Noninvasive thrombolysis using histotripsy beyond the intrinsic threshold (microtripsy).
Histotripsy has been investigated as a noninvasive, drug-free, image-guided thrombolysis method that fractionates blood clots using acoustic cavitation alone. In previous histotripsy-mediated thrombolysis studies, cavitation clouds were generated using multi-cycle pulses and tended to form on vessel wall. To avoid potential cavitational damage to the vessel wall, a new histotripsy approach, termed microtripsy, has been recently discovered in which cavitation is generated via an intrinsic-threshold mechanism using single-cycle pulses. We hypothesize that microtripsy can generate and confine cavitation in vessel lumen without contacting the vessel wall, which results in recanalization within the clot and potentially eliminating vessel damage. To test our hypothesis, microtripsy was investigated for clot recanalization in an in vitro flow model. Clots were formed inside a vessel phantom (6.5 mm inner diameter) in line with a flow system. Microtripsy was applied by a 1-MHz transducer at a pulse repetition frequency of 50 Hz with a peak negative pressure (P-) of 30 MPa or 36 MPa. To create a flow channel through a clot, the cavitation focus was scanned through the clot at an interval of 0.3 or 0.7 mm. The treated clots were 3-D-scanned by a 20-MHz ultrasound probe to quantify the channels. Restored flow rates were measured and clot debris particles generated from the treatments were analyzed. In all treatments, the cavitation cloud was consistently generated in the center of the vessel lumen without contacting the vessel wall. After each treatment, a flow channel was successfully generated through and completely confined inside the clot. The channels had a diameter up to 60% of the vessel diameter, with restored flow up to 500 mL/min. The debris particles were small with more than 99.9% <10 μm and the largest at 153 um. Each clot (2 cm long) was recanalized within 7 min. The size of the flow channels increased by using higher P- and was significantly larger by using the 0.3 mm scan interval than those using 0.7 mm. The results in this study show the potential of this new microtripsy thrombolysis method for fast, precise, and effective clot recanalization, minimizing risks of vessel damage and embolism.


Characterization of a leukotriene C4 export mechanism in human platelets: possible involvement of multidrug resistance-associated protein 1.
Platelets express leukotriene (LT) C4 synthase and can thus participate in the formation of bioactive LTC4. To further elucidate the relevance of this capability, we have now determined the capacity of human platelets to export LTC4. Endogenously formed LTC4 was efficiently released from human platelets after incubation with LTA4 at 37 degrees C, whereas only 15% of produced LTC4 was exported when the cells were incubated at 0 degrees C. The activation energy of the process was calculated to 49.9 +/- 7.7 kJ/mol, indicating carrier-mediated LTC4 export. This was also supported by the finding that the transport was saturable, reaching a maximal export rate of 470 +/- 147 pmol LTC4/min x 10(9) platelets. Furthermore, markedly suppressed LTC4 transport was induced by a combination of the metabolic inhibitors antimycin A and 2-deoxyglucose, suggesting energy-dependent export. The presence in platelets of multidrug resistance-associated protein 1 (MRP1), a protein described to be an energy-dependent LTC4 transporter in various cell types, was demonstrated at the mRNA and protein level. Additional support for a role of MRP1 in platelet LTC4 export was obtained by the findings that the process was inhibited by probenecid and the 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886. The present findings further support the physiological relevance of platelet LTC4 production.


The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis.
In vertebrates, hematopoietic and vascular progenitors develop from ventral mesoderm. The first primitive wave of hematopoiesis yields embryonic red blood cells, whereas progenitor cells of subsequent definitive waves form all hematopoietic cell lineages. In this report we examine the development of hematopoietic and vasculogenic cells in normal zebrafish and characterize defects in cloche and spadetail mutant embryos. The zebrafish homologs of lmo2, c-myb, fli1, flk1, and flt4 have been cloned and characterized in this study. Expression of these genes identifies embryonic regions that contain hematopoietic and vascular progenitor cells. The expression of c-myb also identifies definitive hematopoietic cells in the ventral wall of the dorsal aorta. Analysis of b316 mutant embryos that carry a deletion of the c-myb gene demonstrates that c-myb is not required for primitive erythropoiesis in zebrafish even though it is expressed in these cells. Both cloche and spadetail mutant embryos have defects in primitive hematopoiesis and definitive hematopoiesis. The cloche mutants also have significant decreases in vascular gene expression, whereas spadetail mutants expressed normal levels of these genes. These studies demonstrate that the molecular mechanisms that regulate hematopoiesis and vasculogenesis have been conserved throughout vertebrate evolution and the clo and spt genes are key regulators of these programs.


Statistical analysis of post mortem DNA damage-derived miscoding lesions in Neandertal mitochondrial DNA.
We have analysed the distribution of post mortem DNA damage derived miscoding lesions from the datasets of seven published Neandertal specimens that have extensive cloned sequence coverage over the mitochondrial DNA (mtDNA) hypervariable region 1 (HVS1). The analysis was restricted to C-->T and G-->A miscoding lesions (the predominant manifestation of post mortem damage) that are seen at a frequency of more than one clone among sequences from a single PCR, but do not represent the true endogenous sequence. The data indicates an extreme bias towards C-->T over G-->A miscoding lesions (observed ratio of 67:2 compared to an expected ratio of 7:2), implying that the mtDNA Light strand molecule suffers proportionally more damage-derived miscoding lesions than the Heavy strand. The clustering of Cs in the Light strand as opposed to the singleton pattern of Cs in the Heavy strand could explain the observed bias, a phenomenon that could be further tested with non-PCR based approaches. The characterization of the HVS1 hotspots will be of use to future Neandertal mtDNA studies, with specific regards to assessing the authenticity of new positions previously unknown to be polymorphic.


Age and liver graft: a systematic review with meta-regression.
Increasing organ shortage results in extended criteria donors (ECD) being used to face the growing demand for liver grafts. The demographic change leads to greater use of elderly donors for liver transplantation, historically considered marginal donors. Age is still considered amongst ECD in liver transplantation as it could affect transplant outcomes. However, what is the cutoff for donor age is still unclear and debated. A search of PubMed, Scopus and Cochrane Library was performed. The primary outcome was 1-year graft survival (GS). The secondary outcome was overall biliary complications and 3-5 years of graft and overall survival. A meta-regression model was used to analyse the temporal trend relation in the survival outcome. The meta-analysis included 11 studies. Hazard ratios for 1-year (age cutoff of 70 and 80,) and 5-year GS (I2:0%) were similar irrespectively of the age group. The meta-regression analysis showed a significant correlation between the 1-year graft survival and the year of publication. (coef. 0.00027, 95% CI - 0.0001 to - 0.0003 p = 0.0009). Advanced-age donors showed an increased risk of overall biliary complications with an odd ratio (OR) of 1.89 (95% CI 1-3.65). Liver grafts potentially discharged because of high-risk failure show encouraging results, and GS in ECD has progressively improved with a temporal trend. Currently, the criteria of marginality vary amongst centres. Age alone cannot be considered amongst the extended criteria. First of all, because of the positive results in terms of septuagenarian graft survival. Moreover, the potential elderly donor-related adjunctive risk can be balanced by reducing other risk factors. A prospective multicentre study should investigate a multi-factorial model based on donor criteria, recipient features and new functional biomarkers to predict graft outcome, as proper donor-recipient matching seems to be the critical point for good outcomes.


Update on retinal prosthetic research: the Boston Retinal Implant Project.
The field of retinal prosthetic research, now more than 20 years old, has produced many high-quality technical options that have the potential to restore vision to patients with acquired disease of the outer retina. Five companies have performed Phase I clinical trials demonstrating that blind patients can reliably report basic elements of visual percepts induced by electrical stimulation. However, at present patients and observers generally do not consider the results to be useful enough in the performance of tasks of daily living to justify the risks of surgery and chronic implantation or the costs. Having developed a wireless device implanted in the subretinal space, the Boston Retinal Implant Project has focused its efforts on developing scalable technologies to create a hermetic device that can deliver individually controlled pulses of electrical stimulation to each of hundreds of electrodes. An advanced device with such attributes will be needed to justify the risks of implantation. An assessment of long-term biocompatibility for all devices remains to be done.


IncHI1A plasmids potentially facilitate horizontal flow of antibiotic resistance genes to pathogens in microbial communities of urban residential sewage.
Horizontal gene transfer via plasmids is important for the dissemination of antibiotic resistance genes among medically relevant pathogens. Specifically, the transfer of IncHI1A plasmids is believed to facilitate the spread of antibiotic resistance genes, such as carbapenemases, within the clinically important family Enterobacteriaceae. The microbial community of urban wastewater treatment plants has been shown to be highly permissive towards conjugal transfer of IncP1 plasmids. Here, we tracked the transfer of the P1 plasmid pB10 and the clinically relevant HI1A plasmid R27 in the microbial communities present in urban residential sewage entering full-scale wastewater treatment plants. We found that both plasmids readily transferred to these communities and that strains in the sewage were able to further disseminate them. Furthermore, R27 has a broad potential host range, but a low host divergence. Interestingly, although the majority of R27 transfer events were to members of Enterobacteriaceae, we found a subset of transfer events to other families, even other phyla. This indicates that HI1A plasmids facilitate horizontal gene transfer both within Enterobacteriaceae, but also across families of, in particular, Gammaproteobacteria, such as Moraxellaceae, Pseudomonadaceae and Shewanellaceae. pB10 displayed a similar potential host range to R27. In contrast to R27, pB10 had a high host divergence. By culture enrichment of the transconjugant communities, we show that sewage strains of Enterobacteriaceae and Aeromonadaceae can stably maintain R27 and pB10, respectively. Our results suggest that dissemination in the urban residual water system of HI1A plasmids may result in an accelerated acquisition of antibiotic resistance genes among pathogens.


