Sono-elastography for Differentiating Benign and Malignant Cervical Lymph Nodes: A Systematic Review and Meta-Analysis.
We did this systematic review to determine diagnostic accuracy of sono-elastography in evaluating cervical lymph nodes (LNs). A highly sensitive search for sono-elastography and LNs was performed in MEDLINE, Cochrane Library, ACP Journal Club, EMBASE, Health Technology assessment, and ISI web of knowledge for studies published prior to December 2012. SPSS version 18 (SPSS Inc., Chicago, IL, USA) used for descriptive analysis and meta-disk version 1.4 applied for meta-analysis. Forest plots for pooled estimates and summery of receiver operating characteristic plots for different cut-offs were produced. The literature and manual search yielded 69 articles, of which 10 were eligible to include. A total of 578 individuals with a total number of 936 cervical LNs was evaluated (502 malignant and 434 benign). The summary sensitivity of the scoring and strain ratio (SR) measurements for the differentiation of benign and malignant LNs were 0.76 (95% CI: 0.71-0.8) and 0.83 (95% CI: 0.78-0.87). The summary specificities were 0.8 (95% confidence interval [CI]: 0.75-0.84) and 0.84 (95% CI: 0.79-0.88), respectively. Area under the curve for scoring system was 0.86 (standard error [SE] = 0.03) and 0.95 (SE = 0.02) for SR measurement. Sono-elastograohy has high accuracy in differentiating benign and malignant cervical LNs.


Lenalidomide enhances the protective effect of a therapeutic vaccine and reverses immune suppression in mice bearing established lymphomas.
Immunomodulatory drugs (IMiDs) are effective therapeutic agents with direct inhibitory effects on malignant B- and plasma-cells and immunomodulatory effects on the T-cell activation. This dual function of IMiDs makes them appealing candidates for combination with a cancer vaccine. We investigated the immune stimulatory effects of lenalidomide, administrated to mice in doses, which provided comparable pharmacokinetics to human patients, on the potency of a novel fusion DNA lymphoma vaccine. The combination was curative in the majority of mice with 8d pre-established syngeneic A20 lymphomas compared with vaccine or lenalidomide alone and induced immune memory. In vivo depletion experiments established the requirement for effector CD8(+) and CD4(+) T cells in protective immunity. Unexpectedly, lenalidomide alone was also associated with reduced numbers of systemic myeloid-derived suppressor cell (MDSC) and regulatory T cell (Treg) in tumor-bearing but not naïve mice, an effect that was independent of simple tumor burden reduction. These results confirm and extend results from other models describing the effect of lenalidomide on enhancing T-cell immunity, highlight the potency of this effect, and provide a rationale for clinical application. Independently, a novel mechanism of action reversing tumor-induced immune suppression by MDSC is suggested.


Electrochemical techniques for subsecond neurotransmitter detection in live rodents.
Alterations in neurotransmission have been implicated in numerous neurodegenerative and neuropsychiatric disorders, including Alzheimer disease, Parkinson disease, epilepsy, and schizophrenia. Unfortunately, few techniques support the measurement of real-time changes in neurotransmitter levels over multiple days, as is essential for ethologic and pharmacodynamic testing. Microdialysis is commonly used for these research paradigms, but its poor temporal and spatial resolution make this technique inadequate for measuring the rapid dynamics (milliseconds to seconds) of fast signaling neurotransmitters, such as glutamate and acetylcholine. Enzymatic microelectrode arrays (biosensors) coupled with electrochemical recording techniques have demonstrated fast temporal resolution (less than 1 s), excellent spatial resolution (micron-scale), low detection limits (≤200 nM), and minimal damage (50 to 100 μm) to surrounding brain tissue. Here we discuss the benefits, methods, and animal welfare considerations of using platinum microelectrodes on a ceramic substrate for enzyme-based electrochemical recording techniques for real-time in vivo neurotransmitter recordings in both anesthetized and awake, freely moving rodents.


Pseudo-obstruction-inducing ACTG2R257C alters actin organization and function.
Actin γ 2, smooth muscle (ACTG2) R257C mutation is the most common genetic cause of visceral myopathy. Individuals with ACTG2 mutations endure prolonged hospitalizations and surgical interventions, become dependent on intravenous nutrition and bladder catheterization, and often die in childhood. Currently, we understand little about how ACTG2 mutations cause disease, and there are no mechanism-based treatments. Our goal was to characterize the effects of ACTG2R257C on actin organization and function in visceral smooth muscle cells. We overexpressed ACTG2WT or ACTG2R257C in primary human intestinal smooth muscle cells (HISMCs) and performed detailed quantitative analyses to examine effects of ACTG2R257C on (a) actin filament formation and subcellular localization, (b) actin-dependent HISMC functions, and (c) smooth muscle contractile gene expression. ACTG2R257C resulted in 41% fewer, 13% thinner, 33% shorter, and 40% less branched ACTG2 filament bundles compared with ACTG2WT. Curiously, total F-actin probed by phalloidin and a pan-actin antibody was unchanged between ACTG2WT- and ACTG2R257C-expressing HISMCs, as was ultrastructural F-actin organization. ACTG2R257C-expressing HISMCs contracted collagen gels similar to ACTG2WT-expressing HISMCs but spread 21% more and were 11% more migratory. In conclusion, ACTG2R257C profoundly affects ACTG2 filament bundle structure, without altering global actin cytoskeleton in HISMCs.


Analysis of differentially expressed genes in malignant biliary strictures.
Microarray data were collected from bile duct samples from subjects with malignant biliary strictures by endoscopic retrograde cholangiopancreatography to screen for key genes associated with this disease. A predicted interaction network was constructed for these genes to interpret their functions. The gene expression dataset GSE34166 (10 samples: 6 malignant and 4 benign control samples) was downloaded from the Gene Expression Omnibus database. R package scripts were used to process the data and screen for differentially expressed genes. Genes identified were uploaded to the analysis tool String 8.3 to generate a gene interaction network. A hub gene was identified by calculating the node degree. The interaction network of the hub gene with other genes in the human genome was constructed and screened (score >0.9), and pathway-enrichment analysis was performed to elucidate the hub gene function. In total, 377 differentially expressed genes were identified and a network comprising 209 pairs of interactions was constructed. The most critical hub gene was identified as GSTA1, and a GSTA1-based interaction network was constructed consisting of 25 genes (containing the differentially expressed gene GSTA3). The cytochrome P450 (CYP450)-metabolic pathway displayed the most significant enrichment. Additionally, 4 transcription factors and their binding sites were also identified. In conclusion, we have identified the differentially expressed genes GSTA1 (a hub gene) and GSTA3, which may cause abnormal gene expression and tumorigenesis through CYP450-metabolic pathways. The transcription factors and their binding sites in the promoter of the hub gene provide potential directions for future drug design.


The role of agriculture in women's nutrition: Empirical evidence from India.
In this paper, we establish a statistically important relationship between household agricultural income and women's BMI using a five-year panel dataset of rural households drawn from 18 villages across five Indian states. Using within household variation over time, we estimate both the extent to which short-term changes in agricultural income are associated with short-term changes in BMI, and the effect of agricultural income growth on BMI growth over a longer term. Over the longer term, and for the group of households that regularly farm, we find a 10 percentage point agricultural income growth to be associated with a 0.10 percentage point growth in BMI. Consistent with the literature, this effect is economically modest, but important considering that we do not find a corresponding effect for growth in non-agricultural income. We show that both the own-production and market purchase of food are associated with nutritional improvements. While women's BMI is associated with an increase in the consumption of own-produced cereals, the market plays an important role in facilitating access to more nutritious foods like pulses. Lastly, we also find that effects of agricultural income are driven by younger women, in the age-group 15-25 years, who face a particularly strong nutritional disadvantage in India.


Response of Two Crop Plants, Zea mays L. and Solanum lycopersicum L., to Diclofenac and Naproxen.
Among numerous contaminants, the ubiquitous occurrence of nonsteroidal anti-inflammatory drugs (NSAIDs) in the environment and their plausible harmful impact on nontarget organisms have made them one of the most important areas of concern in recent years. Crop plants can also potentially be exposed to NSAIDs, since the concentration of these pharmaceuticals is constantly rising in the surface water and soil. Our goal was to evaluate the stress response of two crop plants, maize and tomato, to treatment with selected NSAIDs, naproxen and diclofenac. The focus of the research was on the growth response, photosynthetic efficiency, selected oxidative stress factors (such as the H2O2 level and the rate of lipid peroxidation) as well as the total phenolic content, which represents the non-enzymatic protectants against oxidative stress. The results indicate that susceptibility to the NSAIDs that were tested is dependent on the plant species. A higher sensitivity of tomato manifested in growth inhibition, a decrease in the content of the photosynthetic pigments and a reduction in the maximum quantum efficiency of PSII and the activity of PSII, which was estimated using the Fv/Fm and Fv/F0 ratios. Based on the growth results, it was also possible to reveal that diclofenac had a more toxic effect on tomato. In contrast to tomato, in maize, neither the content of the photosynthetic pigments nor growth appeared to be affected by DFC and NPX. However, both drugs significantly decreased in maize Fv and Fm, which are particularly sensitive to stress. A higher H2O2 concentration accompanied, in most cases, increasing lipid peroxidation, indicating that oxidative stress occurred in response to the selected NSAIDs in the plant species that were studied. The higher phenolic content of the plants after NSAIDs treatment may, in turn, indicate the activation of defense mechanisms in response to the oxidative stress that is triggered by these drugs.


