Force loss induced by inhibiting cross-bridge cycling is mitigated in eccentric contraction.
We examined whether the force loss induced by 2,3-butanedione monoxime affects isometric and eccentric forces differently. Single skinned muscle fibers were activated at an average sarcomere length of 2.4 μm and then stretched to 3.0 μm. This trial was performed with and without 2,3-butanedione monoxime to calculate the magnitude of force loss attained at several time points: pre-stretch phase at 2.4 μm, eccentric phase, end of eccentric contraction, and post-stretch phase at 3.0 μm. The magnitude of force loss was significantly larger in the pre-stretch phase than at the other time points. Further, the mitigated force loss in the eccentric contraction was more prominent in the long condition than in the short condition. We suggest that the eccentric force is relatively preserved compared with the reference isometric force (pre-stretch) when cross-bridge cycling is inhibited, possibly because of the contribution of the elastic force produced by titin.


Limitations of object-based feature encoding in visual short-term memory.
The present study investigated object-based feature encoding in visual short-term memory for 2 features within the same dimension that occur on different parts of an object. Using the change-detection paradigm, this experiment studied objects with 2 colors and objects with 2 orientations. Participants found it easier to monitor 1 rather than both features of such objects, even when decision noise was properly controlled for. However, no object-based benefit was observed for encoding the 2 features of each object that were of the same dimension. When similar stimuli were used but the 2 features of each object were from different dimensions (color and orientation), an object-based benefit was observed. These results thus impose a major constraint on object-based feature encoding theories by showing that only features from different dimensions can benefit from object-based encoding.


Soybean lipoxygenase inhibitory and DPPH radical-scavenging activities of aspernolide A and butyrolactones I and II.
Aspernolide A and butyrolactones I and II showed inhibitory activities against soybean lipoxygenase. All of them also had DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity. An analysis of the mechanism for radical scavenging allowed us to deduce that aspernolide A was converted to a quinone methide by a reaction with two molecules of the DPPH radical.


Preface: Special Topic on Dynamics of Polymer Materials in Thin Films and Related Geometries.
The last twenty years have seen a substantial effort to understand relaxation, mechanics, diffusion, and the glass transition in thin polymer films and related geometries. Recent progress in this field is highlighted in this special issue of The Journal of Chemical Physics on "Dynamics of Polymer Materials in Thin Films and Related Geometries." With the goal of providing an entry point to these 35 papers for those not working in this field, we provide some background and perspective in this introduction to the special topic section.


Reoccurrence of retained placenta at a subsequent delivery: an observational study.
To test the generalizability of previously reported increased risk of reoccurrence of retained placenta in yet another setting. In this observational retrospective study we longitudinally followed women who had a vaginal delivery complicated by a partial or complete retained placenta at Edith Wolfson Medical Center between 1 January 2009 and 31 December 2012. The study group included parturient women who had a partial or complete retained placenta after a vaginal delivery (n = 90). The control group included parturient women who did not have a partial or complete retained placenta after a vaginal delivery from the same time period using the same inclusion criteria (n = 90). Retained partial or complete placenta at a previous delivery was found to be an independent risk factor for retained partial or complete placenta in a subsequent delivery (adjusted OR 9.8, 95%CI 1.2 to 80.6, p = 0.032) and for retained partial or complete placenta and/or postpartum hemorrhage in a subsequent delivery (adjusted OR 14.1, 95% CI 1.7 to 111.9, p = 0.012), after controlling for gestational age and induction of labor at previous delivery. Retained partial or complete placenta at an index delivery increases the risk of reoccurrence of retained partial or complete placenta in a subsequent delivery.


Survival and recovery of Salmonella enterica serovar Typhimurium DT104 at low temperature and water activity in a broth system.
This study investigated the survival of Salmonella enterica serovar Typhimurium DT104 in a broth system under conditions of low temperature (4 degrees C) and low water activity (aw, 0.92 to 0.96). Incubation under these conditions resulted in significant reductions in the viability of stationary phase cells, determined by direct plating on selective XLD medium. Reductions in viable numbers were related to injury associated with initial osmotic shock (hyperosmosis) and further injury associated with longer-term storage under the above conditions. Such injured cells were, however, capable of recovering on a nonselective medium (TSA) and contributing to overall viable cell numbers in nonselective post-storage conditions. Storage at more extreme conditions, at lower aw values, led to cell death at rates influenced by storage temperature. Finally, the data obtained are considered in relation to pathogen survival on the surfaces of beef carcasses during chilling.


Intergenerational variation in sexual health attitudes and beliefs among Sudanese refugee communities in Australia.
The aim of this study was to develop intergenerational understanding of the factors perceived to be influencing the sexual health and wellbeing of young Sudanese refugees in Queensland, Australia. Data from 11 semi-structured, face-to-face interviews exploring sexual health knowledge, attitudes and behaviours with young people aged 16 to 24 years, and five focus groups with adults from the broader Queensland Sudanese community, were compared and contrasted. Findings indicate that sexual health-related knowledge, attitudes and beliefs, along with patterns of sexual behaviour, are changing post-resettlement and this creates considerable intergenerational discord and family conflict. Study findings provide an understanding of how the interplay between traditional cultural gender, parenting and relationship norms and perceived normative Australian beliefs and patterns of behaviour influence the construction of both young people's and their parents' attitudes to sexual health post-arrival. We suggest that sexuality education programmes adapted to the specific cultural- and age-related contexts need to be introduced early within the resettlement process for both young people and their families.


Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke.
Theophylline causes potent cerebral vasoconstriction which decreases blood flow in the non-ischaemic areas of the brain and increases collateral blood flow surrounding the ischaemic region. NOTE: This review covers an area where no active research is taking place. It will be updated if relevant information becomes available, e.g. on completion of an appropriate study. The objective of this review was to assess the effect of theophylline and its analogues, aminophylline and caffeine, in people with confirmed or presumed acute ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched November 2003). For the first version, we also searched EMBASE (1980 to 1999), MEDLINE (1966 to 1999) and Science Citation Index (1981 to 1999). We also contacted the principal investigators of the identified trials. Randomised trials of theophylline or an analogue compound compared with placebo or control in people with confirmed or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset. Three reviewers applied the inclusion criteria, assessed trial quality and extracted data for the first version. The review was updated by one reviewer. Two trials involving just 119 patients were included; 6 studies were excluded. Trial quality was good. Both of the trials tested aminophylline. Analysis was by intention-to-treat where possible. No significant difference was shown in early case fatality (within four weeks) between aminophylline and placebo although the confidence intervals were wide (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.49 to 2.56). There was no significant difference for early death and deterioration (OR 0.87, 95% CI 0.41 to 1.88). Death or disability was not significantly reduced by treatment based on 73 patients in one trial (OR 0.64, 95% CI 0.24 to 1.68). Data for late death and disability were not in a form suitable for analysis. No data on quality of life were available. There is not enough evidence to assess whether theophylline or its analogues, e.g. aminophylline, are safe and improve outcome in people with acute ischaemic stroke.


[Abdominal sympathoma in adults. Apropos of 3 cases, with review of the literature].
Three cases of abdominal sympathoma, a tumor generally affecting young children, presented with clinical symptomatology differing from that observed in infants. Diagnosis is much more difficult and the prognosis constantly fatal.


Contrasting Medical and Legal Standards of Evidence: A Precision Medicine Case Study.
As the health care system transitions to a precision medicine approach that tailors clinical care to the genetic profile of the individual patient, there is a potential tension between the clinical uptake of new technologies by providers and the legal system's expectation of the standard of care in applying such technologies. We examine this tension by comparing the type of evidence that physicians and courts are likely to rely on in determining a duty to recommend pharmacogenetic testing of patients prescribed the oral anti-coagulant drug warfarin. There is a large body of inconsistent evidence and factors for and against such testing, but physicians and courts are likely to weigh this evidence differently. The potential implications for medical malpractice risk are evaluated and discussed.


Development of three full-length infectious cDNA clones of distinct brassica yellows virus genotypes for agrobacterium-mediated inoculation.
Brassica yellows virus is a newly identified species in the genus of Polerovirus within the family Luteoviridae. Brassica yellows virus (BrYV) is prevalently distributed throughout Mainland China and South Korea, is an important virus infecting cruciferous crops. Based on six BrYV genomic sequences of isolates from oilseed rape, rutabaga, radish, and cabbage, three genotypes, BrYV-A, BrYV-B, and BrYV-C, exist, which mainly differ in the 5' terminal half of the genome. BrYV is an aphid-transmitted and phloem-limited virus. The use of infectious cDNA clones is an alternative means of infecting plants that allows reverse genetic studies to be performed. In this study, full-length cDNA clones of BrYV-A, recombinant BrYV5B3A, and BrYV-C were constructed under control of the cauliflower mosaic virus 35S promoter. An agrobacterium-mediated inoculation system of Nicotiana benthamiana was developed using these cDNA clones. Three days after infiltration with full-length BrYV cDNA clones, necrotic symptoms were observed in the inoculated leaves of N. benthamiana; however, no obvious symptoms appeared in the upper leaves. Reverse transcription-PCR (RT-PCR) and western blot detection of samples from the upper leaves showed that the maximum infection efficiency of BrYVs could reach 100%. The infectivity of the BrYV-A, BrYV-5B3A, and BrYV-C cDNA clones was further confirmed by northern hybridization. The system developed here will be useful for further studies of BrYV, such as host range, pathogenicity, viral gene functions, and plant-virus-vector interactions, and especially for discerning the differences among the three genotypes.


The role of magnetic resonance imaging in diagnosis and management of breast cancer.
A review of the literature on the current applications of breast magnetic resonance imaging (MRI) indications, their rationale and their place in diagnosis and management of breast cancer was given. Contrast-enhanced breast MRI is developing as a valuable adjunct to mammography and sonography. Its high sensitivity for invasive breast cancer establishes its superiority in evaluation of multifocality/multicentricity, tumor response to neoadjuvant chemotherapy, detection of recurrence, and staging. Emerging applications include spectroscopy, usage of new contrast agents, and MRI-guided interventions, including noninvasive treatment of breast cancer. Its potential benefit in screening high-risk women has yet to be established with prospective studies, particularly with regard to false positive results.


