Bidirectional Droplet Manipulation on Magnetically Actuated Superhydrophobic Ratchet Surfaces.
Droplet manipulation has garnered significant attention in various fields due to its wide range of applications. Among many different methods, magnetic actuation has emerged as a promising approach for remote and instantaneous droplet manipulation. In this study, we present the bidirectional droplet manipulation on a magnetically actuated superhydrophobic ratchet surface. The surface consists of silicon strips anchored on elastomer ridges with superhydrophobic black silicon structures on the top side and magnetic layers on the bottom side. The soft magnetic properties of the strips enable their bidirectional tilting to form a ratchet surface and thus bidirectional droplet manipulation upon varying external magnetic field location and strength. Computational multiphysics models were developed to predict the tilting of the strips, demonstrating the concept of bidirectional tilting along with a tilting angle hysteresis theory. Experimental results confirmed the soft magnetic hysteresis and consequential bidirectional tilting of the strips. The superhydrophobic ratchet surface formed by the tilting strips induced the bidirectional self-propulsion of dispensed droplets through the Laplace pressure gradient, and the horizontal acceleration of the droplets was found to be positively correlated with the tilting angle of the strips. Additionally, a finite element analysis was conducted to identify the critical conditions for dispensed droplet penetration through the gaps between the strips, which hinder the droplet's self-propulsion. The models and findings here provide substantial insights into the design and optimization of magnetically actuated superhydrophobic ratchet surfaces to manipulate droplets in the context of digital microfluidic applications.


High prevalence of smoking among patients with suspected tuberculosis in South Africa.
There is growing evidence that tobacco smoking is an important risk factor for tuberculosis (TB). There are no data validating the accuracy of self-reported smoking in TB patients and limited data about the prevalence of smoking in TB patients from high-burden settings. We performed a cross-sectional analysis of 500 patients with suspected TB in Cape Town, South Africa. All underwent comprehensive diagnostic testing. The accuracy of their self-reported smoking status was determined against serum cotinine levels. Of the 424 patients included in the study, 56 and 60% of those with active and latent TB infection (LTBI), respectively, were current smokers. Using plasma cotinine as a reference standard, the sensitivity of self-reported smoking was 89%. No statistically significant association could be found between smoking and active TB or LTBI. In Cape Town, the prevalence of smoking among patients with suspected and confirmed TB was much higher than in the general South African population. Self-reporting is an accurate measure of smoking status. These results suggest the need to actively incorporate tobacco cessation programmes into TB services in South Africa.


2019 EULAR recommendations for the generic core competences of health professionals in rheumatology.
To maintain and optimise the quality of care provided by health professionals in rheumatology (HPRs), adequate educational offerings are needed. This task force (TF) aimed to develop evidence-based recommendations for the generic core competences of HPRs, with specific reference to nurses, physical therapists (PTs) and occupational therapists (OTs) to serve as a basis for their postgraduate education. The EULAR standardised operating procedures for the development of recommendations were followed. A TF including rheumatologists, nurses, PTs, OTs, patient-representatives, an educationalist, methodologists and researchers from 12 countries met twice. In the first TF meeting, 13 research questions were defined to support a systematic literature review (SLR). In the second meeting, the SLR evidence was discussed and recommendations formulated. Subsequently, level of evidence and strength of recommendation were assigned and level of agreement (LoA) determined (0-10 rating scale). Three overarching principles were identified and 10 recommendations were developed for the generic core competences of HPRs. The SLR included 79 full-text papers, 20 of which addressed the competences, knowledge, skills, attitudes and/or educational needs of HPRs from multiple professions. The average LoA for each recommendation ranged from 9.42 to 9.79. Consensus was reached both on a research and educational agenda. Evidence and expert opinion informed a set of recommendations providing guidance on the generic core competences of HPRs. Implementation of these recommendations in the postgraduate education of HPRs at the international and national level is advised, considering variation in healthcare systems and professional roles.


Empirical comparison of four baseline covariate adjustment methods in analysis of continuous outcomes in randomized controlled trials.
Although seemingly straightforward, the statistical comparison of a continuous variable in a randomized controlled trial that has both a pre- and posttreatment score presents an interesting challenge for trialists. We present here empirical application of four statistical methods (posttreatment scores with analysis of variance, analysis of covariance, change in scores, and percent change in scores), using data from a randomized controlled trial of postoperative pain in patients following total joint arthroplasty (the Morphine COnsumption in Joint Replacement Patients, With and Without GaBapentin Treatment, a RandomIzed ControlLEd Study [MOBILE] trials). Analysis of covariance (ANCOVA) was used to adjust for baseline measures and to provide an unbiased estimate of the mean group difference of the 1-year postoperative knee flexion scores in knee arthroplasty patients. Robustness tests were done by comparing ANCOVA with three comparative methods: the posttreatment scores, change in scores, and percentage change from baseline. All four methods showed similar direction of effect; however, ANCOVA (-3.9; 95% confidence interval [CI]: -9.5, 1.6; P=0.15) and the posttreatment score (-4.3; 95% CI: -9.8, 1.2; P=0.12) method provided the highest precision of estimate compared with the change score (-3.0; 95% CI: -9.9, 3.8; P=0.38) and percent change (-0.019; 95% CI: -0.087, 0.050; P=0.58). ANCOVA, through both simulation and empirical studies, provides the best statistical estimation for analyzing continuous outcomes requiring covariate adjustment. Our empirical findings support the use of ANCOVA as an optimal method in both design and analysis of trials with a continuous primary outcome.


Effect of Nurses' Work Experiences in a COVID-19 Unit on Depression: Mediation Effect of Resilience and Moderated Mediation Effect of Organizational Trust.
Nurses work with a lack of organizational support and perceive an unsafe environment from their organizations, which has been related to depression. This study aimed to investigate the effect of nurses' work experiences in a COVID-19 unit on their depression, the mediation effect of resilience, and the moderated mediation effect of organizational trust. Participants were 132 nurses working at a general hospital. Through questionnaires, data were collected during the COVID-19 pandemic and analyzed using SPSS 25.0 and SPSS PROCESS macro. Mean resilience was 2.15 ± 0.76; mean organizational trust was 3.03 ± 0.74; mean depression was 0.76 ± 0.63. 65.6% nurses with work experience in a COVID-19 unit had depression. Of the 27.2% nurses who showed moderate or higher levels of depression. Nurses' work experiences in a COVID-19 unit had a direct effect on depression and indirectly affected depression via resilience as a mediator. Resilience had a partial mediation effect, and organizational trust had a significant moderated mediation effect in the path from nurses' work experiences in a COVID-19 unit to depression mediated by resilience. This study emphasizes the key role that healthcare organizations play in providing sufficient support to nursing staff to protect them from depression by improving nurses' resilience and organizational trust during the pandemic. Healthcare organizations need to develop a systematic structure to provide organizational support to nurses so that the organizational trust and resilience of nurses can be maximized.


Diagnostic biomarkers for lung cancer prevention.
Lung cancer is the leading cause of death for neoplasm. Lung cancer mortality is frequently associated with late diagnosis, therefore an early diagnosis is a key factor to significantly improve overall survival in high risk populations of asymptomatic patients. Conventional cancer screenings (low-dose computed tomography or chest x-ray) today offer early detection but are invasive and expensive. Previously these studies evaluated the solid and topographic cancer structure and morphology. Today the concept of tumor has been remodelled, being defined as a disease that has its own genetic, biological and metabolic identity; it is on this new awareness that we should base new screening methods. Recent research has shown great reliability of new tests such as exhaled breath analysis, serum biomarkers and urine analysis in early diagnosis of lung cancer. Analysis of new biomarkers associated with the high specificity of these new screening methods, which are non-invasive, safe, inexpensive and simple to perform, could allow a non-invasive approach to determine a big change in the early diagnosis of cancer and its survival rate. Furthermore, these new techniques put the patient at the core of a non-invasive diagnostic process and ensure a better quality of life during medical diagnosis. In this article, we want to analyze the possible benefits of these new and promising methods, suggesting a possible combination between them to ensure, as soon as possible, an early and effective diagnosis of lung cancer with a special focus on the patient, in a new era of personalized medicine.


