate than did their wild-type (WT; Uro-AR(+/y)) littermates. In vitro assay also demonstrated that Uro-AR facilitates the neoplastic transformation of normal urothelial cells to carcinoma. IHC staining exhibited less DNA damage, with much higher expression of p53 and its downstream target protein PNCA in Uro-AR(-/y) than that found in WT urothelium, which suggests that Uro-AR may modulate bladder tumorigenesis through p53-PCNA DNA repair signaling. Indeed, Uro-AR(-/y) mice with the transgene, simian vacuolating virus 40 T (SV40T), in the urothelium (Uro-SV40T-AR(-/y)) had a similar incidence of BCa as did their WT littermates (Uro-SV40T-AR(+/y)), and p53 was inactivated by SV40T in both genotypes. Use of the AR degradation enhancer ASC-J9 led to suppression of bladder tumorigenesis, with few adverse effects in the BBN-induced BCa mouse model. Together, these results provide the first direct in vivo evidence that Uro-AR has an important role in promoting bladder tumorigenesis and BCa progression. Targeting AR with ASC-J9 may provide a novel approach to suppress BCa initiation.


Effect of hydroalcoholic leaves extract of Indigofera spicata Forssk. on blood glucose level of normal, glucose loaded and diabetic rodents.
Diabetes mellitus is found in all parts of the world and is rapidly increasing in its coverage with alarming rate especially in Asia and Africa. Research is increasingly done with the aim of developing a relatively safe and efficacious anti-diabetic plant based products. Parallelly, this investigation was carried out to evaluate the effect of the hydro alcoholic leaves crude extract of Indigofera spicata (ISP) on the blood glucose level(BGL) of normoglycemic, oral glucose loaded and alloxan induced diabetic rodents. The animals were randomly divided into five groups (n = 6) for all the aforementioned three models. In all models, group-I mice provided 2%tween-80, group-II were treated with 5 mg/kg glibenclamide and the remaining three groups (III, IV & V) were treated with 100, 200, and 400 mg/kg dose of the extract respectively. Statistical significance of differences in BGLs within and between groups was analyzed by SPSS version-21 using one way ANOVA followed by Tukey's post hoc multiple comparison. 200 mg/kg and 400 mg/kg extract treated groups of normoglycemic mice showed significant (p < 0.05) BGL reduction compared to the pre-exposure level. In case of OGTT model BGL reduction was statistically significant (p < 0.05) in only 400 mg/kg exposed groups at the 120 min of post-exposure compared to the initial level. However, the BGL reducing effect of doses of the extract at the 4(th), 6(th) and 10(th) hours of post treatment on diabetic mice was found statistically significant compared to both the negative control (p < 0.001) and their respective pretreatment levels (p < 0.05). As it is claimed in ethnobotanical studies, the hydroalcoholic crude extract of ISP leaves have shown prominent anti-diabetic effect and can be therefore used as a good insight for new anti-diabetic drug source with a call for further studies.


Trends in childhood and adolescent obesity prevalence in Oviedo (Asturias, Spain) 1992-2006.
To analyse obesity and overweight prevalence trend in Oviedo (Spain) during the last 14 years. Two cross-sectional studies were conducted in the same five public schools of the urban area of Oviedo in 1992 and 2004-06. One thousand one hundred sixty-five children and young adults between the age of 6 and 17 years were studied in 1992 and 1312 in 2004-06. Obesity and overweight were defined according to the International Obesity Task Force cut-off values. Body mass index (BMI) values (20.5+/-3.6 vs. 20.1+/-3.3 p=0.02) and obesity prevalence (6.3% vs. 4.5% p<0.05) were significantly higher in the 2004-06 cohort, while overweight prevalence showed a non-significant increase. Obesity prevalence increased in both sexes in the 6-11-year group. In adolescent females, a four-fold increase was observed, from 0.9% in 1992 (95% CI: -0.1 to 1.9) to 3.8% in 2004-06 (95% CI: 1.8-6). A slight non-significant decrease was observed in adolescent males (6.6% in 1992 to 5.8% in 2004-06). Obesity and overweight are increasing in children and adolescents in Oviedo at a level similar to that observed in studies conducted in developed countries. This obesity epidemic is becoming an important public health issue.


Inhibitory effects of beryllium chloride on rat liver microsomal enzymes.
A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.