Volume load paradox while preparing for the Fontan: not too much for the ventricle, not too little for the lungs.
Ventricular dysfunction is frequently encountered in Fontan patients. Cardiologists and cardiac surgeons have, therefore, mainly focused on preservation of cardiac function, limiting the early volume overload as much as possible both in magnitude and duration. This resulted in improved cardiac function but, in some patients, also in poor pulmonary artery (PA) growth which in turn resulted in a poor final Fontan circuit. The volume requirements for optimal growth and development of the ventricle and the lungs are different and divergent. Avoiding overload of the ventricle is important, but excessive protection from volume overload may not be necessary and may result in PA hypoplasia, which in turn will severely affect the Fontan circuit.


Efficacy of sublingual lorazepam versus intrarectal diazepam for prolonged convulsions in Sub-Saharan Africa.
In Sub-Saharan Africa, intrarectal diazepam is the first-line anticonvulsant mostly used in children. We aimed to assess this standard care against sublingual lorazepam, a medication potentially as effective and safe, but easier to administer. A randomized controlled trial was conducted in the pediatric emergency departments of 9 hospitals. A total of 436 children aged 5 months to 10 years with convulsions persisting for more than 5 minutes were assigned to receive intrarectal diazepam (0.5 mg/kg, n = 202) or sublingual lorazepam (0.1 mg/kg, n = 234). Sublingual lorazepam stopped seizures within 10 minutes of administration in 56% of children compared with intrarectal diazepam in 79% (P < .001). The probability of treatment failure is higher in case of sublingual lorazepam use (OR = 2.95, 95% CI = 1.91-4.55). Sublingual lorazepam is less efficacious in stopping pediatric seizures than intrarectal diazepam, and intrarectal diazepam should thus be preferred as a first-line medication in this setting.


Gender, age, and pharmacists' job satisfaction.
A comprehensive literature review was conducted on the concept of job satisfaction in the pharmacist workforce field and the facets it comprises, as well as its measurement, aiming to (i) review the nature, mechanisms, and importance of job satisfaction in the context of the pharmacist workforce, (ii) survey some of the most salient facets that configure job satisfaction, and (iii) discuss validity and measurement issues pertaining to it. Although female pharmacists generally hold less appealing jobs, earn lower wages and salaries, and are promoted less frequently than their male counterparts, they report higher levels of job satisfaction. Age has a U-shape effect on job satisfaction, with middle-age pharmacists less satisfied than both younger and older practitioners. Workload, stress, advancement opportunities, job security, autonomy, fairness in the workplace, supervisors, coworkers, flexibility, and job atmosphere are facets contributing to pharmacists' job satisfaction. Finally, discrepancy exists among researchers in measuring job satisfaction as a single global indicator or as a composite measure derived from indices of satisfaction with key aspects of a job. Understanding the mechanisms that affect pharmacists' job satisfaction is important to employers in their pursuit to respond to practitioners' needs, decrease turnover, and increase productivity. As pharmacists' response to work-related conditions and experiences depends on gender and age, a unique set of rewards and incentives may not be universally effective. Additional research into the dynamics of the forces shaping pharmacists' perceptions, opinions, and attitudes is needed in order to design and implement policies that allocate human resources more efficiently within the various pharmacy settings.


Charge designable and tunable GFP as a target pH-responsive carrier for intracellular functional protein delivery and tracing.
A charge designable and tunable green fluorescent protein (GFP)-based protein delivery strategy was proposed. The acquired His29GFP selectively permeates the cell membrane at a target pH of 6.5 and escapes from the endosome efficiently. The delivered RNase A caused substantial mRNA degradation in HeLa cells, and proliferation inhibition in different cell lines and a 3D tumor model at pH 6.5.


Using aging to visually uncover evolutionary processes on networks.
Networks are widely used to describe many natural and technological systems. Understanding how these evolve over time poses a challenge for existing visualization techniques originally developed for fixed network structures. We describe a method of incorporating the concept of aging into evolving networks, where nodes and edges store information related to the amount of local evolutionary change they have experienced. This property is used to generate visualizations that ensure stable substructures maintain relatively fixed spatial positions, allowing them to act as visual markers and providing context for evolutionary change elsewhere. By further supplementing these visualizations with color cues, the resultant animations enable a clearer portrayal of the underlying evolutionary process.


Rational and practical use of imaging in COVID-19 pneumonia.
The severe form of the COVID-19 pandemic caused by the SARS-CoV-2 virus, has largely manifested as a predominant respiratory illness causing severe pneumonia characterized by bilateral, subpleural ground glass haze, progressing to consolidation, and fibrosis on imaging. There is some discrepancy between the governmental guidelines, professional Societies and Radiology and Respiratory Medicine specialists with divided opinions between the use of the chest X-rays and CT scan, and whether the use be screening or diagnostic. So far, the most balanced recommendations have been proposed by the Fleischner Society, which are endorsed by the Radiological Society of Pakistan as well. This writeup describes the approach for a rational use of imaging to the best advantage in the current situation according to local resources, and restricting the spread of infection. The most practical compromise for Pakistan appears to be the use of portable digital radiography equipment, and point-of- care ultrasound; with CT scan reserved for clinical situations not explained by the above two modalities, or demanding disease stratification.


What the public knows and wants to know about medicines research and development: a survey of the general public in six European countries.
To explore public knowledge of, and interest in, learning more about medicines R&D in six European countries. Online survey of 6931 members of the public across Europe. The survey formed part of a public omnibus survey. A quota sampling approach was used with quotas set according to national census data on age, gender and government region. The survey explored the public's knowledge and awareness of medicines R&D, their interest in learning more and the perceived influences on this. The survey was completed by 6931 members of the public, over 75% of whom reported having no or less than good knowledge of medicines R&D. Males were more likely than females to report good knowledge (17% vs 15%), and knowledge appeared to decrease with age. Those who were currently or had previously been involved in medical research were almost five times more likely to report good knowledge of medicines R&D overall (43% vs 13%). Participants reported good knowledge of medicines safety and clinical trials but little knowledge of pharmacoeconomics. They were most interested in learning more about medicines safety and personalised and predictive medicine and least interested in pharmacoeconomics. Older people, women and respondents with current good knowledge of medicines R&D were most interested in learning more about medicines R&D. Experience of medical research appears to play a key role in increasing public awareness of and future interest in medicines R&D. Some groups may need to be specifically targeted to increase their awareness of medicines R&D, for example, women expressed great interest in learning more but reported less knowledge than men. It may be useful to explore further the views of those who are currently uninterested in learning more.


ENERGY CONSUMPTION IN MRI: DETERMINANTS AND MANAGEMENT OPTIONS.
Energy consumption awareness is a known concern, and radiology departments have energy-intensive consuming machines. The means of energy consumption management in MRI scanners have yet to be evaluated. To measure the MRI energy consumption and to evaluate the means to reduce it. Data was retrieved for two MRI scanners through the hospital's automated energy consumption measurement software. After correlation with picture archiving and communication system (PACS) files, they were segmented by machine and mode (as follows: stand-by, idle and active) and analyzed. Active mode data for a specific brain MRI protocol have been isolated, and equivalent low energy consuming protocol was made. Both were performed on phantom and compared. Same protocol was performed on a phantom using 3.0T 16 and 32 head channels coils. Multiples sequences were acquired on phantom to evaluate power consumption. Stand-by mode accounted for 60% of machine time and 40% of energy consumption, active mode accounted for 20% machine time and 40% energy consumption, idle mode for 20% imachine time and 20% consumption. DWI and TOF sequences were the most consuming in our brain-MRI protocol. The low energy consuming protocol allowed a saving of approximately 10% of energy consumption, which amounted for 0.20€ for each examination. This difference was mainly due to an energy consumption reduction of the DWI sequence. There were no difference in consumption between a 3.0T 16 and 32 channels head coils. Sequence's active power and duration (especially considering slice thickness) have to be taken into account when trying to optimize energy consumption. There are two key factors to consider when trying to reduce MRI scan energy consumption. Stand-by mode energy consumption has to be taken into account when choosing an MRI scan, as it can't be changed further on. Active mode energy consumption is dependent of the MRI protocols used, and can be reduced with sequences adaptation, which must take into account sequence's active power and duration, on top of image quality.


Use of an oxfendazole pulse release bolus in the control of parasitic gastroenteritis and parasitic bronchitis in first-season grazing calves.
The efficacy of the oxfendazole pulse release bolus system for the control of parasitic gastroenteritis and parasitic bronchitis in first-season grazing calves was evaluated in Belgium. Twenty-two calves were allocated to two groups. The calves in one group received a bolus at the time of turn out, while the other group remained untreated. The efficacy of the bolus was assessed by comparison of faecal worm egg counts, plasma pepsinogen concentrations, the antibody response to Ostertagia, Cooperia and Dictyocaulus species total plasma protein and albumin concentrations, and weight gains throughout the grazing season and the housing period. The oxfendazole pulse release bolus provided good control of parasitic gastroenteritis dominated by ostertagia. The effects of parasitic gastritis were greatly reduced as shown by the significantly lower values of serum pepsinogen and ostertagia antibody titres. The use of the bolus further reduced the adverse effects of parasitism as indicated by better liveweight gains and normal total plasma protein and albumin concentrations whereas in the untreated control group hypoproteinaemia and hypoalbuminaemia were observed. Most animals exhibited clinical signs of parasitic bronchitis at the end of the grazing season, and the bolus may not adequately control parasitic bronchitis in all cases at all times.


Strain-specific priming of resistance in the red flour beetle, Tribolium castaneum.
As invertebrates lack the molecular machinery employed by the vertebrate adaptive immune system, it was thought that they consequently lack the ability to produce lasting and specific immunity. However, in recent years, it has been demonstrated that the immune defence of invertebrates is by far more complicated and specific than previously envisioned. Lasting immunity following an initial exposure that proves protection on a secondary exposure has been shown in several species of invertebrates. This phenomenon has become known as immune priming. In the cases where it is explicitly tested, this priming can also be highly specific. In this study, we used survival assays to test for specific priming of resistance in the red flour beetle, Tribolium castaneum, using bacteria of different degrees of relatedness. Our results suggest an unexpected degree of specificity that even allows for differentiation between different strains of the same bacterium. However, our findings also demonstrate that specific priming of resistance in insects may not be ubiquitous across all bacteria.