Transport signals and transcription-dependent nuclear localization of the putative DEAD-box helicase MDDX28.
The human protein MDDX28 is a putative RNA helicase and a nucleocytoplasmic shuttling protein also localized to the mitochondria. Its localization is novel among RNA helicases. We have studied its intracellular targeting signals and show that the first 20 amino acids of MDDX28 are necessary and sufficient for both mitochondrial import and nuclear export of the protein. Mutation of the five leucines in the sequence to alanines abolished the mitochondrial targeting signal as well as greatly reducing the nuclear export signal, indicating that these signal sequences are highly overlapping. Two short stretches of basic amino acids separated by 44 residues were both necessary and sufficient for full nuclear localization. However, they were not absolutely essential, because the protein was present in 7% of the nuclei when both signals were mutated. This indicates that MDDX28 contains another unidentified weak nuclear localization signal(s). Three basic domains in the N-terminal half of the protein and its RNA binding ability were essential for nucleolar localization as well as transcription-inhibition-dependent localization to nuclear subcompartments. Two of these basic domains were the same as those constituting the nuclear localization signal, suggesting that they are responsible for bringing the protein into the nucleus to the sites of RNA binding. Our results indicate that MDDX28 nucleo-cytoplasmic shuttling is dependent on the availability of nascent RNA.


[Project work: formation of health-care personnel for self-care of tunnelled central venous catheters in hemodialysis patients of the territory].
Scientific data from current literature demonstrate an incidence of bacteraemia due to tunnelled central venous catheter (tCVC) use accounting for 1.6 / 1000 days per tCVC, with a range of 1.5 to 1.8. In Sicily no data on the incidence of tCVC- related bacteraemia are available. In our hospital, tCVC infection occurs 2.4 times in 1000 days during CVC use. A retrospective analysis carried out from 2006 to 2012 was performed on 650 patients with tunnelled catheters. Of the subjects who received tCVC in our hospital, 90% were destined to undergo haemodialysis in a private health care environment outside our hospital. In order to improve the aforementioned infection outcome, we planned and implemented a specific work project. The work project (WP) was subdivided into two steps: 1) The first step was further subdivided into two sub-phases. The first was principally concerned with the implementation of educational courses, conducted directly on the ward and aimed at the implementation of meticulous nursing regimes for the care of tCVC by our health care nurse. The courses were entitled Management of Vascular Access: from doing - to teaching to do!. These educational courses were organized by the Nephrology Department, which takes care of the management and handling of the major complications of tCVCs for the maintenance of haemodialysis. After this first step, the nurses who had participated became the promoters of the second part of the course, which concerned the development of know-how within an outpatient clinic, which deals exclusively with the nursing management of tCVCs. 2) The title of the second phase was Therapeutic Education: self-Care and understanding and managing your venous access at home. The aim of this step was the integration of correct in-hospital care with that available in outsourced private institutions, via the involvement of the patient in the management of their own central venous access. During our training project, a more detailed analysis of the stakeholder as well as a swot analysis on the feasibility of the project were used to determine ad interim and final targets of the study. A summary of operative planning is included to explain in greater detail the study design, timing and costs of the various phases. Risk management and corrective measures adopted during the project are also mentioned and monitoring of the phases is described in relation to the fulfilling of intermediate goals. The prompt correction of mistakes allows for safer realisation of outcomes. From our experience with this work project, we can conclude that a more accurate management of tCVCs can significantly reduce the morbidity and mortality of patients. The project offers a positive cost-benefit balance through a decrease in costs of hospitalisation for tCVC-related infections and other life.threatening conditions related to the use of tCVCs an important goal for any spending review.


Antisense oligodeoxynucleotide to the Gi2 protein alpha subunit sequence inhibits an opioid-induced increase in the intracellular free calcium concentration in ND8-47 neuroblastoma x dorsal root ganglion hybrid cells.
In ND8-47 cells, a neuroblastoma x dorsal root ganglion hybrid cell line, activation of delta-opioid receptors induced an increase in the intracellular free calcium concentration ([Ca2+]i) through dihydropyridine-sensitive calcium channels. This effect was mediated by pertussis toxin-sensitive G proteins. The G protein alpha subunits alpha i2, alpha i3, alpha q, and alpha s were detected using Western blots, whereas alpha o and alpha i1 were not found in ND8-47 cell membranes. To identify the specific G protein alpha subunit(s) responsible for the increase in [Ca2+]i, we treated ND8-47 cells with antisense oligodeoxynucleotides (AS) complementary to the mRNA for each G protein alpha subunit (alpha i2, alpha i3, or alpha s), at a concentration of 10 microM, for up to 6 days and examined their effects on opioid-induced increases in [Ca2+]i and on the levels of G protein alpha subunits. [Ca2+]i was measured in adherent cells using the fluorescent dye fura-2. Treatment of cells with alpha i2-AS (10 microM, for 6 days) resulted in a 73% inhibition of the [D-Ser2,Leu5]-enkephalin-Thr-induced increase in [Ca2+]i. In contrast, pretreatment of cells with alpha i3-AS (10 microM, for 6 days) or alpha s-AS (10 microM, for 6 days) had no effect on the [D-Ser2,Leu5]-enkephalin-Thr-induced responses. Western blots indicated that the levels of alpha i2 were decreased when cells were exposed to alpha i2-AS (10 microM) for 6 days, whereas the levels of alpha i3, alpha s, and alpha q were not affected by this treatment. Treatment of the cells with alpha i3-AS or alpha s-AS for 6 days significantly reduced alpha i3 or alpha s levels, respectively. These results indicate that the opioid-induced increase in [Ca2+]i in ND8-47 cells is mediated by G alpha i2.


The pathogenesis and treatment of cardiac atrophy in cancer cachexia.
Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia.


The Biology of Vibrio vulnificus.
Vibrio vulnificus, carrying a 50% fatality rate, is the most deadly of the foodborne pathogens. It occurs in estuarine and coastal waters and it is found in especially high numbers in oysters and other molluscan shellfish. The biology of V. vulnificus, including its ecology, pathogenesis, and molecular genetics, has been described in numerous reviews. This article provides a brief summary of some of the key aspects of this important human pathogen, including information on biotypes and genotypes, virulence factors, risk factor requirements and the role of iron in disease, association with oysters, geographic distribution, importance of salinity and water temperature, increasing incidence associated with global warming. This article includes some of our findings as presented at the "Vibrios in the Environment 2010" conference held in Biloxi, MS.


Regulation of type VI secretion gene clusters by sigma54 and cognate enhancer binding proteins.
Type VI secretion systems (T6SS) are bacteriophage-derived macromolecular machines responsible for the release of at least two proteins in the milieu, which are thought to form an extracellular appendage. Although several T6SS have been shown to be involved in the virulence of animal and plant pathogens, clusters encoding these machines are found in the genomes of most species of gram-negative bacteria, including soil, marine, and environmental isolates. T6SS have been associated with several phenotypes, ranging from virulence to biofilm formation or stress sensing. Their various environmental niches and large diversity of functions are correlated with their broad variety of regulatory mechanisms. Using a bioinformatic approach, we identified several clusters, including those of Vibrio cholerae, Aeromonas hydrophila, Pectobacterium atrosepticum, Pseudomonas aeruginosa, Pseudomonas syringae pv. tomato, and a Marinomonas sp., which possess typical -24/-12 sequences, recognized by the alternate sigma factor sigma 54 (σ(54) or σ(N)). σ(54), which directs the RNA polymerase to these promoters, requires the action of a bacterial enhancer binding protein (bEBP), which binds to cis-acting upstream activating sequences. Putative bEBPs are encoded within the T6SS gene clusters possessing σ(54) boxes. Using in vitro binding experiments and in vivo reporter fusion assays, we showed that the expression of these clusters is dependent on both σ(54) and bEBPs.


Relationship between visceral adiposity index and male infertility.
The visceral adiposity index (VAI), which is calculated by using parameters such as body mass index (BMI), waist circumference, triglyceride, and high-density lipoprotein cholesterol, has been reported to be associated with visceral fat distribution and increased cardiometabolic risk. We aimed to investigate the relationship between the VAI and hormone profiles as well as semen analysis in male infertility. This retrospective study included 278 adult men that were admitted to the urology and endocrine outpatient clinics. Patient data were reviewed, and outcomes were recorded. BMI and VAI were calculated and noted separately. BMI was negatively correlated with serum testosterone and testosterone/ estradiol ratio (T/E2) (p < .05 for all). There was no significant relationship between BMI and semen parameters (p > .05 for all). However, there was a significant negative correlation between VAI and semen parameters, total serum testosterone and T/E2 (p < .05 for all). Furthermore, VAI was independently associated with the total motility score. The increase in visceral adiposity that can be demonstrated by VAI may adversely affect male fertility due to its metabolic and hormonal effects. Since infertility occurs as a result of different metabolic conditions, the underlying mechanisms can be better understood from a multidisciplinary perspective.