Joint Probabilities Approach to Quantum Games with Noise.
A joint probability formalism for quantum games with noise is proposed, inspired by the formalism of non-factorizable probabilities that connects the joint probabilities to quantum games with noise. Using this connection, we show that the joint probabilities are non-factorizable; thus, noise does not generically destroy entanglement. This formalism was applied to the Prisoner's Dilemma, the Chicken Game, and the Battle of the Sexes, where noise is coupled through a single parameter μ. We find that for all the games except for the Battle of the Sexes, the Nash inequalities are maintained up to a threshold value of the noise. Beyond the threshold value, the inequalities no longer hold for quantum and classical strategies. For the Battle of the sexes, the Nash inequalities always hold, no matter the noise strength. This is due to the symmetry and anti-symmetry of the parameters that determine the joint probabilities for that game. Finally, we propose a new correlation measure for the games with classical and quantum strategies, where we obtain that the incorporation of noise, when we have quantum strategies, does not affect entanglement, but classical strategies result in behavior that approximates quantum games with quantum strategies without the need to saturate the system with the maximum value of noise. In this manner, these correlations can be understood as entanglement for our game approach.


Use of equine chorionic gonadotropin to control reproduction of the dairy cow: a review.
Equine chorionic gonadotropin (eCG) is a member of the glycoprotein family of hormones along with LH, FSH and thyroid-stimulating hormone. In non-equid species, eCG shows high LH- and FSH-like activities and has a high affinity for both FSH and LH receptors in the ovaries. On the granulosa and thecal cells of the follicle, eCG has long-lasting LH- and FSH-like effects that stimulate oestradiol and progesterone secretion. Thus, eCG administration in dairy cattle results in fewer atretic follicles, the recruitment of more small follicles showing an elevated growth rate, the sustained growth of medium and large follicles and improved development of the dominant and pre-ovulatory follicle. In consequence, the quality of the ensuing CL is improved, and thereby progesterone secretion increased. Based on these characteristics, eCG treatment is utilized in veterinary medicine to control the reproductive activity of the cow by i) improving reproductive performance during early post-partum stages; ii) increasing ovulation and pregnancy rates in non-cyclic cows; iii) improving the conception rate in cows showing delayed ovulation; and finally, iv) eCG is currently included in protocols for fixed-time artificial insemination since after inducing the synchrony of ovulation using a progesterone-releasing device, eCG has beneficial effects on embryo development and survival. The above effects are not always observed in cyclic animals, but they are evident in animals in which LH secretion and ovarian activity are reduced or compromised, for instance, during the early post-partum period, under seasonal heat stress, in anoestrus animals or in animals with a low body condition score.


A case of amyloid myopathy diagnosed during the treatment of myopathy associated with anti-signal recognition particle antibodies.
A 78-year-old man presented with subacute progressive proximal weakness and dysphagia. A biopsy specimen from the left biceps femoris revealed evidence of necrotic and regenerating muscle fibers, but lymphocyte infiltration was not noted. The patient was diagnosed with necrotizing myopathy with anti-signal recognition particle (SRP) antibodies. Concomitant therapy with prednisolone and azathioprine caused the serum CK level to return to normal and it caused clinical manifestations to abate. One year later, however, muscle weakness worsened. Immunoelectrophoresis of serum revealed IgG M protein, and muscle pathology revealed amyloid deposits in numerous blood vessels and at the periphery of a few muscle fibers, and deposits stained positive for anti-λ light chain antibody. The patient was diagnosed with amyloid myopathy, and therapy for systemic amyloid light chain amyloidosis caused muscle weakness to diminish. Amyloidosis is believed to be the primary pathology in this case based on the patient's response to treatment reaction, but the significance of a case involving both amyloid myopathy and necrotizing myopathy warranted examination.


Immunogenicity and safety of a live-attenuated varicella vaccine in a healthy population aged 13 years and older: A randomized, double-blind, controlled study.
Vaccines for prevention against varicella are important for adolescents and adults, who have an increased risk of severe varicella. This study aimed to evaluate the immunogenicity and safety of a two-dose immunization schedule of a live-attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) in healthy adolescents and adults. A randomized, double-blind, controlled clinical trial was conducted in healthy population aged ≥ 13 years old in China. Participants in block 1 were randomly assigned (1:1) to receive two doses of either the test vaccine or an active control vaccine, administered 4, 6 or 8 weeks apart. Participants in block 2 were randomly assigned (2:1) to receive two doses of test vaccine or placebo, administered 10 weeks apart. The primary immunogenicity endpoint was the seroconversion rates and GMTs of varicella zoster virus (VZV) antibodies measured by fluorescent-antibody-to-membrane-antigen (FAMA) 4 weeks post-immunization. The primary safety endpoint was the incidence of adverse reactions within 4 weeks after each dose. A total of 2398 participants were enrolled. The seroconversion rates of VZV antibodies were 79.55 % in the test group and 76.41 % in the active control group respectively 4 weeks after two doses of pooled schedule, with the difference of 3.14 % (95 %CI: -0.69 %, 6.97 %). The GMTs were 1:162.07 and 1:160.04 respectively, with the ratio of 1.013 (95 %CI: 0.910, 1.127). Both the seroconversion rates and GMTs reached the prespecified non-inferiority criteria. Two-dose schedule with an interval of 10 weeks could also induce high immune responses, with a seroconversion rate of 83.22 % and a GMT of 1:160.38 in the test group. Safety profiles were similar among the test group, active control group and placebo group. VarV, manufactured by Sinovac (Dalian), demonstrated higher immune response and better flexibility in the immunization schedule among heathy population aged 13 years and older, without increased safety risk.


Sources of variation in follow-up expenditure after radical cystectomy.
Follow-up care after radical cystectomy is poorly defined, with extensive variation in practice patterns. We sought to determine sources of these variations in care as well as examine the economic effect of standardization of care to guideline-recommended care. Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1992 to 2007, we determined follow-up care expenditures (time and geography standardized) for 24 months after surgery. Accounted expenditures included office visits, imaging studies, urine tests, and blood work. A multilevel model was implemented to determine the effect of region, surgeon, and patient factors on care delivery. We then compared the actual expenditures on care in the Medicare system (interquartile range) with the expenditures if patients received care recommended by current clinical guidelines. Expenditures over 24 months of follow-up were calculated per month and per patient. The mean and median total expenditures per patient were $1108 and $805 respectively (minimum $0, maximum $9,805; 25th-75th percentile $344-$1503). Variations in expenditures were most explained at the patient level. After accounting for surgeon and patient levels, we found no regional-level variations in care. Adherence to guidelines would lead to an increase in expenditures by 0.80 to 10.6 times the expenditures exist in current practice. Although some regional-level and surgeon-level variations in care were found, the most variation in expenditure on follow-up care was at the patient level, largely based on node positivity, chemotherapy status, and final cancer stage. Standardization of care to current established guidelines would create higher expenditures on follow-up care than current practice patterns.


Defects in mitochondrial DNA replication and human disease.
Mitochondrial DNA (mtDNA) is replicated by the DNA polymerase g in concert with accessory proteins such as the mtDNA helicase, single stranded DNA binding protein, topoisomerase, and initiating factors. Nucleotide precursors for mtDNA replication arise from the mitochondrial salvage pathway originating from transport of nucleosides, or alternatively from cytoplasmic reduction of ribonucleotides. Defects in mtDNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mtDNA deletions, point mutations, or depletion which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mtDNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders, such as progressive external ophthalmoplegia (PEO), ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). This review focuses on our current knowledge of genetic defects of mtDNA replication (POLG, POLG2, C10orf2) and nucleotide metabolism (TYMP, TK2, DGOUK, and RRM2B) that cause instability of mtDNA and mitochondrial disease.


Atrial flutter catheter ablation in adult patients with repaired tetralogy of Fallot: mechanisms and outcomes of percutaneous catheter ablation in a consecutive series.
Prior investigators note successful ablation of both typical cavotricuspid isthmus-dependent and scar-related macroreentrant right atrial flutters (AFL) in adult patients with repaired tetralogy of Fallot (TOF). However, an analysis of the mechanisms (including a description of a uniform approach to diagnose such mechanisms), and clinical outcomes of catheter ablation in a consecutive series of adult patients with AFL late after surgical TOF repair has not been previously reported. Background clinical data and follow-up were evaluated in a consecutive series of TOF patients evaluated from September 2001 to June 2008. We report a prevalence of sustained, symptomatic AFL in patients with repaired TOF equal to 20% (28/140 patients), and of recurrent, drug-refractory and/or severely symptomatic AFL to be 11% (16/140 patients). The AFLs manifested variable cycle lengths ranging from 215 to 525 ms. Underlying mechanisms were: (1) cavotricuspid (CTI)-dependent, counterclockwise atrial flutter (n=8 patients); (2) non-CTI-dependent macroreentrant scar-related AFL (n=6 patients); and (3) both CTI- and non-CTI-dependent macroreentrant AFL (n=2 patients). Recurrent arrhythmias occurred in six patients, five of whom were successfully treated with repeat ablation. After a mean follow-up of 23 months, 15 of 16 patients were alive and free of sustained AFL. AFL late after surgical TOF repair occurs in 20% of such patients. In more than half of these patients, the AFLs are drug-refractory and/or severely symptomatic. Despite the presence of congenital heart disease treated with prior cardiac surgery and AFLs with variable atrial cycle lengths, the CTI-dependent mechanism underlies approximately half of the sustained, symptomatic AFLs.


Investigation of factors affecting recruitment and retention in the UK veterinary profession.
Recruitment and retention is currently of major concern and has resulted in the veterinary profession being returned to the UK's Shortage Occupation List in 2019. An online questionnaire of veterinary employees and employers investigating factors contributing to leaving/staying in current employment and the profession. The questionnaire was distributed via specialist veterinary associations' email lists and social media from September to October 2018. Respondents had few job changes (median 3), however, 43.7 per cent (n=2390) reported that they were likely or very likely to leave their employment within two years. Vets who were recently qualified, on lower salaries and female were more likely to plan to leave. Most frequently chosen reasons to stay in a position were: team, location and family. Most commonly cited reasons to leave were: work-life balance, management and salary. Respondents most disliked dealing with people, work-life balance and the physical/emotional impacts of the job. They would most like to change the hours worked, team aspects and management. Employers suggested that it was difficult to employ a veterinary surgeon, especially an experienced individual. The current retention crisis is due in part to the differing requirements between modern-day veterinary employees, their employers, the public and the profession.


