Faculty perceptions of learning while teaching in Doctoring.
To assess the acquisition of clinical knowledge and skills by faculty teaching in Doctoring. Thirty-six faculty teaching in Doctoring II were given surveys at the start and end of six educational modules. These surveys assessed faculty perceptions of their own knowledge and skills related to key learning objectives for each module. Pre-test and post-test means were compared using paired t-tests and 95% confidence limits were calculated. The average response rate was 72% for each module. Faculty reported increases in knowledge and skills for each of the six modules. Post-test mean ratings were significantly higher than pre-test mean ratings for 48 out of the 56 learning objectives. The greatest increases were seen in the domestic violence and smoking cessation modules. Faculty rated tutorial sessions with students highest in terms of contribution to their own learning. The results suggest that faculty acquire new knowledge and skills as a result of teaching in Doctoring. Problem-based courses such as Doctoring that deal in an integrated fashion with subjects such as ethics, law, prevention, evidence-based medicine and domestic violence can serve as important and effective vehicles for faculty development.


Magnetic metal organic framework for pre-concentration of ampicillin from cow milk samples.
The aim of this study is a present of a simple solvothermal synthesis approach to preparation of Cu-based magnetic metal organic framework (MMOF) and subsequently its application as sorbent for ultrasound assisted magnetic solid phase extraction (UAMSPE) of ampicillin (AMP) from cow milk samples prior to high performance liquid chromatography-Ultraviolet (HPLC-UV) determination. Characteristics of prepared MMOF were fully investigated by different techniques which showed the exclusive properties of proposed sorbent in terms of proper functionality, desirable magnetic property and also high specific surface area. Different influential factors on extraction recovery including sorbent dosage, ultrasonic time, washing solvent volume and eluent solvent volume were assessed using central composite design (CCD) based response surface methodology (RSM) as an operative and powerful optimization tool. This is the first report for determination of AMP using MMOF. The proposed method addressed some drawbacks of other methods and sorbents for determination of AMP. The presented method decreases the extraction time (4 min) and also enhances adsorption capacity (250 mg/g). Moreover, the magnetic property of presented sorbent (15 emu/g) accelerates the extraction process which does not need filtration, centrifuge and precipitation procedures. Under the optimized conditions, the proposed method is applicable for linear range of 1.0-5000.0 μg/L with detection limit of 0.29 μg/L, satisfactory recoveries (≥95.0%) and acceptable repeatability (RSD less than 4.0%). The present study indicates highly promising perspectives of MMOF for highly effective analysis of AMP in complicated matrices.


Control and coping in chronic insomnia: a daily diary study.
This daily diary study evaluated the relationships between perceived control over sleep, coping with sleeplessness, and subjective sleep in a sample of 45 adults with chronic insomnia. For seven consecutive days, newspaper-recruited adults completed daily self-report measures of perceived control, coping, general fatigue, mood, and sleep. Using a mixed-model analysis with SAS, we examined the lagged impact of perceived control and coping (either assimilative or accommodative) on next day sleep, mood, and fatigue. Results showed that perceived control over sleep was a significant predictor of next day sleep quality. For those with more chronic presentations, perceived control over sleep was a significant predictor of next day accommodative coping. Results indicated that those with more chronic presentations were more likely to use accommodative coping, and that this was associated with worsened next-day mood and no improvements in sleep. Implications of these findings are that changes in perceived control precede, and do not follow from, changes in sleep. Additionally, results suggest that accommodative coping should be discouraged as it is more likely to worsen next-day mood.


De novo Synthesis and Assembly of rRNA into Ribosomal Subunits during Cold Acclimation in Escherichia coli.
During the cold adaptation that follows a cold stress, bacterial cells undergo many physiological changes and extensive reprogramming of their gene expression pattern. Bulk gene expression is drastically reduced, while a set of cold shock genes is selectively and transiently expressed. The initial stage of cold acclimation is characterized by the establishment of a stoichiometric imbalance of the translation initiation factors (IFs)/ribosomes ratio that contributes to the preferential translation of cold shock transcripts. Whereas de novo synthesis of the IFs following cold stress has been documented, nothing was known concerning the activity of the rrn operons during the cold acclimation period. In this work, we focus on the expression of the rrn operons and the fate of rRNA after temperature downshift. We demonstrate that in Escherichia coli, rRNA synthesis does not stop during the cold acclimation phase, but continues with greater contribution of the P2 compared to the P1 promoter and all seven rrn operons are active, although their expression levels change with respect to pre-stress conditions. Eight hours after the 37°→10 °C temperature downshift, the newly transcribed rRNA represents up to 20% of total rRNA and is preferentially found in the polysomes. However, with respect to the de novo synthesis of the IFs, both rRNA transcription and maturation are slowed down drastically by cold stress, thereby accounting in part for the stoichiometric imbalance of the IFs/ribosomes. Overall, our data indicate that new ribosomes, which are possibly suitable to function at low temperature, are slowly assembled during cold acclimation.


Infrared Thermography in Exercise Physiology: The Dawning of Exercise Radiomics.
Infrared thermography (IRT) is a non-invasive tool to measure the body surface radiation temperature (Tsr). IRT is an upcoming technology as a result of recent advancements in camera lenses, detector technique and data processing capabilities. The purpose of this review is to determine the potential and applicability of IRT in the context of dynamic measurements in exercise physiology. We searched PubMed and Google Scholar to identify appropriate articles, and conducted six case experiments with a high-resolution IRT camera (640 × 480 pixels) for complementary illustration. Ten articles for endurance exercise, 12 articles for incremental exercise testing and 11 articles for resistance exercise were identified. Specific Tsr changes were detected for different exercise types. Close to physical exertion or during prolonged exercise six recent studies described "tree-shaped" or "hyper-thermal" surface radiation pattern (Psr) without further specification. For the first time, we describe the Tsr and Psr dynamics and how these may relate to physiological adaptations during exercise and illustrate the differential responsiveness of Psr to resistance or endurance exercise. We discuss how bias related to individual factors, such as skin blood flow, or related to environmental factors could be resolved by innovative technological approaches. We specify why IRT seems to be increasingly capable of differentiating physiological traits relevant for exercise physiologists from various forms of environmental, technical and individual bias. For refined analysis, it will be necessary to develop and implement standardized and accurate pattern recognition technology capable of differentiating exercise modalities to support the evaluation of thermographic data by means of radiomics.


Effect of oxametacin on endogenous uric acid clearance rate in healthy volunteers.
Oxametacin, a new non steroidal anti-inflammatory compound, with analgesic, antipyretic and anti-inflammatory properties comparable to those of indomethacin, has been claimed to be effective in treatment of acute attacks of gout. The present study comprises an investigation in 8 healthy volunteers of the effect on the endogenous uric acid clearance rate, of oxametacin administered alone or in combination with the conventional hypouricaemic agents benzbromarone or allopurinol. Whether given alone or in combination with these drugs, oxametacin failed to alter the clearance rate of endogenous uric acid. In view of its good tolerance and its possible efficacy in treatment of acute attacks of gout, the present data help to validate use of oxametacin in acute gout.


Major infections following pediatric cardiac surgery pre- and post-CLABSI bundle implementation.
Postoperative infection contributes to the worsening of congenital cardiac surgery (CCS) outcomes. Surgical site infection (SSI), bloodstream infection (BSI) and ventilator associated pneumonia (VAP) are common. An additional bundle of preventive measures against central-line associated bloodstream infection (CLABSI) bundle was implemented in April 2019. To compare the incidence of major infections after pediatric CCS before and after the implementation of the CLABSI bundle and to identify risk factors for major infections. We conducted a single-center, retrospective study to assess the incidence of major infections including bloodstream infection (BSI), surgical site infection (SSI), and ventilator-associated pneumonia (VAP) after pediatric CCS one year before and after implementation of the CLABSI bundle during April 2018-March 2020. The demographics and outcomes of the patients were explored, and risk factors for major infections were identified using multivariate analysis. A total of 548 children (53% male) underwent CCS with a median age of 1.9 years (range 0.01-17.5 years). The median Aristotle Basic Complexity score was 7.1 (range 3-14.5). The CLABSI bundle was applied in 262 patients. Overall mortality was 5.5%. 126 patients (23%) experienced major postoperative infections. During the year after the implementation of the CLABSI bundle, BSI was reduced from 8.4% to 3.1% (p = 0.01), with a smaller reduction in VAP (21% to 17.6%; p = 0.33). The incidence of SSI was unchanged (1.7% to 1.9%; p = 0.77). The independent risk factors for major infections were age at surgery <6 months (p = 0.04), postoperative ventilator usage >2 days (p < 0.01), central line usage >4 days (p = 0.04), and surgery during the pre-CLABSI bundle period (p = 0.01). Following the implementation of the CLABSI prevention package in our pediatric CCS unit, the incidence of BSI was significantly reduced. The incidence of VAP tended to decrease, while the SSI was unchanged. Sustainability of the prevention package through nurse empowerment and compliance audits is an ongoing challenge.


Anti-cancer effects of naturally occurring compounds through modulation of signal transduction and miRNA expression in human colon cancer cells.
Much evidence indicates that various naturally occurring compounds have an anti-cancer effect, but the detailed mechanisms are not well understood. In this study, we selected anti-cancer phytochemicals such as epigallocatechin-3-gallate (EGCG), resveratrol (RES) and α-mangostin (α-M), all of which are well-characterized chemopreventive agents. We sought to elucidate the mechanism of their anti-cancer effects and the synergistic effects obtained by combined treatment with the anti-cancer drug 5-fluorouracil (5-FU) in three human colon cancer cell lines. The numbers of viable cells were consistently decreased by the treatment with EGCG, RES or α-M at more than 10 μM in all three cell lines tested. All compounds mainly induced apoptosis and suppressed the PI3K/Akt signaling pathway. Additionally, α-M, which had the greatest PI3K/Akt-suppressing activity, also suppressed MAP kinase (MAPK)/Erk1/2 signaling. Importantly, the combination treatment with RES and 5-FU induced a remarkably synergistic enhancement of growth inhibition and apoptosis through the additional suppression of the MAPK/Erk1/2 signaling pathway in colon cancer DLD-1 cells. Interestingly, RES increased the intracellular expression level of miR-34a, which down-regulated the target gene E2F3 and its downstream Sirt1, resulting in growth inhibition. These findings indicate that these compounds functioned as chemosensitizers when combined with anti-cancer drugs through the modulation of apoptotic and growth-related signaling pathways. Also, RES exerted its anti-cancer activity in part through a newly defined mechanism, i.e., the miR-34a/E2F3/Sirt1 cascade.