Two distinct protocols for the synthesis of unsymmetrical 3,4-disubstituted maleimides based on transition-metal catalysts.
Two tandem catalytic systems are described for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts as starting materials. 4-Aryl-3-pyrrolyl- and 4-aryl-3-indolyl-maleimides were successfully obtained via a Pd(OAc)2/PPh3 based protocol. In contrast, maleimide-fused pyrrolo and indolo[1,2-a]quinolines were obtained in a complementary methodology using CuI/L-proline. These strategies involved a combination of benzylic amine oxidation, trans-amidation, intramolecular Knoevenagel condensation, and N-arylation reactions. Computational investigations provide further insights into this reaction sequence.


Prognostic Impact of Atrial Fibrillation in Acute Myocardial Infarction and Cardiogenic Shock.
Background It is unclear whether atrial fibrillation (AF) influences prognosis in patients with cardiogenic shock and multivessel disease. We aimed to investigate the prognostic impact of AF in patients with cardiogenic shock complicating acute myocardial infarction. Methods and Results In a subanalysis of the CULPRIT-SHOCK trial (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock), patients were grouped according to the presence of AF during index hospital stay. The primary end point was all-cause death at 30 days, and the key secondary end point was all-cause death at 1 year. AF was documented in 142 (21%) of 686 patients. AF was not a significant predictor of 30-day (adjusted odds ratio, 1.01; 95% CI 0.67-1.54; P=0.95) and 1-year (adjusted odds ratio, 0.80; 95% CI, 0.52-1.22; P=0.30) all-cause mortality. Patients with AF already on admission showed higher all-cause mortality at 30 days (52 of 90, 58% versus 19 of 52, 37%; P=0.02) and 1 year (57 of 90, 63% versus 20 of 52, 39%; P=0.004) compared with patients with newly detected AF during hospital stay. AF was associated with a longer time to hemodynamic stabilization (4, interquartile range, 1-8 days versus 3, interquartile range, 1-6 days; P=0.04) at 30 days. Conclusions In cardiogenic shock complicating acute myocardial infarction, all-cause mortality is similar in patients with and without AF. Adverse outcome was detected in the subgroup of patients showing AF already on hospital admission. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01927549.


A Shift in Hip Arthroscopy Use by Patient Age and Surgeon Volume: A New York State-Based Population Analysis 2004 to 2016.
To perform a population-level analysis of the shifts in use of hip arthroscopy by different age groups and to describe the proportion of hip arthroscopy procedures performed by high-volume surgeons. The Statewide Planning and Research Cooperative System database was combined with New York State census data to calculate changes in annual hip arthroscopy incidence by age and gender (2004-16). Annual (January to January) surgeon volumes were calculated and stratified into 4 thresholds that have been associated with significant differences in revision hip surgery rates to calculate changes in hip arthroscopy rates by surgeon volume over time. There was a 495% increase in hip arthroscopies from 2004 to 2016, from 2.35 to 15.47 per 100,000 residents in New York State. The largest increase was in the 10-19 years age group-a 2,150% increase for female patients (= 1.26, P < .001) and a 1,717% increase for male patients (incident rate ratio = 1.21, P < .001). The number of labral repairs performed with femoroplasty increased 52.8% (P < .001). The number of hip arthroscopy surgeons increased from 3.4 to 6.5 per 1 million residents. The number of hip arthroscopies performed by high-volume surgeons increased from 0% in 2004 to 24.7% in 2016. The use of hip arthroscopy has increased over the past 10 years, especially in the adolescent population ages 10-19. Over the same time period, there has been an emergence of high-volume hip arthroscopy surgeons and an increased proportion of procedures performed by these surgeons. Patients of high-volume surgeons tend to be younger, while lower volume surgeons tend to have older patients. Level IV, case series.


Non-synonymous Single Nucleotide Polymorphisms in Human ACE2 Gene May Affect the Infectivity of SARS-CoV-2 Omicron Subvariants.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which first appeared in December 2019. Angiotensin I converting enzyme 2 (ACE2) receptor, present on the host cells, interacts with the receptor binding domain (RBD) of spike (S) protein of SARS-CoV-2 and facilitates the viral entry into host cells. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the ACE2 gene may have an impact on the protein's stability and its function. The deleterious or harmful nsSNPs of the ACE2 gene that can change the strength as well as the pattern of interaction with the RBD of S protein were selected for this study. The ACE2:RBD interactions were analyzed by protein-protein docking study. The missense mutations A242V, R708W, G405E, D292N, Y633C, F308L, and G405E in ACE2 receptor were found to interact with RBD of Omicron sub-variants with stronger binding affinity. Among the other selected nsSNPs of human ACE2 (hACE2), R768W, Y654S, F588S, R710C, R710C, A191P, and R710C were found to have the lowest binding affinity for RBD of Omicron sub-variants. The findings of this study suggest that the nsSNPs present in the human ACE2 gene alter the structure and function of the protein and, consequently, the susceptibility to Omicron sub-variants.


Karyotype in acute myeloblastic leukemia: prognostic significance for bone marrow transplantation in first remission: a European Group for Blood and Marrow Transplantation study. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).
The presentation cytogenetic result was correlated with outcome for 999 patients with acute myeloblastic leukemia (AML) having bone marrow transplantation (BMT) in first complete remission (CR1). The karyotype at diagnosis was classified according to the modified Chicago classification. Allogeneic BMT (AlloBMT) was performed in 500 patients and autologous BMT (ABMT) in 499 patients. For both groups, an abnormal chromosome (abn) 5 and/or 7 or a hypodiploid karyotype had a poor outcome, whereas t(15;17), pseudodiploidy, hyperdiploidy and diploidy were associated with a standard prognosis. Abn (16) and t(8;21) were also of standard prognosis for ABMT, but favorable for AlloBMT. When comparing AlloBMT and ABMT in patients with favorable or standard cytogenetics, AlloBMT was of benefit for remission duration and leukemia-free survival (LFS). Patients with an unfavorable karyotype had a similar outcome, regardless of type of BMT. By multivariate analysis, cytogenetics at diagnosis had the strongest prognostic value for relapse, LFS, and survival in AlloBMT. In ABMT, cytogenetics influenced relapse and LFS. We concluded that the karyotype at diagnosis had important prognostic implication in AML grafted in CR1.


Mass spectrometry approaches for vitamin E research.
Vitamin E is an important nutrient with antioxidant and non-antioxidant functions, and certain evidence suggests that it has a cardiovascular protective role. It is therefore important to maintain an optimal vitamin E status. In the present paper, a number of MS applications to monitor vitamin E status and its interactions, including the use of stable-isotope-labelled vitamin E and metabonomics, are highlighted. Specifically, stable-isotope studies have been used to monitor vitamin E absorption, hepatic processing and lipoprotein transport. As oxidative stress may influence vitamin E status, a number of studies comparing vitamin E biokinetics and metabolism in cigarette smokers and non-smokers have been able to show differences in vitamin E processing in smokers. Metabonomics represents a method to identify changes to metabolite profiles, offering the potential to investigate interactions between vitamin E and metabolic pathways. These applications represent innovative approaches to investigate the role of vitamin E in health and disease.


The attractor structure of functional connectivity in coupled logistic maps.
Stylized models of dynamical processes on graphs allow us to explore the relationships between network architecture and dynamics, a topic of relevance in a range of disciplines. One strategy is to translate dynamical observations into pairwise relationships of nodes, often called functional connectivity (FC), and quantitatively compare them with network architecture or structural connectivity (SC). Here, we start from the observation that for coupled logistic maps, SC/FC relationships vary strongly with coupling strength. Using symbolic encoding, the mapping of the dynamics onto a cellular automaton, and the subsequent analysis of the resulting attractors, we show that this behavior is invariant under these transformations and can be understood from the attractors of the cellular automaton alone. Interestingly, noise enhances SC/FC correlations by creating a more uniform sampling of attractors. On a methodological level, we introduce cellular automata as a data analysis tool, rather than a simulation model of dynamics on graphs.


Breast striae after cosmetic augmentation.
Breast augmentation is the most popular cosmetic surgery procedure in the United States. Postoperative striae is a known but incompletely understood complication of breast augmentation. The authors investigated their own patient population to discern risk factors for new-onset striae after cosmetic breast augmentation. A retrospective chart review was performed for patients who underwent primary breast augmentation from 2005 to 2012 in a single-surgeon practice. Initial chart review revealed that only patients aged ≤25 years exhibited new striae; therefore, only patients from this age group were included. Potential risk factors examined included age, body mass index (BMI), oral contraceptive use, time of last menstrual period (LMP), parity, smoking and alcohol status, diabetes mellitus, and personal history of striae. Implant and surgical factors examined included implant material (silicone vs saline), volume, and location (submuscular vs subglandular placement) and the site of incision. Of the 549 patients included in the study, 17 (3.10%) had new-onset striae, observed at a mean of 58 days postoperatively. The risk of striae was statistically significantly higher (P<.05) among patients who were younger (3.3 times), were nulliparous (14.38 times), began their LMP>14 days before surgery (9.24 times), and had a history of striae (6.11 times). There was a strong correlation between new-onset breast striae and implant size, as well as BMI (P=.07). There is a strong correlation between new-onset striae and hormone levels, genetic factors, and tissue stretch components in patients who undergo cosmetic breast augmentation. This information can be utilized to better educate patients about this potential complication. 4.