Sec-mediated secretion by Coxiella burnetii.
Coxiella burnetii is a Gram-negative intracellular bacterial pathogen that replicates within a phagolysosome-like parasitophorous vacuole (PV) of macrophages. PV formation requires delivery of effector proteins directly into the host cell cytoplasm by a type IVB secretion system. However, additional secretion systems are likely responsible for modification of the PV lumen microenvironment that promote pathogen replication. To assess the potential of C. burnetii to secrete proteins into the PV, we analyzed the protein content of modified acidified citrate cysteine medium for the presence of C. burnetii proteins following axenic (host cell-free) growth. Mass spectrometry generated a list of 105 C. burnetii proteins that could be secreted. Based on bioinformatic analysis, 55 proteins were selected for further study by expressing them in C. burnetii with a C-terminal 3xFLAG-tag. Secretion of 27 proteins by C. burnetii transformants was confirmed by immunoblotting culture supernatants. Tagged proteins expressed by C. burnetii transformants were also found in the soluble fraction of infected Vero cells, indicating secretion occurs ex vivo. All secreted proteins contained a signal sequence, and deletion of this sequence from selected proteins abolished secretion. These data indicate protein secretion initially requires translocation across the inner-membrane into the periplasm via the activity of the Sec translocase. C. burnetii secretes multiple proteins, in vitro and ex vivo, in a Sec-dependent manner. Possible roles for secreted proteins and secretion mechanisms are discussed.


Quality assurance assessment of a specialized perinatal mental health clinic.
Mood and anxiety issues are the main mental health complaints of women during pregnancy and the postpartum period. Services targeting such women can reduce perinatal complications related to psychiatric difficulties. This quality assurance project aimed to examine changes in mood and anxiety symptoms in pregnant and postpartum women referred to the Women's Health Concerns Clinic (WHCC), a specialized outpatient women's mental health program. We extracted patient characteristics and service utilization from electronic medical records of women referred between 2015 and 2016. We also extracted admission and discharge scores on the Edinburgh Postnatal Depression Scale (EPDS) and the Generalized Anxiety Disorder-7 (GAD-7) scale. Most patients accessed the WHCC during pregnancy (54%), had a diagnosis of major depressive disorder (54.9%), were prescribed a change in their medication or dose (61.9%), and accessed psychotherapy for perinatal anxiety (30.1%). There was a significant decrease in EPDS scores between admission and discharge (t(214) = 11.57; p = .000; effect size d = .86), as well as in GAD-7 scores (t(51) = 3.63; p = .001; effect size d = .61). A secondary analysis showed that patients with more severe depression and anxiety symptoms demonstrated even greater effect sizes. Changes in EPDS and GAD-7 scores indicate that the WHCC is effective in reducing mood and anxiety symptoms associated with the perinatal period. This project highlights the importance of quality assurance methods in evaluating the effectiveness of clinical services targeting perinatal mental health, in order to inform policy and funding strategies.


Screening children for sickle cell vasculopathy: guidelines for transcranial Doppler evaluation.
Cerebral infarction is a major cause of morbidity and mortality in children with sickle cell disease. Prevention of primary stroke might be feasible with a way to identify children at greatest risk. Transcranial Doppler (TCD) has been shown to be a noninvasive, reliable, inexpensive method of identifying children at highest risk for cerebral infarction. The pros and cons of imaging and non-imaging TCD techniques are discussed. The protocol for the stroke prevention trial in sickle cell anemia (STOP), including data acquisition and interpretation, is reviewed. Providing TCD to sickle cell patients can be a valuable service that results in a significant decrease in first stroke rates.


Structural Basis of Reduced Susceptibility to Ceftazidime-Avibactam and Cefiderocol in Enterobacter cloacae Due to AmpC R2 Loop Deletion.
Ceftazidime-avibactam and cefiderocol are two of the latest generation β-lactam agents that possess expanded activity against highly drug-resistant bacteria, including carbapenem-resistant Enterobacterales Here, we show that structural changes in AmpC β-lactamases can confer reduced susceptibility to both agents. A multidrug-resistant Enterobacter cloacae clinical strain (Ent385) was found to be resistant to ceftazidime-avibactam and cefiderocol without prior exposure to either agent. The AmpC β-lactamase of Ent385 (AmpCEnt385) contained an alanine-proline deletion at positions 294 and 295 (A294_P295del) in the R2 loop. AmpCEnt385 conferred reduced susceptibility to ceftazidime-avibactam and cefiderocol when cloned into Escherichia coli TOP10. Purified AmpCEnt385 showed increased hydrolysis of ceftazidime and cefiderocol compared to AmpCEnt385Rev, in which the deletion was reverted. Comparisons of crystal structures of AmpCEnt385 and AmpCP99, the canonical AmpC of E. cloacae complex, revealed that the two-residue deletion in AmpCEnt385 induced drastic structural changes of the H-9 and H-10 helices and the R2 loop, which accounted for the increased hydrolysis of ceftazidime and cefiderocol. The potential for a single mutation in ampC to confer reduced susceptibility to both ceftazidime-avibactam and cefiderocol requires close monitoring.


Destruction and recovery of a nanorod conductive network in polymer nanocomposites via molecular dynamics simulation.
By adopting coarse-grained molecular dynamics simulation, we investigate the effects of end-functionalization and shear flow on the destruction and recovery of a nanorod conductive network in a functionalized polymer matrix. We find that the end-functionalization of polymeric chains can enhance the electrical conductivity of nanorod filled polymer nanocomposites, indicated by the decrease of the percolation threshold. However, there exists an optimal end-functionalization extent to reach the maximum electrical conductivity. In the case of steady shear flow, both homogeneous conductive probability and directional conductive probability perpendicular to the shear direction decrease with the shear rate, while the directional conductive probability parallel to the shear direction increases. Importantly, we develop a semi-empirical equation to describe the change of the homogeneous conductive probability as a function of the shear rate. Meanwhile, we obtain an empirical formula describing the relationship between the anisotropy of the conductive probability and the orientation of the nanorods. In addition, the conductivity stability increases with increasing nanorod volume fraction. During the recovery process of the nanorod conductive network, it can be fitted well by the model combining classical percolation theory and a time-dependent nanorod aggregation kinetic equation. The fitted recovery rate is similar for different nanorod volume fractions. In summary, this work provides some rational rules for fabricating polymer nanocomposites with excellent performance of electrical conductivity.


Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity.
The 'immune risk profile' has been shown to predict mortality in the elderly, highlighting the need to better understand age-related immune dysfunction. While aging leads to many defects affecting all arms of the immune system, this review is focused on the accrual of immuno-suppressive CD4 + T cell populations, including FoxP3 + regulatory T cells, and subsets of IL-10-producing T follicular helper cells. New data suggest that such accumulations constitute feedback mechanisms to temper the ongoing progressive low-grade inflammation that develops with age, the so-called "inflammaging", and by doing so, how they have the potential to promote healthier aging. However, they also impair effector immune responses, notably to infections, or vaccines. These studies also reinforce the idea that the aged immune system should not be considered as a poorly functional version of the young one, but more as a dynamic system in which CD4 + T cells, and other immune/non-immune subsets, differentiate, interact with their milieu and function differently than in young hosts. A better understanding of these unique interactions is thus needed to improve effector immune responses in the elderly, while keeping inflammaging under control.


Social signal manipulation and environmental challenges have independent effects on physiology, internal microbiome, and reproductive performance in tree swallows (Tachycineta bicolor).
The social environment that individuals experience appears to be a particularly salient mediator of stress resilience, as the nature and valence of social interactions are often related to subsequent health, physiology, microbiota, and overall stress resilience. Relatively few studies have simultaneously manipulated the social environment and ecological challenges under natural conditions. Here, we report the results of experiments in wild tree swallows (Tachycineta bicolor) in which we manipulated both ecological challenges (predator encounters and flight efficiency reduction) and social interactions (by experimental dulling of a social signal). In two experiments conducted in separate years, we reversed the order of these treatments so that females experienced either an altered social signal followed by a challenge or vice-versa. Before, during, and after treatments were applied, we tracked breeding success, morphology and physiology (mass, corticosterone, and glucose), nest box visits via an RFID sensor network, cloacal microbiome diversity, and fledging success. Overall, we found that predator exposure during the nestling period reduced the likelihood of fledging and that signal manipulation sometimes altered nest box visitation patterns, but little evidence that the two categories of treatment interacted with each other. We discuss the implications of our results for understanding what types of challenges and what conditions are most likely to result in interactions between the social environment and ecological challenges.