Hemodynamic response to pumpless extracorporeal membrane oxygenation.
Respiratory support by means of arteriovenous extracorporeal membrane oxygenation driven by systemic arterial pressure, in contrast to pump-driven venoarterial extracorporeal membrane oxygenation, is attractive because of its simplicity and lack of trauma to formed blood elements. Although arteriovenous extracorporeal membrane oxygenation has been shown to improve arterial blood gases, useful levels of arteriovenous extracorporeal membrane oxygenation shunt flow may exert detrimental effects on systemic and pulmonary hemodynamics. Therefore the hemodynamic consequences of arteriovenous extracorporeal membrane oxygenation were studied in 11 dogs that were anesthetized, heparinized, and their lungs mechanically ventilated (FIO2 = 0.21) before and after induction of oleic acid pulmonary edema. The data indicate that arteriovenous extracorporeal membrane oxygenation shunt flows adequate to improve arterial blood gases resulted in significant changes in peripheral vascular resistance (-46%; p less than 0.05), systemic arterial blood pressure (-20%; p less than 0.05), and cardiac output (+110%; p less than 0.05). Dopamine infusion (5 micrograms/kg/min) proved to be more effective than volume expansion (15 ml/kg) in maintaining cardiac output, arterial blood pressure, and arterial blood gases. We conclude that pumpless arteriovenous extracorporeal membrane oxygenation, at flow rates adequate for respiratory support, can adversely alter systemic hemodynamics. However, these effects can be beneficially modulated by a moderate dose of inotropic medication.


ASPH-notch Axis guided Exosomal delivery of Prometastatic Secretome renders breast Cancer multi-organ metastasis.
Aspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable prooncogenic secretome delivering and trafficking for long-distance cell-to-cell communication. This study aims to explore molecular mechanisms underlying how ASPH network regulates designated exosomes to program development and progression of breast cancer. Stable cell lines overexpressing or knocking-out of ASPH were established using lentivirus transfection or CRISPR-CAS9 systems. Western blot, MTT, immunofluorescence, luciferase reporter, co-immunoprecipitation, 2D/3-D invasion, tube formation, mammosphere formation, immunohistochemistry and newly developed in vitro metastasis were applied. Through physical interactions with Notch receptors, ligands (JAGs) and regulators (ADAM10/17), ASPH activates Notch cascade to provide raw materials (especially MMPs/ADAMs) for synthesis/release of pro-metastatic exosomes. Exosomes orchestrate EMT, 2-D/3-D invasion, stemness, angiogenesis, and premetastatic niche formation. Small molecule inhibitors (SMIs) of ASPH's β-hydroxylase specifically/efficiently abrogated in vitro metastasis, which mimics basement membrane invasion at primary site, intravasation/extravasation (transendothelial migration), and colonization/outgrowth at distant sites. Multiple organ-metastases in orthotopic and tail vein injection murine models were substantially blocked by a specific SMI. ASPH is silenced in normal adult breast, upregulated from in situ malignancies to highly expressed in invasive/advanced ductal carcinoma. Moderate-high expression of ASPH confers more aggressive molecular subtypes (TNBC or Her2 amplified), early recurrence/progression and devastating outcome (reduced overall/disease-free survival) of breast cancer. Expression profiling of Notch signaling components positively correlates with ASPH expression in breast cancer patients, confirming that ASPH-Notch axis acts functionally in breast tumorigenesis. ASPH-Notch axis guides particularly selective exosomes to potentiate multifaceted metastasis. ASPH's pro-oncogenic/pro-metastatic properties are essential for breast cancer development/progression, revealing a potential target for therapy.


Clinically stable asthmatics have highly reproducible pulmonary function tests.
The reproducibility of standard function tests was evaluated in a group of ten stable asthmatics over a 10-day period. Relationships between repeated measures of pulmonary functions examined by analysis of variance at the 95% confidence level were comparable to studies in normal subjects. This precision helps validate the recommendations of the Committee on Emphysema for assessment of reversibility in airway obstruction.


Identification and characterization of a Drosophila homologue of ATBP.
ATBP [(A+T)-stretch binding protein] activates the Sarcophaga defense protein genes in an (A+T)-stretch dependent manner as shown previously using a luciferase reporter assay [Aozasa et al. (2001) Eur J Biochem, 268, 2506-2511]. We identified the Drosophila homologue of ATBP. Drosophila ATBP has 388 amino acid residues and the amino acid sequence has high similarity with that of the Sarcophaga ATBP. In particular, residues 1-56 and 301-374 are highly conserved between Sarcophaga and Drosophila. Drosophila ATBP activated the Sarcophaga lectin gene promoter in SL-2 cells. The Drosophila ATBP gene is a single copy gene and is located in the 20E region of chromosome X.


Fatal knowledge? Prenatal diagnosis and sex selection.
Moral and social arguments weigh heavily against performing medical procedures solely for purposes of sex selection. The medical profession has a responsibility to abandon its posture of ethical neutrality and take a firm stand now against sex selection.


Immobile survival of motoneuron (SMN) protein stored in Cajal bodies can be mobilized by protein interactions.
Reduced levels of survival of motoneuron (SMN) protein lead to spinal muscular atrophy, but it is still unknown how SMN protects motoneurons in the spinal cord against degeneration. In the nucleus, SMN is associated with two types of nuclear bodies denoted as gems and Cajal bodies (CBs). The 23 kDa isoform of fibroblast growth factor-2 (FGF-2(23)) is a nuclear protein that binds to SMN and destabilizes the SMN-Gemin2 complex. In the present study, we show that FGF-2(23) depletes SMN from CBs without affecting their general structure. FRAP analysis of SMN-EGFP in CBs demonstrated that the majority of SMN in CBs remained mobile and allowed quantification of fast, slow and immobile nuclear SMN populations. The potential for SMN release was confirmed by in vivo photoconversion of SMN-Dendra2, indicating that CBs concentrate immobile SMN that could have a specialized function in CBs. FGF-2(23) accelerated SMN release from CBs, accompanied by a conversion of immobile SMN into a mobile population. Furthermore, FGF-2(23) caused snRNP accumulation in CBs. We propose a model in which Cajal bodies store immobile SMN that can be mobilized by its nuclear interaction partner FGF-2(23), leading to U4 snRNP accumulation in CBs, indicating a role for immobile SMN in tri-snRNP assembly.


The nature of ethical expertise.
Critics of clinical ethicists sometimes claim that if there were expertise in ethics, then there would have to be objective moral knowledge. They also assume that there would be only one kind of ethics expertise, and that it would be a kind of professional specialization. All three assumptions are mistaken.


Australian perspective regarding recommendations for physical activity and exercise rehabilitation in pulmonary arterial hypertension.
To determine the opinion of health care professionals within Australia, regarding acceptable levels of exertion and symptoms, and referral for exercise rehabilitation in patients with pulmonary arterial hypertension (PAH). In 2010, 76 health care professionals at a specialist pulmonary hypertension meeting in Australia were surveyed using a self-administered questionnaire. The questionnaire included case studies of patients with PAH in World Health Organization (WHO) functional classes II-IV. For each case study, respondents were asked to report their opinion regarding the acceptable level of exertion and symptoms during daily activities, and whether they would refer the patient for exercise rehabilitation. Three additional questions asked about advice in relation to four specific physical activities. The response rate was 70% (n = 53). Overall, 58% of respondents recommended patients undertake daily activities 'as tolerated'. There was no consensus regarding acceptable levels of breathlessness or fatigue, but the majority of respondents considered patients should have no chest pain (73%) and no more than mild light-headedness (92%) during daily activities. Overall, 63% of respondents would have referred patients for exercise rehabilitation. There was little difference in opinion regarding the acceptable level of exertion or symptoms, or referral for exercise rehabilitation, according to functional class. However, the patients' functional class did influence the advice given regarding the specific physical activities. In 2010, there were inconsistencies between individual health care professionals within Australia regarding appropriate levels of physical exertion and acceptable symptoms during daily activities. Almost two-thirds of the respondents reported they would refer patients for exercise rehabilitation.


Do-It-Yourself medicine? The impact of light cannabis liberalization on prescription drugs.
Governments worldwide are increasingly concerned about the booming use of CBD (cannabidiol) products. However, we know little about the impact of their liberalization. We study a unique case of unintended liberalization of a CBD-based product (light cannabis) that occurred in Italy in 2017. Using unique and high-frequency data on prescription drug sales and by exploiting the staggered local availability of the new product in each Italian province, we document a significant substitution effect between light cannabis and anxiolytics, sedatives, opioids, anti-depressants and anti-psychotics. Results are informative for regulators and suggest that bans on light cannabis use would disregard the needs of patients to seek effective reliefs of their symptoms.


Caregiving Effectiveness Model evolution to a midrange theory of home care: a process for critique and replication.
A clinically relevant model, grounded in nursing theory, has evolved to become a midrange theory. This article describes the processes used to derive, validate, revise, and test the Caregiving Effectiveness Model. Testing of this midrange theory used prospective longitudinal research with family members caring for patientsrequiring lifelong, complex, technology-based home care. It presents the conceptual critiques and statistical procedures and discusses derivation of model-generated nursing interventions and implications for use of these validation processes in developing nursing knowledge. The article summarizes limitations of the model and presents recommendations for future research.


Cellular internalization and stress response of ingested amorphous silica nanoparticles in the midgut of Drosophila melanogaster.
Amorphous silica nanoparticles (aSNPs) are used for various applications including food industry. However, limited in vivo studies are available on absorption/internalization of ingested aSNPs in the midgut cells of an organism. The study aims to examine cellular uptake of aSNPs (<30nm) in the midgut of Drosophila melanogaster (Oregon R(+)) owing to similarities between the midgut tissue of this organism and human and subsequently cellular stress response generated by these nanoparticles. Third instar larvae of D. melanogaster were exposed orally to 1-100μg/mL of aSNPs for 12-36h and oxidative stress (OS), heat shock genes (hsgs), membrane destabilization (Acridine orange/Ethidium Bromide staining), cellular internalization (TEM) and apoptosis endpoints. A significant increase was observed in OS endpoints in the midgut cells of exposed Drosophila in a concentration- and time-dependent manner. Significantly increased expression of hsp70 and hsp22 along with caspases activation, membrane destabilization and mitochondrial membrane potential loss was also observed. TEM analysis showed aSNPs-uptake in the midgut cells of exposed Drosophila via endocytic vesicles and by direct membrane penetration. aSNPs after their internalization in the midgut cells of exposed Drosophila larvae show membrane destabilization along with increased cellular stress and cell death. Ingested aSNPs show adverse effects on the cells of GI tract of the exposed organism thus their industrial use as a food-additive may raise concern to human health.