Excessive Gestational Weight Gain and Subsequent Maternal Obesity at Age 40: A Hypothetical Intervention.
To model the hypothetical impact of preventing excessive gestational weight gain on midlife obesity and compare the estimated reduction with the US Healthy People 2020 goal of a 10% reduction of obesity prevalence in adults. We analyzed 3917 women with 1 to 3 pregnancies in the prospective US National Longitudinal Survey of Youth, from 1979 to 2012. We compared the estimated obesity prevalence between 2 scenarios: gestational weight gain as reported and under the scenario of a hypothetical intervention that all women with excessive gestational weight gain instead gained as recommended by the Institute of Medicine (2009). A hypothetical intervention was associated with a significantly reduced estimated prevalence of obesity for first (3.3 percentage points; 95% confidence interval [CI] = 1.0, 5.6) and second (3.0 percentage points; 95% CI = 0.7, 5.2) births, and twice as high in Black as in White mothers, but not significant in Hispanics. The population attributable fraction was 10.7% (95% CI = 3.3%, 18.1%) in first and 9.3% (95% CI = 2.2%, 16.5%) in second births. Development of effective weight-management interventions for childbearing women could lead to meaningful reductions in long-term obesity.


Flow dependence of propranolol elimination in perfused rat liver.
The effect of experimental variations of the blood flow rate on hepatic elimination of propranolol was studied in livers from 200 g rats perfused in a recirculating system given a constant infusion of propranolol into the reservoir throughout each experiment. This design ensures that, at steady state, the elimination rate of propranolol is the same as the infusion rate of propranolol, and equal to the hepatic blood flow rate multiplied by the hepatic inlet to outlet propranolol concentration difference. Thus, when flow is increased, the concentration difference will decrease, and vice versa. It is currently a matter of debate whether or not this change in concentration difference will influence the outlet substrate concentration. The venous equilibration model (Rowland et al., J. Pharmacokinet. Biopharm. 1: 123-136, 1973) predicts that at a given elimination rate, the outlet concentration is flow-independent, whereas the sinusoidal perfusion model (Bass et al., J. Theor. Biol. 61: 393-410, 1976) predicts that both inlet and outlet concentrations will change. In 13 of 14 experiments, increasing the flow rate (from an average 9 to 14 ml/min) resulted in a decrease of the inlet concentration and elevation of the outlet concentration (each P less than .005). Thus, the data reject the venous equilibration model but are consistent with the sinusoidal perfusion model under the experimental conditions investigated.


Guiding of relativistic laser pulses by preformed plasma channels.
Guiding of relativistically intense (>10(18) W/cm2) laser pulses over more than 10 diffraction lengths has been demonstrated using plasma channels formed by hydrodynamic shock. Pulses up to twice the self-guiding threshold power were guided without aberration by tuning the guide profile. Transmitted spectra and mode images showed the pulse remained in the channel over the entire length. Experiments varying guided mode power and simulations show a large plasma wave was driven. Operating just below the trapping threshold produces a dark current free structure suitable for controlled injection.


Evidence of common progenitors and patterns of dispersion in rat striatum and cerebral cortex.
To correlate clonal patterns in the rat striatum with adult neuronal phenotypes, we labeled striatal progenitors between embryonic day 14 (E14) and E19 with a retroviral library encoding alkaline phosphatase. In the adult striatum, the majority of E14-labeled neurons (87%) were members of discrete horizontal or radial cell clusters. Radial clusters accounted for only 23% of cell clusters but >34% of labeled cells. Striatal clones also demonstrated an unexpected widespread pattern of clonal dispersion. The majority of striatal clones were widely dispersed within the striatum, and 80% of clones were part of even larger clones that included cortical interneurons. Finally, we observed that PCR-positive cortical interneurons were members of clones containing both interneurons and pyramids (44%), exclusively interneuron clones (24%), or combined striatal-cortical clones (16%), consistent with the view that cortical interneurons have multiple origins in differentially behaving progenitor cells. Our data are also consistent with the notion that similar mechanisms underpin striatal and cortical development.


Lower efficacy of omalizumab in older adults with chronic spontaneous urticaria.
Omalizumab is known to be effective in treating chronic spontaneous urticaria (CSU) with an inadequate response to H1 -antihistamine. Although many reports have described pre-treatment biomarkers to predict the efficacy of omalizumab in CSU, there are few reports that examined the relationship between age and the therapeutic effectiveness of omalizumab. Thus, we aimed to investigate the relationship between response to omalizumab and age. This retrospective study comprised 52 CSU patients receiving three consecutive omalizumab courses during the period from April 2017 to March 2021. Participants were categorized as responders or non/partial responders using the urticaria control test to evaluate clinical variables on week 12. The female rate tended to be higher, and the mean age and the median disease duration tended to be lower with no significance in responders compared with in non/partial responders. In addition, they exhibited no significant differences regarding serum immunoglobulin E levels, basophil counts, eosinophil counts, d-dimer, and autologous serum skin test results reported as predictor in the past between two groups. Interestingly, when patients were categorized as age <65 years or ≥65 years, those in the ≥65 years group had a significantly lower response to omalizumab than those aged <65 years. These findings suggest that physicians should keep in mind that the age of their CSU patients may be a predictor of the therapeutic efficacy of omalizumab.


Appraisal of combination treatment for hepatocellular carcinoma: long-term follow-up and lipiodol-percutaneous ethanol injection therapy.
Since 1988, 124 patients with hepatocellular carcinoma were treated in our departments. Among them, 31 cases treated by surgical resection and 30 cases administered a combination therapy (Lipiodol [Laboratoire Guerbet, Villepinte, France]-transcatheter arterial embolization [L-TAE] and lipiodol-percutaneous ethanol injection therapy [L-PEIT]) were analyzed retrospectively. The 1-, 3-, and 5-year survival rates were, respectively, 89.0%, 72.7%, and 63.6% for the surgical resection group and 93.3%, 72.8%, and 42.0% for the combination therapy group. The follow-up results at less than 4 years after the procedures revealed that the survival rate with the combination therapy was slightly better than that with the surgical treatment. However, in the subsequent 4 years, the survival rate of the combination therapy group decreased rapidly. The reasons for this deterioration were local recurrence and/or new primary lesions of hepatocellular carcinoma, mainly due to inappropriate ethanol injection. To achieve adequate and accurate injection of ethanol, a 10% volume of Lipiodol was mixed with the ethanol so that the location of the injected ethanol could be easily confirmed. The effectiveness of L-PEIT was thus confirmed by computed tomography, performed on the following day. Defective Lipiodol accumulation in the tumor and/ or neighboring tissues was able to be corrected by additional ethanol injections. With this L-PEIT technique, the tumor necrosis rate is now improving. Therefore, a better prognosis is expected.


Managing laboratory test ordering through test frequency filtering.
Modern computer systems allow limits to be set on the periods allowed for repetitive testing. We investigated a computerised system for managing potentially overtly frequent laboratory testing, calculating the financial savings obtained. In consultation with hospital physicians, tests were selected for which 'spare periods' (periods during which tests are barred) might be set to control repetitive testing. The tests were selected and spare periods determined based on known analyte variations in health and disease, variety of tissues or cells giving rise to analytes, clinical conditions and rate of change determining analyte levels, frequency with which doctors need information about the analytes and the logistical needs of the clinic. The operation and acceptance of the system was explored with 23 analytes. Frequency filtering was subsequently introduced for 44 tests, each with their own spare periods. The proportion of tests barred was 0.56%, the most frequent of these being for total cholesterol, uric acid and HDL-cholesterol. The financial savings were 0.33% of the costs of all testing, with HbA1c, HDL-cholesterol and vitamin B12 yielding the largest savings. Following the introduction of the system the number of barred tests ultimately decreased, suggesting accommodation by the test requestors. Managing laboratory testing through computerised limits to prevent overtly frequent testing is feasible. The savings were relatively low, but sustaining the system takes little effort, giving little reason not to apply it. The findings will serve as a basis for improving the system and may guide others in introducing similar systems.


Detection and genotyping of Korean porcine rotaviruses.
Porcine group A rotavirus (GARV) is considered to be an important animal pathogen due to their economic impact in the swine industry and its potential to cause heterologous infections in humans. This study examined 475 fecal samples from 143 farms located in 6 provinces across South Korea. RT-PCR and nested PCR utilizing primer pairs specific for the GARV VP6 gene detected GARV-positive reactions in 182 (38.3%) diarrheic fecal samples. A total of 98 porcine GARV strains isolated from the GARV-positive feces were analyzed for G and P genotyping. Based on the sequence and phylogenetic analyses, the most predominant combination of G and P genotypes was G5P[7], found in 63 GARV strains (64.3%). The other combinations of G and P genotypes were G8P[7] (16 strains [16.3%]), G9P[7] (7 strains [7.1%]), G9P[23] (2 strains [2.0%]), and G8P[1] (1 strain [1.0%]). The counterparts of G or P genotypes were not determined in three G5, five P[7], and one P[1] strains. Interestingly, phylogenetic analysis indicated that all Korean G9 strains were more closely related to lineage VI porcine and human viruses than to other lineages (I-V) of GARVs and to Korean human G9 strains (lineage III). These results show that porcine GARV infections are common in diarrheic piglets in South Korea. The infecting strains are genetically diverse, and include homologous (G5P[7]), heterologous (G8P[1]), and reassortant (G8P[7]), as well as emerging G9 GARV strains.


Economic evaluation of ropinirole prolonged release for treatment of Parkinson's disease in the Netherlands.
By using the findings obtained from the PREPARED study, we aimed to estimate the cost effectiveness of ropinirole prolonged release (PR) [Requip-Modutab(®)] in Parkinson's disease (PD) versus ropinirole immediate release (IR). In the PREPARED study, ropinirole PR provided a significantly greater improvement in time spent 'off' than ropinirole IR when used as an add-on to levodopa. A health state transition model was developed-based on Hoehn and Yahr (HY) stages in PD-to compare the two treatment strategies. The Markov model included the following treatment-related aspects: (i) rate of disease progression; (ii) rates of dyskinesia; and (iii) medication adherence. In our approach, the base-case analysis showed a favourable pharmacoeconomic profile of ropinirole PR versus ropinirole IR. In particular, general cost savings were estimated combined with modest gains in quality of life, due to reduced disease progression and lower dyskinesia rates. Sensitivity analyses showed that this result was rather robust for varying parameters deterministically, although cost savings were lost in some instances. In particular, the treatment benefits of lower dyskinesia rates and improved adherence influenced the cost-effectiveness outcome. Nonetheless, the cost effectiveness remained acceptable within the limits that were investigated. Probabilistic sensitivity analysis revealed that the probability of accepting PR over IR exceeded 95 % for all relevant 'willingness-to-pay' thresholds. The results of our study indicate a high likelihood of ropinirole PR being cost saving or at least being considered cost effective for use in the Netherlands. However, claims included in our model regarding dyskinesia and improved medication adherence should be further supported by data from daily practice.