Traumatic dislocation of the first metatarsophalangeal joint with tibial sesamoid fracture: a case report of a type III B dislocation.
We present a case report about traumatic dislocation of the first metatarsophalangeal joint and patterns of injury. We are unaware of previous reports in the literature describing this unusual variant.


[Nuclear magnetic resonance spectroscopy and hepatic metabolism. Real time study of cell energy and intermediate metabolism in the isolated and perfused rat liver].
Nuclear magnetic resonance spectroscopy is increasingly used to study cellular metabolism in a manner respecting cell integrity. The contribution of phosphorus-31 and carbon-13 NMR is discussed and illustrated by specific examples taken from work on hepatic metabolism carried out in this laboratory. Particular emphasis is laid on metabolite identification, quantitation and fluxes as studied by phosphorus-31 NMR which provides a direct insight of energy metabolism. The analysis of perfused rat liver by naturally abundant carbon-13 NMR illustrates the potential of the method to study non invasively lipid and carbohydrate metabolism in living systems. The use of carbon-13 enriched substrates to pinpoint a specific pathway of the intermediary metabolism is described in the case of excised rat liver perfused with (2-13C)-acetate.


Confident to seek help: the development of skill and judgement in nurse practitioners. A mixed methods study.
Healthcare is undergoing a transformation in terms of traditional role and skill assignations of staff, with an attendant blurring of boundaries. Expert judgement is used in order to develop and assess learners as they prepare for these new roles. To determine factors related to the perceived usefulness of feedback, to find out how participants use expert judgement, to develop skill and to examine how the context of learning affects the development of judgement. Four NHS Health Board areas within Scotland. 95 nurse practitioners who had successfully completed a specified course of skills based education between September 2008 and August 2010. 10 participants agreed to follow up interview. Survey and follow-up semi-structured interviews. Mixed methods. 20 item, internet based questionnaire (n = 85) and semi-structured interviews (n = 10), collected between September 2010 and February 2011. Response rate was 55%-confidence level of 99%, this sample yields a confidence interval of 12.9%. The results demonstrate that the demonstration of skill and the perception of expertise of the supervisor are related to the perceived usefulness of feedback (p < 0.004). The participants use feedback as one strategy to develop skill and judgement, although the mining of the tacit knowledge of medical colleagues, reference to associated theory and peer support and learning strategies are also seen to be important. The development of judgement is restricted by the tightly controlled learning environment. Identification of participants with the expertise of the supervisory group reveals a group who are highly aspirational and for whom the governance of learning leads the participants to be confident to seek help and not the confidence to identify learning needs. Learning is seen to be dominated by the context in which it is set and as the participants learn motor skills, they learn to fit in and manage a brittle working environment.


Intraabdominal adhesion formation after preperitoneal dissection in the murine model.
The laparoscopic approach to hernia repair has been advocated by many as a potentially superior method of herniorraphy. Several techniques have been described, each with its own proposed advantages. These techniques involve different anatomic approaches, the most recent of which is the totally extraperitoneal approach (TEPA). One presumed advantage of the extraperitoneal approach is the avoidance of adhesion formation because the peritoneum is not entered and mesh is not placed in direct contact with intra-abdominal structures. We hypothesize, however, that when the peritoneum is dissected from the abdominal wall, it is partially devascularized, leading to scar formation and potential adhesion formation. This would suggest that the TEPA method of herniorraphy may not completely avoid the risks of intra-abdominal adhesion formation. After appropriate approval was obtained, 88 male Sprague-Dawley rats were divided into two equal groups. One group underwent laparotomy followed by careful blunt dissection of the peritoneum from the left abdominal wall. The control group underwent laparotomy without manipulation of the peritoneum. All animals were re-explored 14 days later, and the abdominal cavity was examined for adhesions. The type and location of any adhesion was recorded. Adhesion formation occurred in 10 of 44 (23%) subjects in the peritoneal dissection group, compared with 3 of 44 (7%) in the nondissection group (p < 0.05). Dissection of the peritoneum from the overlying abdominal wall in the murine model leads to intra-abdominal adhesion formation. This suggests that peritoneal dissection in the TEPA method of herniorraphy may lead to intra-abdominal adhesion formation.