Dietary modifications in patients receiving miglustat.
Weight loss and gastrointestinal disturbances are often seen during miglustat therapy for lysosomal storage diseases. A retrospective analysis of data from a mixed group of patients treated with miglustat at two UK centres was performed to evaluate the effect of two different dietary interventions on body weight and gastrointestinal tolerability during the initial 6 months of miglustat therapy. Neurological outcomes in these patients are not discussed herein. Data were analysed from a total of 29 patients with varied neurolipidoses (21 children/adolescents; 8 adults). Negative mean changes in body weight were seen in children/adolescents on an unmodified diet (-8.1%), and in adults (-4.1%) and children/adolescents (-5.2%) on a low-lactose diet. Patients on the low-disaccharide diet showed a positive mean change in body weight (+2.0%), although there was high variability in this group. Non-parametric sub-analysis of median body-weight change in children/adolescents also showed high variability both within and between diet groups, with no statistically significant difference between the effects of different diets on body weight (p = 0.062). The low-lactose diet reduced gastrointestinal disturbances; single small doses of loperamide were required in some patients. Patients on the low-disaccharide diet showed the lowest frequency of gastrointestinal effects. In conclusion, simple dietary modifications allowed the maintenance of body-weight gain in line with normal growth potential during miglustat therapy in young patients with lysosomal storage diseases, and reduced gastrointestinal disturbances.


Research on timed AI in beef cattle: Past, present and future, a 27-year perspective.
This review aimed to (1) summarize the results from fixed-timed artificial insemination (TAI) fertility studies performed during the last 27 years; (2) compile and evaluate, as examples from the literature base, the direct comparisons made of specific manipulations to synchronization protocols; (3) evaluate the impact of the TAI programs on the reproductive performance during the breeding season, and (4) provide perspective on the future of TAI programs in beef cattle. A search of the literature published from 1995 to 2021 was conducted to identify experiments in which synchronization of ovulation and TAI in beef cattle was performed. The primary outcome of interest was fertility expressed as pregnancies per TAI. The literature included two search engines, the SIS Web of Science and the US National Library of Medicine Institutes of Health through PubMed. After the initial search and screening, a total of 228 manuscripts were selected containing a total of 272,668 TAI. A dramatic increase in the number of publications and TAIs occurred throughout the years. Most of them were from Brazil and United States, followed by Canada, Argentina, Uruguay, and Australia. Two main types of TAI programs were identified: GnRH-based and E2/P4-based protocols. In terms of GnRH-based programs, two variations were evaluated in the present manuscript. First, we evaluated the effect of the progesterone implant during the protocol. The progesterone implant increased pregnancy/TAI (P/TAI) from 44.3 to 54.3%. Second, the use of a second prostaglandin F2α treatment in 5-d CO-synch program increased the P/TAI from 53.2 to 60.9%. In E2/P4-based programs, use of GnRH at TAI increased P/TAI from 54.7 to 59.2% in cows. However, no increase was detected in heifers. Other research showed that use of TAI can increase the overall proportion of the cows pregnant at end of the breeding season and produce earlier calvings compared with bulls. In conclusion, there have been a large number of excellent research studies that have been performed during the last 27 years on TAI in beef cattle. This technology is being utilized successfully in the beef cattle industry. This success is largely because of the valid research that underlies the application of the technology and the economic value of the technology.


Comparison of Vpu sequences from diverse geographical isolates of HIV type 1 identifies the presence of highly variable domains, additional invariant amino acids, and a signature sequence motif common to subtype C isolates.
We compared the Vpu sequences from 101 strains of HIV-1 isolated from diverse geographical regions and various subtypes in order to identify regions of high variability, and those amino acid residues that were highly conserved or invariant. In addition to the highly conserved casein kinase II (CKII) phosphorylation sites, our analysis identified additional invariant residues in the transmembrane domain and in the first and second alpha-helical domains. Our analysis revealed that all subtype C sequences had a conserved LRLL motif at the C terminus that was also found in A/C intersubtype recombinants. While our analysis demonstrated the conservation of CKII domains in HIV-1 group M and O isolates, the number of potential CKII phosphorylation sites was variable in SIVcpz sequences. The results of this study will provide a basis for future mutagenesis studies to examine the role of certain amino acid residues in the structure and function of Vpu.


Fatty acid synthesis and metabolism of phospholipid acyl groups in strain L mouse fibroblasts.
Strain L mouse fibroblasts grown in medium supplemented with 2.5% delipidized horse serum were found capable of desaturating oleic and linoleic acid to dienoic and trienoic acid(s), respectively. Although 40-60% of de novo fatty acid synthesis from [2-3H]acetate was inhibited by the administration of exogenous oleic or linoleic acid, sterole synthesis was only slightly affected. Within 24-48 h after incorporation, phospholipid fatty acyl groups could undergo active exchange between phospholipids. After this dynamic transition period was over, not only were the phospholipid acyls retained but some vicinal fatty acyl pairs of phospholipid also appeared to be stable and remained together throughout the depletion period. At any time in the experiment, however, introduction of exogenous fatty acid perturbed this phospholipid acyl retention, delayed the time at which the phospholipid acyl groups no longer moved between phospholipids and also decreased the ultimate number of phospholipid acyl groups retained by strain L mouse fibroblasts.


miR-487b, miR-3963 and miR-6412 delay myogenic differentiation in mouse myoblast-derived C2C12 cells.
Skeletal muscle differentiation is a multistep, complex pathway in which several important signaling molecules are involved. Recently, microRNAs (miRNAs), endogenous non-coding small RNAs that regulate mRNAs, have been proposed to be involved in skeletal muscle differentiation. In this study, we identified skeletal muscle differentiation-associated miRNAs by comparing miRNA expression profiles between C2C12 cells and Wnt4 over-expressing C2C12 cells (W4-08), which can spontaneously differentiate into myotubes. We identified miR-206, miR-133a, and miR-133b as up-regulated miRNAs and miR-487b, miR-3963 and miR-6412 as down-regulated miRNAs in differentiating cells. We focused on the down-regulated miRNAs because their functions were largely unknown. Transfection of mimics of these miRNAs into C2C12 cells resulted in significantly reduced expression of myogenic differentiation markers, including troponin T and myosin heavy chain fast type and slow type, but did not affect the expression of the myogenic transcription factors, MyoD and myogenin. These miRNAs were characterized as new myogenic differentiation-associated miRNAs which may delay late myogenic differentiation or maturation.


Swarna Bhasma in cancer: A prospective clinical study.
Despite the advances in the treatment of cancer, mortality is still high. Complementary and alternative medicine is emerging as a potent modality in cancer treatment. 'Swarna Bhasma' (SB), containing gold particles, is an ancient Indian medicine has shown its anticancer activity. This present study was conducted to detect the effect of SB on solid malignancies. A total of 43 patients were included in this study received SB for 1 year. Seventeen patients showed response. The response was best in rectal cancer group 70% (7/10). Nearly 41.02% patients survived for 1 year after treatment but after 5 years this came down to 15.38%.


The influence of extracellular matrix on gene expression: is structure the message?
The study of the regulation of gene expression in cultured cells, particularly in epithelial cells, has been both hampered and facilitated by the loss of function that accompanies culture on traditional plastic substrata. Initially, investigations of differentiated function were thwarted by the inadequacy of tissue culture methods developed to support growth of mesenchymal cells. However, with the recognition that the unit of function in higher organisms is larger than the cell itself, and that gene expression is dependent upon cell interactions with hormones, substrata and other cells, came the understanding that the epithelial cell phenotype is profoundly influenced by the extracellular environment. In the last decade research on epithelial cells has centred on culture conditions that recreate the appropriate environment for function with very promising and important results. The investigations into the modulation of phenotype in culture produced not only a better model, but also contributed to a better understanding of the regulation of normal function. Using cultured mammary gland epithelial cells as a primary model of these interactions, our studies of gene expression are based on three premises. (1) That the extracellular matrix (ECM) on which the cells sit is an extension of the cells and an active participant in the regulation of cellular function; i.e. the ECM is an 'informational' entity in the sense that it receives, imparts and integrates structural and functional signals. (2) That ECM-induced functional differentiation in the mammary gland is mediated through changes in cell shape, i.e. that the structure is in large part 'the message' required to maintain differentiated gene expression. (3) That the unit of function includes the cell plus its extracellular matrix; in a larger context, the unit is the organ itself. These tenets and the data presented below are consistent with a model of 'Dynamic Reciprocity', where the ECM is postulated to exert an influence on gene expression via transmembrane proteins and cytoskeletal components. In turn, cytoskeletal association with polyribosomes affects mRNA stability and rates of protein synthesis, while its interaction with the nuclear matrix could affect mRNA processing and, possibly, rates of transcription.


Ultrasound transit time gives direct measurement of muscle fibre length in vivo.
The movement occurring in whole muscle during contraction is divided between the muscle fibres, the tendon and the longitudinal change in length due to a change in pennation angle. The relative importance of each of these components varies between muscles and with how they are being used. To date it has not been possible to measure each of these movements. By suturing piezoelectric crystals to each end of a small group of muscle fibres in cat medial gastrocnemius muscle, the transit time of ultrasound between the crystals was measured. Assuming a constant velocity of sound in muscle of 1580 m/s, the transit time was used to calculate the muscle fibre length. In "isometric" tetanic contractions the muscle fibres shortened by up to 25% at the expense of the tendons. Lengthening the muscle by 4 mm between each two tetanii, produced less than 4 mm stretch of the muscle fibres as some of the movement was taken up by a change in pennation angle. Except at long lengths, when passive tensions were present, none of this movement between tetanii could be accounted for by stretch of the tendon.