Counterevidence of crime-reduction effects from federal grants of military equipment to local police.
In 2017, the Trump Administration restored local law enforcement agencies' access to military weapons and some other types of surplus military equipment (SME) that had been prohibited by the Obama Administration. The Justice Department background paper used to justify this decision cited two papers published by the American Economic Association. These papers used SME data collected with a 2014 Freedom of Information Act request and concluded that SME, supplied to local law enforcement by the federal government via the 1033 Program, reduces crime. Here we show that the findings of these studies are not credible due to problems with the data. Using more detailed audit data on 1033 SME, we show that the 2014 data are flawed and that the more recent data provide no evidence that 1033 SME reduces crime.


Gentiana Scabra Bge Extract (GSE) Protects Against Alcoholic Liver Disease by Regulating the TLR4/NF-κB Pathway in Mice.
Alcohol abuse leads to alcoholic liver disease (ALD), for which no effective treatment is yet known. Gentiana Scabra Bge is a traditional Chinese medicine; its extract has a significant liver protection effect, but its effects on the mechanism of improving alcohol-induced toxicity remain unclear. Therefore, this study used cell and mouse models to investigate how Gentiana Scabra Bge extract (GSE) might affect the TLT4/NF-κB inflammation pathway in ALD. In mice, we induced the alcoholic liver injury model by applying alcohol and induced the inflammatory cell model by lipopolysaccharide (LPS)-induced macrophages. Using an enzyme-linked immunosorbent assay (ELISA) kit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured in liver tissue; we also performed histological analysis of liver tissue sections to assess the hepatoprotective effect of GSE on alcohol. Using real-time fluorescence quantification, we determined the expression of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA levels; we used Western blotting to detect the expression of TLR4/NF-κB signaling pathway-related proteins. We demonstrate that GSE decreased AST and ALT activity, ameliorated liver dysfunction, decreased cytokine levels, and reduced LPS-induced cellular inflammation. In addition, GSE protected mouse liver cells from the inflammatory response by reducing alcohol-induced liver pathological damage and downregulating genes and proteins such as nuclear factors. GSE can attenuate liver injury in mice through the TLR4/NF-κB pathway by inhibiting the activation of nuclear factors.


Sequential changes of serum ferritin levels and their clinical significance in lamivudine-treated patients with chronic viral hepatitis B.
To study the sequential changes of serum ferritin levels in lamivudine-treated patients with chronic viral hepatitis B and the clinical implications. Thirty-eight patients with chronic viral hepatitis B were prospectively studied during their treatment with lamivudine. Each patient received 100 mg oral lamivudine daily for 12 mo, and was observed and tested for blood biochemistry and hepatitis B virus (HBV) DNA levels and serum ferritin levels at baseline and at 3, 6 and 12 mo during the treatment. Serum HBV DNA levels were quantitatively determined using fluorescent quantitative polymerase chain reaction (FQ-PCR), and serum ferritin levels were measured by radioimmunoassay. The sequential changes of serum ferritin levels and their relationships with virological, serological and biochemical responses in the patients were analyzed. All the patients had a baseline HBV DNA level higher than 1 x 10(7) copies/L as determined by FQ-PCR and positive HBsAg and HBeAg and abnormal ALT levels. At the end of the 12-mo treatment, 19 of the 38(50.00%) patients had undetectable serum HBV DNA levels by FQ-PCR, and 12(31.58%) became negative for serum HBeAg and 10(26.32%) had seroconversion from HBeAg to HBeAb. Nineteen out of the 38(50.00%) patients had biochemically normal ALT levels after 12-mo lamivudine treatment. Sequential determination showed that lamivudine treatment significantly reduced ferritin levels in chronic hepatitis B patients. When the patients were divided into different groups according to their post-treatment virological, serological and biochemical responses for analysis of the sequential changes of ferritin levels, it was found that the decrease of ferritin levels in HBV DNA-negative group was significantly more obvious than that in HBV DNA-positive group at 6 mo during the treatment (P=0.013). Consecutive comparisons showed that ferritin levels at 3 mo of treatment were obviously decreased as compared with the baseline levels (P<0.05) in HBeAg-negative group, and the decrease of serum ferritin levels in patients with normalized ALT was more significant than that in patients with abnormal ALT at the end of the 12-mo treatment (P=0.048). Lamivudine treatment can reduce the serum ferritin levels in chronic viral hepatitis B patients and decreases of ferritin levels can be more significant in patients exhibiting virological, serological and biochemical responses, indicating that dynamic observation of serum ferritin levels in patients with chronic viral hepatitis B during lamivudine treatment might be helpful for monitoring and predicting patients' responses to the therapy.


A Review of the Environmental Trigger and Transmission Components for Prediction of Cholera.
Climate variables influence the occurrence, growth, and distribution of Vibrio cholerae in the aquatic environment. Together with socio-economic factors, these variables affect the incidence and intensity of cholera outbreaks. The current pandemic of cholera began in the 1960s, and millions of cholera cases are reported each year globally. Hence, cholera remains a significant health challenge, notably where human vulnerability intersects with changes in hydrological and environmental processes. Cholera outbreaks may be epidemic or endemic, the mode of which is governed by trigger and transmission components that control the outbreak and spread of the disease, respectively. Traditional cholera risk assessment models, namely compartmental susceptible-exposed-infected-recovered (SEIR) type models, have been used to determine the predictive spread of cholera through the fecal-oral route in human populations. However, these models often fail to capture modes of infection via indirect routes, such as pathogen movement in the environment and heterogeneities relevant to disease transmission. Conversely, other models that rely solely on variability of selected environmental factors (i.e., examine only triggers) have accomplished real-time outbreak prediction but fail to capture the transmission of cholera within impacted populations. Since the mode of cholera outbreaks can transition from epidemic to endemic, a comprehensive transmission model is needed to achieve timely and reliable prediction with respect to quantitative environmental risk. Here, we discuss progression of the trigger module associated with both epidemic and endemic cholera, in the context of the autochthonous aquatic nature of the causative agent of cholera, V. cholerae, as well as disease prediction.


Exposure to chronic, low-dose rate gamma-radiation at Chornobyl does not induce point mutations in Big Blue mice.
Empirical genetic effects resulting from low-dose rate irradiation and chronic, cumulative exposure are poorly characterized. Expected effects are based on epidemiological studies and downward, linear extrapolations from nonthreshold models derived from acute, high-dose exposures. These extrapolations and their associated risk coefficients have no experimental support, and because of their inherent uncertainty they are the subject of considerable debate. The expectation of deleterious genetic effects resulting from low-dose rate irradiation and chronic exposure is in need of empirical assessment because this type of exposure is typical of those encountered in occupational, residential, and environmental settings. Recent acute low-dose (<10 cGy) studies using cytogenetic and point mutation endpoints indicate that observed effects range from those lower than spontaneous to an increase in the frequency of point mutations. Using the Big Blue assay, we examined the ability of chronic, continuous gamma-irradiation (2.3 x 10(-3) cGy/min) in the Chornobyl environment to induce point mutations. This system has demonstrated a significant point mutation sensitivity (4.5-fold increase) to acute, high-dose (1-3 Gy) gamma-radiation. Mutant frequencies and the mutation spectra were examined in exposed and reference samples of Big Blue mice following 90 days exposure (cumulative absorbed dose = 3 Gy) to the Chornobyl environment. No significant increase in the mutant frequency or bias in the mutational spectrum was observed in exposed individuals. This finding suggests that low-dose rate gamma-irradiation at Chornobyl does not induce point mutations and that cumulative, chronically absorbed doses do not induce the same genetic effects as acute doses of the same magnitude.


Sex differences in electrocortical activity in human neonates.
Cerebral cortical activity in healthy, full-term human neonates (10 boys and 10 girls) was evaluated using spectral estimation of electroencephalogram frequency content with new equipment and analysis technique allowing the assessment of the lowest frequencies (i.e. infraslow waves). The activity was analysed under quiet sleep and active wakefulness taking sex into consideration. During sleep, the mean amount of infraslow activity was 27% larger in boys, whereas during wakefulness the average amount of higher frequencies was 17% larger in girls. Both these differences indicate an earlier maturation of cortical function in girls than in boys.


Assessing Ventilatory Threshold in Individuals With Motor-Complete Spinal Cord Injury.
To assess the feasibility of measuring ventilatory threshold (VT) in higher-level motor-complete spinal cord injury (SCI) using 4 different analysis methods based on noninvasive gas exchange. Observational. Laboratory testing. Individuals with C4-T6 motor-complete SCI (16 paraplegia, 22 tetraplegia; American Spinal Injury Association Impairment Scale A/B; 42±10 years old). Not applicable. VT from a graded arm cycling test to volitional exhaustion using 4 methods: ventilatory equivalents, excess CO2, V-slope, and combined method. VT could be identified in all individuals with paraplegia, but in only 68% of individuals with tetraplegia. Individuals without observable VT completed the graded exercise test with lower ventilatory rate, peak power output, and peak oxygen consumption (Vo2peak) (all P<.05), compared to those with a detectable VT. Bland-Altman plots indicate minimal bias between methods (range: 0.01-0.03 L/min), with 95% limits of agreement of the difference within 0.25 L/min. Absolute V.o2 at VT with individual methods were all correlated to peak power output (r>0.74; P<.01) and Vo2peak (r>0.91; P<.01), with negligible differences between methods. The assessment of VT is a feasible alternative to peak exercise testing for aerobic fitness in individuals with higher-level, motor-complete SCI, although care should be taken when interpreting VT in individuals with tetraplegia who have lower cardiorespiratory fitness and lower peak power outputs.


SpoVM, a small protein essential to development in Bacillus subtilis, interacts with the ATP-dependent protease FtsH.
The spoVM gene encodes a 26-amino-acid polypeptide that is essential for spore formation in Bacillus subtilis. A transposon insertion within the spoVM open reading frame has been shown to encode a chimeric protein which is biologically inactive and produces a phenotype identical to that of a deletion and insertion mutation. A genetic approach was used to identify possible interacting proteins, and the membrane-bound FtsH protease was identified. Mutations in ftsH suppressed the sporulation defect of certain spoVM mutants but not others. However, production of the mother cell sigma factors, sigmaE and sigmaK, was abnormal in the suppressed strains, and mutations in either spoVM or ftsH alone impaired sigma factor production and sporulation gene expression. Using FtsH purified from Escherichia coli, we demonstrated that in vitro (i) SpoVM inhibits FtsH protease activity and (ii) SpoVM is a substrate for the FtsH protease. We propose that during sporulation, SpoVM serves as a competitive inhibitor of FtsH activity. This interaction appears to be important for completion of the prespore engulfment step of sporulation, based on the phenotype of certain spoVM ftsH double mutants.