Morpho-molecular signal correlation between optical coherence tomography and Raman spectroscopy for superior image interpretation and clinical diagnosis.
The combination of manifold optical imaging modalities resulting in multimodal optical systems allows to discover a larger number of biomarkers than using a single modality. The goal of multimodal imaging systems is to increase the diagnostic performance through the combination of complementary modalities, e.g. optical coherence tomography (OCT) and Raman spectroscopy (RS). The physical signal origins of OCT and RS are distinctly different, i.e. in OCT it is elastic back scattering of photons, due to a change in refractive index, while in RS it is the inelastic scattering between photons and molecules. Despite those diverse characteristics both modalities are also linked via scattering properties and molecular composition of tissue. Here, we investigate for the first time the relation of co-registered OCT and RS signals of human bladder tissue, to demonstrate that the signals of these complementary modalities are inherently intertwined, enabling a direct but more importantly improved interpretation and better understanding of the other modality. This work demonstrates that the benefit for using two complementary imaging approaches is, not only the increased diagnostic value, but the increased information and better understanding of the signal origins of both modalities. This evaluation confirms the advantages for using multimodal imaging systems and also paves the way for significant further improved understanding and clinically interpretation of both modalities in the future.


Insulin and leptin relations in obesity: a multimedia approach.
Obesity has been recognized as a worldwide public health problem. It significantly increases the chances of developing several diseases, including Type II diabetes. The roles of insulin and leptin in obesity involve reactions that can be better understood when they are presented step by step. The aim of this work was to design software with data from some of the most recent publications on obesity, especially those concerning the roles of insulin and leptin in this metabolic disturbance. The most notable characteristic of this software is the use of animations representing the cellular response together with the presentation of recently discovered mechanisms on the participation of insulin and leptin in processes leading to obesity. The software was field tested in the Biochemistry of Nutrition web-based course. After using the software and discussing its contents in chatrooms, students were asked to answer an evaluation survey about the whole activity and the usefulness of the software within the learning process. The teaching assistants (TA) evaluated the software as a tool to help in the teaching process. The students' and TAs' satisfaction was very evident and encouraged us to move forward with the software development and to improve the use of this kind of educational tool in biochemistry classes.


pH-Controlled assembly of two novel Dawson-sandwiched clusters involving the in situ reorganization of trivacant α-[P2W15O56](12-) into divacant α-[P2W16O57](8.).
Modified classical trivacant Wells-Dawson α-[P2W15O56](12-) and the assembly of related sandwiched transition metal clusters are of interest, but surprisingly few reports of these materials exist because of the sensitivity of α-[P2W15O56](12-) to the assembly environment. Herein, we describe the pH-controlled assembly of two novel Dawson-sandwiched clusters, (H2bpz)6[Co2(P2W16O57)2]·22H2O (1, bpz = 3,3',5,5'-tetramethyl-4,4'-bipyrazole) and (H2bpz)6[Co3H2(P2W16O57)(P2W15O56)(H2O)]·12H2O (2), involving the in situ transformation of α-[P2W15O56](12-). Both clusters were characterized by X-ray single-crystal diffraction, FT-IR spectroscopy, UV-Visible spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and elemental analyses. X-ray crystallography showed that both heteropolytungstates become divacant α-[P2W16O57](8-) and symmetrically encapsulate two edge-shared CoO6 octahedra in the interior in 1, while only one divacant α-[P2W16O57](8-) is observed in 2, which combined with another trivacant α-[P2W15O56](12-) to asymmetrically clamp three edge-shared CoO6 octahedra. The α-[P2W16O57](8-) heteropolytungstate should be generated in situ from α-[P2W15O56](12-)via self-decomposition equilibria in solution. Their electrochemical behaviors reveal characteristic multi-electron redox processes related to W(VI) centers. The electrocatalytic reduction performances toward nitrite, hydrogen peroxide, chlorate, bromate and iodate were fully measured and discussed; among these species, both clusters exhibit the best electrocatalytic activity towards the reduction of bromate. Magnetic measurements indicate weak ferromagnetic exchange interactions between Co atoms sandwiched by vacant polyoxometalates.


NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL.
Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive. Here we evaluated whether NG2 distinguishes leukemia-initiating/propagating cells (L-ICs) and/or CNS-infiltrating cells (CNS-ICs) in iMLLr-B-ALL. Clinical data from the Interfant cohort of iMLLr-B-ALL demonstrated that high NG2 expression associates with lower event-free survival, higher number of circulating blasts and more frequent CNS disease/relapse. Serial xenotransplantation of primary MLL-AF4+ leukemias indicated that NG2 is a malleable marker that does not enrich for L-IC or CNS-IC in iMLLr-B-All. However, NG2 expression was highly upregulated in blasts infiltrating extramedullar hematopoietic sites and CNS, and specific blockage of NG2 resulted in almost complete loss of engraftment. Indeed, gene expression profiling of primary blasts and primografts revealed a migratory signature of NG2+ blasts. This study provides new insights on the biology of NG2 in iMLLr-B-ALL and suggests NG2 as a potential therapeutic target to reduce the risk of CNS disease/relapse and to provide safer CNS-directed therapies for iMLLr-B-ALL.


Improved proliferation and differentiation capacity of human mesenchymal stromal cells cultured with basement-membrane extracellular matrix proteins.
In vitro cultured mesenchymal stromal cells (MSC) are characterized by a short proliferative lifespan, an increasing loss of proliferation capacity and progressive reduction of differentiation potential. Laminin-1, laminin-5, collagen IV and fibronectin are important constituents of the basement membrane extracellular matrix (ECM) that are involved in a variety of cellular activities, including cell attachment and motility. The in vitro proliferation capacity of MSC was significantly improved when the cells were incubated in the presence of basement membrane ECM proteins. For example, a mixture of proteins improved proliferation capacity 250-fold in comparison with standard conditions after five passages. Furthermore, in colony-forming unit-fibroblast (CFU-F) assays colony numbers and size were significantly extended. Blocking specific integrin cell-surface receptors, positive effects on the proliferation capacity of MSC were inhibited. Additionally, when MSC were co-cultivated with ECM proteins, cells maintained their multipotential differentiation capacity throughout many culture passages in comparison with cells cultivated on plastic. However, expansion of MSC on laminin-5 suppressed any subsequent chondrogenic differentiation. Our results suggest that expansion of bone marrow-derived MSC in the presence of ECM proteins is a powerful approach for generating large numbers of MSC, showing a prolonged capacity to differentiate into mesodermal cell lineages, with the exception of the lack of chondrogenesis by using laminin-5 coating.


Rigid nasal endoscopy in the diagnosis and treatment of epistaxis.
Epistaxis is one of the common symptoms encountered in the Otorhinolaryngology department. Many times the cause for epistaxis is not found on anterior and posterior rhinoscopy. The present study was undertaken to assess the role of rigid nasal endoscope in the diagnosis and treatment of epistaxis, where normal anterior and posterior rhinoscopy did not reveal any specific finding. Fifty patients with epistaxis were studied using rigid nasal endoscope under local anaesthesia. Patients who were above 15 years with nasal bleeding and who were willing for rigid nasal endoscopy were included in the study. Patients less than 15 years were not included in the study because nasal endoscopy was difficult in them under local anaesthesia. Only those patients in whom, the cause for epistaxis could not be made out on anterior and posterior rhinoscopy were chosen for the study, this was done in order to remove the bias for nasal endoscopy. The use of the nasal endoscope allowed diagnosis of bleeding points and treating them directly. Epistaxis was more in male patients especially in the 3rd and after the 5th decade. On endoscopic examination,the bleeding points were identified as coming from the crevices of the lateral nasal wall, posterior spur on the septum, posterior deviation of the septum with ulcer, congested polyps, enlarged and congested adenoids, scabs or crusts in the crevices of the lateral nasal wall and angiofibroma. Endoscope also helps in the treatment of epistaxis, which includes endoscopic selective nasal packing using gelfoam, endoscopic cautery or diathermy and endoscopic polypectomy. Other patients with adenoids, scabs and crusts and angiofibroma were managed on their merits. Nasal endoscopy helps not only in the localisation of the bleeding point but also in the treatment of those bleeding areas that are situated in the posterior and lateral part of the nose.