Semiautomatic interictal electric source localization based on long-term electroencephalographic monitoring: A prospective study.
Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor- and cost-intensive. Semiautomatic ESI analysis (SAEA) has been proposed as an alternative and has previously shown benefit. Computer-assisted automatic spike cluster retrieval, averaging, and source localization are carried out for each cluster and are then reviewed by an expert neurophysiologist, to determine their relevance for the individual case. Here, we examine its yield in a prospective single center study. Between 2017 and 2022, 122 patients underwent SAEA. Inclusion criteria for the current study were unifocal epilepsy disorder, epilepsy surgery with curative purpose, and postoperative follow-up of 2 years or more. All patients (N=40) had continuous video-electroencephalographic (EEG) monitoring with 37 scalp electrodes, which underwent SAEA. Forty patients matched our inclusion criteria. Twenty patients required intracranial monitoring; 13 were magnetic resonance imaging (MRI)-negative. Mean duration of analyzed EEG was 4.3 days (±3.1 days), containing a mean of 12 749 detected IEDs (±22 324). The sensitivity, specificity, and accuracy of SAEA for localizing the epileptogenic focus of the entire group were 74.3%, 80%, and 75%, respectively, leading to an odds ratio (OR) of 11.5 to become seizure-free if the source was included in the resection volume (p < .05). In patients with extratemporal lobe epilepsy, our results indicated an accuracy of 68% (OR=11.7). For MRI-negative patients (n = 13) and patients requiring intracranial EEG (n = 20), we found a similarly high accuracy of 84.6% (OR=19) and 75% (OR = 15.9), respectively. In this prospective study of SAEA of long-term video-EEG, spanning several days, we found excellent localizing information and a high yield, even in difficult patient groups. This compares favorably to high-density ESI, most likely due to marked improved signal-to-noise ratio of the averaged IEDs. We propose including ESI, or SAEA, in the workup of all patients who are referred for epilepsy surgery.


Consumption of ultra-processed foods and all-cause and cause-specific mortality in the Southern Community Cohort Study.
Higher intake of ultra-processed foods (UPF) has been linked with higher risks of cancer, cardiovascular disease, and diabetes, as well as all-cause mortality. However, studies on UPF and cause-specific mortality remain limited, especially among disadvantaged populations. We aimed to examine associations of UPF intake with all-cause and cause-specific mortality among low-income Americans. In the Southern Community Cohort Study (SCCS), a prospective cohort of mostly low-income Black and White Americans, we included 77,060 participants who completed a food frequency questionnaire (FFQ) at baseline (2002-2009) and had at least 1 year follow-up. All 89 items in the FFQ were categorized using the Nova classification. UPF intake was calculated as % of daily foods intake by weight (grams). Cox regression was used to estimate HR (95% CI) for the association of UPF intake (quartile or per 10% increase) with total and cause-specific mortality (cancer, coronary heart disease [CHD], stroke, and diabetes) after adjusting for sociodemographics, lifestyles, and disease history. Of 77,060 participants, 46,175 (59.9%) were women, 49,857 were Black (64.7%), and mean age was 52.4 (SD: 8.8) years at baseline. The mean intake of UPF was 41.0% (SD: 15.7%). UPF intake was inversely associated with Healthy Eating Index and intakes of fiber, minerals, and vitamins but positively associated with intakes of sugars and fats (all PFDR<0.0001). During an average follow-up of 12.2 years, we documented 17,895 total deaths, including 4267 from cancer, 2208 from CHD, 867 from stroke, and 997 from diabetes. In the fully adjusted model, higher UPF intake was not associated with all-cause, cancer, CHD, or stroke mortality but showed a significant association with increased diabetes mortality (HR [95% CI] = 1.32 [1.07, 1.62] for the highest versus lowest quartiles [>51.1% vs. <29.3%] and 1.09 [1.04, 1.15] per 10% increase). The adverse UPF-diabetes mortality association was noted regardless of sex, race, income, neighborhood deprivation, lifestyles, and cardiometabolic disease history, while particularly evident in participants with no more than high school education or a history of hypercholesterolemia (HR [95% CI] per 10% increase = 1.12 [1.05, 1.18] and 1.14 [1.07, 1.22], respectively; both Pinteraction<0.05). Among predominantly low-income Black and White American adults, UPF intake was associated with increased diabetes mortality, especially for individuals with limited education or hypercholesterolemia. Our findings suggest the potential impact of increasing access and intake of un/minimally processed food to replace UPF on reducing diabetes-related mortality among populations facing socioeconomic and health disparities.


Association of cardiometabolic risk status with clinical activity and damage in systemic lupus erythematosus patients: A cross-sectional study.
Cardiometabolic status is a key factor in mortality by cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). This study evaluated the association of cardiometabolic risk status with clinical activity and damage in SLE patients. A cross-sectional study was conducted in 158 SLE patients and 123 healthy subjects (HS). Anthropometry, glucose, hs-CRP, lipid profile, oxLDL, sCD36, anti-oxLDL antibodies, and cardiometabolic indexes were evaluated. SLE patients had dyslipidemia, higher sCD36, anti-oxLDL antibodies, hs-CRP, and risk (OR > 2) to present Castelli score ≥ 4.5, HDL-C < 40 mg/dL and LDL-C ≥ 100 mg/dL. Disease evolution time was correlated with glucose and BMI, damage with TG, and clinical activity with TG, TG/HDL-C ratio, and Kannel index. Active SLE patients had risk (OR > 2) to present a Castelli score ≥ 4.5, Kannel score ≥ 3, TG/HDL-C ratio ≥ 3 and HDL-C < 40 mg/dL. In conclusion, SLE patients have high cardiometabolic risk to CVD related to disease evolution time, and clinical activity.


Erythropoiesis-stimulating agents: favorable safety profile when used as indicated.
Several studies with erythropoiesis-stimulating agents (ESAs) have raised a number of safety issues. Therefore, a discussion of available data in light of the current EORTC guidelines 2006 on the use of ESAs in anemic patients is warranted. Literature is reviewed with respect to experimental and clinical data on the effect of ESA therapy on tumor growth both in the preclinical setting and on patient survival. Studies showing an adverse effect of ESA therapy on patient survival generally exhibit considerable methodological deficiencies. Moreover, they investigated treatment situations for which ESAs are not approved and/or did not involve recommended baseline ("intervention") or target hemoglobin levels. When used as indicated, ESAs are valuable and safe drugs for the treatment of anemia and do not negatively affect patient survival. In particular, the data situation confirms the importance and correctness of the EORTC guidelines 2006 and their recently updated version. It is therefore recommended that these guidelines continue to be strictly followed in the treatment of chemotherapy-induced anemia.


Microfluidic extraction and stretching of chromosomal DNA from single cell nuclei for DNA fluorescence in situ hybridization.
We have developed a novel method for genetic characterization of single cells by integrating microfluidic stretching of chromosomal DNA and fiber fluorescence in situ hybridization (FISH). In this method, individually isolated cell nuclei were immobilized in a microchannel. Chromosomal DNA was released from the nuclei and stretched by a pressure-driven flow. We analyzed and optimized flow conditions to generate a millimeter-long band of stretched DNA from each nucleus. Telomere fiber FISH was successfully performed on the stretched chromosomal DNA. Individual telomere fiber FISH signals from single cells could be resolved and their lengths measured, demonstrating the ability of the method to quantify genetic features at the level of single cells.


Advanced but not mild liver disease is a predictor of decreased survival in children with cystic fibrosis, with far greater impact in females: A 27-year real-life cohort study.
Improved survival of children with CF has increased our need to understand the relevance of cystic fibrosis-associated liver disease (CFLD). We assessed the impact of liver disease and disease severity on the survival of children with cystic fibrosis. A real life, single center cohort study with 27 years follow up was conducted. Mild CFLD was diagnosed as children with abnormal serum liver function tests and abnormal ultrasound. Advanced CFLD was established by detection of cirrhosis or portal hypertension. A directed acyclic graph, Kaplan-Meier (KM) and Cox regression analysis were used to model survival. 290 patients were enrolled, 48 (16.5%) had mild CFLD and 55 (19%) had advanced CFLD. Ten children with advanced CFLD and 1 with mild CFLD died. Based on the KM analysis, the mean (SE) overall survival age of all CF children was 29.1 years (0.50). The mean (SE) survival among females with advanced CFLD was 24.7 years (1.58) compared to 30.4 years (0.66) for females without advanced CFLD (p = 0.0027). Advanced CFLD was a predictor of decreased survival when adjusted for sex and diabetes (HR 2.54, 95%CI 1.05-6.15, p = 0.039). Mild CFLD was not associated with decreased survival. The effect of advanced CFLD on survival was mainly borne by females (HR = 6.37, 95%CI 1.62-25.06 vs. males, HR = 1.00, 95%CI 0.25-4.01). Advanced but not mild CFLD was associated with an increased risk of death when adjusted for sex and diabetes, and resulted in premature death in females with cystic fibrosis by approximately 6 years.


Fermented food products in the era of globalization: tradition meets biotechnology innovations.
Omics tools offer the opportunity to characterize and trace traditional and industrial fermented foods. Bioinformatics, through machine learning, and other advanced statistical approaches, are able to disentangle fermentation processes and to predict the evolution and metabolic outcomes of a food microbial ecosystem. By assembling microbial artificial consortia, the biotechnological advances will also be able to enhance the nutritional value and organoleptics characteristics of fermented food, preserving, at the same time, the potential of autochthonous microbial consortia and metabolic pathways, which are difficult to reproduce. Preserving the traditional methods contributes to protecting the hidden value of local biodiversity, and exploits its potential in industrial processes with the final aim of guaranteeing food security and safety, even in developing countries.


Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.
Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.


In situ catalytic growth of large-area multilayered graphene/MoS2 heterostructures.
Stacking various two-dimensional atomic crystals on top of each other is a feasible approach to create unique multilayered heterostructures with desired properties. Herein for the first time, we present a controlled preparation of large-area graphene/MoS2 heterostructures via a simple heating procedure on Mo-oleate complex coated sodium sulfate under N2 atmosphere. Through a direct in situ catalytic reaction, graphene layer has been uniformly grown on the MoS2 film formed by the reaction of Mo species with Species, which is from the carbothermal reduction of sodium sulfate. Due to the excellent graphene "painting" on MoS2 atomic layers, the significantly shortened lithium ion diffusion distance and the markedly enhanced electronic conductivity, these multilayered graphene/MoS2 heterostructures exhibit high specific capacity, unprecedented rate performance and outstanding cycling stability, especially at a high current density, when used as an anode material for lithium batteries. This work provides a simple but efficient route for the controlled fabrication of large-area multilayered graphene/metal sulfide heterostructures with promising applications in battery manufacture, electronics or catalysis.