A gold exchange: a mechanistic study of a reversible, formal ethylene insertion into a gold(III)-oxygen bond.
The Au(III) complex Au(OAc(F))2(tpy) (1, OAc(F) = OCOCF3; tpy = 2-p-tolylpyridine) undergoes reversible dissociation of the OAc(F) ligand trans to C, as seen by (19)F NMR. In dichloromethane or trifluoroacetic acid (TFA), the reaction between 1 and ethylene produces Au(OAc(F))(CH2CH2OAc(F))(tpy) (2). The reaction is a formal insertion of the olefin into the Au-O bond trans to N. In TFA this reaction occurs in less than 5 min at ambient temperature, while 1 day is required in dichloromethane. In trifluoroethanol (TFE), Au(OAc(F))(CH2CH2OCH2CF3)(tpy) (3) is formed as the major product. Both 2 and 3 have been characterized by X-ray crystallography. In TFA/TFE mixtures, 2 and 3 are in equilibrium with a slight thermodynamic preference for 2 over 3. Exposure of 2 to ethylene-d4 in TFA caused exchange of ethylene-d4 for ethylene at room temperature. The reaction of 1 with cis-1,2-dideuterioethylene furnished Au(OAc(F))(threo-CHDCHDOAc(F))(tpy), consistent with an overall anti addition to ethylene. DFT(PBE0-D3) calculations indicate that the first step of the formal insertion is an associative substitution of the OAc(F) trans to N by ethylene. Addition of free (-)OAc(F) to coordinated ethylene furnishes 2. While substitution of OAc(F) by ethylene trans to C has a lower barrier, the kinetic and thermodynamic preference of 2 over the isomer with CH2CH2OAc(F) trans to C accounts for the selective formation of 2. The DFT calculations suggest that the higher reaction rates observed in TFA and TFE compared with CH2Cl2 arise from stabilization of the (-)OAc(F) anion lost during the first reaction step.


Optimization of Brillouin optical correlation domain analysis system based on intensity modulation scheme.
We report a novel method to enhance the performance of Brillouin optical correlation domain analysis system based on the intensity modulation of light source. The suppression and the modification of the background noise in Brillouin gain spectrum is experimentally demonstrated with different intensity modulation schemes. In an optimum configuration, the signal to noise ratio is improved more than 40%, which extends the measurable strain limit and leads to the substantial increase of measurement range.


Angina-like syndrome with diazoxide therapy for hypertensive crisis.
In 14 patients with hypertensive crisis treated with diazoxide, close monitoring of blood pressure, heart rate, and symptoms was performed. Standard 12-lead electrocardiograms were recorded before and after diazoxide. All patients showed a significant fall in blood pressure after drug administration. Seven patients (50%) showed significant ST-T changes after diazoxide. Six patients (43%) developed substernal discomfort demonstrated by substernal pain of tightness. Five patients (35%) had both chest discomfort and ST-T changes. One of these patients with substernal pain and ST elevation had evidence of acute myocardial infarction with serial enzyme studies. In the patients with significant ST-T changes, the average fall in blood pressure was significantly greater than the average fall in blood pressure in the patients without significant ST-T changes. These findings suggest that both ST-T changes and substernal discomfort were due to myocardial ischemia secondary to a sudden severe drop in blood pressure.


Comparison of the oestrogen and progesterone receptor status in primary breast carcinomas as evaluated by immunohistochemistry and immunocytochemistry: a consecutive series of 267 patients.
The use of cytological specimens to evaluate tumour biomarkers in metastatic breast cancer lesions has attracted increased interest because of the considerable number of reports that have shown discordance between the primary tumour and metastatic lesion. Oestrogen receptor (ER) and progesterone receptor (PgR) assays are crucial for the management of patients with breast cancer, in both adjuvant and palliative settings. The aim of this study was to compare the ER and PgR immunocytochemical analysis of fine needle aspiration (FNA) samples with the immunohistochemistry (IHC) of surgical specimens and core biopsies from primary breast cancers. The FNA specimens were prepared as cell blocks (n = 25) or ThinPreps (n = 258) for the immunocytochemistry (IC) ER and PgR analyses. Sixteen patients were excluded because of lack of follow-up (n = 1), neoadjuvant therapy (n = 3) or cell counts in their fine needle aspirates that were too low (n = 12). The results of IC on 25 cell blocks and 242 ThinPreps were compared with IHC on the corresponding core needle biopsies (n = 16) or excised tumours (n = 251). The ER and PgR status was defined as negative (when less than 10% of the nuclei were stained) or positive (when equal or more than 10% of the nuclei were stained). Kappa statistics were used to evaluate the concordance. The ER concordance was 98% with ThinPrep (κ = 0.93) and 92% with cell block (κ = 0.82). The corresponding values for PgR were 96% (κ = 0.91) and 96% (κ = 0.92). Our results confirm that, in cases in which biopsies or surgical specimens are not available, IC (with either cell block or ThinPrep techniques) is a reliable method for the determination of the ER and PgR status performed under strict conditions using primary breast carcinomas, and is therefore potentially useful in metastatic settings.


Dynamical changing patterns of glycogen and enzyme histochemical activities in rat liver graft undergoing warm ischemia injury.
To investigate the changing patterns of glycogen and enzyme histochemical activities in rat liver graft under a different warm ischemia time (WIT) and to predict the tolerant time limitation of the liver graft to warm ischemia injury. The rats were randomized into five groups, WIT was 0, 15, 30, 45, 60 min, respectively, and histochemical staining of liver graft specimens was observed. The recovery changes of glycogen and enzyme histochemistry activities were measured respectively 6 and 24 h following liver graft implantation. The activities of succinic dehydrogenase, cytochrome oxidase, apyrase (Mg++-ATPase) and content of glycogen were decreased gradually after different WIT in a time-dependent manner. The changes were significant when WIT was over 30 min. Hepatic injury is reversible within 30 min of warm ischemia injury. Glycogen and enzyme histochemistry activities of liver grafts and their recovery potency after reperfusion may serve as criteria to evaluate the quality of liver grafts.


Embodied choice: how action influences perceptual decision making.
Embodied Choice considers action performance as a proper part of the decision making process rather than merely as a means to report the decision. The central statement of embodied choice is the existence of bidirectional influences between action and decisions. This implies that for a decision expressed by an action, the action dynamics and its constraints (e.g. current trajectory and kinematics) influence the decision making process. Here we use a perceptual decision making task to compare three types of model: a serial decision-then-action model, a parallel decision-and-action model, and an embodied choice model where the action feeds back into the decision making. The embodied model incorporates two key mechanisms that together are lacking in the other models: action preparation and commitment. First, action preparation strategies alleviate delays in enacting a choice but also modify decision termination. Second, action dynamics change the prospects and create a commitment effect to the initially preferred choice. Our results show that these two mechanisms make embodied choice models better suited to combine decision and action appropriately to achieve suitably fast and accurate responses, as usually required in ecologically valid situations. Moreover, embodied choice models with these mechanisms give a better account of trajectory tracking experiments during decision making. In conclusion, the embodied choice framework offers a combined theory of decision and action that gives a clear case that embodied phenomena such as the dynamics of actions can have a causal influence on central cognition.


Isolation and characterization of linear deoxyribonucleic acid plasmids from Kluyveromyces lactis and the plasmid-associated killer character.
Two linear deoxyribonucleic acid plasmids, designated pGK11 and pGK12, were isolated from the yeast Kluyveromyces lactis IFO 1267. pGK11 and pGK12 had molecular weights of 5.4 X 10(6) and 8.4 X 10(6), respectively. Both plasmids possessed the same density of 1.687 g/cm3, lighter than the densities of mitochondrial (1.692 g/cm3) and nuclear (1.699 g/cm3) deoxyribonucleic acids. A restriction map of pGK11 was constructed from digestions by EcoRI, HindIII, PstI, and BamHI. pGK12 was cleaved by EcoRI into seven fragments and by BamHI into two fragments K. lactis IFO 1267 killed Saccharomyces cerevisiae sensitive and killer strains and certain strains of Saccharomyces italicus, K. lactis, Kluyveromyces thermotolerans, and K. vanudenii. All K. lactis strains lacking the pGK1 plasmids were nonkillers. A hybrid was constructed between K. lactis IFO 1267 and a nonkiller K. lactis strain lacking the plasmids and subjected to tetrad analysis after sporulation. The killer character was extrachromosomally transmitted in all tetrads in association with the pGK1 plasmids. The double-stranded ribonucleic acid killer plasmid could not be detected in any K. lactis killer strains. It is thus highly probable that the killer character is mediated by the linear deoxyribonucleic acid plasmids. A single chromosomal gene was found which was responsible for the resistance to the K. lactis killer.


Changes in physicochemical, textural, and sensorial properties of pork meatballs made with the addition of hemp oil during storage.
This research aimed to evaluate the quality characteristics of cooked and vacuum-packed meatballs reformulated with cold-pressed hempseed oil as a partial pork substitute (0.8%, 2.5%, 4.2%, and 7.5%) during 12 days of storage. The water activity, cooking, and storage losses increased with a higher content of hemp oil (P < 0.05). The total saturated fatty acids were reduced by 37.6%, whereas the polyunsaturated fatty acids content improved by 96.1%. Hemp oil addition decreased protein and lipid oxidation during the storage period (P < 0.05). The inhibition effect on carbonyl content reached 34.9% and on TBARS values reached 17.5%. Sensory analysis revealed no significant changes to the texture, odour, and taste attributes over 12 days of storage in vacuum packaging. The results indicate that cold-pressed hemp oil can be an alternative ingredient for the production of meat products with improved nutritional value, particularly by enriching them with n-3 α-linolenic fatty acid.