In Vitro Phagocytosis of Different Dinoflagellate Species by Coral Cells.
Coral-dinoflagellate symbiosis is a unique biological phenomenon, in which animal cells engulf single-celled photosynthetic algae and maintain them in their cytoplasm mutualistically. Studies are needed to reveal the complex mechanisms involved in symbiotic processes, but it is difficult to answer these questions using intact corals. To tackle these issues, our previous studies established an in vitro system of symbiosis between cells of the scleractinian coral Acropora tenuis and the dinoflagellate Breviolum minutum, and showed that corals direct phagocytosis, while algae are likely engulfed by coral cells passively. Several genera of the family Symbiodiniaceae can establish symbioses with corals, but the symbiotic ratio differs depending on the dinoflagellate clades involved. To understand possible causes of these differences, this study examined whether cultured coral cells show phagocytotic activity with various dinoflagellate strains similar to those shown by intact A. tenuis. We found that (a) A. tenuis larvae incorporate Symbiodinium and Breviolum, but not Cladocopium, and very few Effrenium, (b) cultured coral cells engulfed all four species but the ratio of engulfment was significantly higher with Symbiodinium and Breviolum than Cladocopium and Effrenium, (c) cultured coral cells also phagocytosed inorganic latex beads differently than they do dinoflagellates . It is likely that cultured coral cells preferentially phagocytose Symbiodinium and Breviolum, suggesting that specific molecular mechanisms involved in initiation of symbiosis should be investigated in the future.


Gli3-deficient mice exhibit cleft palate associated with abnormal tongue development.
Palatogenesis depends on appropriate growth, elevation, and fusion of the palatal shelves and aberration in these processes can lead to palatal clefting. We observed a high incidence of palate clefting in mice deficient in Gli3, known for its role as a repressor in the absence of Shh signaling. In contrast with several current mouse models of cleft palate, Meckel's cartilage extension, cranial neural crest migration, palatal shelf proliferation, apoptosis, and key signaling components mediated by Shh, Bmp, Fgf, and Tgfbeta, appeared unaffected in Gli3-/- mice. Palatal clefting in Gli3-/- mice was consistently associated with tongue abnormalities such as failure to flatten and improper positioning, implicating a critical role of Gli3 and normal tongue morphogenesis for timely palatal shelf elevation and joining. Furthermore, Gli3-/- palatal shelves grown in roller cultures without tongue can fuse suggesting that the abnormal tongue is likely an impediment for palatal shelf joining in Gli3-/- mutants.


[Radical treatment of invasive bladder cancer].
We have conducted a retrospective analysis of radical cystectomy in 53 patients (45 males and 8 females, 85 and 15%, respectively) with invasive bladder cancer (BC) treated in the Research Institute of Urology in 1997-2002. Stages T2N0M0, pT3aN0M0, T3bN0M0, pT4aN0M0, pT4aN1-2M0 were in 4 (7.5%), 13 (25%), 21 (40%), 7 (12.5%), 8 (15%) cases, respectively. Well differentiated transitional cell BC (G1) was detected in 1 (2%) patient, moderately differentiated (G2) in 16 (30%) cases, poorly differentiated (G3) in 36 (68%) patients. The following methods of urine derivation were used: orthotopic plastic surgery (n = 3, 6%), ureterocutaneostomy (n = 4, 8%), Mainz pouch II operation (n = 16, 30%), Hassan operation (n = 5, 9%), Bricker procedure (n = 22, 44%), transureteroanastomosis (n = 3, 6%). In the postoperative period there was one lethal outcome, early complications in 5 (9%) patients, late complications in 9 (17%) patients. Distant metastases to the lungs, bones and iliac lymph nodes after treatment were detected in 3, 2 and 3 patients, respectively. One patient had a local pelvic recurrence. For 53 patients 2-year corrected survival was 68 +/- 12.0%. We have come to the conclusion that the only radical surgical treatment of invasive BC is cystectomy, limitations to which are connected only with complexity of subsequent urine derivation.


Optimizing research methods used for the evaluation of antimicrobial stewardship programs.
Antimicrobial stewardship programs (ASPs) are an increasingly common intervention for optimizing antimicrobial therapy in healthcare settings. These programs aim to improve patient care and limit the emergence and spread of multidrug-resistant organisms by supporting prudent antimicrobial use. However, pressure from the current reimbursement climate necessitates that ASPs operate as cost-cutting programs rather than focus on patient outcomes. This has forced the research that is evaluating ASP interventions to concentrate heavily on economic outcomes. As the science of antimicrobial stewardship advances, it is essential that well-conducted evaluations, focused on patient and microbial outcomes, serve as the evidence base that directs optimal ASP intervention design and implementation. In this review, we provide guidance and recommendations for the design of studies to evaluate the impact of ASP interventions on patient and microbial outcomes.


Uveal melanoma survival in Sweden from 1960 to 1998.
To investigate the crude and relative survival rates in patients with uveal melanoma in Sweden during the period from 1960 to 1998. A population-based national survey revealed 2997 cases of uveal melanoma in the Swedish Cancer Registry. The survival rates were calculated by the Hakulinen life-table method, using relative survival as an estimate for deaths due to uveal melanoma. The excess mortality rates were calculated with confidence intervals for the first 15 years after diagnosis. Multivariate regression analysis was undertaken to evaluate the influence of gender, age, and calendar period on relative survival the first 5 years after diagnosis. The underlying causes of deaths in the patients with uveal melanoma, as found in the Cause of Death Registry were also investigated. Up to December 31, 1998, 2003 patients had died. The 5-year crude survival rate was 60.3% and the relative survival 70.1%. After 10 years, the rates were 42.5% and 59.4%, respectively. Significant excess mortality existed up to 5.5 years after diagnosis. In the multivariate model, younger age (P < 0.001) and later calendar period (P = 0.002), but not gender (P = 0.117), were associated with better relative survival. Deaths due to uveal melanoma were misclassified in the Cause of Death Registry in more than half of the cases. This study, covering more than 95% of the uveal melanoma cases in the Swedish population revealed an improvement in relative survival rates for patients with uveal melanoma over time and a significant excess mortality up to 5.5 years after diagnosis.


Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage.
The epidermis is a highly regenerative barrier protecting organisms from environmental insults, including UV radiation, the main cause of skin cancer and skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and alters the amplitude of the skin circadian clock and affects the expression of approximately 10% of the skin transcriptome. Furthermore, a large number of skin-expressed genes are acutely regulated by food intake. Although the circadian clock is required for daily rhythms in DNA synthesis in epidermal progenitor cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis. However, RF alters both diurnal sensitivity to UVB-induced DNA damage and expression of the key DNA repair gene, Xpa. Together, our findings indicate regulation of skin function by time of feeding and emphasize a link between circadian rhythm, food intake, and skin health.


Rethinking access for minority segments in rural health: An LGBTQI+ perspective.
This paper nuances the notion of access when considering minority segments and their use of health care services in rural communities. It argues that access needs to be considered as both the availability and the perceived ability to use a service without fear of retribution. By taking such a stance, this paper addresses the inequality in LGBTQI+ care in rural communities. It claims equitable care can only be achieved if the appropriate environment is created where individuals can disclose their identity and seek appropriate treatment. Given the complexity surrounding rural communities, their prevailing culture and perceptions, as well as stigmas and poor health outcome, a multilevel approach is taken to identify implications. It is argued that to address the individual and systemic barriers to equitable health care, a human rights-centred approach to health needs to be adopted considering the individual, the community and the health system.