Laparoscopic pancreaticoduodenectomy in pancreatic cancer: Our initial experience.
Pancreas cancer is an important cause of mortality worldwide. It has no particular symptoms, and may cause different complaints according to tumor diameter and localization. Local invasion may develop in the short term and distant metastasis may occur in vascular structures in its neighborhood. That's why, resectability rates are low at the time of diagnosis with a negative effect on survival rates. Minimally invasive surgery is being increasingly implemented in pancreas lesions owing to the positive short-term oncologic results of the technique in many other procedures. Traditionally, conventional open surgery is performed in pancreatic head tumors. As laparoscopic resection of pancreatic head cancer has serious technical difficulties and requires advanced laparoscopic experience, minimal invasive attempts in this field have not yet reached sufficient acceptance worldwide. Besides the fact that laparoscopic pancreaticoduodenectomy may provide sufficient short-term oncologic results that are comparative with open surgery, it can be implemented in selected patients in centers with advanced laparoscopic resection capacity. In this case series, we aimed to present our experience of laparoscopic pancreaticoduodenectomy in pancreatic head cancer patients.


p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha.
The death receptor (DR) KILLER/DR5 gene has recently been identified as a doxorubicin-regulated transcript that was also induced by exogenous wild-type p53 in p53-negative cells. KILLER/DR5 gene encodes a DR containing cell surface protein that is highly homologous to DR4, another DR of the tumor necrosis factor (TNF) receptor family. Both DR4 and KILLER/DR5 independently bind to their specific ligand TRAIL and engage the caspase cascade to induce apoptosis. TRID (also known as TRAIL-R3) is an antiapoptotic decoy receptor that lacks the cytoplasmic death domain and competes with KILLER/DR5 and DR4 for binding to TRAIL. In this study, we demonstrate that the DR KILLER/DR5 gene is regulated in a p53-dependent and -independent manner during genotoxic and nongenotoxic stress-induced apoptosis. Just like other p53-regulated genes, ionizing radiation induction of KILLER/DR5 occurs in p53 wild-type cells, whereas methyl methanesulfonate regulation of KILLER/DR5 occurs in a p53-dependent and -independent manner. However, unlike other p53-regulated genes, KILLER/DR5 is not regulated following UV irradiation. TNF-alpha, a nongenotoxic cytokine, also induced the expression of KILLER/DR5 in a number of cancer cell lines, irrespective of p53 status. TNF-alpha did not alter the KILLER/DR5 mRNA stability, suggesting that the TNF-alpha regulation of KILLER/DRS expression appears transcriptional. We also provide evidence that KILLER/DR5 is regulated in a trigger and cell type-specific manner and that its induction by TNF-alpha, p53, or DNA damage is not the consequence of apoptosis induced by these agents. Unlike KILLER/DR5, none of the other KILLER/DR5 family members, including DR4, TRID, or the ligand TRAIL, displayed genotoxic stress or TNF-alpha regulation in a p53 transcription-dependent manner. Thus, KILLER/DR5 appears a bona fide downstream target of p53 that is also regulated in a cell type-specific, trigger-dependent, and p53-independent manner.


Respiration of Nitrate and Nitrite.
Nitrate reduction to ammonia via nitrite occurs widely as an anabolic process through which bacteria, archaea, and plants can assimilate nitrate into cellular biomass. Escherichia coli and related enteric bacteria can couple the eight-electron reduction of nitrate to ammonium to growth by coupling the nitrate and nitrite reductases involved to energy-conserving respiratory electron transport systems. In global terms, the respiratory reduction of nitrate to ammonium dominates nitrate and nitrite reduction in many electron-rich environments such as anoxic marine sediments and sulfide-rich thermal vents, the human gastrointestinal tract, and the bodies of warm-blooded animals. This review reviews the regulation and enzymology of this process in E. coli and, where relevant detail is available, also in Salmonella and draws comparisons with and implications for the process in other bacteria where it is pertinent to do so. Fatty acids may be present in high levels in many of the natural environments of E. coli and Salmonella in which oxygen is limited but nitrate is available to support respiration. In E. coli, nitrate reduction in the periplasm involves the products of two seven-gene operons, napFDAGHBC, encoding the periplasmic nitrate reductase, and nrfABCDEFG, encoding the periplasmic nitrite reductase. No bacterium has yet been shown to couple a periplasmic nitrate reductase solely to the cytoplasmic nitrite reductase NirB. The cytoplasmic pathway for nitrate reduction to ammonia is restricted almost exclusively to a few groups of facultative anaerobic bacteria that encounter high concentrations of environmental nitrate.


[Long-term outcome after surgical treatment of breast asymmetry: analysis of the patient's perspective in 51 cases].
Literature provides 3 studies only investigating the long-term outcome after surgical correction of breast asymmetry. The goal of this study was to analyse from a patient's perspective, which factors influence postoperative satisfaction most. All patients undergoing surgical treatment for breast asymmetry between 2000 and 2009 were included. With help of the visual analogue scale the patients conducted a subjective assessment of their own long-term result using the following parameters: overall satisfaction, symmetry, size, shape, scarring and sensitivity. Anthropometric measurements of the breasts followed. 51 patients (80% follow-up) were seen 2-11 (mean 5±2.5) years postoperatively. The following mean values were recorded for overall satisfaction 8.31 (±1.91), symmetry 7.86 (±2.25), size 8.42 (±1.93), shape 8.12 (±2.03), scarring 7.82 (±1.94) and sensitivity 7.92 (±2.19). Overall satisfaction increased significantly with good scores for the parameters symmetry [p=0.01] and shape [p=0.048]. Neither size [p=0.46] nor scarring [p=0.69] nor sensitivity [p=0.34] had a statistically significant influence on overall satisfaction. Furthermore, overall satisfaction did not depend on the surgical technique, preoperative size, preoperative asymmetry, age of the patient at time of surgery, period of time between the operation and the assessment, resected weight (absolute and difference between left and right) or on postoperative symmetry of the nipple areola complex. In our patients, long-term overall satisfaction after surgical correction of breast asymmetry was primarily dependent on symmetry and shape. Size, scarring and sensitivity did not have a statistically significant influence on postoperative overall satisfaction. This also applied to preoperative size, preoperative extent of asymmetry, age of the patient at time of surgery, surgical technique and the time span between the operation and the assessment.


Pathogenic mechanisms of invasive group A Streptococcus infections by influenza virus-group A Streptococcus superinfection.
Group A Streptococcus (GAS) are pathogenic bacteria of the genus Streptococcus and cause severe invasive infections that comprise a wide range of diverse diseases, including acute respiratory distress syndrome, renal failure, toxic shock-like syndrome, sepsis, cellulitis and necrotizing fasciitis. The essential virulence, infected host and external environmental factors required for invasive GAS infections have not yet been determined. Superinfection with influenza virus and GAS induced invasive GAS infections was demonstrated by our team in a mouse model, after which clinical cases of invasive GAS infections secondary to influenza virus infection were reported by other investigators in Japan, USA, Canada, UK China, and other countries. However, the pathogenic mechanisms underlying influenza virus-GAS superinfection are not yet fully understood. The present review describes the current knowledge about invasive GAS infections by superinfection. Topics addressed include the bacteriological, virological and immunological mechanisms impacting invasion upon superinfection on top of underlying influenza virus infection by GAS and other bacteria (i.e., Streptococcus pneumoniae and Staphylococcus aureus). Future prospects are also discussed.


Pathoanatomy and classification of low back disorders.
Over the past decade research into the effectiveness of low back disorders (LBDs) has focused on the classification of subgroups more likely to respond to specific treatment. Much of this research has explicitly excluded a focus on pathoanatomical factors based on a questionable interpretation of the biopsychosocial model. Common justifications and potential issues with this approach are explored with recommendations made for future clinical and research practice.


[The formation of eating behavior].
Food behaviour involves the totality of the actions of man which aim at satisfying his nutritional need. It is based on psychical reflection, decision and assessment processes. Food behaviour has social and historical determinants and forms accordingly to the dialectic relation of biological, social and economic conditions. Hunger, thirst and appetite are perceived as nutritional need which results from the requirements of energy, nutrients and liquid, and is satisfied by the food behaviour in conformity with the actual material potential, situational influences, subjective ideas, interests, attitudes and knowledge as well as other psychical properties. Consequently, food behaviour is rich in variations with dynamic and conservative features. Motives as well as will components are essential constituent conditions of food behaviour. For this reason, empirical studies arteo provide psychological cognition concerning the subjective reflection of the nutritional requirements, the requirement-standard integration, the sensation of stimulation and the decision-making in food behaviour, the ultimate goal being to deduce measures for food behaviour guidance.


Correlating dynamics and selectivity in adsorption of semiconductor nanocrystals onto a self-organized pattern.
Selective adsorption of semiconductor nanocrystals onto an organic self-organized pattern shows a time-dependent behavior. By studying the wetting behavior of delivered solvent (1-phenyloctane) on a lipid self-organized pattern and determining the adhesion energy between semiconductor nanocrystals and substrate, we obtain a correlation between dynamics and selectivity in adsorption of semiconductor nanocrystals onto the pattern by constructing a potential energy landscape. Two consecutive steps for selective adsorption of nanocrystals onto the self-organized pattern have been established: the first one is the molecule exchange of 1-phenyloctane and lipid molecules to form the adsorption sites for nanocrystals, and the second one is the adsorption of nanocrystals onto the adsorption sites due to the strong interaction between nanocrystals and substrate.