[Role of calcium in the mechanism underlying the inhibitory effect of streptomycin on carotid sinus baroreflex in rats].
The effect of streptomycin (SM) on carotid baroreflex was examined in 23 anesthetized rats with isolated carotid sinus perfusion. The results obtained are as follows. (1) In response to perfusion with SM (200 micromol/L), the functional curve of carotid baroreflex was shifted to the right and upward with a decrease of peak slope (PS) and a reflex decrease in mean arterial pressure (RD)(P<0.01), indicating an inhibitory effect of SM on carotid sinus baroreflex. (2) By perfusing the isolated carotid sinus with high Ca(2+) solution (4 mmol/L), the inhibitory effect of SM on carotid baroreflex was partially eliminated. The functional curve of SM was shifted to the left and downward with PS increasing from 0.27+/-0.04 kPa to 0.37+/-0.02 kPa (P<0.01) and RD was enhanced from 4.32+/-0.14 kPa to 6.18+/-0.17 kPa (P<0.01). On the other hand, the threshold pressure (TP) and saturation pressure (SP) were significantly decreased from 10.29+/-0.29 kPa to 9.98+/-0.33 kPa (P<0.05) and from 27.26+/-0.42 kPa to 25.22+/-0.38 kPa (P<0.05), respectively. (3) By pretreatment with Bay K 8644 (500 nmol/L), an agonist of calcium channels, the effect of SM on carotid baroreflex was completely abolished. (4) Exposure of the carotid sinus to SM following pretreatment with charybdotoxin (ChTX,100 nmol/L), a blocker of the Ca(2+)-activated K(+) channel (KCa), still inhibited the baroreflex. These results suggest that the inhibitory action of SM on carotid baroreflex may be mediated by suppressing Ca(2+) influx.


[Tactics in the management of patients with mechanical jaundice].
On the basis of examination of 320 patients with mechanical jaundice the authors recommend to begin the examination by performing retrograde cholangiopancreatography and if necessary to add transcutaneous transhepatic cholangiography. In all the cases an attempt should be made to resolve the jaundice before operation by means of nasobiliary drainage of bile ducts, endoscopic papillotomy, transhepatic cholangiostomy. In aggravating nonresolved jaundice the examination and attempts to resolve the jaundice by conservative measures should not take more than 4-5 days.


Bubble Continuous Positive Airway Pressure Oxygen Therapy in Children Under Five Years of Age with Respiratory Distress in Pediatric Intensive Care Unit.
Continuous positive airway pressure (CPAP) has been used in children with bronchiolitis for a long time. Currently in the low-resource settings, the method of providing oxygen therapy via bubble CPAP (bCPAP) to children with respiratory distress is not standardized and the existing low-flow oxygen therapy has a high mortality rate. To study the effectiveness and safety of bCPAP as a respiratory support in children with respiratory distress. This prospective observational study was conducted in a tertiary care pediatric intensive care unit (PICU) over a period of 3 months. Children with respiratory distress were administered with bCPAP oxygen therapy. Baseline demographic data, such as age, sex, weight, severity of illness was collected. Changes in heart rate, respiratory rate, saturation, respiratory distress score and failure rate after bCPAP therapy were studied. During the study period, 30 children were recruited. Most common cause of respiratory distress requiring bCPAP was pneumonia (66.7%) followed by pleural effusion (20%) and bronchiolitis (13.3%). The median (IQR) CPAP duration and PICU stay in the study was 48 hours (27-48) and 4 days (4-8), respectively. Heart rate and respiratory rate, respiratory distress score improved significantly after CPAP therapy (p < 0.05). CPAP therapy failed in one child and required invasive ventilation. We did not observe any complications due to bCPAP therapy. The use of bCPAP in the treatment of respiratory distress is safe and effective. Lalitha AV, Pujari CG, Raj JM. Bubble Continuous Positive Airway Pressure Oxygen Therapy in Children Under Five Years of Age with Respiratory Distress in Pediatric Intensive Care Unit. Indian J Crit Care Med 2023;27(11):847-854.


Piloting a mHealth intervention to improve newborn care awareness among rural Cambodian mothers: a feasibility study.
Globally, the World Health Organization reports that the chances of a child dying is highest in the first month of life, the neonatal period. The neonatal mortality rate in Cambodia is 18 per 1000 live births. In the province of Kampong Chhnang, that rate is the fifth highest among the 24 provinces of Cambodia at 27 per 1000 live births. We piloted a project to determine the feasibility of using a mHealth intervention (the use of mobile devices to improve health outcomes) to increase mothers' awareness about neonatal care and promote the government policy 'Safe Motherhood Protocols for Health Centres' which are in line with WHO recommendations for neonatal care. Between September and December 2013, we piloted an Interactive Voice Response system that sent pre-recorded messages to mothers of newborns using the theme 'It takes a village to raise a baby'. Four hundred fifty-five mothers were registered onto this program and the intervention involved delivering seven periodic 60 to 90 s voice messages directly to the mobile phones of these mothers from day three of their neonate's life to day 28. An evaluation of the pilot was conducted in December 2013. One hundred twenty-nine mothers were randomly selected from the 455 registered mothers and interviewed using a quantitative questionnaire. We also held two focus group discussions with three mothers and seven health workers. Quantitative and qualitative results of 126 respondents were included for analysis. They indicate that the intervention was well accepted. Seventy-one percent of respondents reported that they would recommend the intervention to other mothers, and 83% reported that they would be willing to pay for the service. This type of mHealth intervention is an acceptable and feasible way of promoting the awareness of newborn care to rural Cambodian mothers.


Use of MRI and CT image indexing to assess cerebral injuries in neonates with hypoxic-ischemic encephalopathy.
The aim of this study is to explore the application of magnetic resonance imaging (MRI) and computed tomography (CT) image indexing in the assessment of cerebral injury of hypoxic-ischemic encephalopathy (HIE) neonate. The clinical data of 100 HIE children, who were admitted to the Department of Radiology, Xuzhou Children's Hospital, Jiangsu, from June 2013 to June 2014, were statistically analyzed. Among the imaging data of 100 HIE children, the detection rate and false negative rate were 91.4% and 8.6%, respectively. The MRI detection rate was 100%. There was significant correlation between clinical indexing and CT indexing and MRI indexing (coefficient of contingency 0.731 and 0.723, P<0.05). MRI and CT image indexing could be used as important diagnostic indications in the assessment of cerebral injury of HIE neonate. MRI had a higher detection rate for abnormality than CT, it could detect the basal ganglia damage earlier, and CT could identify subarachnoid hemorrhage, both methods were valuable in clinical applications.


Positive and Negative Regulation of Type I Interferons by the Human T Cell Leukemia Virus Antisense Protein HBZ.
The pathogenesis of human T cell leukemia virus type 1 (HTLV-1) is strongly linked to the viral regulatory proteins Tax1 and HBZ, whose opposing functions contribute to the clinical outcome of infection. Type I interferons alpha and beta (IFN-α and IFN-β) are key cytokines involved in innate immunity, and IFN-α, in combination with other antivirals, is extensively used in the treatment of HTLV-1 infection. The relationship between HTLV-1 and IFN signaling is unclear, and to date the effect of HBZ on this pathway has not been examined. Here we report that HBZ significantly enhances interferon regulatory factor 7 (IRF7)-induced IFN-α- and IFN-stimulated response element (ISRE) promoter activities and IFN-α production and can counteract the inhibitory effect of Tax1. In contrast to this, we show that HBZ and Tax1 cooperate to inhibit the induction of IFN-β and ISRE promoters by IRF3 and IFN-β production. In addition, we reveal that HBZ enhances ISRE activation by IFN-α. We further show that HBZ enhances IRF7 and suppresses IRF3 activation by TBK1 and IKKε. We demonstrate that HBZ has no effect on virus-induced nuclear accumulation of IRF3, suggesting that it may inhibit IRF3 activity at a transcriptional level. We show that HBZ physically interacts with IRF7 and IKKε but not with IRF3 or TBK1. Overall, our findings suggest that both HBZ and Tax1 are negative regulators of immediate early IFN-β innate immune responses, while HBZ but not Tax1 positively regulates the induction of IFN-α and downstream IFN-α signaling.IMPORTANCE Type I interferons are powerful antiviral cytokines and are used extensively in the treatment of HTLV-1-induced adult T cell leukemia (ATL). To date, the relationship between HTLV-1 and the IFN pathway is poorly understood, and studies so far have focused on Tax1. Our study is unique in that it examined the effect of HBZ, alone or in combination with Tax1, on type I IFN signaling. This is important because HBZ is frequently the only viral protein expressed in infected cells, particularly at later stages of infection. A better understanding of the how HBZ regulates IFN signaling may lead to the development of therapeutics that can modify such responses and improve the clinical outcome for infected individuals.


Effects of risperidone on event-related potentials in schizophrenic patients.
In order to examine the effects of risperidone on cognitive impairment in schizophrenia, event-related potentials (ERPs) were recorded before and after switching from conventional neuroleptics to risperidone in schizophrenic patients. ERPs were recorded during two auditory discrimination tasks (an oddball task and a distraction task) in 10 medicated schizophrenic patients during conventional neuroleptic and risperidone treatments. The amplitudes and latencies of N 100 and P300 component were measured in ERPs for target stimuli in the oddball task and in ERPs for target and novel stimuli in the distraction task. Although N 100 amplitude and latency and P 300 amplitude did not change significantly after switching the drug compared to that during conventional neuroleptic treatment, P 300 latency for target stimuli shortened significantly during risperidone treatment in both tasks, accompanied by the shortening of the reaction time in the distraction task. The P 300 latency change did not correlate with the change of the severity of psychopathology. These findings suggest that risperidone may speed the information processing in schizophrenic patients, contributing to the improvement of cognitive functions.


Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze.
The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. Inclusion criteria were as follows: full-term, 3-23 months of age; doctor -diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body plethysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analysed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function was correlated with AHR (P = .047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (P = .057 and 0.056, respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (P = .031). These findings do not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.


TRPA1 and sympathetic activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust.
Diesel exhaust (DE), which is emitted from on- and off-road sources, is a complex mixture of toxic gaseous and particulate components that leads to triggered adverse cardiovascular effects such as arrhythmias. We hypothesized that increased risk of triggered arrhythmias 1 day after DE exposure is mediated by airway sensory nerves bearing transient receptor potential (TRP) channels [e.g., transient receptor potential cation channel, member A1 (TRPA1)] that, when activated by noxious chemicals, can cause a centrally mediated autonomic imbalance and heightened risk of arrhythmia. Spontaneously hypertensive rats implanted with radiotelemeters were whole-body exposed to either 500 μg/m³ (high) or 150 μg/m³ (low) whole DE (wDE) or filtered DE (fDE), or to filtered air (controls), for 4 hr. Arrhythmogenesis was assessed 24 hr later by continuous intravenous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR) and electrocardiogram (ECG) were monitored. Rats exposed to wDE or fDE had slightly higher HRs and increased low-frequency:high-frequency ratios (sympathetic modulation) than did controls; ECG showed prolonged ventricular depolarization and shortened repolarization periods. Rats exposed to wDE developed arrhythmia at lower doses of aconitine than did controls; the dose was even lower in rats exposed to fDE. Pretreatment of low wDE-exposed rats with a TRPA1 antagonist or sympathetic blockade prevented the heightened sensitivity to arrhythmia. These findings suggest that a single exposure to DE increases the sensitivity of the heart to triggered arrhythmias. The gaseous components appear to play an important role in the proarrhythmic response, which may be mediated by activation of TRPA1, and subsequent sympathetic modulation. As such, toxic inhalants may partly exhibit their toxicity by lowering the threshold for secondary triggers, complicating assessment of their risk.


The effects of Brassica green manures on plant parasitic and free living nematodes used in combination with reduced rates of synthetic nematicides.
Brassica plants once incorporated into soil as green manures have recently been shown to have biofumigant properties and have the potential of controlling plant-parasitic nematodes. In Washington State, plant-parasitic nematodes are successfully managed with synthetic nematicides. However, some of the synthetic nematicides became unavailable recently or their supply is limited leaving growers with few choices to control plant-parasitic nematodes. The objective of this project was to evaluate the effects of Brassica green manures on their own and in combination with reduced rates of synthetic nematicides on plant-parasitic nematodes and free living nematodes. In a greenhouse experiment and field trials in three seasons, Brassica green manures in combination with half the recommended rate of 1,3-dichloropropene (1,3-D, Telone) reduced root knot nematode, Meloidogyne chitwoodi to below detection levels, and reduced lesion nematodes, Pratylenchus penetrans and stubby root nematodes, Paratrichodorus allius, to below economic thresholds. The combination treatments did not affect the beneficial free-living nematode populations and the non-pathogenic Pseudomonas. The total cost of growing and soil-incorporating Brassica crops as green manures in combination with reduced rates of 1,3-D was approximately 35% lower than the present commercial costs for application for the full rate of this fumigant. Integrating conventional management practices with novel techniques fosters sustainability of production systems and can increase economic benefit to producers while reducing chemical input.


The operation of a corporate medical department.
Medical departments within industry vary widely. Some large companies have virtually no medical department. Some have a dispensary-type set up, where band aids or aspirin are dispensed, and the nurse refers out anything more serious. In contrast to this, some companies employ full-time internists or preventive medicine specialists, part or full-time orthopedists, part or full-time psychiatrists, and even offer the services of full-time dentists. The purpose of this article is to describe an industrial medical department which functions somewhere between the two extremes above in an average-size company involved in the aerospace field.


Combined quantification of pulmonary Pneumocystis jirovecii DNA and serum (1->3)-β-D-glucan for differential diagnosis of pneumocystis pneumonia and Pneumocystis colonization.
This study assessed a quantitative PCR (qPCR) assay for Pneumocystis jirovecii quantification in bronchoalveolar lavage (BAL) fluid samples combined with serum (1→3)-β-d-glucan (BG) level detection to distinguish Pneumocystis pneumonia (PCP) from pulmonary colonization with P. jirovecii. Forty-six patients for whom P. jirovecii was initially detected in BAL fluid samples were retrospectively enrolled. Based on clinical data and results of P. jirovecii detection, 17 and 29 patients were diagnosed with PCP and colonization, respectively. BAL fluid samples were reassayed using a qPCR assay targeting the mitochondrial large subunit rRNA gene. qPCR results and serum BG levels (from a Fungitell kit) were analyzed conjointly. P. jirovecii DNA copy numbers were significantly higher in the PCP group than in the colonization group (1.3 × 10(7) versus 3.4 × 10(3) copies/μl, P < 0.05). A lower cutoff value (1.6 × 10(3) copies/μl) achieving 100% sensitivity for PCP diagnosis and an upper cutoff value (2 × 10(4) copies/μl) achieving 100% specificity were determined. Applying these two values, 13/17 PCP patients and 19/29 colonized patients were correctly assigned to their patient groups. For the remaining 14 patients with P. jirovecii DNA copy numbers between the cutoff values, PCP and colonization could not be distinguished on the basis of qPCR results. Four of these patients who were initially assigned to the PCP group presented BG levels of ≥100 pg/ml. The other 10 patients, who were initially assigned to the colonization group, presented BG levels of <100 pg/ml. These results suggest that the combination of the qPCR assay, applying cutoff values of 1.6 × 10(3) and 2 × 10(4) copies/μl, and serum BG detection, applying a 100 pg/ml threshold, can differentiate PCP and colonization diagnoses.


Case studies of laser Doppler imaging system for clinical diagnosis applications and management.
The laser Doppler perfusion imager (LDPI) is a recent development in the field of laser Doppler flowmetry. It has great potential in many medical applications for the non-invasive diagnosis of problems based on microvascular perfusion. Established applications include assessment of breast skin blood flow, wound healing, skin burn, and systemic sclerosis. This paper aims to enhance the usability of LPDI for diagnostics testing through the examination of two major issues. The first issue deals with the performance of the LDPI technique. Two case studies are used not only to highlight the potential applications of LDPI, but also to illustrate the general procedure/precautions needed for ensuring the consistency and quality of the captured perfusion images. The first case study deals with the perfusion across the proximal interphalangeal joints of patients with osteoarthritis. The results showed that LDPI could provide an objective and specific assessment of hyperaemia over the interphalangeal joints in patients with rheumatoid arthritis. The second case study deals with the blood flow on the stomach region during acupuncture. The results indicated that LDPI could provide an objective and specific assessment of the stimulation level on acupuncture point. The issues discussed in these case studies would be useful for the evolution of other novel LDPI applications and the standardization of the proper clinical procedure for the capturing of the LDP images. The second issue deals with the intelligent management of the LDPI results to facilitate the prescription of treatment based on analysis of similar cases previously encountered. The framework of an intelligent diagnostics assistant is proposed to automate the search and retrieval of relevant past cases based on the LDPI diagnosis. The paper uses skin burn as an example to discuss the considerations and techniques for the implementation of the proposed intelligent diagnostics system. This work constitutes initial efforts to increase the productivity of the doctors in diagnostics testing using LDPI.


Influence of recovery time on warm-up effects in male adolescent athletes.
The purpose of this study was to examine the influence of recovery time following a dynamic warm-up (DY) and a static stretch warm-up (SS) on power performance in adolescent athletes. Following baseline measures, 19 males (16.5 +/- 1.1 yrs) performed the vertical jump (VJ) and seated medicine ball toss (MB) at the following time points after DY and SS: 2, 6, 10, 14, 18, 22 min. Analysis of variance revealed that VJ was significantly greater following DY than SS at 2, 6, 10, 14 and 18 min. Main effects indicated a significant increase in VJ from baseline at 2 and 6 min following DY (2.6-3.9%) and a significant decrease in VJ from baseline at 2, 6, 10, 14 and 18 min following SS (-3.2% to -7.0%). No significant interaction effects between DY and SS were observed for MB. These findings indicate that lower body power performance in male adolescent athletes can be enhanced following DY as compared with SS during the first 18 min of the post warm-up period.


Evaluation of (111)In labeled antibodies for SPECT imaging of mesothelin expressing tumors.
Mesothelin is expressed in many cancers, especially in mesothelioma and lung, pancreatic and ovarian cancers. In the present study, we evaluate (111)In labeled antimesothelin antibodies as an imaging bioprobe for the SPECT imaging of mesothelin-expressing tumors. We radiolabeled the antimesothelin antibodies mAbMB and mAbK1 with (111)In using the p-SCN-bn-DTPA chelator. The immunoreactivity, affinity (K(d)) and internalization properties of the resulting two (111)In labeled antibodies were evaluated in vitro using mesothelin-expressing A431K5 cells. The biodistribution and microSPECT/CT imaging studies with (111)In labeled antibodies were performed in mice bearing both mesothelin positive (A431K5) and mesothelin negative (A431) tumors. In vitro studies demonstrated that (111)In-mAbMB bound with a higher affinity (K(d)=3.6±1.7 nM) to the mesothelin-expressing A431K5 cells than did the (111)In-mAbK1 (K(d)=29.3±2.3 nM). (111)In-mAbMB was also internalized at a greater rate and extent into the A431K5 cells than was the (111)In-mAbK1. Biodistribution studies showed that (111)In-mAbMB was preferentially localized in A431K5 tumors when compared to A431 tumors. At the low dose, the peak A431K5 tumor uptake of 9.65±2.65% ID/g (injected dose per gram) occurred at 48 h, while at high dose tumor uptake peaked with 14.29±6.18% ID/g at 72 h. Non-specific localization of (111)In-mAbMB was mainly observed in spleen.(111)In-mAbK1 also showed superior localization in A431K5 tumors than in A431 tumors, but the peak uptake was only 3.04±0.68% ID/g at 24 h. MicroSPECT/CT studies confirmed better visualization of A431K5 tumors with (111)In-mAbMB, than with (111)In-mAbK1. SPECT imaging of mesothelin expressing tumors was demonstrated successfully. Our findings indicate that the antimesothelin antibody mAbMB has the potential to be developed into a diagnostic agent for imaging mesothelin-expressing cancers.