Involvement of reverse transcription in the replication of cauliflower mosaic virus: a detailed model and test of some aspects.
A model is presented according to which cauliflower mosaic virus (CaMV) DNA is replicated via an RNA intermediate. The model explains the typical S1 nuclease-sensitive sites in mature CaMV DNA, the occurrence of the large, terminally redundant transcript, the local separation of CaMV transcription and CaMV assembly, the abundance of knotted CaMV DNA forms, and the high recombination frequency. A site of perfect homology to plant tRNA was detected. Extracts from a mixture of nuclei and inclusion bodies can be separated into fast-sedimenting complexes elongating endogenous CaMV RNA, and slow-sedimenting ones elongating endogenous CaMV DNA. The CaMV DNA synthesis can be partly inhibited both by RNAase and actinomycin D, suggesting the presence of a mixture of RNA- and DNA-templates.


Geographic variation in shape and size of anuran tadpoles: Interpopulation comparisons in Scinax fuscovarius (Anura, Hylidae).
Among anuran species with biphasic life cycle, the occurrence of intraspecific larval morphotypes has been related to variations in developmental time, diet, geographical variation, or response to predators. Here, we evaluated the external morphological variation of larvae among three populations, located more than 270 km apart, of the anuran hylid Scinax fuscovarius by linear and geometric methods, to elucidate the presence of geographically different morphs. Comparisons targeted development, growth, and external morphology. Studied populations exhibited differences in reproductive seasonality, growth rate, timing of development, shape, and size. Shape and size comparisons revealed two well-differentiated morphs, one of them shared by the two closest populations. Morphological differences evidenced a smaller and depressed form of the entire body plan in the most distant population, which showed continuous reproduction throughout the rainy season and under more unpredictable conditions. We interpret the occurrence of the two different larval morphs in S. fuscovarius as a by-product of local geographical conditions, and discuss on possible associations with biotic and abiotic factors cues.


Effect of Kangaroo Mother Care on Cerebral Hemodynamics in Preterm Neonates Assessed by Transcranial Doppler Sonography in Middle Cerebral Artery.
To study the effect of KMC in premature newborns on cerebral hemodynamics in the middle cerebral artery (MCA) using transcranial doppler sonography. In this descriptive study, 40 clinically stable preterm neonates admitted to the neonatal intensive care unit of our institute and undergoing Kangaroo mother care (KMC) were enrolled. Physiological and cerebral blood flow parameters of MCA were obtained by using transcranial doppler sonography at baseline, at 60 minutes of KMC, and after 60 minutes of stopping KMC. Of the 40 enrolled neonates (24 males), the mean (SD) birth weight, gestation age, and postnatal age were 1698.25 (495.44) g, 33.00 (1.67) wk, and 6.80 (4.51) days, respectively. The mean (SD) cerebral blood flow velocities increased (peak systolic velocity (PSV), P=0.03; end diastolic velocity, P<0.001; mean velocity, P<0.001) and doppler indices decreased (resis-tive index, P=0.001; pulsatility index, P<0.001) significantly; whereas, heart rate (P<0.001) decreased but SpO2 (P=0.001) and mean blood pressure (P=0.003) increased significantly at 60 minutes of KMC as compared to baseline. Sixty minutes after stopping KMC, all parameters (except PSV) were higher than baseline, indicating post KMC effect. KMC improves cerebral hemodynamics in clinically stable preterm neonates.


Are there advances in the treatment of extracapsular hip fractures in the elderly?
While the rate of failure following hip fracture surgery for extracapsular hip fractures in the elderly is low, an incidence of implant cutout from the femoral head remains regardless of whether fixation is by sliding hip screw or intramedullary nail. In general, a well-executed osteosynthesis is the best assurance of a good outcome with few complications, and typically a less than ideal placement of the implant in the femoral head is the reason for cut-out and failure of the operation. It is clear that there is no difference in the incidence of complications or functional outcome between a sliding hip screw and an intramedullary nail for pertrochanteric fractures (AO/OTA 31-A1 and A2), while the implant of choice in the elderly for the true intertrochanteric fracture (AO/OTA 31-A3; reverse intertrochanteric) is a nail. However, what is less clear is whether there are newer ideas and/or implant designs that represent true advances in the treatment of extracapsular fractures in the elderly. The following review focuses on just this issue.