A comparative study of endothelin- and platelet-activating-factor-mediated signal transduction and prostaglandin synthesis in rat Kupffer cells.
Endothelin-3 (ET-3) stimulated phosphoinositide metabolism and synthesis of prostaglandins in cultured rat Kupffer cells. ET-3-induced hydrolysis of phosphoinositides was characterized by the production of various inositol phosphates and of glycerophosphoinositol. The mechanism of ET-3-stimulated metabolism of phosphoinositides and synthesis of prostaglandins appeared to be distinct from the effect of platelet-activating factor (PAF) on these processes described previously [Gandhi, Hanahan & Olson (1990) J. Biol. Chem. 265, 18234-18241]. On a molar basis ET-3 was significantly more potent than PAF in stimulating phosphoinositide metabolism, e.g. ET-3-induced hydrolysis of phosphoinositides occurred at 1 pM, whereas PAF was ineffective at concentrations less than 1 nM. Upon challenging Kupffer cells with both ET-3 and PAF, an additive stimulation of phosphoinositide metabolism was observed, suggesting that the actions of these factors may be exerted on separate phosphoinositide pools. Treatment of Kupffer cells with pertussis toxin resulted in an inhibition of ET-3-induced phospholipase C activation; in contrast, cholera toxin treatment caused potentiation of ET-3-stimulated phospholipase C activity. Both toxins, however, inhibited PAF-stimulated phospholipase C activity. The present results suggest that the stimulatory effects of ET-3 and PAF on the phosphodiesteric metabolism of phosphoinositides in Kupffer cells require different guanine-nucleotide-binding proteins. Furthermore, the effects of bacterial toxins on ET-3- and PAF-induced phosphoinositide metabolism were not mediated by cyclic AMP. ET-3-induced metabolism of phosphoinositides was inhibited completely in Kupffer cells pretreated with ET-3, suggesting homologous ligand-induced desensitization of the ET-3 receptors. In contrast, similar experiments using PAF showed only a partial desensitization of subsequent PAF-induced phosphoinositide metabolism. In contrast to the increased production of prostaglandins E2 and D2 observed upon stimulation of Kupffer cells with PAF, ET-3 stimulated the biosynthesis of prostaglandin E2 only. Consistent with their additive effects on phosphoinositide metabolism, PAF and ET-3 exhibited an additive stimulation of the synthesis of prostaglandin E2.


Rotavirus contamination of surface waters from the northwest of Argentina.
Fecal pollution of water is a serious concern because it is associated with the transmission of pathogens. The aim of this study was to analyze the occurrence of group A rotavirus (RVA) in surface waters from the Arias-Arenales River in Salta, a northern city in Argentina, and to define possible sources of fecal viral pollution. A total of 116 water samples were analyzed and RVA was detected in 3.4% (95% CI: 0.1-7.0%), with concentrations ranging from 1.9 × 105 to 3.8 × 106 genome copies per liter. RVA strains were characterized as G1P[8], G4P[8] and G9P[8], which are common genotypes circulating in the local population. The Arias-Arenales River presented unusual and sporadic contamination by RVA, originated from stormwater discharges and a variety of non-identified sources, and support the essential need of viral indicators for enhanced monitoring of water quality.


Molecular epidemiology of rabies in Thailand.
For the purpose of making clear the dynamics of rabies viruses that are prevalent among dogs in Asia, especially Thailand, nucleoprotein (N) genes of isolates derived from Thailand were partially sequenced, and a phylogenetic analysis was performed on the basis of the sequencing data. Firstly, all 27 isolates from Thailand belonged to one group that was distantly related to an isolate from China and was separated into at least six lineages. On the other hand, the isolate from Japan was related to viruses from the Arctic. Secondly, in order to analyze the diversity of the N gene more conveniently, restriction fragment length polymorphism (RFLP) analysis was performed on the N gene of 27 isolates from Thailand. The RFLP analysis could distinguish the lineages of each isolate, and the lineages of additional 34 isolates were deduced by this method. On examination of the geographical distribution of the six lineages, based on the results of phylogenetic and RFLP analyses, it was clear that infection cycles of the rabies virus in Thailand have tended to be maintained endemically.


Has Data Quality of an Antimicrobial Resistance Surveillance System in a Province of Nepal Improved between 2019 and 2022?
An operational research study was conducted in 2019 to assess the quality of data submitted by antimicrobial resistance (AMR) surveillance sites in the Bagmati Province of Nepal to the National Public Health Laboratory for Global Antimicrobial Resistance and Use Surveillance System (GLASS). Measures were implemented to enhance the quality of AMR surveillance by strengthening capacity, improving infrastructure, implementing data sharing guidelines, and supervision. The current study examined reports submitted by surveillance sites in the same province in 2022 to assess whether the data quality had improved since 2019. The availability of infrastructure at the sites was assessed. Of the nine surveillance sites in the province, seven submitted reports in 2022 versus five in 2019. Completeness in reporting improved significantly from 19% in 2019 to 100% in 2022 (p < 0.001). Timely reports were received from two sites in 2019 and only one site in 2022. Specimen-pathogen consistency in accordance with the GLASS guidelines for urine, feces, and genital swab specimens improved, with ≥90% consistency at all sites. Overall, the pathogen-antibacterial consistency improved significantly for each GLASS priority pathogen. The study highlights the importance of dedicated infrastructure and institutional arrangements for AMR surveillance. Similar assessments covering all provinces of the country can provide a more complete country-wide picture.


Fetal electrocardiogram waveform analysis in labour.
ST-waveform analysis of the fetal electrocardiogram (ECG) has emerged from experimental and observational studies to clinical use based on the outcome of two large randomized controlled trials and a European Union-supported project on the structured dissemination of knowledge and experience by establishing regional centres of excellence. The review focuses on the outcome from the host of studies and those recently published. The database is dominated by a Swedish randomized controlled trial demonstrating not only improved outcome with regard to cord-artery metabolic acidosis and fewer operative interventions for non-reassuring fetal state but, most importantly, the marked and significant reduction in the risk of neonates showing signs of moderate or severe neonatal encephalopathy. The first report from the European Union project is presented, verifying the clinical relevance of the STAN methodology. The outcome of the large European Union project of 8000 deliveries confirms the observations of the randomized controlled trials. A study on the outcome shows improvements in accuracy and consistency among clinicians when automated ST analysis is added to the fetal heart rate trace. After years of dedicated research, it appears as though ST analysis of the fetal ECG has become an additional source of information allowing detailed analysis of fetal responses and more accurate identification of a non-reassuring fetal status. The technology provides continuous information throughout labour. As with any new methodology, structured efforts on training and user feedback are required to fully implement the STAN methodology in clinical practice.


Antibody to carcinoembryonic antigen in hamsters bearing GW-39 human tumors.
The appearance of anti-carcinoembryonic antigen (CEA) activity in the sera of hamsters bearing i.m. heterografts of GW-39, a CEA-producing colonic tumor of human origin, was demonstrated in radioimmunoassay using radioiodinated CEA purified from GW-39. Column chromatography, sucrose gradient ultracentrifugation, and radioimmunoelectrophoresis of pooled sera from tumor-bearing hamsters showed that the CEA antibody was of the immunoglobulin M type. The CEA antibody in tumor sera contained two specificities that reacted with different determinants on the CEA. On specificity reacted with a blood group-related determinant, whereas the remaining specificity was against a unique site on the CEA. Sequential analysis of individual tumor-bearing animals revealed that an increase in tumor growth paralleled the concomitant appearance of circulating CEA and highest antibody titer, suggesting that immunoglobulin M antibody, antigen, or complexes thereof influence tumor growth in this model.


Coronary artery bifurcation biomechanics and implications for interventional strategies.
The treatment of atherosclerotic plaques near and involving coronary bifurcations is especially challenging for interventional procedures. Optimization of these treatment strategies should begin with an understanding of how disease came to be localized to these regions, followed by careful design of the interventional tools and implanted devices. This manuscript reviews the basic biomechanics of coronary bifurcations, stented arteries, and the complex biomechanical challenges associated with bifurcation stenting. Flow patterns in bifurcations are inherently complex, including vortex formation and creation of zones of low and oscillating wall shear stress that coincide with early intimal thickening. Bifurcation geometry (in particular, the angle between the side branches), is of paramount importance in creating these proatherogenic conditions. This predilection for disease formation leads to a large number of bifurcation lesions presenting for clinical intervention. Therefore, several strategies have developed for treating these challenging lesions, including both dedicated devices and creative adaptation of single vessel lesion technologies. The biomechanical implications of these strategies are likely important in short and long term clinical outcomes. While the biomechanical environment in a stented coronary bifurcation is extremely challenging to model, computational methods have been deployed recently to better understand these implications. Enhancement of clinical success will be best achieved through the collaborative efforts of clinicians, biomechanicians, and device manufacturers.


Hypercoagulation and hypofibrinolysis in horses with colic and DIC.
Changes in haemostasis in horses with colic were assessed by using specific and sensitive markers of coagulation and fibrinolysis activity. Blood samples from 41 horses with severe colic and from 30 healthy control horses were tested. Diagnosis of DIC was based on the findings of at least 3 of 6 abnormalities: thrombocytopenia, prolonged clotting times (PT and APTT), increased polyclonal FDPs, decreased fibrinogen and decreased AT-III activity. Plasma thrombin-antithrombin III complexes (TAT), monoclonal fibrin degradation products fragment D (D-dimer) and monoclonal fibrinogen degradation products (FgDP) were also tested by using ELISA kits. DIC was diagnosed in 16 of 41 horses with colic. Compared to control and non-DIC colic values, TAT was significantly (P < 0.000) greater in horses with colic and DIC (Control group, mean +/- s.d. 2.6 +/- 2; non-DIC colic group, 7.5 +/- 9, and DIC colic group, 30.9 +/- 36 ng/ml). Also, D-dimer was significantly (P < 0.000) less in the DIC group when compared to control and non-DIC colic values (mean +/- s.d. 677 +/- 119, 682 +/- 220 and 399 +/- 234 ng/ml, respectively). Compared to non-DIC colic values, FgDP was significantly (P < 0.05) lower in the DIC group (363 +/- 111, 437 +/- 230 and 293 +/- 187 ng/ml respectively). Both PT and APTT showed a significant positive correlation with TAT. DIC was more common among nonsurvivors and horses with ischaemic bowel. We conclude that a hypercoagulative state was detected in horses with colic, which was stronger in horses with colic and DIC. Hypofibrinolysis was present only in horses with DIC. Therefore, marked hypercoagulation together with hypofibrinolysis are associated with DIC in horses.