Probabilistic assessment of the intake of trace elements by consumption of weaning foods in Spain.
A probabilistic model was developed to estimate the intake level for Fe, Zn, Ca, P, Mg, Mn, Cu, Na, and K derived from consumption of weaning foods in Spain. They were pooled into 10 different categories based on the main ingredient used in its formulation (chicken, chicken-veal, hake, ham, varied vegetables, chicken-ham, lamb, veal, sole, and beef-ham). The results reported that trace elements contents were especially low and inadequate according to the Dietary Reference Intake especially to Fe, Zn, and Ca and in less extent for Cu and P. Instead, Na contents were moderately high and near to upper limit of this element.


The 5-Factor Modified Frailty Index as a More Useful Associated Factor Than Chronological Age After Unruptured Cerebral Aneurysm Surgery: A Nationwide Registry Study.
Although chronological age is associated with mortality and morbidity after surgery for unruptured cerebral aneurysms (UCAs), there is little evidence regarding an association between the simplified 5-factor modified frailty index (mFI-5) and postoperative outcomes based on age group. To investigate the association of the mFI-5 score with worse outcomes, mortality, and complications in patients after surgery for UCA by chronological age groups using a Japanese national database. This study included 32 902 patients with UCAs enrolled in a Japanese national database between 2011 and 2015. Age group (younger than 65 years, 65-74 years, and 75 years or older), sex, UCA location, treatment, medications, Barthel Index (BI), medical history, mFI-5 score, and in-hospital mortality and complications were evaluated. We identified risk factors for worsening BI score, in-hospital mortality, and overall postoperative complications in each age group. In total, 14 465 patients were enrolled in this study. Multivariable analysis showed that elderly groups and patients with an mFI-5 score ≥2 items were associated with worsening BI scores (odds ratio 1.95; 95% CI 1.52-2.51) and in-hospital complications (odds ratio 1.79; CI 1.49-2.15), despite having no association with in-hospital mortality. Multivariable analysis by age groups showed that the mFI-5 score ≥2 items was associated with in-hospital complications in all age groups, unlike chronological age in patients younger than 74 years. The mFI-5 score was a more useful associated factor of in-hospital complications than chronological age in patients younger than 74 years undergoing surgery for UCA.


Microsomal receptor for steroid hormones: functional implications for nuclear activity.
Target tissues for steroid hormones are responsive by virtue of and to the extent of their content of functional intracellular receptors. Recent years have seen a shift in considerations of the cellular dynamics and distribution of these receptors, with current views favoring predominant intranuclear localization in the intact cell. This paper summarizes our analyses of the microsomal estrogen and androgen binding capability of rat uterine and ventral prostate tissue, respectively; these studies have revealed a set of high affinity sites that may act as a conduit for estrogen traversing the cell en route to the nucleus. These sites have many properties in common with cytosolic receptors, with the salient difference of a failure to activate to a more avid DNA-binding form under conditions which permit such activation of cytosolic receptors. The microsomal estrogen-binding proteins also have appreciable affinity for progesterone, another distinction from other known cellular estrogen receptor species. Various experimental approaches were employed to demonstrate that the microsomal receptors were not simply cytosol contaminants; the most convincing evidence is the recent successful separation of the cytosolic and microsomal forms by differential ammonium sulfate precipitation. Discrete subfractionation of subcellular components on successive sucrose gradients, with simultaneous assessments of binding capability and marker enzyme concentrations, indicates that the major portion of the binding is localized within the vesicles of the endoplasmic reticulum free of significant plasma membrane contamination. The microsomal receptors are readily solubilized by extraction with high- or low-salt-containing buffers or with steroid. The residual microsomes following such extraction have the characteristics of saturable acceptor sites for cytosolic estrogen-receptor complexes. The extent to which these sites will accept the cytosolic complexes is equal to the concentration of microsomal binding sites extracted. These observations suggest three possible roles for the microsomal receptor-like proteins: (a) modulation of estrogen access to nuclear binding sites; (b) formation of functional complexes which diffuse to other extranuclear sites to alter non-genomic cellular processes; (c) regulation of nuclear concentration of estrogen-receptor complexes by virtue of producing microsomal acceptor sites for uptake of free or loosely associated nuclear complexes, previously thought to exist in the cytoplasm.


Network location and clustering of genetic mutations determine chronicity in a stylized model of genetic diseases.
In a highly simplified view, a disease can be seen as the phenotype emerging from the interplay of genetic predisposition and fluctuating environmental stimuli. We formalize this situation in a minimal model, where a network (representing cellular regulation) serves as an interface between an input layer (representing environment) and an output layer (representing functional phenotype). Genetic predisposition for a disease is represented as a loss of function of some network nodes. Reduced, but non-zero, output indicates disease. The simplicity of this genetic disease model and its deep relationship to percolation theory allows us to understand the interplay between disease, network topology and the location and clusters of affected network nodes. We find that our model generates two different characteristics of diseases, which can be interpreted as chronic and acute diseases. In its stylized form, our model provides a new view on the relationship between genetic mutations and the type and severity of a disease.


Intraoperative Positioning in Maxillofacial Trauma Patients With Cervical Spine Injury - Is It Safe? Radiological Simulation in a Healthy Volunteer.
Observational. To investigate the effects on the cervical spine of positioning patients for maxillofacial procedures by simulating intraoperative positions for common maxillofacial procedures. Magnetic resonance imaging was used to assess the effects of head position in common intraoperative configurations - neutral (anterior mandible position), extended (tracheostomy position) and laterally rotated (mandibular condyle position) on the C-spine of a healthy volunteer. In the tracheostomy position, maximal movement occurred in the sagittal plane between the cervico-occipital junction and C4-C5, as well as at the cervico-thoracic junction. Minimal movement occurred at C2 (on C3), C5 (on C6) and C6 (on C7). In the mandibular condyle position, C-spine movements occurred in both rotational and sagittal planes. Maximal movement occurred above the level of C4, concentrated at atlanto-occipital and atlanto-axial (C1-2) joints. Neck extension is likely to be relatively safe in injuries that are stable in flexion and extension, such as odontoid peg fracture and fractures between C5 and C7. Head rotation is likely to be relatively safe in fractures below C4, as well as vertebral body fractures, and laminar fractures without disc disruption. Early dialogue with the neurosurgical team remains a central tenet of safe management of patients with combined maxillofacial and C-spine injuries.


Hepatic steatosis in hepatitis C virus genotype 3 infection: does it correlate with body mass index, fibrosis, and HCV risk factors?
Hepatic steatosis is a recognized feature of hepatitis C viral infection, particularly in genotype 3. The demographics and the associations contributing to moderate to severe steatosis in genotype 3 are not very well studied. The aim of this study is to determine the demographics and association of steatosis with fibrosis, obesity, diabetes, lipid levels, and risk factors among patients with hepatitis C virus (HCV) genotype 3. Two hundred ninety-three consecutive HCV patients (genotype 1, n = 218; genotype 2, n = 43; genotype 3, n = 32) at our institution were studied retrospectively. Demographic information such as height, weight, genotype, risk factors, serum cholesterol and triglyceride, and liver biopsy was collected. Steatosis was graded using the Brunt classification. HCV genotype 3-infected patients were younger (P < 0.04) and had lower serum cholesterol levels (P < 0.02) compared to nongenotype 3 patients. Moderate to severe steatosis was more prevalent in HCV genotype 3 patients (P < 0.001) with intravenous drug abuse as a risk factor (P = 0.04). Genotype 3 was the independent predictor of steatosis in all patients. There was no statistical association between grade of steatosis and body mass index, fibrosis, necroinflammation, or hyperlipidemia when only HCV genotype 3 patients were included in the multivariate logistic model. Hepatic steatosis is a feature of genotype 3. Patients with HCV genotype 3 are younger and have lower serum cholesterol levels. Genotype 3 is the independent predictor for steatosis in HCV patients. HCV genotype 3 patients with moderate to severe steatosis are more likely to have intravenous drug use as a risk factor.


Bottom-up assembly of viral replication cycles.
Bottom-up synthetic biology provides new means to understand living matter by constructing minimal life-like systems. This principle can also be applied to study infectious diseases. Here we summarize approaches and ethical considerations for the bottom-up assembly of viral replication cycles.


Could Zonulin and Presepsin Be Biomarkers and Therapeutic Targets for Acute Myocarditis?
The diagnosis of acute myocarditis is usually made with clinical and laboratory parameters. This can sometimes be mixed up with diseases that have similar clinical features, making the diagnosis difficult. Therefore, the use of more specific biomarkers, in addition to the classically used biomarkers such as troponin, will accelerate the diagnosis. In addition, these biomarkers may help us to understand the mechanism of myocarditis development and thus predict unpredictable clinical outcomes. This study aims to reveal the possible relationship between intestinal permeability and acute myocarditis. In this study, we wanted to evaluate serum levels of zonulin and presepsin in 138 consecutive subjects, including 68 patients with myocarditis and another 70 as the control group, matched for age, gender, and cardiovascular risk factors. P-values <0.05 were considered to be statistically significant. Compared to the control group, zonulin and presepsin were significantly higher in the patient group with myocarditis (p < 0.001, for all). Zonulin levels were positively correlated with presepsin, peak CK-MB, and peak troponin levels (r = 0.461, p < 0.001; r = 0.744, p < 0.001; r = 0.627, p < 0.001; respectively). In regression analysis, presepsin and zonulin were determined as independent predictors for myocarditis (OR 1.002, 95% CI 1.001-1.003, p = 0.025; OR 12.331, 95% CI 4.261-35.689; p < 0.001; respectively). The predictive value of acute myocarditis of presepsin and zonulin in ROC curve analysis was statistically significant (p < 0.001, for both). This study showed that zonulin and presepsin could be biomarkers that can be used in the diagnosis of myocarditis, and they can also be therapeutic targets by shedding light on the developmental mechanism of myocarditis.