Surgical Versus Noninvasive Manual Repositioning After Cochlear Implant Partial Magnet Dislocation.
Objectives: To compare surgical magnet repositioning (SMR) and noninvasive manual magnet repositioning (MMR) as treatments for partial magnet dislocation (PMD) of the internal magnet in a cochlear implant (CI) caused by magnetic resonance imaging (MRI). The primary objective was the success rate, while the secondary objectives were total postinterventional CI downtime and complications. Methods: This single-center retrospective study was conducted at a tertiary referral medical center. Patients with CI treated for PMD between January 1, 2007 and September 30, 2022 were included. SMR served as primary treatment until June 2019 and as secondary treatment after the introduction of MMR. Results: A total of 51 cases of PMD were observed in 42 patients and 43 devices (18 ♀; 24 ♂; 12 with bilateral CI). MMR was performed successfully in 19 out of 20 cases (95%), while 32 cases were managed successfully by SMR. The median age at first magnet repositioning was 53.8 years (minimum 19 years, maximum 93 years). When MMR was performed, the mean time from diagnosis to treatment (0.5 ± 1.5 days vs 9.8 ± 7.6 days; P < .01), the mean time from repositioning to CI reactivation (1.4 ± 4.3 days vs 13.1 ± 6.7 days; P < .01), and the mean total CI downtime (1.9 ± 4.8 days vs 22.9 ± 11.9 days; P < .01) were significantly shorter compared to SMR. Significantly fewer complications were experienced with MMR [n = 0 (0%) vs n = 8 (25%); P = .04]. Conclusion: In case of PMD caused by MRI, noninvasive MMR shows a high success rate with a shorter total CI downtime as well as a lower complication rate compared to SMR. Therefore, MMR should be considered as first line treatment with SMR as a second option in case of failure.


Nerve growth factor and vascular endothelial growth factor: retrospective analysis of 63 patients with salivary adenoid cystic carcinoma.
To detect the expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in salivary adenoid cystic carcinoma (SACC) tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox's proportional hazard regression model were applied to assess predictors of survival. NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues (P < 0.05), and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high-expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates (P < 0.05). NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent


Development of a new genotyping assay for detection of the BDNF Val66Met polymorphism using melting-curve analysis.
Brain-derived neurotrophic factor (BDNF) plays a critical role in the growth, differentiation and survival of neurons in the CNS. Recent research has suggested that BDNF may be implicated in the etiology of mood disorders and schizophrenia, as well as in the therapeutic action of some drugs, such as antidepressants and antipsychotics. This study aimed to develop a simple, fast and accurate new method for detecting the Val66Met polymorphism of the BDNF gene in schizophrenia patients using melting-curve analysis and a DNA-specific dye, SYBR Green I. A group of 30 schizophrenia patients were analyzed to detect the BDNF Val66Met polymorphism (rs6265) using the new genotyping method based on the analysis of fluorescence melting curves of PCR products that were labeled with SYBR Green I. The genotype results were confirmed for all 30 samples using the specific BDNF TaqMan allele discrimination assay. This new method allows the analysis of both alleles in the same reaction tube using SYBR Green I, with no need for additional steps. The addition of a GC clamp makes this method universally applicable, since the melting temperature of one allele can be adjusted as necessary to give the distinctive separation of melting curves. Therefore, this new method is simple, fast and accurate for determining the presence of the BDNF Val66Met polymorphism. It may also be useful for the analysis of other SNPs in pharmacogenetic studies.


Noninferiority Studies with Multiple New Treatments and Heterogeneous Variances.
The objective of a noninferiority (NI) trial is to affirm the efficacy of a new treatment compared with an active control by verifying that the new treatment maintains a considerable portion of the treatment effect of the control. Compensation by benefits other than efficacy is usually the justification for using a new treatment, as long as the loss of efficacy is within an acceptable margin (NI margin) from the standard treatment. A popular approach is to express this margin in terms of the efficacy difference between the new treatment and the active control. Based on this approach and the realization that NI trials often comprise several new treatments, statistical procedures that simultaneously conduct NI tests of several new treatments have been developed. However, these procedures rely on the assumption that the variances of the treatments are homogeneous. In this article, we discuss the undesirable effect of using these procedures on the familywise Type I error rate when the treatment responses have heterogeneous variances. To alleviate this problem, we reveal potential procedures that are more appropriate. Further, a power study is conducted to compare the different procedures to provide guidance on the selection of adequate testing procedures in NI trials. Clinical examples are given for illustrative purposes.


Epidermolytic ichthyosis in a dog: clinical, histopathological, immunohistochemical and ultrastructural findings.
Epidermolytic hyperkeratosis (EH) in man is a complex of congenital, ichthyosiform skin diseases characterized clinically by blistering and hyperkeratosis. These clinical signs are the result of a collapse of the cytoskeleton, seen ultrastructurally as tonofilament clumping and cytolysis within terminally differentiating epidermal cells. In man, specific mutations in keratin 1, 2e, 9 or 10 underlie the various types of EH. This report describes the clinical, histopathological, immunohistochemical and ultrastructural findings in a 6-month-old dog with severe multifocal hyperkeratosis. The morphological changes were comparable with those of EH in man, indicating that this disease, presumably with a similar underlying pathogenetic mechanism, also occurs in the dog.


Cadmium and manganese accumulation in Phytolacca americana L. and the roles of non-protein thiols and organic acids.
Phytolacca americana L. can accumulate large amounts of heavy metals in its aerial tissues, especially cadmium (Cd) and manganese (Mn). It has great potential for use in phytoextraction of metals from multi-metal-contaminated soils. This study was conducted to further investigate the Cd- and Mn-tolerance strategies of this plant. Concentrations of non-protein thiols (NPTs) and phytochelatins (PCs) in leaves and roots increased significantly as the concentration of Cd in solution increased. The molar ratios of PCs:soluble Cd ranged from 1.8 to 3.6 in roots and 8.1 to 31.6 in leaves, suggesting that the cellular response involving PC synthesis was sufficient to complex Cd ions in the cytosol, especially that of leaves. In contrast, excess Mn treatments did not result in a significant increase in NPT or PC concentrations in leaves or roots. Oxalic acid concentrations in leaves of plants exposed to 2 or 20 mM Mn reached 69.4 to 89.3 mg (0.771 to 0.992 mmol) g(-1) dry weight, respectively, which was approximately 3.7- to 8.6-fold higher than the Mn level in the 0.6 M HCl extract. Thus, oxalic acid may play an important role in the detoxification of Mn.


Coinfection with Borrelia burgdorferi sensu stricto and Borrelia garinii alters the course of murine Lyme borreliosis.
Ixodes ricinus ticks and mice can be infected with both Borrelia burgdorferi sensu stricto and Borrelia garinii. The effect of coinfection with these two Borrelia species on the development of murine Lyme borreliosis is unknown. Therefore, we investigated whether coinfection with the nonarthritogenic B. garinii strain PBi and the arthritogenic B. burgdorferi sensu stricto strain B31 alters murine Lyme borreliosis. Mice simultaneously infected with PBi and B31 showed significantly more paw swelling and arthritis, long-standing spirochetemia, and higher numbers of B31 spirochetes than did mice infected with B31 alone. However, the number of PBi spirochetes was significantly lower in coinfected mice than in mice infected with PBi alone. In conclusion, simultaneous infection with B. garinii and B. burgdorferi sensu stricto results in more severe Lyme borreliosis. Moreover, we suggest that competition of the two Borrelia species within the reservoir host could have led to preferential maintenance, and a rising prevalence, of B. burgdorferi sensu stricto in European I. ricinus populations.


Hydrogen sulfide exposure at a waste treatment facility.
Occupational Safety and Health Administration (OSHA) regulations require employers to report workplace-related fatalities.((1)) OSHA inspection policy and procedures require that a workplace fatality or workplace hazards with potential imminent danger receive the highest priority for inspection.((2)) This inspection began on a Saturday when a local fire department advised the OSHA area office of a workplace fatality. The fire department also reported that the death was due to natural causes, based on a county coroner's report that stated the worker had died from a heart attack. Under normal circumstances OSHA begins a workplace fatality investigation within one day of notification. Workplace deaths due to natural causes, as was initially reported in this case, may not receive an OSHA inspection. However, subsequent to the incident, a family member contacted the OSHA area office and reported that the death may have been due to chemical vapor exposures, based on information from co-workers of the deceased. The family had already requested a toxicological screening of the victim and the coroner had agreed. Based on this new information, the local OSHA area office opened a facility inspection.