Individual differences in behavior of inbred Lewis rats are associated with severity of joint destruction in adjuvant-induced arthritis.
The aim of our study was to test the hypothesis that differences in behavioral characteristics are linked to severity of arthritis in association with neuro-endocrine and immune reactivity in an inbred strain of rats. Lewis rats were selected as high-active (HA) and low-active (LA) animals based on their exploratory activity in the open field. Subsequently, adjuvant-arthritis (AA) was induced in both groups. We observed no differences in the severity of inflammation as determined by paw swelling and redness. However, LA and HA animals differed in the severity of bone destruction as determined on radiographs taken on day 30 after induction of AA. LA rats had more osteoporosis, periostal new bone formation, and bone destruction than HA rats. There were no differences between HA and LA rats in corticosterone response after acute or chronic immune challenge. Splenocytes of LA rats had a lower mitogen-induced IL-10 and IFNgamma production during AA. Histological examination revealed more intense factor VIII staining in arthritic joints of LA animals, indicating more pronounced synovial angiogenesis. In addition, LA rats had higher plasma VEGF, an important angiogenic factor. Expression of RANKL, a crucial factor promoting bone resorption, was also higher in joints of LA animals. Our data demonstrate that activity in the open field, a behavioral trait, is associated with the severity of bone destruction in AA. Lower production of bone-protective cytokines and a higher rate of angiogenesis leading to more synovial proliferation may be responsible for the more severe joint destruction in LA animals.


Hypnosis with etomidate during total intravenous anaesthesia.
Etomidate (Hypnomidate; Ethnor) in an alcoholic solution was used as the hypnotic component of a technique of total intravenous anaesthesia in an open pilot evaluation in 50 patients undergoing surgery. No anaesthetic gases were used. Despite cardiovascular stability, lack of respiratory depression and a short awakening time, unwanted movements by the patients made total intravenous anaesthesia with this technique unsatisfactory.


Synthesis, chiroptical properties and absolute configuration of spiro[1,3-benzodioxole-methanocyclooct[b]indole].
The synthesis of chiral 1'H-spiro[1,3-benzodioxole-2,12'-[6',10']methanocyclooct[b]indole] 3, a fused polycyclic structure derived from bicyclo[3.3.1]nonane, was accomplished via the Fisher indolization reaction. Enantiomers of this structure were obtained by chiral HPLC enantiomer separation on a swollen microcrystalline triacetylcellulose column. Chiroptical properties of the resolved enantiomers containing indole and 1,2-methylenedioxybenzene chromophores were studied. Application of the sector rule to the 1,2-methylenedioxybenzene chromophore to establish the absolute configuration of this polycyclic structure did not lead to an unequivocal conclusion which is likely to be due to the transannular interaction of the chromophores. The enantiospecific synthesis from enantiomerically enriched (-)-(1R,5S)-bicyclo[3.3.1]nonane-2,9-dione 1 was performed to prove unequivocally the (+)-(6'R,10'S)-configuration of the title structure. This study demonstrates that semiempirical rules should be applied cautiously to the determination of the absolute configuration of molecules containing several chromophores.


Alisertib induces cell cycle arrest and autophagy and suppresses epithelial-to-mesenchymal transition involving PI3K/Akt/mTOR and sirtuin 1-mediated signaling pathways in human pancreatic cancer cells.
Pancreatic cancer is the most aggressive cancer worldwide with poor response to current therapeutics. Alisertib (ALS), a potent and selective Aurora kinase A inhibitor, exhibits potent anticancer effects in preclinical and clinical studies; however, the effect and underlying mechanism of ALS in the pancreatic cancer treatment remain elusive. This study aimed to examine the effects of ALS on cell growth, autophagy, and epithelial-to-mesenchymal transition (EMT) and to delineate the possible molecular mechanisms in human pancreatic cancer PANC-1 and BxPC-3 cells. The results showed that ALS exerted potent cell growth inhibitory, pro-autophagic, and EMT-suppressing effects in PANC-1 and BxPC-3 cells. ALS remarkably arrested PANC-1 and BxPC-3 cells in G2/M phase via regulating the expression of cyclin-dependent kinases 1 and 2, cyclin B1, cyclin D1, p21 Waf1/Cip1, p27 Kip1, and p53. ALS concentration-dependently induced autophagy in PANC-1 and BxPC-3 cells, which may be attributed to the inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase (p38 MAPK), and extracellular signal-regulated kinases 1 and 2 (Erk1/2) but activation of 5'-AMP-dependent kinase signaling pathways. ALS significantly inhibited EMT in PANC-1 and BxPC-3 cells with an increase in the expression of E-cadherin and a decrease in N-cadherin. In addition, ALS suppressed the expression of sirtuin 1 (Sirt1) and pre-B cell colony-enhancing factor/visfatin in both cell lines with a rise in the level of acetylated p53. These findings show that ALS induces cell cycle arrest and promotes autophagic cell death but inhibits EMT in pancreatic cancer cells with the involvement of PI3K/Akt/mTOR, p38 MAPK, Erk1/2, and Sirt1-mediated signaling pathways. Taken together, ALS may represent a promising anticancer drug for pancreatic cancer treatment. More studies are warranted to investigate other molecular targets and mechanisms and verify the efficacy and safety of ALS in the treatment of pancreatic cancer.


Clinical utility of 18F-FDG PET/CT in the follow-up of a large cohort of patients with high-risk differentiated thyroid carcinoma.
To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC. Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in 4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31). 18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease. 18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.


[Complex radiodiagnosis of osteomyelitis].
In 23 patients with chronic osteomyelitis roentgenography of the bones and three-phase scintigraphy including radionuclide angiography, investigation of the soft tissues and bones were performed. In comparison of the data of clinical examination, roentgenography and radionuclide methods of diagnosis, the correspondence of the data of radionuclide angiography to the phase of an inflammatory process was established.


Conformational changes in the A3 domain of von Willebrand factor modulate the interaction of the A1 domain with platelet glycoprotein Ib.
Bitiscetin has recently been shown to induce von Willebrand factor (vWF)-dependent aggregation of fixed platelets (Hamako J, et al, Biochem Biophys Res Commun 226:273, 1996). We have purified bitiscetin from Bitis arietans venom and investigated the mechanism whereby it promotes a form of vWF that is reactive with platelets. In the presence of bitiscetin, vWF binds to platelets in a dose-dependent and saturable manner. The binding of vWF to platelets involves glycoprotein (GP) Ib because it was totally blocked by monoclonal antibody (MoAb) 6D1 directed towards the vWF-binding site of GPIb. The binding also involves the GPIb-binding site of vWF located on the A1 domain because it was inhibited by MoAb to vWF whose epitopes are within this domain and that block binding of vWF to platelets induced by ristocetin or botrocetin. However, in contrast to ristocetin or botrocetin, the binding site of bitiscetin does not reside within the A1 domain but within the A3 domain of vWF. Thus, among a series of vWF fragments, 125I-bitiscetin only binds to those that overlap the A3 domain, ie, SpIII (amino acid [aa] 1-1365), SpI (aa 911-1365), and rvWF-A3 domain (aa 920-1111). It does not bind to SpII corresponding to the C-terminal part of vWF subunit (aa 1366-2050) nor to the 39/34/kD dispase species (aa 480-718) or T116 (aa 449-728) overlapping the A1 domain. In addition, bitiscetin that does not bind to DeltaA3-rvWF (deleted between aa 910-1113) has no binding site ouside the A3 domain. The localization of the binding site of bitiscetin within the A3 domain was further supported by showing that MoAb to vWF, which are specific for this domain and block the interaction between vWF and collagen, are potent inhibitors of the binding of bitiscetin to vWF and consequently of the bitiscetin-induced binding of vWF to platelets. Thus, our data support the hypothesis that an interaction between the A1 and A3 domains exists that may play a role in the function of vWF by regulating the ability of the A1 domain to bind to platelet GPIb.


Regulation of membrane trafficking and subcellular organization of endocytic compartments revealed with FM1-43 in resting and activated human T cells.
FM1-43, a fluorescent styryl dye that penetrates into and stains membranes, was used to investigate kinetics of constitutive endocytosis and to visualize the fate of endocytic organelles in resting and activated human T lymphocytes. The rate of dye accumulation was strongly temperature dependent and approximately 10-fold higher in activated than in resting T cells. Elevation of cytosolic free Ca2+ concentration with thapsigargin or ionomycin further accelerated the rate of FM1-43 accumulation associated with cytosolic actin polymerization. Direct modulation of actin polymerization affected membrane trafficking. Actin condensation beneath the plasma membrane with calyculin A abolished FM1-43 internalization, whereas actin depolymerization with cytochalasin D had no effect. Photoconversion of DAB by FM1-43 revealed altered endocytic compartment targeting associated with T cell activation. Internalized cargo was carried to lysosome-like compartments in resting T cells and to multivesicular bodies (MVB) in activated T cells. Externalization of exosomes from MVB occurred commonly in activated but not in resting T cells. T cell exosomes contained raft-associated CD3 proteins, GM1 glycosphingolipids, and phosphatidylserine at the outer membrane leaflet. The present study demonstrates the utility of FM1-43 as a marker of membrane trafficking in T cells and reveals possible mechanisms of its modulation during T cell activation.