Neutrophilic Asthma and Potentially Related Target Therapies.
Neutrophilic asthma is generally associated with the absence of eosinophils and activation of non- predominant type 2 immunological pathways. It involves bronchial inflammation followed by different degrees of airway remodeling. Neutrophilic inflammation activates specific cellular and molecular pathways due to inhalation of environmental trigger factors such as exhaust fumes, cigarette smoke, occupation-related agents, and infections. This review discusses the involvement of neutrophils in asthma and potentially related target therapies. Corticosteroid resistance is the hallmark of neutrophilic asthma which increases disease severity and leads to difficult-to-control asthma. Patients with neutrophil-dominant asthma are characterized by low levels of (or absence of) Th2 cytokines. Due to the shortage of effective treatments for neutrophilic asthma newer biologics are being developed that target type 2 asthma symptoms and phenotypes. Understanding different biomarkers, inflammatory pathways and treatment strategies involved in neutrophilic asthma will help to decrease adverse effects related to corticosteroid insensitivity. Better insight of targets involved in neutrophilic inflammation can lead to improved therapies. Further evaluation and clinical trials of emerging biologics involved in neutrophilic asthma needs to be performed before bringing them into clinical practice.


Comparing modeling approaches for assessing priorities in international agricultural research.
This article examines how the estimated impacts of crop technologies vary with alternate methods and assumptions, and also discusses the implications of these differences for the design of studies to inform research prioritization. Drawing on international potato research, we show how foresight scenarios, realized by a multi-period global multi-commodity equilibrium model, can affect the estimated magnitudes of welfare impacts and the ranking of different potato research options, as opposed to the static, single-commodity, and country assumptions of the economic surplus model which is commonly used in priority setting studies. Our results suggestthatthe ranking oftechnolo- gies is driven by the data used for their specification and is not affected by the foresight scenario examined. However, net benefits vary significantly in each scenario and are greatly overestimated when impacts on non-target countries are ignored. We also argue that the validity of the singlecommodity assumption underpinning the economic surplus model is case-specific and depends on the interventions examined and on the objectives and criteria included in a priority setting study.


Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): Randomized Double-Blind Exploratory Study.
Pantoprazole is frequently administered to critically ill patients for prophylaxis against gastrointestinal bleeding. However, comparison to placebo has been inadequately evaluated, and pantoprazole has the potential to cause harm. Our objective was to evaluate benefit or harm associated with pantoprazole administration. Prospective randomized double-blind parallel-group study. University-affiliated mixed medical-surgical ICU. Mechanically ventilated critically ill patients suitable for enteral nutrition. We randomly assigned patients to receive either daily IV placebo or pantoprazole. Major outcomes were clinically significant gastrointestinal bleeding, infective ventilator-associated complication or pneumonia, and Clostridium difficile infection; minor outcomes included overt bleeding, hemoglobin concentration profiles, and mortality. None of the 214 patients randomized had an episode of clinically significant gastrointestinal bleeding, three patients met the criteria for either an infective ventilator-associated complication or pneumonia (placebo: 1 vs pantoprazole: 2), and one patient was diagnosed with Clostridium difficile infection (0 vs 1). Administration of pantoprazole was not associated with any difference in rates of overt bleeding (6 vs 3; p = 0.50) or daily hemoglobin concentrations when adjusted for transfusion rates of packed red cells (p = 0.66). Mortality was similar between groups (log-rank p = 0.33: adjusted hazard ratio for pantoprazole: 1.68 [95% CI, 0.97-2.90]; p = 0.06). We found no evidence of benefit or harm with the prophylactic administration of pantoprazole to mechanically ventilated critically ill patients anticipated to receive enteral nutrition. The practice of routine administration of acid-suppressive drugs to critically ill patients for stress ulcer prophylaxis warrants further evaluation.


An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT™ is functionally superior to Freund's adjuvant.
Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund's adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund's adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.


A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Thyroid cancer: reports up to date and a review.
Evidence to date from a number of studies, indicates that there is an increased incidence of thyroid cancer among A-bomb survivors, and that the incidence rises with increase of dose and is especially predominant in females exposed at younger ages. Although 45 years have elapsed since A-bomb exposure, there are still some questions about the development of thyroid cancer: 1) Is the incidence now decreasing? 2) What factors, other than radiation exposure, are involved? 3) What is the incidence of multiple cancer, including thyroid cancer? With these questions in mind, it is apparent that studies in this field must continue for some time to come.


Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring.
Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat feeding can modulate glucose and lipid metabolism in the early life of offspring is less understood. Furthermore, we explored the underlying mechanisms that influence the phenotype. Using C57BL/6J mice, we examined the effects on the offspring at weaning from dams fed with a high-fat diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time PCR were performed in the liver tissues of the offspring mice. The offspring of the dams fed the high-fat diet had a heavier body weight, impaired glucose tolerance, decreased insulin sensitivity, increased serum cholesterol and hepatic steatosis at weaning. Bioinformatic analyses indicated that all differentially expressed genes of the offspring between the two groups were mapped to nine pathways. Genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were verified by quantitative real-time PCR and these genes were significantly up-regulated in the high-fat diet offspring. A maternal high-fat diet during pregnancy and lactation can modulate hepatic glucose, lipid homeostasis, and gene expression in the PPAR signaling in the early life of offspring, and our results suggested that potential mechanisms that influences this phenotype may be related partially to up-regulate some gene expression in the PPAR signalling pathway.


Regioselective Oxybromination of Benzene and Its Derivatives by Bromide Anion with a Mononuclear Nonheme Mn(IV)-Oxo Complex.
Oxybromination of aromatic compounds by high-valent metal-oxo intermediates has yet to be explored despite extensive studies on the oxybromination of aliphatic C-H bonds of hydrocarbons. Herein, we report the regioselective oxybromination of methoxy-substituted benzenes by a nonheme MnIV-oxo complex binding scandium ions, [(Bn-TPEN)MnIV(O)]2+-(Sc(OTf)3)2 (1), in the presence of tetrabutylammonium bromide. The regioselective oxybromination occurs at the carbon atom with the highest positive charge via electron transfer (ET) from the methoxy-substituted benzenes to 1. ET driving force dependence of the rate constants of ET from methoxy-substituted benzenes to 1 is well fitted in light of the Marcus theory of ET. Under photoirradiation, the oxybromination of benzene by 1 can be achieved via ET from benzene to the photoexcited state of 1, although no reaction occurs between benzene and the ground state of 1 in the dark. To the best of our knowledge, this is the first example of reporting the stoichiometric regioselective oxybromination of the benzene ring by a synthetic high-valent Mn(IV)-oxo complex and the catalytic regioselective oxybromination reaction with a Mn(II) complex and a terminal oxidant.


Clinical features and outcomes of 25 patients with primary adenosquamous cell carcinoma of the prostate.
The aim of the present study was to examine the epidemiology, natural history, treatment and long-term survival of patients with adenosquamous cell carcinoma of the prostate. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify ASCC of prostate cases between January 1973 and December 2006. Survival probabilities were estimated using the Kaplan-Meier methods and compared using the log-rank test. A total of 25 patients with adenosquamous cell carcinoma of the prostate were identified during the study period. The median age was 74 years (range 53-98). Twenty percent of study subjects presented with metastatic disease. Among those patients with known grade (n=16), 75% had poorly or undifferentiated histology. A total of 40% of study subjects received radical prostatectomy, while 24% of the patients had primary radiation therapy. The 1-, 3-, and 5-year cancer specific survival rates for the entire cohort were 55.2%, 37.8%, and 30.3%, respectively. For patients who underwent prostatectomy, the 1-, 3-, and 5-year survival rates were 78%, 78%, and 63%, respectively. For the patients who did not receive prostatectomy, the 1-year survival rates were 38.7% and none survived to three years. Adenosquamous cell carcinoma is a rare aggressive subtype of prostate cancer with poor cancer specific survival. The development of new therapeutic approaches for this aggressive tumor is urgently needed.


microRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study.
Around 70% of breast cancers (BCs) are estrogen receptor-α (ERα)-positive. Adjuvant endocrine therapy is used to reduce estrogen levels and inhibit signal transduction through the ER. The anti-estrogen drugs that are most commonly used in endocrine therapy belong to the selective ER modulator (SERM) class and include tamoxifen. Although it has been used for three decades in cases of early-stage and ERα-positive BC, resistance to tamoxifen is a common problem. microRNAs (miRNAs) have a potential role in demonstrating BC resistance to tamoxifen therapy. Hence, there is a need to investigate the expression of miRNA-221 (miR-221) in luminal-subtype BC patients receiving tamoxifen therapy. This case-control study investigated luminal-subtype BC patients who had undergone endocrine therapy for at least 1 year. The case group comprised patients with local or metastatic recurrence, and the control group comprised patients without local or metastatic recurrence. There was a significant difference in miR-221 expression (p = 0.005) between the case and control groups. There were no significant differences between the groups that were positive and negative for the progesterone receptor (PR) (p = 0.25), had high and low marker of proliferation Ki-67 levels (p = 0.60), were positive and negative for lymphovascular invasion (p = 0.14), and had stage 2 and stage 3 cancer (p = 0.25). miR-221 expression was higher in tamoxifen-resistant BC cases. miR-221 is a potential biomarker of tamoxifen resistance.