Feeding of a well-cooked beef diet containing a high heterocyclic amine content enhances colon and stomach carcinogenesis in 1,2-dimethylhydrazine-treated rats.
Epidemiologic studies have linked the consumption of red meat and the consumption of highly browned meats containing high levels of heterocyclic aromatic amines (HCAs) to increased risk of colorectal cancer or polyps. The present study determined the effects of long-term feeding of beef-containing diets with low and high levels of HCAs (in the context of a low or high beef tallow diet) on a standard 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis protocol. Very lean beef was cooked by a variety of methods at different temperatures, and the levels of the major HCAs (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine) were measured by high-performance liquid chromatography. Diets incorporating beef containing low or high levels of HCAs were fed for 12 weeks, during which DMH was administered to induce colon tumors, followed by various dietary regimens as promotional stimuli. Feeding of a beef diet high in HCAs resulted in more DMH-induced colon adenocarcinomas, but only in the context of a low-fat diet. The high-HCA diets increased stomach tumors in all DMH-treated rats. An apparent interaction of high HCA with a high fat level reduced the colon tumor incidence and tumor numbers in those diets containing both factors. These results support the epidemiologic data linking well-cooked meat to increased risk for colon and stomach cancer, but the role of dietary fat level remains puzzling.


Improved generalized regularized phase tracker for demodulation of a single fringe pattern.
A generalized regularized phase tracker (GRPT) for demodulation of a single fringe pattern was recently proposed. It is very successful for many fringe patterns. However, the GRPT has poor performance in the area where the fringe pattern is sparse. An improved GRPT (iGRPT) with two novel improvements is proposed to overcome the problem. First, the fixed window used in the GRPT is replaced by a spatially adaptive window. Second, a background regularization term and a modulation regularization term are incorporated in the cost function. With these two improvements, the proposed iGRPT can successfully demodulate sparse fringes and thus improves the demodulation capability of the GRPT. Simulation and experimental results are presented to verify the performance of the iGRPT.


The accuracy of 3D fluoroscopy (XT) vs computed tomography (CT) registration in deep brain stimulation (DBS) surgery.
Stereotactic registration is the most critical step ensuring accuracy in deep brain stimulation (DBS) surgery. 3D fluoroscopy (XT) is emerging as an alternative to CT. XT has been shown to be safe and effective for intraoperative confirmation of lead position following implantation. However, there is a lack of studies evaluating the suitability of XT to be used for the more crucial step of registration and its capability of being merged to a preoperative MRI. This is the first study comparing accuracy, efficiency, and radiation exposure of XT- vs CT-based stereotactic registration and XT/MRI merging in deep brain stimulation. Mean absolute differences and Euclidean distance between planned (adjusted for intraoperative testing) and actual lead trajectories were calculated for accuracy of implantation. The radiation dose from each scan was recorded as the dose length product (DLP). Efficiency was measured as the time between the patient entering the operating room and the initial skin incision. A one-way ANOVA compared these parameters between patients that had either CT- or XT-based registration. Forty-one patients underwent DBS surgery-25 in the CT group and 16 in the XT group. The mean absolute difference between CT and XT was not statistically significant in the x (p = 0.331), y (p = 0.951), or z (p = 0.807) directions. The Euclidean distance between patient groups did not differ significantly (p = 0.874). The average radiation exposure with XT (220.0 ± 0.1 mGy*cm) was significantly lower than CT (1269.3 ± 112.9 mGy*cm) (p < 0.001). There was no significant difference in registration time between CT (107.8 ± 23.1 min) and XT (106.0 ± 18.2 min) (p = 0.518). XT-based frame registration was shown to result in similar implantation accuracy and significantly less radiation exposure compared with CT. Our results surprisingly showed no significant difference in registration time, but this may be due to a learning curve effect.


An application of Orem's theory to the nursing management of pertussis.
In recent years, there has been a dramatic resurgence of Bordetella pertussis infection in the United States. This infection is affecting all age groups. A case study of one family's experience with pertussis is examined. This paper presents a review of the epidemiology, pathogenesis, clinical features, complications, diagnostic tests, vaccines, and treatment of pertussis. Dorothea Orem's Self-Care Deficit Theory of nursing is the theoretical concept used to characterize the school nurse's approach to the care of this family and school community in regard to pertussis and the vaccines.


Are women with recurrent spontaneous preterm births different from those without such history?
This study was undertaken to determine whether women with recurrent spontaneous preterm births (rSPBs) have different clinical characteristics or systemic markers than those with isolated preterm (iSPBs) or recurrent term births (rTBs), when assessed remote from delivery. We compared clinical characteristics and findings (including cervical ultrasound, bacterial vaginosis, fetal fibronectin), maternal plasma markers obtained at 22 to 24 weeks' gestation (inflammatory cytokines, cortisol, and corticotrophin-releasing hormone), between women with rSPBs (2 or 3 consecutive SPBs and no TBs), iSPBs (1 SPB and 1 or 2 TBs), and rTBs (2 or 3 consecutive TBs and no SPBs). A total of 1257 women met our inclusion criteria; 47 rSPBs, 241 iSPBs (80 current and 161 prior iSPBs), and 969 rTBs. Before pregnancy, women with rSPBs had lower weights (P < .0001) and body mass indexes (BMIs) (P < .001), and were more likely to be less than 100 lbs (P = .008) or less than 19.8 kg/m2 BMI (P = .001). At 22 to 24 weeks those with rSPBs remained lighter and leaner, and had more advanced Bishop scores than iSPBs and rTBs. Ultrasound demonstrated progressive decrease in cervical length for those with rTBs, prior iSPBs, current iSPBs, and rSPBs, and also progressively more frequent short cervixes with worsening history (P < .001). Cervical length was shorter for women of lower pregravid weight and BMI, but not with shorter height. At 22 to 24 weeks, women with rSPBs had more common uterine contractions and tocolytic agents, but not more infections or antibiotic therapy. Those with an SPB in the current gestation had higher fetal fibronectin levels and more frequent vaginal bleeding, regardless of prior outcome. Maternal cortisol and corticotrophin-releasing hormone were higher in women with iSPBs and rSPBs than in rTB controls, (P = .001 and .0027), a finding more apparent with SPB in the current pregnancy. However, maternal cytokines were not increased with either iSPBs or rSPBs. Women with rSPBs are leaner, contract more, have shorter cervixes, and have more advanced Bishop scores than women with iSPBs or rTBs.


Estradiol Treatment Initiated Early After Ovariectomy Regulates Myocardial Gene Expression and Inhibits Diastolic Dysfunction in Female Cynomolgus Monkeys: Potential Roles for Calcium Homeostasis and Extracellular Matrix Remodeling.
Background Left ventricular ( LV ) diastolic dysfunction often precedes heart failure with preserved ejection fraction, the dominant form of heart failure in postmenopausal women. The objective of this study was to determine the effect of oral estradiol treatment initiated early after ovariectomy on LV function and myocardial gene expression in female cynomolgus macaques. Methods and Results Monkeys were ovariectomized and randomized to receive placebo (control) or oral estradiol at a human-equivalent dose of 1 mg/day for 8 months. Monkeys then underwent conventional and tissue Doppler imaging to assess cardiac function, followed by transcriptomic and histomorphometric analyses of LV myocardium. Age, body weight, blood pressure, and heart rate were similar between groups. Echocardiographic mitral early and late inflow velocities, mitral annular velocities, and mitral E deceleration slope were higher in estradiol monkeys (all P<0.05), despite similar estimated LV filling pressure. MCP1 (monocyte chemoattractant protein 1) and LV collagen staining were lower in estradiol animals ( P<0.05). Microarray analysis revealed differential myocardial expression of 40 genes (>1.2-fold change; false discovery rate, P<0.05) in estradiol animals relative to controls, which implicated pathways associated with better calcium ion homeostasis and muscle contraction and lower extracellular matrix deposition ( P<0.05). Conclusions Estradiol treatment initiated soon after ovariectomy resulted in enhanced LV diastolic function, and altered myocardial gene expression towards decreased extracellular matrix deposition, improved myocardial contraction, and calcium homeostasis, suggesting that estradiol directly or indirectly modulates the myocardial transcriptome to preserve cardiovascular function.