Lipidation of an FlrC-dependent protein is required for enhanced intestinal colonization by Vibrio cholerae.
Vibrio cholerae, the causative agent of cholera, has a sheathed, polar flagellum, and motility has been linked to virulence. An operon with two genes, flgO and flgP (VC2207 and VC2206), is positively regulated by FlrC, the activator of class III flagellar genes. Deletion of flgP results in a nonmotile phenotype, demonstrating the requirement of this gene for V. cholerae motility. V. cholerae delta flgP cells synthesize fragile and defective flagella but transcribe flagellar genes similar to the wild-type strain. PhoA fusion analysis indicated that the putative lipoprotein FlgP is localized external to the cytoplasm, and fractionation demonstrated that it was localized to the outer membrane. Mutagenesis of the site of lipidation of FlgP (C18G) prevented [3H]palmitate incorporation and outer membrane localization. Interestingly, FlgP with the mutation C18G [FlgP(C18G)] could complement the delta flgP mutant for motility, and the cells synthesized wild-type flagella. The delta flgP mutant strain was defective for intestinal colonization (approximately 20-fold), but FlgP(C18G) was unable to complement this defect, demonstrating that lipidation of FlgP is essential for its role in intestinal colonization but not flagellar synthesis. FlgP thus represents a novel V. cholerae intestinal colonization factor that is regulated by the flagellar transcription hierarchy.


Diabetes bingo: research prioritization with the Filipino community.
This community-based participatory research, conducted in partnership between a European-American academic researcher and a professional group of Filipino nurses, aimed to determine the diabetes research priority for the Filipino community on the island of Oahu in Hawaii, and to evaluate the multi-voting technique to seek input from the community. The study design was a qualitative, cross-sectional interactive process consisting of an educational presentation followed by data collection from the audience. Ten community presentations about the impact of diabetes on the Filipino community were conducted by a Filipino nurse with participants (N=265). Following the educational session, the participants selected priorities for research using a multi-vote technique developed as a Diabetes Bingo card. Community voting results identified prevention and a focus on adults as important priorities for research. Based on the results of the multi-voting, the research partners were able to come to consensus on a research priority area of prevention of type 2 diabetes in adults. Multi-voting using a Diabetes Bingo card, preceded by an educational presentation by a Filipino nurse, was a culturally competent community-based participatory research method that gave voice to the participants and direction to the research partners for future projects. The multi-voting technique was readily accepted and enjoyed by participants.


Tumor vasculature in young and old hosts: scanning electron microscopy of microcorrosion casts with microangiography, light microscopy and transmission electron microscopy.
Tumor growth in vivo is dependent upon new blood vessel formation. When B16-F10 melanoma cells are implanted subcutaneously in young (3 mo) and old (24 mo) C57BL/6 mice the rate of growth is dependent on the age of the mice. This study involved a wide range of histological and microscopic techniques but was limited primarily to the initial phase of tumor growth. Stereological point counting from light microscopy (LM) of standard histological sections has been used to yield data regarding blood content. Tumor-bearing mice were perfused through the aorta with a fixation solution and were infused with a low-viscosity radiopaque gel (Microfil) or resin (Mercox). Soft x-rays of the whole animal were used for identifying the feeding vessels to the tumor. Tumors with Microfil were sliced and used for microangiography and light-microscopic observation while those with resin were used to make corrosion casts for scanning electron microscopy (SEM). The different characteristics of the tumor blood vessels in different aged mice were most obvious through SEM of vascular corrosion casts. In comparison with tumors in young mice those of similar size in old hosts had more necrosis, reduced presence of angiogenic features, decreased vessel density, reduced penetration into the tumor, and enhanced tortuosity of the vessel lumen. Transmission electron microscopy (TEM) revealed incompletely developed wall structure of the vessels regardless of host. The above results are consistent with the hypothesis that retarded angiogenesis may be responsible in part for the limited growth of tumors in old hosts.


Altered map of visual space in the superior colliculus of mice lacking early retinal waves.
During the development of the mammalian retinocollicular projection, a coarse retinotopic map is set up by the graded distribution of axon guidance molecules. Subsequent refinement of the initially diffuse projection has been shown to depend on the spatially correlated firing of retinal ganglion cells. In this scheme, the abolition of patterned retinal activity is not expected to influence overall retinotopic organization, but this has not been investigated. We used optical imaging of intrinsic signals to visualize the complete retinotopic map in the superior colliculus (SC) of mice lacking early retinal waves, caused by the deletion of the beta2 subunit of the nicotinic acetylcholine receptor. As expected from previous anatomical studies in the SC of beta2(-/-) mice, regions activated by individual visual stimuli were much larger and had less sharp borders than those in wild-type mice. Importantly, however, we also found systematic distortions of the entire retinotopic map: the map of visual space was expanded anteriorly and compressed posteriorly. Thus, patterned neuronal activity in the early retina has a substantial influence on the coarse retinotopic organization of the SC.


Bringing the history of mathematics home: Entangled practices of domesticity, gender, and mathematical work.
Although much scholarship on nineteenth and twentieth century mathematics has focused on processes of professionalization, historical mathematicians themselves rarely experienced their lives as neatly divisible into the professional and the private. Taking marriage as a focal point, this introduction brings the fruitful historiography of gender, collaborative couples, and domesticity in science into a broader conversation with the history of mathematics. By historicizing marriage and its relationship to mathematical careers, we lay the groundwork for the special issue which uncovers the myriad ways in which spousal collaboration and support have been central to mathematical work.


Compton Scattering in Clinical PET/CT With High Resolution Half Ring PET Insert Device.
The integration of a high resolution PET insert into a conventional PET system can significantly improve the resolution and the contrast of its images within a reduced imaging field of view. For the rest of the scanner imaging field of view, the insert is a highly attenuating and scattering media. In order to use all available coincidence events (including coincidences between 2 detectors in the original scanner, namely the scanner-scanner coincidences), appropriate scatter and attenuation corrections have to be implemented. In this work, we conducted a series of Monte Carlo simulations to estimate the composition of the scattering background and the importance of the scatter correction. We implemented and tested the Single Scatter Simulation (SSS) algorithm for a hypothetical system and show good agreement between the estimated scatter using SSS and Monte Carlo simulated scatter contribution. We further applied the SSS to estimate scatter contribution from an existing prototype PET insert for a clinical PET/CT scanner. The results demonstrated the applicability of SSS to estimate the scatter contribution within a clinical PET/CT system even when there is a high resolution half ring PET insert device in its imaging field of view.


Adjunctive agents to facilitate rapid tissue expansion.
A rodent model was used to study tissue expansion. Three chemical agents--hyaluronidase, prostaglandin E2, and colchicine--were administered and their effects on tissue expansion studied. Hyaluronidase and colchicine both enhanced the rate of expansion when compared with results in control animals (p less than 0.05). Although prostaglandin E2 had less effect on expansion rate, it did significantly enhance tissue oxygen tension of expanded skin when compared with controls (p less than 0.05). Clinical implications include the possibility of pretreating patients with these agents to increase the rate of expansion and to improve the safety of current methods of expansion.


Quantifying the likelihood of co-existence for communities with asymmetric competition.
Trade-offs in performance of different ecological functions within a species are commonly offered as an explanation for co-existence in natural communities. Single trade-offs between competitive ability and other life history traits have been shown to support a large number of species, as a result of strong competitive asymmetry. We consider a single competition-fecundity trade-off in a homogeneous environment, and examine the effect of the form of asymmetry on the likelihood of species co-existing. We find conditions that allow co-existence of two species for a general competition function, and show that (1) two species can only co-exist if the competition function is sufficiently steep when the species are similar; (2) when competition is determined by a linear function, no more than two species can co-exist; (3) when the competition between two individuals is determined by a discontinuous step function, this single trade-off can support an arbitrarily large number of species. Further, we show analytically that as the degree of asymmetry in competition increases, the probability of a given number of species co-existing also increases, but note that even in the most favourable conditions, large numbers of species co-existing along a single trade-off is highly unlikely. On this basis, we suggest it is unlikely that single trade-offs are able to support high levels of bio-diversity without interacting other processes.


Sterilization and Cross-Linking Combined with Ultraviolet Irradiation and Low-Energy Electron Irradiation Procedure: New Perspectives for Bovine Pericardial Implants in Cardiac Surgery.
Bovine pericardium is the major natural source of patches and aortic valve substitutes in cardiac repair procedures. However, long-term tissue durability and biocompatibility issues lead to degeneration (e.g., calcification) that requires reoperation. Tissue preparation strategies, including glutaraldehyde fixation, are reasons for the deterioration of pericardial tissues. We describe a pretreatment procedure involving sterilization and cross-linking combined with ultraviolet (UV) irradiation and low-energy electron irradiation (SULEEI). This innovative, glutaraldehyde-free protocol improves the mechanical aspects and biocompatibility of porcine pericardium patches. We adopted the SULEEI protocol, which combines decellularization, sterilization, and cross-linking, along with UV irradiation and low-energy electron irradiation, to pretreat bovine pericardium. Biomechanics, such as ultimate tensile strength and elasticity, were investigated by comparing SULEEI-treated tissue with glutaraldehyde-fixed analogues, clinical patch materials, and an aortic valve substitute. Histomorphological and cellular aspects were investigated by histology, DNA content analysis, and degradability. Mechanical parameters, including ultimate tensile strength, elasticity (Young's modulus), and suture retention strength, were similar for SULEEI-treated and clinically applied bovine pericardium. The SULEEI-treated tissues showed well-preserved histoarchitecture that resembled all pericardial tissues investigated. Fiber density did not differ significantly. DNA content after the SULEEI procedure was reduced to less than 10% of the original tissue material, and more than 50% of the SULEEI-treated pericardium was digested by collagenase. The SULEEI procedure represents a new treatment protocol for the preparation of patches and aortic valve prostheses from bovine pericardial tissue. The avoidance of glutaraldehyde fixation may lessen the tissue degeneration processes in cardiac repair patches and valve prostheses.