[Clinico-neurophysiological features of the course of the disease in patients with paroxysmal atrial fibrillation].
The subjects of the study were 32 patients with paroxysmal atrial fibrillation (AF) and 19 ':ealthy individuals using a clinical and neurophysiological method of toposelective mapping of electroencephalogram (EEG). EEG was done during the inter-attack, pre-attack, and post-attack periods, as well as during a paroxysm. During the inter-attack period, the patients had a lower beta-rhythm power vs. the healthy controls, while there were no significant differences between them in the power of alpha- and beta-activity. Before an attack, the patients had a significant increase in beta, alpha-, and theta-range power, reflecting the intensification of the activity of the metaencephalic reticular formation, thalamocortical, and hypothalamosepto-hyppocampal systems, respectively. During an AF paroxysm, the activity of the thalamocortical and reticular systems was lowered, while the activity of the hypothalamo-hyppocampal system further increased. After an attack, the activity of all the mentioned systems went down to the initial state of the "optimal" brain functioning after an excessive excitation. It is assumed that generalized one-way direction of EEG changes before an attack reflects tensed functioning of practically all activation systems, which increases the probability of a "breakdown" in a form of an AF paroxysm. The data of the study evidence a cyclic character of the disease and stresses an important role in AF pathogenesis played by disturbances associated with the functional condition of non-specific temporal-limbic and reticular brain structures, especially in patients without organic myocardial alterations.


Aerosol-Processed Nanomaterials for Antimicrobial Air Filtration.
Health-care products are a dominant application of various nanotechnologies. Silver nanoparticles are widely used in commercial products requiring antimicrobial activity. Due to the limitations of wet processing in nanotechnology applications, dry aerosol processes have been developed for indoor antimicrobial air filtration. In this work, various aerosol processes for the synthesis or generation of nanomaterials, natural-product nanoparticles, and hybrid nanoparticles are reviewed. Key aerosol processes and the morphologies of various antimicrobial nanoparticles generated using a variety of systems or deposited on filter fibers are introduced.


Uncovering novel inter- and intrachromosomal chromosome 1 aberrations in follicular lymphomas by using an innovative multicolor banding technique.
Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21), which is the initial genetic perturbation in this disease. Additional genetic mutations are required to generate a fully malignant phenotype. Secondary chromosomal alterations seen in FL include prominent involvement of chromosome 1 in the form of balanced or unbalanced translocations, insertions, deletions, and duplications involving both the p and q arms. We investigated a diagnostically well defined set of 55 t(14;18)-positive FL cases with complex karyotypes by means of multicolor karyotyping. Sixteen cases showed involvement of chromosome 1 and were analyzed in further detail by a novel multicolor banding technique for this chromosome. We defined three groups showing varying complexity of chromosome 1 alterations. The first group revealed simple translocations, such as t(1;2), t(1;6), t(1;8), and t(1;17), involving breakpoints on either the p or the q arm of chromosome 1. The second group showed more complex rearrangements with translocations, insertions, regional duplications, and involvement of more than one partner chromosome with either the p or the q arm of chromosome 1. The third group was defined by highly complex rearrangements involving translocations, regional duplications, amplifications, and intrachromosomal band relocations affecting the entire chromosome 1. All three groups shared interchromosomal rearrangements of chromosome 1 with chromosome 8, often involving the MYC protooncogene site, amplification involving region 1q21-q31, and deletion involving region 1p36. Thus, the use of sophisticated multicolor molecular cytogenetic assays in the investigation of malignant lymphoma allows precise characterization of chromosomal alterations and will provide a better understanding of their biology.


Clinicians' preferences for managing aneurysmal subarachnoid hemorrhage using endothelin receptor antagonists.
The endothelin receptor antagonist (ERA) clazosentan is being investigated for the medical prevention of cerebral vasospasm and associated complications, such as delayed cerebral ischemia (DCI), after aneurysmal subarachnoid hemorrhage (aSAH). This study quantified how clinicians weigh the benefits and risks of ERAs for DCI prevention to better understand their treatment needs and expectations. An online choice experiment was conducted to elicit preferences of neurologists, intensivists, and neurosurgeons treating aSAH in the US and UK for the use of ERAs. The design of the choice experiment was informed by a feasibility assessment (N = 100), one-on-one interviews with clinicians (N = 10), a qualitative pilot (N = 13), and a quantitative pilot (N = 50). Selected treatment attributes included in the choice experiment were: one benefit (likelihood of DCI); and three risks (lung complications, hypotension, and anemia). In the choice experiment, clinicians repeatedly chose best and worst treatment options based on a scenario of a patient being treated in the ICU after aneurism repair. A correlated mixed logit model determined the relative attribute importance (RAI) and associated highest density interval (HDI) as well as acceptable benefit-risk trade-offs. The final choice experiment was completed by 350 clinicians (116 neurologists, 129 intensivists/intensive care clinicians, and 105 neurosurgeons; mean age, 47.4 years). Reducing the likelihood of DCI (RAI = 56.5% [HDI, 53.6-59.5%]) had the largest impact on clinicians' treatment choices, followed by avoiding the risks of lung complications (RAI = 29.6% [HDI, 27.1-32.3%]), hypotension (RAI = 9.2% [HDI, 7.5-10.8%]), and anemia (RAI = 4.7% [HDI, 3.7-5.8%]). Clinicians expected the likelihood of DCI to decrease by ≥8.1% for a 20% increase in the risk of lung complications, ≥2.4% for a 20% increase in the risk of hypotension, and ≥1.2% for a 20% increase in the risk of anemia. Clinicians were willing to accept certain increased risks of adverse events for a reduced risk of DCI after aSAH. The likelihood of DCI occurring after aSAH can therefore be considered a clinically relevant endpoint in aSAH treatment development. Thus, evaluations of ERAs might focus on whether improvements (i.e., reductions) in the likelihood of DCI justify the risks of adverse events.


Predicting reactivities of protein surface cysteines as part of a strategy for selective multiple labeling.
A variety of biophysical methods used to study proteins requires protein modification using conjugated molecular probes. Cysteine is the main residue that can be modified without the risk of altering other residues in the protein chain. It is possible to label several cysteines in a protein using highly selective labeling reactions, if the cysteines react at very different rates. The reactivity of a cysteine residue introduced into an exposed surface site depends on the fraction of cysteine in the deprotonated state. Here, it is shown that cysteine reactivity differences can be effectively predicted by an electrostatic model that yields site-specifically the fractions of cysteinate. The model accounts for electrostatic interactions between the cysteinyl anion and side chains, the local protein backbone, and water. The energies of interaction with side chains and the main chain are calculated by using the two different dielectric constants, 40 and 22, respectively. Twenty-six mutants of Escherichia coli adenylate kinase were produced, each containing a single cysteine at the protein surface, and the rates of the reaction with 5,5'-dithiobis(2-nitrobenzoic acid) (Ellman's reagent) were measured. Cysteine residues were chosen on the basis of locations that were expected to allow modification of the protein with minimal risk of perturbing its structure. The reaction rates spanned a range of 6 orders of magnitude. The correlation between predicted fractions of cysteinate and measured reaction rates was strong (R = 92%) and especially high (R = 97%) for cysteines at the helix termini. The approach developed here allows reasonably fast, automated screening of protein surfaces to identify sites that permit efficient preparations of double- or triple-labeled protein.


Mevinolin (lovastatin) inhibits androstenedione production by porcine ovarian theca cells at the level of the 17 alpha-hydroxylase:C-17,20-lyase complex.
Mevinolin, putatively a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme-A reductase, was used to assess the contribution of de novo synthesized cholesterol to androgen production by ovarian thecal cells in vitro. Enzymatically dispersed thecal cells from 3- to 6-mm follicles of prepubertal gilts were incubated at 150,000 cells/ml with a maximally effective dose of LH (250 ng/ml) for 24 h. Mevinolin (3-50 microM) caused dose-dependent inhibition of androstenedione production. Addition of 25-hydroxycholesterol (0.025-25 microM) failed to restore androstenedione production to levels seen in the absence of mevinolin, suggesting an additional site of action of mevinolin beyond 3-hydroxy-3-methylglutaryl coenzyme reductase. The site of this inhibitory effect was determined by measuring steroid products formed in the presence of relevant steroid precursors. Mevinolin (12 microM) inhibited the production of 17 alpha-hydroxyprogesterone from progesterone and that of androstenedione from 17 alpha-hydroxyprogesterone, while 25-hydroxycholesterol to progesterone and pregnenolone to progesterone conversions were unimpaired. That mevinolin did not affect 3 beta-hydroxysteroid dehydrogenase:delta 5-delta 4-isomerase reactions was confirmed by demonstrating that conversions of pregnenolone, 17 alpha-hydroxypregnenolone, and dehydroepiandrosterone to progesterone, 17 alpha-hydroxyprogesterone, and androstenedione, respectively, were not affected by 12 microM mevinolin. These results indicate that mevinolin has an additional inhibitory action at the level of the 17 alpha-hydroxylase:C-17,20-lyase complex. The degree of inhibition of androstenedione production was not decreased with increased concentrations of progesterone or 17 alpha-hydroxyprogesterone substrate, suggesting that the inhibition was not competitive in nature. As the dose of mevinolin was increased up to 50 microM, progesterone accumulation was unaffected, but pregnenolone concentrations in medium greatly increased. While the mechanism of this effect is unclear, this finding suggests that preformed intracellular cholesterol, rather than that synthesized de novo, is supplying steroidogenic substrate in these cells.