Recurrent paroxysmal supraventricular tachycardia: a complication of ventricular pacing in a patient with occult Wolff-Parkinson-White syndrome.
A 60 year old man suffering from syncope believed to be due to the sick sinus syndrome was treated with a permanent demand ventricular pacemaker. This led to almost continous bouts of paroxysmal supraventricular tachycardia (SVT) over the ensuing two years, mistakenly believed to be part of the sick sinus syndrome. Careful study showed that this man had a type A Wolff-Parkinson-White accessory atrioventricular connection which consistently conducted retrogradely, but only rarely antegradely, during applications of carotid sinus massage. Episodes of SVT were repeatedly induced whenever ventricular-paced impulses captured the atria retrogradely. All episodes of SVT stopped when the ventricular pacemaker was removed. Following insertion of an atrial pacemaker, the patient had no episodes of SVT or syncope over a nineteen month follow-up period. This case illustrates the care required in selecting a proper site for protective pacing in patients who suffer from paroxysmal SVT.


Validation of fetal cerebellar volume by three-dimensional ultrasonography in Brazilian population.
To validate the prediction equation of the volume of fetal cerebellum by three-dimensional ultrasonography determined for Taiwan's population in Brazilian population. A longitudinal prospective study was performed with 52 normal pregnant women between 20 and 32 weeks. The measurement of fetal cerebellar volume was done by virtual organ computer-aided analysis (VOCAL) method, with a rotation angle of 30 degrees. To establish the correlation of fetal cerebellar volume with gestational age, a polynomial regression analysis was performed, with cerebellar volume as dependent variable and gestational age as independent variable. To compare the prediction equation of the volume of fetal cerebellum in Taiwan's population and the equation established in this study, with the values obtained from Brazilian population (referential), we used the intraclass correlation coefficient, with the averages compared by paired Student's t test. The volume of fetal cerebellum was highly correlated with gestational age, and the best prediction equation obtained was of the second degree. The equation established in this study predicted cerebellar volumes more accurately than the equation established for Taiwan's population, since the average values of fetal cerebellar volume were more similar to the average values of reference. The equation established for Taiwan's population presented less accuracy in Brazilian population, possibly due to the strong ethnical differences between both populations.


Glycolytic lactate production supports status epilepticus in experimental animals.
Status epilepticus (SE) requires rapid intervention to prevent cerebral injury and mortality. The ketogenic diet, which bypasses glycolysis, is a promising remedy for patients with refractory SE. We tested the role of glycolytic lactate production in sustaining SE. Extracellular lactate and glucose concentration during a seizure and SE in vivo was measured using lactate and glucose biosensors. A lactate dehydrogenase inhibitor, oxamate, blocked pyruvate to lactate conversion during SE. Video-EEG recordings evaluated seizure duration, severity, and immunohistochemistry was used to determine neuronal loss. Genetically encoded calcium indicator GCaMP7 was used to study the effect of oxamate on CA1 pyramidal neurons in vitro. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded from CA1 neurons to study oxamate's impact on neurotransmission. The extracellular glucose concentration dropped rapidly during seizures, and lactate accumulated in the extracellular space. Inhibition of pyruvate to lactate conversion with oxamate terminated SE in mice. There was less neuronal loss in treated compared to control mice. Oxamate perfusion decreased tonic and phasic neuronal activity of GCaMP7-expressing CA1 pyramidal neurons in vitro. Oxamate application reduced the frequency, but not amplitude of sEPSCs recorded from CA1 neurons, suggesting an effect on the presynaptic glutamatergic neurotransmission. A single seizure and SE stimulate lactate production. Diminishing pyruvate to lactate conversion with oxamate terminated SE and reduced associated neuronal death. Oxamate reduced neuronal excitability and excitatory neurotransmission at the presynaptic terminal. Glycolytic lactate production sustains SE and is an attractive therapeutic target.


The Use of Ribosomal DNA for Comparative Cytogenetics.
Fluorescence in situ hybridization (FISH) with ribosomal DNA (rDNA) sequences provides excellent chromosome markers for comparative cytogenetic analyses, especially in non-model plant species. The tandem repeat nature of a sequence and the presence of a highly conserved genic region make rDNA sequences relatively easy to isolate and clone. In this chapter, we describe the use of rDNA as markers for comparative cytogenetics studies. Traditionally, cloned probes labeled with Nick-translation have been used to detect rDNA loci. Recently, pre-labeled oligonucleotides are also employed quite frequently to detect both 35S and 5S rDNA loci. Ribosomal DNA sequences, together with other DNA probes in FISH/GISH or with fluorochromes such as CMA3 banding or silver staining, are very useful tools in comparative analyses of plant karyotypes.


Submucosal Tunnel Endoscopic Resection of Gastric Lesion Before Obesity Surgery: a Case Series.
Submucosal tumors (SMTs) of the gastrointestinal tract are a rare pathological entity comprising a wide variety of neoplastic and non-neoplastic lesions. Even if most SMTs are benign tumors (e.g., leiomyomas), a smaller portion may have a malignant potential (e.g., gastrointestinal stromal tumor (GIST)). Preoperative diagnosis of SMT in bariatric patients may arise challenging clinical dilemmas. Long-term surveillance may be difficult after bariatric surgery. Moreover, according to SMT location, its presence may interfere with planned surgery. Submucosal tunneling endoscopic resection (STER) has emerged as an effective approach for minimally invasive en bloc excision of SMTs. This is the first case series of STER for SMTs before bariatric surgery. Seven female patients underwent STER for removal of SMTs before bariatric surgery. All lesions were incidentally diagnosed at preoperative endoscopy. STER procedural steps comprised mucosal incision, submucosal tunneling, lesion enucleation, and closure of mucosal defect. En bloc removal of SMT was achieved in all cases. Mean procedural time was of 45 min (SD 18.6). No adverse event occurred. Mean size of the lesions was 20.6 mm (SD 5.8). Histological diagnoses were 5 leyomiomas, 1 lipoma, and 1 low grade GIST. Bariatric procedure was performed after a mean period of 4.1 months (SD 1.6) from endoscopic resection. STER is a safe and effective treatment for the management of SMT even in bariatric patients awaiting surgery. Preoperative endoscopic resection of SMTs has the advantages of reducing the need for surveillance and removing lesions that could interfere with planned surgery. STER did not altered accomplishment of bariatric procedures.


Adolescent and young adult HPV vaccination in Australia: achievements and challenges.
Australia commenced an ongoing school based government funded human papillomaviruses (HPV) (cervical cancer prevention) vaccination program in April 2007 for adolescent females aged 12-13 years. In addition, up to December 31, 2009, a catch-up program for young females 13-26 years of age was offered: a school-based vaccination program was used to offer HPV vaccine to girls enrolled in school (14-17 years), and general practitioners or other community health provider offered vaccine to young women aged 18-26 years. To date, only the quadrivalent vaccine (HPV 6/11/16/18) has been utilized in the funded program. Acceptance of the vaccine is high with coverage of 3 doses of the HPV vaccine in the school age cohort around 70%, and just over 30% in the older age cohort. Since the vaccination program was initiated, a reduction in new cases of genital warts of 73% among vaccine eligible age females has been evidenced in STI clinics across Australia. A reduction of 44% of new cases in young males (not a part of the free program) was also documented during this same time period, suggesting significant herd immunity. Similarly, in the state of Victoria, a small but significant decrease in high grade abnormalities in Pap screening findings has been reported in young women<18 years for the period 2007-9, as compared to pre-vaccination. Challenges for the future include how we can sustain and improve HPV vaccination coverage in young Australian women, while maintaining cervical cancer screening participation and reviewing cervical cancer screening methods.


Microbial applications for sustainable space exploration beyond low Earth orbit.
With the construction of the International Space Station, humans have been continuously living and working in space for 22 years. Microbial studies in space and other extreme environments on Earth have shown the ability for bacteria and fungi to adapt and change compared to "normal" conditions. Some of these changes, like biofilm formation, can impact astronaut health and spacecraft integrity in a negative way, while others, such as a propensity for plastic degradation, can promote self-sufficiency and sustainability in space. With the next era of space exploration upon us, which will see crewed missions to the Moon and Mars in the next 10 years, incorporating microbiology research into planning, decision-making, and mission design will be paramount to ensuring success of these long-duration missions. These can include astronaut microbiome studies to protect against infections, immune system dysfunction and bone deterioration, or biological in situ resource utilization (bISRU) studies that incorporate microbes to act as radiation shields, create electricity and establish robust plant habitats for fresh food and recycling of waste. In this review, information will be presented on the beneficial use of microbes in bioregenerative life support systems, their applicability to bISRU, and their capability to be genetically engineered for biotechnological space applications. In addition, we discuss the negative effect microbes and microbial communities may have on long-duration space travel and provide mitigation strategies to reduce their impact. Utilizing the benefits of microbes, while understanding their limitations, will help us explore deeper into space and develop sustainable human habitats on the Moon, Mars and beyond.


Identification and characterization of microRNAs in Biomphalaria tenagophila and comparative analysis of their expression in Schistosoma mansoni-resistant and -susceptible snail populations.
Schistosomiasis is a neglected tropical disease caused by Schistosoma and affects over 240 million people worldwide. One of the most prominent causative agents is Schistosoma mansoni, which develops inside the intermediate host. Biomphalaria tenagophila is the second most important vector of schistosomiasis in Brazil and the Taim population is completely resistant to infection by S. mansoni. This study aims to identify and characterize B. tenagophila microRNAs (miRNAs) and evaluate their differential expression in S. mansoni-susceptible and -resistant populations of B. tenagophila. Two populations of B. tenagophila snails, susceptible and resistant to S. mansoni infection, were used to investigate the small RNA response of these snails after being infected with the parasite. Small RNA sequencing and quantitative real-time PCR were employed to identify and validate differentially expressed miRNAs. Bioinformatics analysis were performed to identify miRNA precursors and mature and evaluate their differential expression. The study predicted 173 mature miRNAs and 123 precursors. Among them were six Lophotrochozoa-specific miRNAs, three mollusk-specific miRNAs, and six pre-miRNAs in a cluster. The small RNA sequencing and RT-PCR of B. tenagophila samples allowed assessing the expression patterns of miRNAs. The results obtained may support future studies in Biomphalaria spp., generating a global impact on disease control.