Organizational change in a perinatal treatment setting: integration of clinical practice and policies on tobacco and smoking cessation.
Perinatal smoking presents serious health risks to the fetus, mother, and child. Despite extensive evidence of risk and high rates of smoking among in-treatment perinatal women substance abusers, tobacco-related practice and policy change has not been widely transferred for application in drug abuse treatment programs for pregnant and parenting women. This qualitative study investigated the process of change and the resultant adoption of clinical policy and treatment innovation in a residential drug abuse treatment program that converted from tobacco-tolerant to tobacco-free with provision of smoking cessation services. Informed by the Organizational Readiness for Change Model, staff interviews and data analysis were conducted to examine program characteristics affecting adoption. An organizational climate of openness to change and the program's clarity of mission, expressed in perinatal-specific motivators for change, influenced the adoption of tobacco-related clinical practice and policy. Re-allocation of time, previously occupied by smoking behaviors, allowed for added promotion of maternal-child interaction and positive role-modeling for children.


Comparing Anesthesiology Residency Training Structure and Requirements in Seven Different Countries on Three Continents.
Little has been published comparing the graduate medical education training structure and requirements across multiple countries. The goal of this study was to summarize and compare the characteristics of anesthesiology training programs in the USA, UK, Canada, Japan, Brazil, Denmark, and Switzerland as a way to better understand efforts to train anesthesiologists in different countries. Two physicians trained in each of the seven countries (convenience sample) were interviewed using a semi-structured approach. The interview was facilitated by use of a predetermined questionnaire that included, for example, the duration of post-medical school training and national requirements for certain rotations, a number of cases, faculty supervision, national in-training written exams, and duty hour limits. These data were augmented by review of each country's publicly available residency training documents as available on the internet. Post-medical school anesthesia residency duration varied: three years (Brazil), four years (USA), five years (Canada and Switzerland), six years (Japan and Denmark) to nine years (UK), as did the number of explicitly required clinical rotations of a defined duration: zero (Denmark), one (Switzerland and UK), four (Brazil), six (Canada), and 12 (USA). Minimum case requirements exist in the USA, Japan, and Brazil, but not in the other countries. National written exams taken during training exist for all countries studied except Japan and Denmark. The countries studied increasingly aim to have competency-based education with milestone assessments. Training duty hour limits also varied including for example 37 hours/week averaged over a one month with limitations on night duties (Denmark), a weekly average of 48 hours taken over a 17 week period (UK), 50 hours/week maximum (Switzerland), 60 hours/week maximum (Brazil), and 80 hours/week averaged over four weeks (USA). Some countries have highly structured training programs with multiple national requirements with training principally carried out at a home institution. Other countries have a more decentralized and unregulated approach with fewer (if any) specific case or rotation requirements, where the trainee creates his/her own customized training to meet broad objectives and goals. The countries studied have different national training requirements, unique duty hour rules and are at varying stages in transitioning to an outcome based model of residency.


Two Cases of Severe COVID-19 Pneumonia Effectively Treated with Extracorporeal Membrane Oxygenation in Addition to Favipiravir and Corticosteroid.
Case 1: A 65-year-old man with novel coronavirus infection (COVID-19) complicated with acute respiratory failure. On admission, the patient was started on favipiravir and corticosteroid. However, due to a lack of significant improvement, he was introduced to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Although iliopsoas hematoma occurred as a complication, the patient recovered. Case 2: A 49-year-old man with COVID-19 had been started on favipiravir and corticosteroid. Due to progressive respiratory failure, the patient underwent mechanical ventilation and ECMO. The patient recovered without complications. We successfully treated these severe cases with a multimodal combination of pharmacological and non-pharmacological supportive therapy.


Altered mucin core peptide immunoreactivity in the colon polyp-carcinoma sequence.
Altered mucin glycosylation occurs in colonic adenomas and can correlate with risk for malignant transformation. The purpose of this study was to determine if immunoreactivity of core tandem repeat peptides of specific mucin genes correlates with histopathologic criteria of malignant potential in the colon. Expression of MUC1, MUC2, and MUC3 core tandem repeat proteins was examined in specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous polyps (n = 89), and invasive cancer (n = 19). An immunohistochemical scoring system that takes into account specimen heterogeneity and yields an integrated numerical score subject to statistical analysis was used. RNA message levels from tubular and tubulovillous adenomas (n = 13), normal colon (n = 12), and moderately differentiated adenocarcinomas (n = 8) were determined using RNA slot blot analysis with mucin-specific cDNA probes. MUC1 staining was rarely present in normal colon. MUC2 immunoreactivity was limited to goblet cells in most normal colonic crypts, and MUC3 staining was weakly expressed in the upper crypt regions only. In comparison with normal and hyperplastic specimens, MUC1 and MUC3 immunoreactivity scores were significantly increased in adenomas of increasing villous histology, size, and dysplasia. MUC2 scores were significantly increased in adenomas of greater villous histology and size. Comparable MUC1, MUC2, and MUC3 mRNA levels were present in adenomas and normal colon, whereas mucin mRNA levels were decreased in adenocarcinomas. We conclude that enhanced immunoreactivity of MUC1, MUC2 and MUC3 mucin tandem repeats occurs in adenomatous polyps and is associated with an increased risk for malignant transformation.


The alkaline tide goes out and the nitrogen stays in after feeding in the dogfish shark, Squalus acanthias.
In light of previous work showing a marked metabolic alkalosis ("alkaline tide") in the bloodstream after feeding in the dogfish shark (Squalus acanthias), we evaluated whether there was a corresponding net base excretion to the water at this time. In the 48 h after a natural voluntary meal (teleost tissue, averaging 5.5% of body weight), dogfish excreted 10,470 micromol kg(-1) more base (i.e. HCO3- equivalents) than the fasted control animals (which exhibited a negative base excretion of -2160 micromol kg(-1)). This large activation of branchial base excretion after feeding thereby prevented a potentially fatal alkalinization of the body fluids by the alkaline tide. The rate peaked at 330 micromol kg(-1) h(-1) at 12.5-24 h after the meal. Despite a prolonged 1.7-fold elevation in MO2 after feeding ("specific dynamic action"), urea-N excretion decreased by 39% in the same 48 h period relative to fasted controls. In contrast, ammonia-N excretion did not change appreciably. The N/O2 ratio declined from 0.51 in fasted animals to 0.19 in fed sharks, indicating a stimulation of N-anabolic processes at this time. These results, which differ greatly from those in teleost fish, are interpreted in terms of the fundamentally different ureotelic osmoregulatory strategy of elasmobranchs, and recent discoveries on base excretion and urea-retention mechanisms in elasmobranch gills.


Maternal serum levels of C-reactive protein at early pregnancy to predict fetal growth restriction and preterm delivery: A prospective cohort study.
A considerable evidence suggests that maternal inflammation dysregulation may play as a risk factor for both maternal and neonatal outcomes. Objective: The study's objectives were designed to evaluate the correlation between serum C-reactive protein (CRP) levels, as an inflammation factor, preterm delivery, and small for gestational age (SGA) births. This prospective cohort study was conducted on 120 singleton pregnant women with gestational age less than 20 wk. Maternal CRP serum concentration was measured before 20 wk gestation. Patients were followed-up until the delivery and final outcomes of pregnancy were recorded in terms of preterm delivery and SGA births. Results: Serum CRP levels in participants with normal fetuses and SGA births were 4.09 ± 1.35 mg/l and 6.04 ± 3.29 mg/l, respectively (p = 0.19), while in cases of preterm delivery, it was 9.63 ± 5.78 mg/l (p < 0.001). By using receiver operating characteristic (ROC) curve, serum CRP levels (cut-off point 5.27 mg/l, area 0.836) had acceptable diagnostic accuracy value in distinguishing preterm delivery (sensitivity (75%), specificity (86.1%), positive predictive value (37.5%), negative predictive value (96.87%), accuracy (85%)) and serum CRP levels (cut-off point 6.67 mg/l, area 0.673) in distinguishing SGA births (sensitivity (50%), specificity (91.2%), positive predictive value (23.07%), and negative predictive value (97.19%), and accuracy (89.16 %)). Higher maternal serum CRP levels measured early in pregnancy may associate with higher risk of preterm delivery and SGA.


Cyclosporine and low-dose ketoconazole in renal transplant recipients: a single-center experience.
The high cost of cyclosporine A (CsA) is an impediment for low-income patients. Previous studies have used ketoconazole at doses between 200 and 400 mg/day to lower CsA consumption. Ketoconazole and CsA were administered prospectively to renal transplant patients. Patients treated historically with CsA were used as a reference group. At different intervals posttransplant, clinical and laboratory data were recorded. The reference group (n=14) was treated with CsA from 1992 to 1997 and the CsA plus ketoconazole group (n=17) from 1998 to 2002. Follow-up was 76+/-22 and 29+/-14 months, respectively. CsA doses throughout the study were 4.0+/-1.3 and 1.6+/-0.6 mg/kg/day (a 60% reduction, P =0.00). Trough levels of CsA were 194+/-87 and 193+/-69 ng/mL, respectively. The ketoconazole dose was 54+/-17 mg/day. The monthly cost of CsA was reduced by 60%, including the cost of ketoconazole. CsA with ketoconazole resulted in a substantial dose and cost reduction that proved safe and effective.