Commissural closure for the treatment of commissural mitral valve prolapse or flail.
Mitral regurgitation (MR) due to commissural prolapse/flail represents a challenging surgical problem for which a variety of reconstructive approaches have been proposed. The study aim was to report the authors' experience with commissural closure within such a difficult setting. Between 1998 and July 2007, a total of 115 patients (mean age 56.5 +/- 15.5 years) with MR due to pure commissural prolapse/flail of one or both leaflets underwent commissural closure associated with annuloplasty. The etiology of the disease was degenerative in 90.4% of cases and post-endocarditis in 9.6%. The commissural region involved by chordal rupture/elongation was the posterior-medial in 88 patients (76.5%) and the anterior-lateral in 27 (23.5%). The mean NYHA class was 1.9 +/- 0.8, and mean ejection fraction 58.2 +/- 7.7%. There was one in-hospital death (0.9%). Among patients undergoing isolated mitral repair, the cardiopulmonary bypass and cross-clamp times were 58 +/- 11.6 min and 43 +/- 11.7 min, respectively. Actuarial survival at one and five years was 96.1 +/- 2.2% and 91 +/- 5.3%, respectively. At a mean follow up of 2.3 +/- 1.98 years (median 2.0; range: 1-8.3 years), two patients underwent mitral valve replacement for recurrence of severe MR. At the most recent echocardiographic study (performed in 108 patients), MR was absent in 60 patients (55.6%), mild in 43 (39.8%), moderate in three (2.8%) and severe in two (1.9%, both reoperated on). The mean mitral valve area was 2.8 +/- 0.63 cm2, and the mitral gradient 4.2 +/- 1.05 mmHg. Commissural prolapse/flail of the mitral valve can be effectively corrected by suturing together the margins of the anterior and posterior leaflets in the commissural area. This type of repair is not time-consuming, and is easily reproducible and durable. In the authors' experience of this surgery, no signs of mitral stenosis were ever detected.


Concentration Effects on the Entropy of Electrochemical Lithium Deposition: Implications for Li(+) Solvation.
The solvation behavior of Li(+) in ethylene carbonate and dimethylcarbonate upon dilution has been investigated by electrochemical microcalorimetry. We measured the heat effects at a Li electrode upon electrochemical Li deposition and dissolution from Li(+) solutions of varying concentration. The exchanged heat is correlated to the entropy of lithium deposition and therefore reveals information about the solvation of Li(+). Lithium deposition from electrolytes with lower concentrations showed less entropy gain than deposition from electrolytes with higher concentrations. This can be fully explained by the entropy of dilution of the Li(+) ions. From our data we further concluded that the inner coordination shell of the Li(+) ions does not significantly change between 0.01 and 1 M Li(+) concentration. The results also suggest that contact ion pairs, which are probably present in the electrolyte, show a similar solvation behavior as regular lithium ions.


Spreading of silent chromatin: inaction at a distance.
One of the oldest unsolved problems in genetics is the observation that gene silencing can 'spread' along a chromosome. Although spreading has been widely perceived as a process of long-range assembly of heterochromatin proteins, such 'oozing' might not apply in most cases. Rather, long-range silencing seems to be a dynamic process, involving local diffusion of histone-modifying enzymes from source binding sites to low-affinity sites nearby. Discontinuous silencing might reflect looping interactions, whereas the spreading of continuous silencing might be driven by the processive movement of RNA or DNA polymerases. We review the evidence for the spreading of silencing in many contexts and organisms and conclude that multiple mechanisms have evolved that silence genes at a distance.


Behaviour of the neutrophil to lymphocyte ratio in young subjects with acute myocardial infarction.
In the last years the neutrophil to lymphocyte ratio (NLR) has been examined in cardiovascular disorders and in particular in coronary artery disease and acute myocardial infarction (AMI). Now we examined this parameter in subjects with juvenile myocardial infarction at the initial stage and after 3 and 12 months. We enrolled 123 young subjects (112 men and 11 women, mean age 39.4 ± 5.8 yrs) with AMI. The time interval between the AMI onset and the investigation was 13 ± 7 days. The mean value of NLR observed in young AMI subjects was significantly increased compared to normal controls (N = 1.817 ± 0.711; young AMI subjects = 2.376 ± 0.873, p < 0.0001). NLR does not discriminate STEMI (2.427 ± 0.878) and non STEMI (2.392 ± 0.868) or diabetics (2.604 ± 1.000) and non diabetics (2.324 ± 0.853), but it differentiates smokers (2.276 ± 0.853) and non smokers (2.837 ± 1.072). NLR at the initial stage is not correlated with the number of cardiovascular risk factors or with the extent of the coronary disease. In this study we found a significant decrease of neutrophil count at 3 and 12 months later AMI without any significant variation of lymphocyte and consequently we observed a decrease in NLR at these two intervals of time in comparison with the initial stage. Despite some limitations present in this study, it is interesting to underline that also in juvenile myocardial infarction this low-cost haematological marker may be considered together with other inflammatory indicators.


Optical Coherence Tomography Angiography in Macular Edema.
OCT angiography is a promising new method to visualize the retinal vasculature and choroidal vascular layers in the macular area and provides depth resolved functional information of the blood flow in the vessels. Given that the main moving elements in the eye fundus are contained in vessels, determining a vascular decorrelation signal enables visualization of 3-dimensional retinal and choroidal vascular network without the administration of intravenous dye and thus reducing the risk of potential adverse events.


Chemical and Isotopic Tracers Illustrate Pathways of Nitrogen Loss in Cranberry Floodwaters.
Limited research exists on the sources of nitrogen (N) in cranberry floodwaters, which have been identified as a prominent cause of concern to watershed N loading in the cranberry-producing region of southeastern Massachusetts. In this study, we used naturally occurring chemical and isotopic tracers to infer the sources of N transported by harvest floodwaters. In 2012, the cranberry bed was a net source of total N (TN), exporting 0.8 kg N ha (primarily as organic N) to a nearby lake. Systematic increases in TN concentration were associated with increasing fractions of pre-event soil water and groundwater ("porewater") in discharge. Results showed that N concentrations in porewater generally derive from the natural mixing of soil water and perched groundwater within the cranberry bed but locally display a connection to deep groundwater where the underlying peat is absent. These findings illustrate the environmental significance of stored pools of porewater in cranberry beds and the ability to focus on moments of disproportionate N transfer to most efficiently curtail floodwater N losses (i.e., 58% of N export occurred in only 22% of floodwater discharge).


HDL as a contrast agent for medical imaging.
Contrast-enhanced MRI of atherosclerosis can provide valuable additional information on a patient's disease state. As a result of the interactions of HDL with atherosclerotic plaque and the flexibility of its reconstitution, it is a versatile candidate for the delivery of contrast-generating materials to this pathogenic lesion. We herein discuss the reports of HDL modified with gadolinium to act as an MRI contrast agent for atherosclerosis. Furthermore, HDL has been modified with fluorophores and nanocrystals, allowing it to act as a contrast agent for fluorescent imaging techniques and for computed tomography. Such modified HDL has been found to be macrophage specific, and, therefore, can provide macrophage density information via noninvasive MRI. As such, modified HDL is currently a valuable contrast agent for probing preclinical atherosclerosis. Future developments may allow the application of this particle to further diseases and pathological or physiological processes in both preclinical models as well as in patients.


Hierarchy of partially synchronous states in a ring of coupled identical oscillators.
In coupled identical oscillators, complete synchronization has been well formulated; however, partial synchronization still calls for a general theory. In this work, we study the partial synchronization in a ring of N locally coupled identical oscillators. We first establish the correspondence between partially synchronous states and conjugacy classes of subgroups of the dihedral group D_{N}. Then we present a systematic method to identify all partially synchronous dynamics on their synchronous manifolds by reducing a ring of oscillators to short chains with various boundary conditions. We find that partially synchronous states are organized into a hierarchical structure and, along a directed path in the structure, upstream partially synchronous states are less synchronous than downstream ones.


Longitudinal patterns of illicit drug use, antiretroviral therapy exposure and plasma HIV-1 RNA viral load among HIV-positive people who use illicit drugs.
HIV-positive people who use illicit drugs (PWUD) experience elevated rates of HIV-associated morbidity and mortality compared with members of other key affected populations. Although suboptimal levels of access and adherence to antiretroviral therapy (ART) are common among HIV-positive PWUD, there is a need for studies investigating the possible biological impacts of noninjection illicit drug use among people living with HIV in real-world settings. We accessed data from the ACCESS study, an ongoing prospective cohort of illicit drug users with systematic HIV viral load monitoring in a setting with universal care and ART dispensation records. We used multivariable generalized linear mixed models to estimate the longitudinal associations between noninjection use of crack cocaine, powder cocaine, opioids, methamphetamine, cannabis and alcohol on plasma HIV-1 RNA viral load, adjusted for ART exposure and relevant confounders. Between 2005 and 2018, 843 individuals from the ACCESS cohort were included and contributed to 8698 interviews. At baseline, the mean age was 43 years, 566 (67%) reported male sex and 659 (78%) used crack cocaine in the previous 6 months. In multivariable models adjusted for ART exposure, only crack cocaine use in the last 6 months was found to be significantly associated with higher HIV viral load. We observed significantly higher HIV viral load during periods of crack cocaine use independent of ART exposure. Our findings support further research to investigate the possible biological mechanisms of this effect.


The composite quality score for the appraisal of prospective controlled clinical therapy trials in systematic reviews and its limits.
Systematic reviews of prospective controlled clinical therapy trials are one of the most important sources of information in modern medicine. Besides the systematic search for and statistical pooling of current clinical trial data for a particular type of therapy, systematic reviews also have the task of appraising the quality of trial results. The quality of trial results may be diminished by low internal trial validity, due to systematic error (bias). A high risk of bias may likely cause the reported trial results to be diverted from the actual true therapeutic effect and thus render it unsuitable for clinical guidance. According to the Cochrane Collaboration, the risk of bias in clinical therapy trials should be assessed using its Risk of Bias tool, Version 2 (RoB 2). However, the tool has been established to have poor inter-rater reliability, with a limited empirical evidence base and described as complex and demanding. Against this background, the composite quality score (CQS) has been developed as a possible alternative trial appraisal tool, characterised by high epistemic rigour, empirical evidence base, inter-rater reliability and ease of use. This article presents the current evidence of the CQS and its limitations.