Vascular insufficiency in Okihiro's syndrome secondary to hypothenar hammer syndrome.
The presence of Okihiro's syndrome (congenital thenar hypoplasia and Duane's anomaly) in a patient became clinically significant when a hypothenar hammer syndrome developed. The ulnar artery occlusion resulted in a compromise of the hand's vascular supply because of a congenital hypoplastic radial artery. Resection of the thrombosed ulnar artery and insertion of an interposition vein graft restored circulation to the hand. Anatomic features in this case include a hypoplastic radial artery and double motor branch of the median nerve. Clinicians should consider Okihiro's syndrome in the differential diagnosis of thenar muscle atrophy since there are genetic, diagnostic, and clinical implications.


Characterization of acetyl-CoA: L-lysine N6-acetyltransferase, which catalyses the first step of carbon catabolism from lysine in Saccharomyces cerevisiae.
The carbon catabolism of L-lysine starts in Saccharomyces cerevisiae with acetylation by an acetyl-CoA:L-lysine N6-acetyltransferase. The enzyme is strongly induced in cells grown on L-lysine as sole carbon source and has been purified about 530-fold. Its activity was specific for acetyl-CoA and, in addition to L-lysine, 5-hydroxylysine and thialysine act as acetyl acceptor. The following apparent Michaelis constants were determined: acetyl-CoA 0.8 mM, L-lysine 5.8 mM, DL-5-hydroxylysine, 2.8 mM, L-thialysine 100 mM. The enzyme had a maximum activity at pH 8.5 and 37 degrees C. Its molecular mass, estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, was 52 kDa. Since the native molecular mass, determined by gel filtration, was 48 kDa, the enzyme is a monomer.


A method for measuring and reporting manual data extraction reliability.
As health care costs have risen dramatically, the use of clinical data to analyze the quality of health care provided has increased. Central to this analysis is the means by which the clinical data itself is obtained. The reliability and validity of the data must be established in order to insure credible use of the data. The Wisconsin Ambulatory Review Project (WARP) is a three-year study of the nature of care in the ambulatory setting based on clinical data extracted retrospectively from written medical charts. This paper focuses on the method used to measure and report the reliability of the extraction process in the WARP study. The implementation of this methodology as a custom C program is described in detail.


Ultrasound and MRI appearance of abnormally adherent placenta in a woman with Asherman's syndrome.
Although 10% of pregnancies following treatment of Asherman's syndrome are estimated to have abnormal placental adhesion, there is a paucity of reports describing imaging features in such cases. We describe ultrasound and MRI features in one of such cases, showing a peculiar pattern of shallow but diffuse abnormally adherent placenta.


NMDA receptor-mediated Ca(2+) influx triggers nucleocytoplasmic translocation of diacylglycerol kinase ζ under oxygen-glucose deprivation conditions, an in vitro model of ischemia, in rat hippocampal slices.
Diacylglycerol kinase (DGK) plays a key role in pathophysiological cellular responses by regulating the levels of a lipid messenger diacylglycerol. Of DGK isozymes, DGKζ localizes to the nucleus in various cells such as neurons. We previously reported that DGKζ translocates from the nucleus to the cytoplasm in hippocampal CA1 pyramidal neurons after 20 min of transient forebrain ischemia. In this study, we examined the underlying mechanism of DGKζ translocation using hippocampal slices exposed to oxygen-glucose deprivation (OGD) to simulate an ischemic model of the brain. DGKζ-immunoreactivity gradually changed from the nucleus to the cytoplasm in CA1 pyramidal neurons after 20 min of OGD and was never detected in the nucleus after reoxygenation. Intriguingly, DGKζ was detected in the nucleus at 10 min OGD whereas the following 60 min reoxygenation induced complete cytoplasmic translocation of DGKζ. Morphometric analysis revealed that DGKζ cytoplasmic translocation correlated with nuclear shrinkage indicative of an early process of neuronal degeneration. The translocation under OGD conditions was blocked by NMDA receptor (NMDAR) inhibitor, and was induced by activation of NMDAR. Chelation of the extracellular Ca(2+) blocked the translocation under OGD conditions. These results show that DGKζ cytoplasmic translocation is triggered by activation of NMDAR with subsequent extracellular Ca(2+) influx. Furthermore, inhibition of PKC activity under OGD conditions led to nuclear retention of DGKζ in about one-third of the neurons, suggesting that PKC activity partially regulates DGKζ cytoplasmic translocation. These findings provide clues to guide further investigation of glutamate excitotoxicity mechanisms in hippocampal neurons.


Visualization of Oligonucleotide-Based Probes Along Pseudochromosomes Using RIdeogram, KaryoploteR, and Circlize (Circos).
Fluorescence in situ hybridization (FISH) using oligonucleotide-based probes is an innovative modification of classic FISH techniques, enabling karyotypic identifications. Here, we exemplarily describe the design and in silico visualization of oligonucleotide-based probes derived from the Cucumis sativus genome. Additionally, the probes are also plotted comparatively to the closely related Cucumis melo genome. The visualization process is realized in R using various libraries for linear or circular plots including RIdeogram, KaryoploteR, and Circlize.


In vivo effects of epidermal and fibroblast growth factors on DNA replication in mouse skin.
A method was developed for measuring in vivo DNA synthesis after exposure to epidermal growth factor (EGF) or fibroblast growth factor (FGF) in a local area of mouse skin using ring-shaped forceps in combination with autoradiography. The technique should be useful for analysing the effects of growth factors on individual cells of the skin in vivo. EGF induced semisynchronized DNA synthesis in basal cells of the epidermis dose-dependently, but FGF did not. Time course study showed that EGF-induced DNA synthesis in basal cells increased with time for 24 h, and then decreased rapidly. EGF-induced DNA synthesis in basal cells was proportional to the time exposed to EGF (0-60 min). FGF and EGF both had little effect on dermal fibroblastic cells. The discrepancy between in vivo observations and those with cultured mammalian cells is discussed.


Labyrinthectomy: Our Experience in a Tertiary Care Centre.
Labyrinthectomy is an effective surgical procedure for the management of poorly compensated unilateral peripheral vestibular dysfunction in the presence of a nonserviceable hearing. It involves removal of labyrinthine portion of the inner ear and exenteration of the neuroepithelium. In our institution, 8 cases underwent surgical labyrinthectomy from a period of 2013-2018 for various extensive disease manifestations, age ranges from 2 to 48 years. Includes, a child of 2 years age presented with bilateral foul smelling otorrhoea with external auditory canal cartilaginous stenosis, 5 cases of extensive cholesteatoma with labrynthitis and 2 cases of purulent labrynthitis among them 1 were suffering from Tuberculosis and was on Category 1 ATT and other one suffering from extensive granulation at the tympanomastoid area which was inconclusive of the diagnosis even after histopathological examination, so treated as tuberculosis and started on prophylactic antitubercular treatment in addition to surgery. All patients except the child gave past history of giddiness, but at the time of presentation they were not having giddiness or noticeable nystagmus and all had profound unilateral sensorineural hearing loss. Thus all the patients underwent a radical mastoidectomy with total labyrinthectomy and blind sac closure in 2 patients.


Molecular cloning of cDNAs for auxin-induced mRNAs and developmental expression of the auxin-inducible genes.
By differential hybridization, two auxin-inducible cDNA clones (lambda SAR1 and lambda SAR2) have been isolated from a cDNA library constructed to poly(A)+ mRNA from auxin-treated strawberry receptacles. Both the clones have been used as probes to study the expression of the auxin-induced genes in pollinated and unpollinated fruits of various stages of development and in different organs. A high level of auxin-induced mRNAs is found in pollinated fruits as compared to unpollinated fruits of the same age, suggesting that the expression of the auxin-induced genes is developmentally regulated and the level of auxin-induced mRNAs is regulated by endogenous auxin. Furthermore, our data on the expression of lambda SAR1 and lambda SAR2 genes in pollinated and unpollinated fruits revealed a positive correlation between growth of strawberry fruit and the induction of mRNA corresponding to the lambda SAR1 and lambda SAR2 clones. Ethylene has no effect on the expression of the auxin-induced mRNAs. lambda SAR1 mRNA is not detected in other parts of strawberry plants whereas lambda SAR2 mRNA is present in roots. Furthermore, mRNA corresponding to lambda SAR1 and lambda SAR2 is not detected in other auxin-responsive plant systems such as pea epicotyls and bean explants.


Structural neuroimaging in partial epilepsy. Magnetic resonance imaging.
MR imaging is the structural neuroimaging procedure of choice in patients with intractable partial epilepsy being considered for surgical treatment. The results of the MR imaging study may be used to identify appropriate candidates for epilepsy surgery. The MR imaged pathology may be of prognostic importance, alter the presurgical evaluation, and affect the operative strategy. Favorable candidates for epilepsy surgery include patients with medial temporal lobe epilepsy related to MTS and patients with lesional epileptic syndromes. Postoperative MR imaging may be useful to determine the extent of lesional and cortical resection.


Distal Femoral Osteotomy for the Valgus Knee: Medial Closing Wedge Versus Lateral Opening Wedge: A Systematic Review.
(1) To determine the radiographic correction/healing rate, patient-reported outcomes, reoperation rate, and complication rate after distal femoral osteotomy (DFO) for the valgus knee with lateral compartment pathology. (2) To summarize the reported results of medial closing wedge and lateral opening wedge DFO. We conducted a systematic review of PubMed, MEDLINE, and CINAHL to identify studies reporting outcomes of DFOs for the valgus knee. Keywords included "distal femoral osteotomy," "chondral," "cartilage," "valgus," "joint restoration," "joint preservation," "arthritis," and "gonarthrosis." Two authors first reviewed the articles; our study exclusion criteria were then applied, and the articles were included on the basis relevance defined by the aforementioned criteria. The Methodological Index for Nonrandomized Studies scale judged the quality of the literature. Sixteen studies were relevant to the research questions out of 191 studies identified by the original search. Sixteen studies were identified reporting on 372 osteotomies with mean follow-up of 45 to 180 months. All studies reported mean radiographic correction to a near neutral mechanical axis, with 3.2% nonunion and 3.8% delayed union rates. There was a 9% complication rate and a 34% reoperation rate, of which 15% were converted to arthroplasty. There were similar results reported for medial closing wedge and lateral opening wedge techniques, with a higher conversion to arthroplasty in the medial closing wedge that was confounded by longer mean follow-up in this group (mean follow-up 100 v 58 months). DFOs for the valgus knee with lateral compartment disease provide improvements in patient-reported knee health-related quality of life at midterm follow-up but have high rates of reoperation. No evidence exists proving better results of either the lateral opening wedge or medial closing wedge techniques. Level IV, systematic review of Level IV studies.