Management of acute calvarial burns in children.
Although rare, head burns involving the calvarium are a serious complication of burns and electrical injury, and present therapeutic challenges to the surgical burn care team. We evaluated our experiences and compared available strategies to address this challenge. Records of all burned children between January 1986 and December 2000 were reviewed. Twenty-seven children (15 boys and 12 girls) with scalp burns extending at least into the outer table of bone were identified and compared with a matched group of 30 patients admitted for acute thermal burns without skull injury. Flame burn was the injury mechanism in 78% of these patients and electrical injury was the injury mechanism in 22%. The incidence of calvarial burns in our patient population was 1.2% for thermal burns and 5.6% for electrical injuries during the study period. The age distribution was biphasic, with maximums in infancy for thermal burns and in puberty for electrical injuries. Eight of 27 patients (29.6%) developed full-thickness calvarial bone defects. In 23 patients, calvarial burn wound coverage was achieved with bone debridement and immediate or delayed placement of autograft skin. In four patients (all with electrical injury), local scalp flaps were required for closure. The length of hospital stay and overall number of acute operative procedures significantly increased for patients with calvarial burns. Acute calvarial burns are safely managed by bone debridement in combination with staged autografting or early flap coverage. Although flap coverage reduces the number of required procedures, the extensive wound size in thermal burns restricts acute flap procedures primarily to electrical injuries. Compared with patients without skull injury, length of hospital stay and the number of acute operative procedures are tremendously increased in patients with calvarial burns.


Age-related reduction of hemispheric lateralisation for spatial attention: An EEG study.
A group-level visuospatial attention bias towards the left side of space (pseudoneglect) is consistently observed in young adults, which is likely to be a consequence of right parieto-occipital dominance for spatial attention. Conversely, healthy older adults demonstrate a rightward shift of this behavioural bias, hinting that an age-related reduction of lateralised neural activity may occur within visuospatial attention networks. We compared young (aged 18-25) and older (aged 60-80) adults on a computerised line bisection (landmark) task whilst recording event-related potentials (ERPs). Full-scalp cluster mass permutation tests identified a larger right parieto-occipital response for long lines compared to short in young adults (confirming Benwell et al., 2014a) which was not present in the older group. To specifically investigate age-related differences in hemispheric lateralisation, cluster mass permutation tests were then performed on a lateralised EEG dataset (RH-LH electrodes). A period of right lateralisation was identified in response to long lines in young adults, which was not present for short lines. No lateralised clusters were present for either long or short lines in older adults. Additionally, a reduced P300 component amplitude was observed for older adults relative to young. We therefore report here, for the first time, an age-related and stimulus-driven reduction of right hemispheric control of spatial attention in older adults. Future studies will need to determine whether this is representative of the normal aging process or an early indicator of neurodegeneration.


Screening of Bioactive Properties in Brown Algae from the Northwest Iberian Peninsula.
Algae are an underexploited source of natural bioactive compounds in Western countries, so an increasing interest in the valorization of these marine organisms has emerged in recent years. In this work, the effect of extracting solvent on the extraction yield, phenolic content, antioxidant capacity, and antimicrobial activity of nine brown macroalgae species (Ascophyllum nodosum, Himanthalia elongata, Undaria pinnatifida, Pelvetia canaliculata, Saccharina latissima, Bifurcaria bifurcata, Laminaria ochroleuca, Sargassum muticum, and Fucus spiralis) was assessed. Total phenolic content (TPC) and the antioxidant properties of extracts by different assays: radical scavenging activity (DPPH-RSA) and ferric reducing antioxidant power (FRAP) were performed. The antimicrobial activity of extracts was studied against six different foodborne microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Escherichia coli, Salmonella enteritidis, and Pseudomonas aeruginosa. The highest extraction yield was achieved in ethanolic extracts. However, the highest TPC and FRAP values were obtained on the ethyl acetate extracts, especially from A. nodosum. Concerning algal species, the highest TPC and FRAP values were found in A. nodosum, while the highest DPPH-RSA values were achieved in the hexane extracts of B. bifurcata. The antimicrobial activity of algal extracts varied according to the solvent and alga selected, suggesting the species- and solvent-dependent behavior of this property, with B. bifurcata extracts showing the highest results for a wide range of bacteria. Our results provide insight on the characterization of widespread brown algae in the coasts of the North-Western region of the Iberian Peninsula, reflecting multiple health-enhancing properties which may lead to their exploitation in food, pharmacological, and cosmetic industries.


re-Searcher: GUI-based bioinformatics tool for simplified genomics data mining of VCF files.
High-throughput sequencing platforms generate a massive amount of high-dimensional genomic datasets that are available for analysis. Modern and user-friendly bioinformatics tools for analysis and interpretation of genomics data becomes essential during the analysis of sequencing data. Different standard data types and file formats have been developed to store and analyze sequence and genomics data. Variant Call Format (VCF) is the most widespread genomics file type and standard format containing genomic information and variants of sequenced samples. Existing tools for processing VCF files don't usually have an intuitive graphical interface, but instead have just a command-line interface that may be challenging to use for the broader biomedical community interested in genomics data analysis. re-Searcher solves this problem by pre-processing VCF files by chunks to not load RAM of computer. The tool can be used as standalone user-friendly multiplatform GUI application as well as web application (https://nla-lbsb.nu.edu.kz). The software including source code as well as tested VCF files and additional information are publicly available on the GitHub repository (https://github.com/LabBandSB/re-Searcher).


The patient-generated subjective global assessment is a promising screening tool for cancer cachexia.
Cancer cachexia is a complex metabolic syndrome characterised by a loss of muscle with or without loss of fat mass, and is associated with high morbidity and mortality. Despite its clinical importance, there is a lack of simple tools to screen patients for cancer cachexia. The aim of this study was to evaluate and validate the patient-generated subjective global assessment (PG-SGA) as a screening tool for cancer cachexia. This is a secondary analysis of a multicentre, cross-sectional, observational study. Cancer cachexia was diagnosed when there was weight loss ≥5% during the past 12 months and at least three of the five following conditions were present: decreased muscle strength, fatigue, anorexia, low Fat-Free Mass Index (FFMI) and abnormal laboratory findings. A quadratic discriminant analysis was conducted for the ability of PG-SGA to predict cachexia. A total of 4231 patients with cancer were included in this analysis, and 351 patients (8.3%) were diagnosed as having cachexia. The highest incidence of cachexia was found among patients with pancreatic cancer (32.5%), oesophageal cancer (21.5%) and gastric cancer (17.9%). Compared with patients without cachexia, patients with cachexia had a lower body mass index, FFMI, hand grip strength, total protein, prealbumin, albumin, haemoglobin and Karnofsky performance status (p<0.05), while they had a higher C reactive protein level and PG-SGA Score (4.71±3.71 vs 10.87±4.84, p<0.05). The best cut-off value for PG-SGA was 6.5, with 79.8% of sensitivity and 72.3% specificity for cachexia, and the area under the receiver operating characteristic curve was 0.846 (95% CI 0.826 to 0.866, p<0.001). PG-SGA is a highly specific tool that can be used to screen patients for cancer cachexia.


Kohn-Sham exchange-correlation potentials from second-order reduced density matrices.
We describe a practical algorithm for constructing the Kohn-Sham exchange-correlation potential corresponding to a given second-order reduced density matrix. Unlike conventional Kohn-Sham inversion methods in which such potentials are extracted from ground-state electron densities, the proposed technique delivers unambiguous results in finite basis sets. The approach can also be used to separate approximately the exchange and correlation potentials for a many-electron system for which the reduced density matrix is known. The algorithm is implemented for configuration-interaction wave functions and its performance is illustrated with numerical examples.


Tobacco-Derived and Tobacco-Free Nicotine cause differential inflammatory cell influx and MMP9 in mouse lung.
Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) have propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with both tobacco-derived nicotine (TDN) composed of S-nicotine and synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently there is limited knowledge of the potential differences in the toxicity of TFN vs TDN. We hypothesized that exposure of TFN salts to C57BL/6J mice will result in a differential response in inflammation and lung protease and antiprotease imbalance compared to TDN salts exposed mice. We studied the toxicological impact of these isomers by exposing mice to air, PG/VG, PG/VG with TFN salts, or PG/VG with TDN salts by nose-only exposure and measured the cytokine levels in BALF and lung homogenate along with MMP protein abundance in the lungs of exposed mice. Exposure to the humectants, PG/VG, used in e-cigarettes alone was able to increase cytokine levels- IL-6, KC, and MCP-1 in BALF and KC levels in lung homogenate. Further, it showed differential responses on exposure to PG/VG with TDN salts and PG/VG with TFN salts since PG/VG with TDN salts did not alter the cytokine levels in lung homogenate while PG/VG with TFN salts resulted in an increase in KC levels. PG/VG with TDN salts increased the levels of MMP9 protein abundance in female exposed mice, while PG/VG with TFN salts did not alter MMP9 levels in female mice. The metabolism of nicotine or the clearance of cotinine from TFN may differ from the metabolism of nicotine or the clearance of cotinine from TDN. Thus exposure of humectants alone to induce an inflammatory response while PG/VG with TFN salts and PG/VG with TDN salts may differentially alter inflammatory responses and lung proteases in acute exposures. These data suggest the harmful effects of synthetic/natural nicotine and PG/VG and potential toxicological risk for users.


Diagnosing lagophthalmos using artificial intelligence.
Lagophthalmos is the incomplete closure of the eyelids posing the risk of corneal ulceration and blindness. Lagophthalmos is a common symptom of various pathologies. We aimed to program a convolutional neural network to automatize lagophthalmos diagnosis. From June 2019 to May 2021, prospective data acquisition was performed on 30 patients seen at the Department of Plastic, Hand, and Reconstructive Surgery at the University Hospital Regensburg, Germany (IRB reference number: 20-2081-101). In addition, comparative data were gathered from 10 healthy patients as the control group. The training set comprised 826 images, while the validation and testing sets consisted of 91 patient images each. Validation accuracy was 97.8% over the span of 64 epochs. The model was trained for 17.3 min. For training and validation, an average loss of 0.304 and 0.358 and a final loss of 0.276 and 0.157 were noted. The testing accuracy was observed to be 93.41% with a loss of 0.221. This study proposes a novel application for rapid and reliable lagophthalmos diagnosis. Our CNN-based approach combines effective anti-overfitting strategies, short training times, and high accuracy levels. Ultimately, this tool carries high translational potential to facilitate the physician's workflow and improve overall lagophthalmos patient care.