A Meta-Learning Approach for Fast Personalization of Modality Translation Models in Wearable Physiological Sensing.
Modality translation grants diagnostic value to wearable devices by translating signals collected from low-power sensors to their highly-interpretable counterparts that are more familiar to healthcare providers. For instance, bio-impedance (Bio-Z) is a conveniently collected modality for measuring physiological parameters but is not highly interpretable. Thus, translating it to a well-known modality such as electrocardiogram (ECG) improves the usability of Bio-Z in wearables. Deep learning solutions are well-suited for this task given complex relationships between modalities generated by distinct processes. However, current algorithms usually train a single model for all users that results in ignoring cross-user variations. Retraining for new users usually requires collecting abundant labeled data, which is challenging in healthcare applications. In this paper, we build a modality translation framework to translate Bio-Z to ECG by learning personalized user information without training several independent architectures. Furthermore, our framework is able to adapt to new users in testing using very few samples. We design a meta-learning framework that contains shared and user-specific parameters to account for user differences while learning from the similarity amongst user signals. In this model, a meta-learner approximated by a neural network learns how to learn user-specific parameters and can efficiently update them in testing. Our experiments show that the proposed model reduces the percentage root mean square difference (PRD) by 41% compared to training a single model for all users and by 36% compared to training independent models for each user. When adapting the model to new users, our model outperforms fine-tuning a pre-trained model through back-propagation by 40% using as few as two new samples in testing.


Retreatment of regression after photorefractive keratectomy for myopia.
To study results of retreatment after regression in myopic patients who underwent photorefractive keratectomy (PRK). Procedures were performed with the Nidek EC-5000 excimer laser. This was a retrospective study of 20 of 2127 patients, with follow-up of at least 6 months, who underwent repeated excimer laser ablation. No patient with low myopia had regression. We evaluated six eyes (group I) with moderate myopia; 13 eyes (group II) with high myopia; and ten eyes (group III) with extreme myopia. Average uncorrected visual acuity at 6 months after retreatment was 0.73 +/- 0.21 in group I, 0.64 +/- 0.35 in group II, and 0.61 +/- 0.38 in group III. At six months after retreatment, the average was -0.36 +/- 1.05 D in group I, -0.42 +/- 1.12 D in group II, and -1.40 +/- 1.62 D in group III. The amount and frequency of regression was higher in patients with high and extreme myopia; however, the preliminary results of retreatment of regression were satisfactory.


Predicting the number of COVID-19 infections and deaths in USA.
Uncertainties surrounding the 2019 novel coronavirus (COVID-19) remain a major global health challenge and requires attention. Researchers and medical experts have made remarkable efforts to reduce the number of cases and prevent future outbreaks through vaccines and other measures. However, there is little evidence on how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection entropy can be applied in predicting the possible number of infections and deaths. In addition, more studies on how the COVID-19 infection density contributes to the rise in infections are needed. This study demonstrates how the SARS-COV-2 daily infection entropy can be applied in predicting the number of infections within a given period. In addition, the infection density within a given population attributes to an increase in the number of COVID-19 cases and, consequently, the new variants. Using the COVID-19 initial data reported by Johns Hopkins University, World Health Organization (WHO) and Global Initiative on Sharing All Influenza Data (GISAID), the result shows that the original SAR-COV-2 strain has R0<1 with an initial infection growth rate entropy of 9.11 bits for the United States (U.S.). At close proximity, the average infection time for an infected individual to infect others within a susceptible population is approximately 7 minutes. Assuming no vaccines were available, in the U.S., the number of infections could range between 41,220,199 and 82,440,398 in late March 2022 with approximately, 1,211,036 deaths. However, with the available vaccines, nearly 48 Million COVID-19 cases and 706, 437 deaths have been prevented. The proposed technique will contribute to the ongoing investigation of the COVID-19 pandemic and a blueprint to address the uncertainties surrounding the pandemic.


Getting what you need from the hospital to succeed as a traumatologist.
Currently, the market for orthopaedic trauma surgeons is varied. The market consists of university employed, university private, medical group employed, medical group private, private employed, private contracted, and private. Each option has its positives and negatives. The orthopaedic trauma surgeon needs to determine which setting is appropriate for his/her given needs and wants. An experienced mentor(s) is invaluable for advice and guidance. The surgeon then needs to find an administrative leader to initiate, implement, and evaluate certain processes to succeed.


Levinas's ethics as a basis of healthcare - challenges and dilemmas.
Levinas's ethics has in the last decades exerted a significant influence on Nursing and Caring Science. The core of Levinas's ethics - his analyses of how our subjectivity is established in the ethical encounter with our neighbour or the Other - is applied both to healthcare practice and in the project of building an identity of Nursing and Caring Science. Levinas's analyses are highly abstract and metaphysical, and also non-normative. Thus, his analyses cannot be applied directly to practical problems and questions. Theorists in Nursing and Caring Science are generally aware of this. Nevertheless, many of them use Levinas's analyses to explore and solve questions of practical and normative character. This article focuses on the challenges and dilemmas of using Levinas in this manner. The article is divided into two parts. The first part presents some central ideas of Levinas's ethics based on the latter part of his authorship. The main focus is on the radicalism of Levinas's critique of the symbolic order (which includes concepts, categories, knowledge, etc.) - or as he puts it 'the said' - as a basis for subjectivity and responsibility. Levinas's notions of saying, anarchy, and singularity accentuate this point of view. These notions refer to conditions in the language, which counteract the symbolic order in the ethical encounter to such an extent that it becomes an incomprehensible. Levinas gives the argumentation a metaphysical frame: The encounter with the incomprehensible is an encounter with the Holy, which is not the ontological God, but a metaphysical desire. It is a mystery as to what this means, and herein lies possibly the main challenge when using Levinas's ethics in science and research: How to maintain the radicalism of his critique of the symbolic order when this is to be communicated in a scientific context that expects clarification of statements and ideas? The second part of the article explores this question by examining how some theorists use Levinas's ethics on questions and problems in the area of healthcare and Nursing and Caring Science. The focus is especially on the theorists' reception and use of the just mentioned notions. The study reveals that these theorists to a large extent transform Levinas's ethics according to their own approaches, with the result that his ethics loses its critical radicalism. Thus, I question the reason why they use Levinas.


Reversion reactions of beta-galactosidase (Escherichia coli).
The reversion reactions of beta-galactosidase (Escherichia coli) produced beta-galactosyl-galactoses and beta-galactosyl-glucoses. About 10 beta-galactosyl-galactose and 10 beta-galactosyl-glucose gas-liquid chromatographic peaks were detected and it is thus very likely that every possible isomer of beta-galactosyl-galactose and beta-galactosyl-glucose was formed by the reversion reactions (taking into account both anomers for each isomer). The presence of lactose and allolactose among the beta-galactosyl-glucoses was confirmed with standards. An important finding relating to the role of allolactose as an inducer of the lac operon was that allolactose (beta-D-galactosyl-(1----6)-D-glucose) was the only disaccharide formed initially, and at equilibrium it was present in the largest amount (50%). Obviously the enzyme is specific in its ability to form allolactose, and allolactose is the most stable beta-galactosyl-glucose, both important inducer properties. The equilibrium constant (concentration of disaccharides divided by the concentration of reactants at equilibrium) of the reaction was about 9.5 mM-1. This is the first report of an equilibrium constant for the beta-galactosidase reaction. Of mechanistic significance is the fact that only three compounds were able to replace D-galactose as a reversion reactant. Two of these (L-arabinose and D-fucose) had alterations at carbon 6. The 6 position, therefore, is not essential for reactivity. The third compound was D-galactal. Any other sugars tested (even with very minor changes relative to D-galactose) did not react. Of special consequence is the 2 position. The results strongly suggest that there has to be either an equatorial hydroxyl at the 2 position of a sugar or a special reactivity (as with D-galactal) in order for the enzyme to catalyze the beta-galactosidase reaction.


A novel determinant (comA) essential for natural transformation competence in Neisseria gonorrhoeae and the effect of a comA defect on pilin variation.
A novel genetic determinant (comA) has been identified and found to be required for the transformation of piliated Neisseria gonorrhoeae. Mutants in comA of strain MS11 grow normally and are DNA-uptake proficient but blocked in the translocation of DNA into the cytoplasm. Here we show by site-specific mutagenesis and genetic complementation that only one of two open reading frames identified in comA is essential for competence: it encodes a protein (ComA) with a predicted size of 74 kDa. The comA gene maps upstream of the iga locus and is transcribed in the opposite orientation, probably under the control of a putative sigma 54-type promoter. While DNA probes specific for the N. gonorrhoeae iga locus reveal only a little cross-reactivity with commensal Neisseria species, the neighbouring comA gene appears to be present in most of them. ComA fusion proteins were obtained by in vitro translation. The synthesized gene products migrated atypically in SDS gels indicating its strong hydrophobicity. Several transmembrane alpha-helices were predicted from the amino acid sequence of ComA which, in the context of an observed sequence similarity with other inner membrane proteins, suggests a location for the protein in the inner membrane. Using piliated and non-piliated comA mutants the consequences of transformation deficiency on pilin phase variation were assessed. We show that the comA defect affects some but not all types of DNA rearrangements associated with pilE variation. The results are in agreement with previous observations supporting the notion that multiple recombination pathways contribute to the variability of pilE.


Carotidynia.
Carotidynia has an extensive differential diagnosis, including such conditions as pharyngitis, otitis, bruxism, temporomandibular joint syndrome, neuralgia, myalgia and temporal arteritis. Carotidynia may be divided into three distinct classifications: migrainous, nonmigrainous (or classic) and arteriosclerotic. Successful treatment depends on correct classification of the disorder. Ergotamine, propranolol and tricyclic antidepressants have been effective treatments in patients with migrainous carotidynia, and steroids and nonsteroidal anti-inflammatory drugs have proved effective for the classic type of carotidynia. Further investigation is required before it can be determined if treatment for the arteriosclerotic type should be medical or surgical.


Severe muscular dystrophy in girls.
Twelve girls and 2 boys with severe but not congenital muscular dystrophy were found in a national survey. An autosomal recessive gene is likely to account for most if not all of these cases. The condition differs slightly from X-linked Duchenne muscular dystrophy in showing prominent early toe-walking, a milder course, relatively more weakness of the deltoid muscles, normal intelligence, a normal ECG and a more focal pattern of muscle pathology.