Incidence and risk factors of chronic opioid use after sleep apnea surgery.
To assess the incidence and risk factors of chronic opioid use after obstructive sleep apnea surgery. Using IBM MarketScan research database, adults (>18 years) who underwent a variety of sleep surgery procedures between 2007 and 2015 were identified. Individuals with 1 year of insurance coverage before and after the surgical procedure were included. Additional anesthesia event(s) in the year following the procedure of interest and those who filled an opioid prescription within the year prior to surgery (not naive) were excluded. Outcomes included rates of persistent opioid use (additional opioid prescriptions filled 90-180 days postoperatively), prolonged use (additional opioid prescriptions filled 181-365 days postoperatively), and inappropriate use (> 100 morphine milligram equivalents). Evaluated variables include demographics, surgical procedures, and comorbidities. A total of 10,766 surgical procedures met the inclusion criteria. There was a trend of increased rates of perioperative opioid prescription. After multivariable logistic regression analysis, perioperative opioid prescription and smoking were independent risk factors for inappropriate opioid use (odds ratio [OR] = 31.51, P < .001; OR = 1.41, P = .016, respectively). Opioid prescription and hypertension were independent risk factors for persistent opioid use (OR = 37.8, P < .001, OR = 1.38, P = .008). Perioperative opioid prescription, previous opioid dependence diagnosis, smoking, and male sex were associated with continuous prolonged opioid use (OR = 73.1, 8.13, 1.95, and 1.55, respectively; P < .001, P = .020, P = .024, and P = .032, respectively). While efforts by different societies are being implemented to control the opioid crisis, we found that perioperative opioid prescription for airway surgery targeting obstructive sleep apnea is an independent risk factor for persistent, prolonged, and inappropriate opioid use. Abdelwahab M, Marques S, Howard J, et al. Incidence and risk factors of chronic opioid use after sleep apnea surgery. J Clin Sleep Med. 2022;18(7):1805-1813.


The teacher simulation exercise: changes in physician teaching emphasis and strategy. The SGIM Task Force on the Medical Interview.
The objective of the study was to determine the effect of a faculty development course in teaching medical interviewing on participants' ability to provide effective feedback to interviewers. The study used a non-concurrent control group design which randomized subjects into two groups before the intervention. The two groups completed different pre-tests; each group then completed the other group's pre-test as its post-test. The post-course scores of one group were compared with the pre-course scores of the other group to establish differences. The research was conducted at the 1985 faculty development course sponsored by the SGIM Task Force on the Medical Interview. 49 of 52 teachers of medical interviewing attending the course completed the study. The week-long intervention consisted of a variety of educational activities which assisted the participants in defining and actively pursuing their learning objectives in interviewing, teaching, and self-awareness. In their assessment of two videotaped segments of initial medical visits, participants were more likely after the course to comment on the interviewer's lack of attention to patient affect (69.0% versus 27.2%, p = 0.005 in one segment) and somewhat more likely to identify teaching strategies that actively involved the interviewer (47.2% vs. 35.0%, p = 0.09 in one segment). Both shifts were congruent with assessments made by course faculty. Faculty development can influence teachers to recognize the need to provide feedback on skills that expert teachers would emphasize. The non-concurrent control group design provides an innovative approach to common constraints in evaluating faculty development courses.


Impact of defecation dysfunction on quality of life in mid-low rectal cancer patients following sphincter-sparing surgery.
A large proportion of mid-low rectal cancer patients develop low anterior resection syndrome (LARS) after Sphincter-sparing surgery. This study aimed to investigate the effect of low anterior resection syndrome (LARS) on quality of life (QoL) in Chinese rectal cancer patients following sphincter-sparing surgery. This was a comparative cross-sectional study. Between Jan 2019 to Jun 2020, 146 mid-low rectal cancer patients following sphincter-sparing surgery were enrolled. The low anterior resection syndrome (LARS) score was used to assess bowel dysfunction. According to the LARS score, patients were divided into three levels, no LARS (n = 34), minor LARS (n = 60), and major LARS (n = 52). The Functional Assessment of Cancer Therapy-Colorectal (FACT-C) was used to assess the QoL of the patients. The major LARS group had a significantly shorter level of tumor from the dentate line than the no LARS group. The total FACT-C score of 146 patients was 98.45 ± 17.83. The total FACT-C score and the score of each dimension (physical, emotional, functional dimensions, and colorectal cancer subscale) were significantly different between the minor LARS and major LARS groups, as well as between the no LARS and major LARS groups. Subgroups analyses of the FACT-C score stratified by each item in the LARS scales showed that except for flatus incontinence, patients with different frequencies of other symptoms (bowel frequency, liquid stool incontinence, liquid stool incontinence, stool clustering, urgent bowel movement) had a significantly different total score of FACT (all P < 0.01). The LARS had a significant impact on the QoL in Chinese mid-low rectal cancer patients following sphincter-sparing surgery, especially in patients with major LARS.


Kinetic and isotherm modeling of Cd (II) adsorption by L-cysteine functionalized multi-walled carbon nanotubes as adsorbent.
In this study, multi-walled carbon nanotubes were functionalized by L-cysteine to show the kinetic and isotherm modeling of Cd (II) ions onto L-cysteine functionalized multi-walled carbon nanotubes. The adsorption behavior of Cd (II) ion was studied by varying parameters including dose of L-MWCNTs, contact time, and cadmium concentration. Equilibrium adsorption isotherms and kinetics were also investigated based on Cd (II) adsorption tests. The results showed that an increase in contact time and adsorbent dosage resulted in increase of the adsorption rate. The optimum condition of the Cd (II) removal process was found at pH=7.0, 15 mg/L L-MWCNTs dosage, 6 mg/L cadmium concentration, and contact time of 60 min. The removal percent was equal to 89.56 at optimum condition. Langmuir and Freundlich models were employed to analyze the experimental data. The data showed well fitting with the Langmuir model (R2=0.994) with q max of 43.47 mg/g. Analyzing the kinetic data by the pseudo-first-order and pseudo-second-order equations revealed that the adsorption of cadmium using L-MWSNTs following the pseudo-second-order kinetic model with correlation coefficients (R2) equals to 0.998, 0.992, and 0.998 for 3, 6, and 9 mg/L Cd (II) concentrations, respectively. The experimental data fitted very well with the pseudo-second-order. Overall, treatment of polluted solution to Cd (II) by adsorption process using L-MWCNT can be considered as an effective technology.


Structures in focus--filopodia.
Filopodia are thin cell surface extensions filled with tight parallel bundles of actin filaments. They are highly dynamic structures which rapidly extend and retract as well as sweep up and down and from side to side, and can be found at the leading edge of many types of motile cells such as fibroblasts and keratinocytes, as well as the growth cone tips of migrating axons. Cells appear to use filopodia to explore the extracellular matrix (ECM) and surfaces of other cells, identifying appropriate targets for adhesion or in the case of a migrating growth cone, for sensing guidance cues that enable the axon to navigate to it's appropriate target. As well as this sensory role, filopodia have also recently been shown to play an important mechanical role in epithelial adhesion, and are likely to be key players in developmental processes that require migrating epithelial sheets to zipper and fuse to one another. Their dynamic properties as well as their tendency to be damaged or lost after fixation mean they are best analysed using live imaging techniques. As this field improves, the number of tissues in which filopodia are seen to be playing key roles is fast increasing.


Determination of the cytotoxic effect of Clostridium histolyticum culture supernatant on HeLa cells in the presence of protease inhibitors.
Clostridium histolyticum culture supernatant contains numerous enzymes, which exert a cytotoxic effect on host cells. This includes lethal toxin, clostripain and high-potassium-sensitive toxin. Since the number of C. histolyticum infections increased during the last several years, it seems worthwhile to evaluate whether protease inhibitors, used for the treatment of many diseases, could influence toxicity, and thus, pathogenicity of C. histolyticum. In this study we evaluated in vitro the influence of four common protease inhibitors: aprotinin, phenylmethylsulphonyl fluoride (PMSF), l-1-chloro-3-[4-tosylamido]-7-amino-2-heptanone-HCl (TLCK) and chymostatin on the toxicity of C. histolyticum supernatant towards human epithelial HeLa cells. We show that aprotinin has no effect, while PMSF, TLCK and chymostatin potentiate the cytotoxic activity of C. histolyticum, probably by hindering natural defence mechanisms of cells. In addition, PMSF and TLCK block clostripain enzymatic activity, while chymostatin leaves it intact. Elevated cytotoxicity of the supernatant is not related to the quantity of high-potassium-sensitive toxin, as was reported previously, since desalted supernatant still exerted its strong toxic effect. Our results show that addition of protease inhibitors for treating diseases complicated by concurrent C. histolyticum infection must require special attention.


Communicating AIDS information to Hispanics: the importance of language and media preference.
Though Hispanics are the fastest-growing minority group in the United States and have a high cumulative incidence of acquired immunodeficiency syndrome (AIDS), very little data are available concerning attitudes and beliefs concerning AIDS in this population. In January 1988, 216 Hispanics from three clinics in Oregon participated in a survey regarding AIDS information acquisition and knowledge. Overall, respondents reported receiving more information about AIDS from broadcast media such as television (42.6%) and radio (19.9%) and less from print media such as newspapers (18.5%) and pamphlets (17.6%). Respondents whose primary language was Spanish tended to have fewer information sources and relied relatively more on broadcast media than on print media. Though over 90% of the sample believed AIDS could be transmitted sexually, only 50% thought condoms could prevent transmission. Compared to primarily English speakers, respondents whose primary language was Spanish were more likely to believe that AIDS could be casually transmitted and less likely to believe that condoms could prevent transmission. This study suggests that more information delivered in an effective manner, both culturally and linguistically, is needed.


Patients should have greater involvement in treatment plans.
A GUIDELINE to improve quality of life for older people with social care needs and multiple long-term conditions has been issued by the National Institute for Health and Care Excellence.