A randomized trial of Parents Who Care: effects on key outcomes at 24-month follow-up.
This study was designed to test the efficacy of Parents Who Care (PWC), a seven-session universal prevention program which includes parenting, youth, and family components designed to prevent substance use and other problem behaviors. Using an intent-to-treat experimental design, this study tests the program efficacy across race within a balanced sample of European American (EA) and African American (AA) youth and their parents (n = 331 n AA = 163; n EA = 168). Families were recruited, randomly assigned to three conditions (group-administered [PA], self-administered with telephone support [SA], and no-treatment control) and the intervention was administered when the adolescents were in the eighth grade. Analyses on key teen outcomes of the Parent's Who Care program at 24-month follow-up are reported here and include perceptions of drug use harm; favorable attitudes about drug use; delinquent and violent behavior; and initiation into cigarette, alcohol, other drug use, or sexual activity. Repeated measures mixed model regressions found no effect of the intervention on rate of change in attitudes about drug use or frequency of delinquent or violent behavior. Regression analyses with multiple imputations for missing data detected group differences in means at 24-month follow-up. Both program formats reduced favorable attitudes toward drug use among youth (SA d = 0.39, PA d = 0.22); and AA youth in the self-administered intervention reported significantly less violent behavior than their control counterparts (d = 0.45). No effects were found for drug use harm or delinquency. Finally, logistic regression predicting a combined outcome measure of initiation of alcohol, tobacco, drug use, and/or sexual activity found AA youth in both the group- and self-administered intervention conditions significantly less likely to initiate substance use and/or sexual activity than those in the control condition. Odds ratios indicated the chances of initiating sex or substance use were reduced by almost 70% (OR = 0.31) for AA teens in the SA condition compared to controls, and 75% (OR = 0.25) for the AA teens in the PA compared to controls.


Intraocular management of endophthalmitis. A systematic approach.
Antibiotics were administered intravitreally to 26 patients with culture-verified endophthalmitis. Vitrectomy surgery was combined with intravitreal antibiotic therapy in 14 of the cases. Pretreatment selection into a vitrectomy or nonvitrectomy group was determined by the duration of the disease, type of predisposing injury, and echographic findings. This diagnostic-treatment grouping allowed management to be initiated on the basis of the existing and potential virulence of the infecting process. The less virulent and often successfully managed Staphylococcus epidermidis accounted for 67% of cases in the nonvitrectomy group and only 14% in the vitrectomized series. During a mean follow-up period of 32 months (range, one to five years), retinal changes were monitored by visual acuity determination, electroretinography, and fluorescein angiography. An overall visual improvement (greater than or equal to 20/400) was found in 73% of the eyes treated. The causes for failure in the remaining cases may be related to retinal damage from the initiating trauma, organism response, and intraocular antibiotic therapy.


Is a Transdisciplinary Theory of Engagement in Organized Settings Possible? A Concept Analysis of the Literature on Employee Engagement, Consumer Engagement and Patient Engagement.
Organizations are experiencing increased competition, disruptive innovation, and continuous changes in their social and economic context. Furthermore, the decrease of resources (economic and human) in such a demanding context make it imperative for organizations to find new models and strategies to make their service delivery more sustainable at the economic, environmental and psychological levels. In such a complex scenario the concept of engagement of the individuals involved in organized settings (either as service providers or as final receivers) is a promising lever for innovation. However, despite the number of studies on the matter, the debate on engagement is still very fragmented because the corpus of literature addressing the different areas of engagement is divided and diverse in its nature. In this paper, we discuss the results of a conceptual analysis of the literature conducted in order to investigate overlapping features and areas of divergence among three different areas of investigation and application of the engagement phenomenon in organized settings: the domains of employee engagement, consumer engagement, and patient engagement. These are deliberately selected as prototypical of the phenomenon of engagement along the "inside/outside" of organizational settings. The analysis consisted in a qualitative conceptual survey? Of the scholarly literature indexed with the key terms "employee engagement," "consumer engagement," and "patient engagement." We performed a key-word based survey? Of the literature in the Scopus database. A total of 163 articles were selected and analyzed. The analysis cast light on the following areas of conceptual overlap among employee, consumer and patient engagement: (1) engagement is different from empowerment and activation; (2) engagement is a multi-componential psychological experience; (3) engagement is a self-transformative experience; (4) engagement develops within a relational context; (5) engagement is a systemic phenomenon. These findings, although preliminary and in need of further investigation, suggest the feasibility of promoting a transdisciplinary reflection on the phenomenon of engagement in organized settings.


Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival.
Despite recent attention and impressive results with damage control resuscitation, the appropriate ratio of blood products to be transfused has yet to be defined. The purpose of this study was to evaluate whether suggested blood product ratios yield superior survival rates. After IRB approval, a retrospective evaluation was performed on all trauma exsanguination protocol (TEP, n = 118) activations from February 1, 2006 to July 31, 2007. A comparison cohort (pre-TEP, n = 140) was selected from all trauma admissions between August 1, 2004 and January 31, 2006 that (1) underwent immediate surgery by the trauma team and (2) received greater than 10 units of PRBC in the first 24 hours. We then compared those who received FFP:RBC (2:3) and platelet:RBC (1:5) ratios with those who did not reach these ratios. Multivariate analysis was performed for independent predictors of mortality. A total of 259 patients were available for study. Patients receiving FFP:RBC at a ratio of 2:3 or greater (n = 64) had a significant reduction in 30-day mortality compared with those who received less than a 2:3 ratio (n = 195); 41% versus 62%, p = 0.008. Patients receiving platelets:RBC at a ratio of 1:5 or greater (n = 63) had a lower 30-day mortality when compared with those with who received less than this ratio (n = 196); (38% vs. 61%, p = 0.001). Regression model demonstrated that a ratio of FFP to PRBC is an independent predictor of 30-day mortality, controlling for age and TRISS (OR 1.78, 95% CI 1.01-3.14). Increased FFP:PRBC and PLT:PRBC ratios during a period of massive transfusion improved survival after major trauma. Massive transfusion protocols should be designed to achieve these ratios to provide maximal benefit.


pH-responsive physical gels from poly(meth)acrylic acid-containing crosslinked particles: the relationship between structure and mechanical properties.
Gels that feature high internal porosity and have both high elasticity and ductility have potential to provide immediate load support and enable subsequent tissue regeneration of damaged soft tissue if combined with cells. Herein, we report results from a recent investigation of novel poly(methyl methacrylate-co-methacrylic acid), (PMMA-MAA) and poly(ethyl acrylate-co-methacrylic acid), (PEA-MAA) biodegradable, pH-sensitive particle gels which are with high porosity, elasticity and ductility. These gels formed at physiological pH range and are potentially injectable. The particles were prepared using solvent evaporation. They were functionalized by crosslinking the MAA groups of the particles via bis-amide formation with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP) which simultaneously incorporated reversibility due to the presence of disulphide bonds within the crosslinker. The crosslinked particles were observed by dynamic light scattering to swell appreciably in size upon increasing the pH. Concentrated dispersions formed elastic and ductile physical gels within the physiological pH range. A key finding of this study was that for crosslinked particles of similar composition the formation of considerably more elastic and ductile gels was observed from the most lightly crosslinked particles. Furthermore, compared to the PMMA-MAA/CYS and PEA-MAA/CYS gels, those formed from DTP-crosslinked particles had higher elasticity, thicker pore walls and improved interconnectivity. For the PMMA-MAA/DTP gels an elastic modulus value as high as 100 kPa and a yield strain greater than 100% were observed for a gel containing only 5 wt% of particles. The improved mechanical properties of these new gel-forming dispersions imply that they now have good potential for future application as injectable gels for regenerative medicine.


[Teaching neonatal resuscitation at public hospitals in Brazilian state capitals].
To analyze the teaching of neonatal resuscitation offered by Brazilian public hospitals to undergraduate doctors and nurses, pediatric residents and neonatal fellows. This cross-sectional multicenter study included 36 hospitals in 20 Brazilian State capitals during June/2003. Local coordinators collected data regarding what the institutions offer to undergraduate doctors and nurses, pediatric residents and neonatal fellows in terms of neonatal resuscitation training and practical activities in neonatal delivery room care. Descriptive analysis was performed. Twenty-three of the 36 institutions had undergraduate doctors: at 13 of them students had clinical activities in the delivery room, 12 offered neonatal resuscitation training, and at two of the 13 hospitals, interns cared for neonates in the delivery room without specific training. Twenty-three of the 36 hospitals had undergraduate nurses: at eight of them students had clinical activities in the delivery room and at seven of them nursing students cared for neonates in the delivery room without specific training. Twenty-seven of the 36 institutions had pediatric residence programs: at all of them, trained residents cared for neonates in the delivery room, but the training was heterogeneous: theoretical training (2-3 hours) at four institutions and theoretical and practical training (4-64 hours) at 23. Additionally, 15 had neonatal fellowship programs: at all of these, trained fellows cared for neonates in the delivery room, but the training was heterogeneous: theoretical training (2 hours) at one hospital and theoretical and practical training (3-68 hours) at 14. Formal neonatal resuscitation training is insufficient during medical and nursing graduation and heterogeneously offered to pediatric residents and neonatal fellows.


Tailored Planning of Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.


Endovascular renal denervation: a novel sympatholytic with relevance to chronic kidney disease.
Endovascular renal denervation (sympathectomy) is a novel procedure developed for the treatment of resistant hypertension. Evidence suggests that it reduces both afferent and efferent sympathetic nerve activity, which may offer clinical benefit over and above any blood pressure-lowering effect. Studies have shown objective improvements in left ventricular mass, ventricular function, central arterial stiffness, central haemodynamics, baroreflex sensitivity and arrhythmia frequency. Benefits have also been seen in insulin resistance, microalbuminuria and glomerular filtration rate. In chronic kidney disease, elevated sympathetic activity has been causally linked to disease progression and cardiovascular sequelae. Effecting a marked reduction in sympathetic hyperactivity may herald a significant step in the management of this and other conditions. In this in-depth review, the pathophysiology and clinical significance of the sympatholytic effects of endovascular renal denervation are discussed.