Estimating gas emissions from multiple sources using a backward Lagrangian stochastic model.
Manure storage tanks and animals in barns are important agricultural sources of methane. To examine the possibility of using an inverse dispersion technique based on a backward Lagrangian Stochastic (bLS) model to quantify methane (CH4) emissions from multiple on-farm sources, a series of tests were carried out with four possible source configurations and three controlled area sources. The simulated configurations were: (C1) three spatially separate ground-level sources, (C2) three spatially separate sources with wind-flow disturbance, (C3) three adjacent ground-level sources to simulate a group of adjacent sources with different emission rates, and (C4) a configuration with a ground level and two elevated sources. For multiple ground-level sources without flow obstructions (C1 and C3), we can use the condition number (K, the ratio of the uncertainty in the calculated emission rate to the uncertainty in the predicted ratio of concentration to emission rate) to evaluate the applicability of this inverse dispersion technique and a preliminary threshold of K <10 is recommended. For multiple sources with wind disturbance (C2) or an even more complex configuration including ground level and elevated sources (C4), a low kappa is not sufficient to provide reasonable discrete and total emission rates. The effect of flow obstructions can be neglected as long as the distance between the source and the measurement location is greater than approximately 10 times the height of the flow obstructions. This study shows that the bLS model has the potential to provide accurate discrete emission rates from multiple on-farm emissions of gases provided that certain conditions are met.


Childhood Sexual Abuse Profiles and Psychological Functioning in Adult Males.
This study used a person-centered approach to generate profiles of males' sexual abuse characteristics and then link profiles to other types of childhood maltreatment and adversity, and adult outcomes. Data were drawn from 215 North American males (86% Caucasian) aged 17-61 years recruited from websites offering support for sexual abuse. Latent profile analysis identified three profiles, ranging from 1-2 instances of fondling by an unfamiliar extrafamilial perpetrator to chronic, penetrative abuse by individuals within and outside the family. Profiles were labeled Severe (26%), More Severe (33%), and Most Severe (41%). Chi-squares and analysis of variance showed that men in the Most Severe profile were more likely to experience childhood emotional and physical abuse, and a greater number of non-victimization adversities, than men in the other two profiles. After controlling for multiple victimization and adversity, men in the More Severe and Most Severe profiles reported significantly greater internalizing problems than men in the Severe profile, and men in the Most Severe profile reported significantly more trauma symptoms than men in the Severe profile. While these results require replication, they suggest that treatment should be tailored to the individual needs of male survivors.


Sustained selective attention in adolescence: Cognitive development and predictors of distractibility at school.
Despite much research into the development of attention in adolescence, mixed results and between-task differences have precluded clear conclusions regarding the relative early or late maturation of attention abilities. Moreover, although adolescents constantly face the need to pay attention at school, it remains unclear whether laboratory measures of attention can predict their ability to sustain attention focus during lessons. Therefore, here we devised a task that was sensitive to measure both sustained and selective attention and tested whether task measures could predict adolescents' levels of inattention during lessons. In total, 166 adolescents (aged 12-17 years) and 50 adults performed a sustained selective attention task, searching for letter targets while ignoring salient yet entirely irrelevant distractor faces, under different levels of perceptual load-an established determinant of attention in adults. Inattention levels during a just preceding classroom lesson were measured using a novel self-report classroom distractibility checklist. The results established that sustained attention (measured with response variability) continued to develop throughout adolescence across perceptual load levels. In contrast, there was an earlier maturation of the effect of perceptual load on selective attention; load modulation of distractor interference was larger in the early adolescence period compared with later periods. Both distractor interference and response variability were significant unique predictors of distractibility in the classroom, including when controlling for interest in the lesson and cognitive aptitude. Overall, the results demonstrate divergence of development of sustained and selective attention in adolescence and establish both as significant predictors of attention in the important educational setting of school lessons.


Consequences of niche overlap for ecosystem functioning: an experimental test with pond grazers.
While the number of studies investigating the effects of species diversity on ecosystem properties continues to expand, few have explicitly examined how ecosystem functioning depends quantitatively on the degree of niche complementarity among species. We report the results of a microcosm experiment where similarity in habitat use among aquatic snail species was evaluated as a predictor of changes in community and ecosystem properties due to increasing species richness. Replicate microcosms with all possible one- and two-species combinations of a guild of six snail species were stocked with identical initial snail biomass. Microcosms with two species of snails had greater final snail biomass, lower attached algae biomass, and less total organic matter than monocultures. Snail species differed in their use of five distinct habitat types in the microcosms. Similarity in habitat use between a species pair was negatively related to the magnitude of change (e.g., deltaEF [change in ecosystem function]) in dissolved oxygen. periphyton biomass, and accrual of organic matter with a change in diversity. However, using the most stringent criterion for complementarity effects (e.g., Dmax [proportional deviation of the total polyculture yield from the highest yielding monoculture]), a relationship between species' niche similarity and changes in function with increasing species richness was only observed for dissolved oxygen. The identity of snail species present in the microcosms had strong effects on total organic matter, snail biomass, dissolved oxygen, periphyton biomass, and sedimentation rate. In this study, herbivore identity, sampling effects, and niche complementarity all appear to contribute to species richness effects on pond ecosystem properties and community structure. The analytical approach employed here may profitably be used in other systems to quantify the role of niche complementarity in species richness-ecosystem function relationships.


Revved-up reporting.
As federal quality reporting mandates and noncompliance penalties add up, experts say registries can help take the sting out of the process and rev up quality improvement for physician practices. The online reporting tool is also taking a front seat over claims-based reporting as Medicare signals its plans to eventually phase out that less efficient and less clinically accurate option.


Inhibition of T cell adhesion to extracellular matrix glycoproteins by histamine: a role for mast cell degranulation products.
Mast cells, which are capable of releasing a multitude of preformed and newly generated biological mediators and cytokines, are involved in various inflammatory processes. We studied whether histamine, a mast cell degranulation product, influences the adhesive interactions of T cells with extracellular matrix (ECM) glycoproteins, an event that occurs at sites of inflammation and is mediated primarily by virtue of cell-surface receptors of the beta 1-integrin subfamily. A prerequisite of lymphocyte-ECM interactions is activation of the cells, which modulates the affinity of the otherwise inactive integrins. Isolated rat CD4+ T cells were preincubated with histamine and activated with phorbol myristate acetate (PMA), and their ability to adhere to immobilized ECM components (fibronectin and laminin) was determined. Preincubation with histamine resulted in a 40-50% decrease in the adhesion of the CD4+ cells to both fibronectin or laminin. The notion that inhibition of T cell adhesion to ECM proteins by histamine-induced increase of the cells' intracellular levels of cAMP, thus interfering with calcium influx-associated events that occur during T cell activation, is supported by the finding that T cell adhesion was also abrogated by pharmacological inducers of cAMP. When the T cells were preincubated with supernatants of immunologically activated mast cells and then activated with PMA, a 40-50% inhibition of their adhesion to fibronectin or laminin was also observed. The inhibitory moiety present in the mast cell degranulation supernatants was resistant to heat (80 degrees C). Histamine exerted its suppressive effect on adhesion of T cells via their H2 receptors, as pretreatment with H2 antagonists abrogated the inhibitory effect. Thus, both purified histamine and mast cell-secreted histamine appear to be capable of affecting T cell interactions with ECM.


Persistence of measles, mumps, and rubella protective antibodies 3 years after revaccination in HIV-infected children receiving antiretroviral therapy.
Three years after measles, mumps, and rubella revaccination in 38 human immunodeficiency virus-infected children who had achieved immune recovery after antiretroviral therapy, the prevalence of protective antibody levels was 85% for measles, 61% for mumps, and 79% for rubella, compared with 88%, 84%, and 100%, respectively, 1 month after revaccination.


Chemical waves with line defects in the Belousov-Zhabotinsky reaction.
We report our experimental observations of line-defected chemical waves in a quasi-two-dimensional reaction-diffusion system of Belousov-Zhabotinsky reaction. The observed line defects are explicit, which can be directly monitored in real time. In the parameter space, the state of the chemical waves with line defects is located between two regimes of the defect-mediated turbulence. The line defects appear in target waves as well as in spiral waves. We demonstrate that the line defects come out in traveling waves as the later reorganize their spatial topologies to adapt to the change in the local dynamics from simple to complex oscillations or vice versa.


Src docks to A-kinase anchoring protein gravin, regulating beta2-adrenergic receptor resensitization and recycling.
Gravin (AKAP12) is a membrane-associated scaffold that provides docking for protein kinases, phosphatases, and adaptor molecules obligate for resensitization and recycling of beta(2)-adrenergic receptors. Gravin binds to the cell membrane in a Ca(2+)-sensitive manner and to receptors through well characterized protein-protein interactions. Although the interaction of serine/threonine, cyclic AMP-dependent protein kinase with protein kinase A-anchoring proteins is well described and involves a kinase regulatory subunit binding domain in the C terminus of these proteins, far less is known about tyrosine kinase docking to members of this family of scaffolds. The non-receptor tyrosine kinase Src regulates resensitization of beta(2)-adrenergic receptors and docks to gravin. Gravin displays nine proline-rich domains distributed throughout the molecule. One class I ligand for Src homology domain 3 docking, found in the N terminus ((10)RXPXXP(15)) of gravin, is shown to bind Src. Binding of Src to gravin activates the intrinsic tyrosine kinase of Src. Mutagenesis/deletion of the class I ligand (P15A,P16A) on the N terminus of gravin abolishes both the docking of Src to gravin as well as the receptor resensitization and recycling catalyzed by gravin. The Src-binding peptide-(1-51) of gravin behaves as a dominant-negative for AKAP gravin regulation of receptor resensitization/recycling. The tyrosine kinase Src plays an essential role in the AKAP gravin-mediated receptor resensitization and recycling, an essential aspect of receptor biology.


Ordered Van der Waals Hetero-nanoribbon from Pressure-Induced Topochemical Polymerization of Azobenzene.
Pressure-induced topochemical polymerization of molecular crystals with various stackings is a promising way to synthesize materials with different co-existing sub-structures. Here, by compressing the azobenzene crystal containing two kinds of intermolecular stacking, we synthesized an ordered van der Waals carbon nanoribbon (CNR) heterostructure in one step. Azobenzene polymerizes via a [4 + 2] hetero-Diels-Alder (HDA) reaction of phenylazo-phenyl in layer A and a para-polymerization reaction of phenyl in layer B at 18 GPa, as evidenced by in situ Raman and IR spectroscopies, X-ray diffraction, as well as gas chromatography-mass spectrometry and the solid-state nuclear magnetic resonance of the recovered products. The theoretical calculation shows that the obtained CNR heterostructure has a type II (staggered) band gap alignment. Our work highlights a high-pressure strategy to synthesize bulk CNR heterostructures.


Academic activism on behalf of children during the COVID-19 pandemic in Israel; beyond public health advocacy.
Among the challenges presented by the SARS-CoV2 pandemic are those related to balancing societal priorities with averting threats to population health. In this exceptional context a group of Israeli physicians and public health scholars (multidisciplinary academic group on children and coronavirus [MACC]) coalesced, examining the role of children in viral transmission and assessing the necessity and consequences of restricted in-class education. Combining critical appraisal and analytical skills with public health experience, MACC advocated for safe and monitored school re-opening, stressing the importance of education as a determinant of health, continuously weighing this stance against evolving COVID-19-risk data. MACC's activities included offering research-based advice to government agencies including Ministries of Health, Finance, and Education. In a setting where government bodies were faced with providing practical solutions to both decreasing disease transmission and maintaining society's vital activities, and various advisors presented decision-makers with disparate views, MACC contributed epidemiological, clinical and health policy expertise to the debate regarding school closure as a pandemic control measure, and adaptations required for safe re-opening. In this paper, we describe the evolution, activities, policy inputs and media profile of MACC, and discuss the role of academics in advocacy and activism in the midst of an unprecedented public health crisis. A general lesson learned is that academics, based on the rigor of their scientific work and their perceived objectivity, can and should be mobilized to pursue and promote policies based on shared societal values as well as empiric data, even when considerable uncertainty exists about the appropriate course of action. Mechanisms should be in place to open channels to multidisciplinary academic groups and bring their input to bear on decision-making.


Gut microbiome modulation during treatment of mucositis with the dairy bacterium Lactococcus lactis and recombinant strain secreting human antimicrobial PAP.
Mucositis is an inflammatory condition of the gut, caused by an adverse effect of chemotherapy drugs, such as 5-fluorouracil (5-FU). In an attempt to develop alternative treatments for the disease, several research groups have proposed the use of probiotics, in particular, Lactic Acid Bacteria (LAB). In this context, the use of recombinant LAB, for delivering anti-inflammatory compounds has also been explored. In previous work, we demonstrated that either Lactococcus lactis NZ9000 or a recombinant strain expressing an antimicrobial peptide involved in human gut homeostasis, the Pancreatitis-associated Protein (PAP), could ameliorate 5-FU-induced mucositis in mice. However, the impact of these strains on the gut microbiota still needs to be elucidated. Therefore, in the present study, we aimed to characterize the effects of both Lactococci strains in the gut microbiome of mice through a 16 S rRNA gene sequencing metagenomic approach. Our data show 5-FU caused a significant decrease in protective bacteria and increase of several bacteria associated with pro-inflammatory traits. The Lactococci strains were shown to reduce several potential opportunistic microbes, while PAP delivery was able to suppress the growth of Enterobacteriaceae during inflammation. We conclude the strain secreting antimicrobial PAP was more effective in the control of 5-FU-dysbiosis.


Underlying mechanism of Sirt1 on apoptosis and extracellular matrix degradation of osteoarthritis chondrocytes.
The study investigated the effects and underlying mechanisms of silent information regulation of transcription 1 (Sirt1) action on apoptosis in chondrocytes and degradation of the extracellular matrix. Cartilage tissue samples were derived from knee arthroplasty of patients with osteoarthritis (OA). The three groups were as follows: Control, resveratrol (Res) and Res+small interfering (si)RNA (Res+siRNA Sirt1). The level of Sirt1 protein expression significantly increased in the Res group (1.03±0.10) compared with the control (0.22±0.03) and Res+siRNA (0.18±0.01) groups (both P<0.05). Early and late stage cell apoptosis rates decreased in the Res group and increased in the Res+siRNA group (both P<0.05). B‑cell lymphoma 2 (Bcl‑2) expression levels were upregulated and Bcl‑2‑associated X protein (Bax) expression levels were downregulated in the Res group compared with the control group. Protein expression levels of MMP1 and MMP13 and the phosphorylation levels of extracellular signal regulated kinase (ERK), c‑Jun N‑terminal kinase (JNK) and p38 were downregulated in the Res group and upregulated in the Res+siRNA group. In conclusion, upregulation of Sirt1 expression may inhibit OA chondrocyte apoptosis and extracellular matrix degradation by increasing Bcl‑2 expression and decreasing Bax, MMP1 and MMP13 expression, via downregulation of p38, JNK and ERK phosphorylation.


Effects of S-Allylcysteine-Rich Garlic Extract and Dietary Inorganic Nitrate Formula on Blood Pressure and Salivary Nitric Oxide: An Open-Label Clinical Trial Among Hypertensive Subjects.
The conversion of dietary inorganic nitrate (NO3-) to nitric oxide (NO) is a non-canonical pathway that plays an important role in NO biology, especially under pathological conditions. Inorganic NO3- supplementation is a proven method for controlling mild hypertension. Recent reports have suggested that another gaseous transmitter, hydrogen sulfide (H2S), influences NO biosynthesis and metabolism. Here, data are presented from an open-label clinical trial examining the effect of an encapsulated formulation (Vascanox® HP) that combines dietary sources of inorganic NO3- and S-allylcysteine (SAC), a source of H2S from garlic, on NO bioavailability and blood pressure in subjects experiencing elevated blood pressure or mild hypertension. An open-label clinical trial was conducted among patients with hypertension. Participants took Vascanox® for four weeks. Blood pressure was measured at baseline, two weeks, and four weeks. Salivary nitrite (NO2-), a surrogate of NO bioavailability, and NO3- were assessed prior to and two, six, and 24 hours after dosing on the first day of the study and prior to and two hours after dosing at subsequent study visits using saliva NO test strips. Changes in study outcomes over time were evaluated via analysis of variance (ANOVA) and paired t-tests. Twelve participants completed the clinical trial. Vascanox® HP decreased systolic blood pressure by ~11 mmHg (p < 0.001) at two weeks and persisted beyond four weeks with daily supplementation. It also decreased the diastolic blood pressure of hypertensive subjects but not normotensive ones. The magnitude of the decrease was 11 mmHg (p < 0.01) at four weeks of study. Measurements of salivary concentrations of NO2- revealed high peak levels (743 uM) at two hours post-administration and a slow decay to elevated levels (348 uM) at 24 hours. NO2- salivary concentrations, a surrogate biomarker of NO bioavailability, remained above baseline for the duration of the study. Vascanox® HP was shown to be a safe, effective, quick-acting, and long-lasting dietary supplement for controlling mild hypertension.


The use of TCP based EUD to rank and compare lung radiotherapy plans: in-silico study to evaluate the correlation between TCP with physical quality indices.
To apply the equivalent uniform dose (EUD) radiobiological model to estimate the tumor control probability (TCP) scores for treatment plans using different radiobiological parameter settings, and to evaluate the correlation between TCP and physical quality indices of the treatment plans. Ten radiotherapy treatment plans for lung cancer were generated. The dose distributions were calculated using anisotropic analytical algorithm (AAA). Dose parameters and quality indices derived from dose volume histograms (DVH) for target volumes were evaluated. The predicted TCP was computed using EUD model with tissue-specific parameter (a=-10). The assumed radiobiological parameter setting for adjuvant therapy [tumor dose to control 50% of the tumor (TCD50) =36.5 Gy and γ50=0.72] and curative intent (TCD50=51.24 Gy and γ50=0.83) were used. The bootstrap method was used to estimate the 95% confidence interval (95% CI). The coefficients (ρ) from Spearman's rank test were calculated to assess the correlation between quality indices with TCP. Wilcoxon paired test was used to calculate P value. The 95% CI of TCP were 70.6-81.5 and 46.6-64.7, respectively, for adjuvant radiotherapy and curative intent. The TCP outcome showed a positive and good correlation with calculated dose to 95% of the target volume (D95%) and minimum dose (Dmin). Consistently, TCP correlate negatively with heterogeneity indices. This study confirms that more relevant and robust radiobiological parameters setting should be integrated according to cancer type. The positive correlation with quality indices gives chance to improve the clinical out-come by optimizing the treatment plans to maximize the Dmin and D95%. This attempt to increase the TCP should be carried out with the respect of dose constraints for organs at risks. However, the negative correlation with heterogeneity indices shows that the optimization of beam arrangements could be also useful. Attention should be paid to obtain an appropriate optimization of initial plans, when comparing and ranking radiotherapy plans using TCP models, to avoid over or underestimated for TCP outcome.


Ex Vivo Study of Transepithelial Corneal Cross-linking.
To perform in vitro assessment of different techniques of transepithelial corneal cross-linking (CXL) and to compare the results to deepithelialized CXL. Transepithelial CXL was performed after pre-treatment with or without penetration enhancers (gum cellulose, 0.44% sodium chloride, and 0.01% benzalkonium chloride) for 15 or 60 minutes. Deepithelialized corneas underwent CXL after pretreatment with riboflavin for 15 minutes, according to the Dresden protocol. All corneas were incubated in 0.3% collagenase A solution and the time to total dissolution was measured. Corneas were also imaged with confocal microscopy to evaluate the corneal epithelium, subbasal nerve plexus, and depth of stromal keratocyte nuclei as a means of measuring the depth of collagen CXL. Deepithelialized CXL corneas with 15 minutes of pretreatment dissolved after 15.4 ± 3.1 hours, significantly longer (P = .001) than deepithelialized untreated corneas (8.5 ± 0.6 hours). Transepithelial CXL corneas with 15 minutes of pretreatment with or without penetration enhancers dissolved after 8.3 ± 2.1 and 7.4 ± 1.6 hours, respectively. A longer pretreatment of 60 minutes with penetration enhancers resulted in greater resistance to degradation of the transepithelial CXL corneas (14.6 ± 2.2 hours), which was similar to deepithelialized CXL corneas. The results of the biological assay correlated well with the imaging results obtained by confocal microscopy. Corneas treated by transepithelial CXL with an extended pretreatment time of 60 minutes and penetration enhancers exhibited similar characteristics as corneas treated by the deepithelialized CXL approach. By confocal imaging, the transepithelial approach with extended pretreatment time demonstrated evidence of epithelial damage, which may have improved the treatment effect of this group. [J Refract Surg. 2017;33(3):171-177.].