A fish with no sex: gonadal and adrenal functions partition between zebrafish NR5A1 co-orthologs.
People with NR5A1 mutations experience testicular dysgenesis, ovotestes, or adrenal insufficiency, but we do not completely understand the origin of this phenotypic diversity. NR5A1 is expressed in gonadal soma precursor cells before expression of the sex-determining gene SRY. Many fish have two co-orthologs of NR5A1 that likely partitioned ancestral gene subfunctions between them. To explore ancestral roles of NR5A1, we knocked out nr5a1a and nr5a1b in zebrafish. Single-cell RNA-seq identified nr5a1a-expressing cells that co-expressed genes for steroid biosynthesis and the chemokine receptor Cxcl12a in 1-day postfertilization (dpf) embryos, as does the mammalian adrenal-gonadal (interrenal-gonadal) primordium. In 2dpf embryos, nr5a1a was expressed stronger in the interrenal-gonadal primordium than in the early hypothalamus but nr5a1b showed the reverse. Adult Leydig cells expressed both ohnologs and granulosa cells expressed nr5a1a stronger than nr5a1b. Mutants for nr5a1a lacked the interrenal, formed incompletely differentiated testes, had no Leydig cells, and grew far larger than normal fish. Mutants for nr5a1b formed a disorganized interrenal and their gonads completely disappeared. All homozygous mutant genotypes lacked secondary sex characteristics, including male breeding tubercles and female sex papillae, and had exceedingly low levels of estradiol, 11-ketotestosterone, and cortisol. RNA-seq showed that at 21dpf, some animals were developing as females and others were not, independent of nr5a1 genotype. By 35dpf, all mutant genotypes greatly under-expressed ovary-biased genes. Because adult nr5a1a mutants form gonads but lack an interrenal and conversely, adult nr5a1b mutants lack a gonad but have an interrenal, the adrenal, and gonadal functions of the ancestral nr5a1 gene partitioned between ohnologs after the teleost genome duplication, likely owing to reciprocal loss of ancestral tissue-specific regulatory elements. Identifying such elements could provide hints to otherwise unexplained cases of Differences in Sex Development.


Intrathecal upregulation of granulocyte colony stimulating factor and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis.
To investigate cytokine/chemokine changes in amyotrophic lateral sclerosis (ALS), we simultaneously measured 16 cytokine/chemokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony stimulating factor [G-CSF], macrophage chemoattractant protein-1 [MCP-1], and macrophage inflammatory protein-1beta) in cerebrospinal fluid (CSF) and sera from 37 patients with sporadic ALS and 33 controls using a multiplexed fluorescent bead-based immunoassay. We also conducted immunohistochemical analyses from 8 autopsied ALS cases and 6 nonneurologic disease controls as well as cell culture analyses of relevant cytokines and their receptors. We found that concentrations of G-CSF and MCP-1 were significantly increased in ALS CSF compared with controls. In spinal cords, G-CSF was expressed in reactive astrocytes in ALS cases but not controls, whereas G-CSF receptor expression was significantly decreased in motor neurons of spinal cords from ALS cases. Biologically, G-CSF had a protective effect on the NSC34 cell line under conditions of both oxidative and nutritional stress. We suggested that G-CSF has potentially neuroprotective effects on motor neurons in ALS and that downregulation of its receptor might contribute to ALS pathogenesis. On the other hand, MCP-1 correlated with disease severity, which may aggravate motor neuron damage.


Evaluation of three techniques of ventral decompression of the cervical spinal cord in the dog.
Three techniques for ventral decompression of the cervical spinal cord were performed on 21 dogs (3 groups of 7 dogs each). The techniques involved cutting various-sized defects in the vertebral bodies and disks of the cervical vertebral column. The defects were not filled with bone grafts. Two of the 3 techniques (short, wide defect and long, narrow defect) were successful, and the other technique (long, wide defect) gave questionable results.


Loss of BRCC3 deubiquitinating enzyme leads to abnormal angiogenesis and is associated with syndromic moyamoya.
Moyamoya is a cerebrovascular angiopathy characterized by a progressive stenosis of the terminal part of the intracranial carotid arteries and the compensatory development of abnormal and fragile collateral vessels, also called moyamoya vessels, leading to ischemic and hemorrhagic stroke. Moyamoya angiopathy can either be the sole manifestation of the disease (moyamoya disease) or be associated with various conditions, including neurofibromatosis, Down syndrome, TAAD (autosomal-dominant thoracic aortic aneurysm), and radiotherapy of head tumors (moyamoya syndromes). Its prevalence is ten times higher in Japan than in Europe, and an estimated 6%-12% of moyamoya disease is familial in Japan. The pathophysiological mechanisms of this condition remain obscure. Here, we report on three unrelated families affected with an X-linked moyamoya syndrome characterized by the association of a moyamoya angiopathy, short stature, and a stereotyped facial dysmorphism. Other symptoms include an hypergonadotropic hypogonadism, hypertension, dilated cardiomyopathy, premature coronary heart disease, premature hair graying, and early bilateral acquired cataract. We show that this syndromic moyamoya is caused by Xq28 deletions removing MTCP1/MTCP1NB and BRCC3. We also show that brcc3 morphant zebrafish display angiogenesis defects that are rescued by endothelium-specific expression of brcc3. Altogether, these data strongly suggest that BRCC3, a deubiquitinating enzyme that is part of the cellular BRCA1 and BRISC complexes, is an important player in angiogenesis and that BRCC3 loss-of-function mutations are associated with moyamoya angiopathy.


Investigation on the molecular, electronic and spectroscopic properties of rosmarinic acid: an intuition from an experimental and computational perspective.
Various drugs such as corticosteroids, salbutamol, and β2 agonist are available for the treatment of asthma an inflammatory disease and its symptoms, although the ingredient and the mode of action of these drugs are not clearly elucidated. Hence this research aimed at carrying out improved scientific research with respect to the use of natural product rosmarinic acid which poses minima, side effects. Herein, we first carried out extraction, isolation, and spectroscopic (FT-IR, 1H-NMR and 13C-NMR) investigation, followed by molecular modeling analysis on the naturally occurring rosmarinic acid extracted from Rosmarinus officinalis. A detailed comparison of the experimental and theoretical vibrational analysis has been carried out using five DFT functionals: BHANDH, HSEH1PBE, M06-2X, MPW3PBE and THCTHHYB with the basis set 6-311++G (d, p) to investigate into the structural, reactivity, and stability of the isolated compound. Frontier molecular orbital analysis and appropriate quantum descriptors were calculated. Results showed that the compound was more stable at M06-2X and more reactive at HSEH1PBE with an energy gap of 6.43441 eV and 3.8047 eV, respectively, which was later affirmed by the global quantum reactivity parameters. From natural bond orbital analysis, π* →π* is the major contributor to electron transition with the summation perturbation energy of 889.57 kcal/mol, while π →π* had the perturbation energy totaling of 145.3 kcal/mol. Geometry analysis shows BHANDH to have lower bond length values and lesser deviation from 120° in carbon-carbon angle. The potency of the title molecule as an asthma drug was tested via a molecular docking approach and the binding score of -8.2 kcal/mol was observed against -7.0 of salbutamol standard drug, suggesting romarinic acid as a potential natural organic treatment for asthma.Communicated by Ramaswamy H. Sarma.


Do thermal treatments influence the ultrafast opto-thermal processes of eumelanin?
After light absorption, melanin converts very rapidly the energy gained into heat. The time scale of this process ranges from tens of femtoseconds to a few nanoseconds. Femtosecond transient absorption allows for exploration of such photo-induced carrier dynamics to observe the de-excitation pathways of the biological complex. Here, we report on the ultrafast relaxation of suspensions of Sepia melanin in DMSO at room temperature using a femtosecond broadband pump and probe technique by photoexciting in the UV and probing in the entire visible range. In particular, we focus on the possible role that different heat treatments, performed in the temperature range 30-80 °C might have on the relaxation of charge carriers photogenerated by UV radiation in such suspensions. Experimental data indicate that in all the investigated suspensions, photoexcited carriers always follow a tri-exponential route to relaxation. Moreover, we find that the relaxation time constants are essentially the same in all cases, within the experimental error. We take this as evidence that all the investigated suspensions essentially exhibit the same relaxation dynamics, regardless of the temperature at which the heat treatment has been performed and of the heat-induced denaturation of the proteinaceous compounds bound to the photoactive pigment. Our experiments represent a significant step towards the understanding of the stability of melanin with respect to temperature changes.


An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn's Disease in Japanese Populations.
Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.


Aerobic training in patients with myotonic dystrophy type 1.
The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing and muscle morphology before and after training. Patients increased their maximal oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter increased significantly, and creatine kinase did not increase with training. The study indicates that aerobic training is safe and can improve fitness effectively in patients with myotonic dystrophy.


Carbon flow of heliobacteria is related more to clostridia than to the green sulfur bacteria.
The recently discovered heliobacteria are the only Gram-positive photosynthetic bacteria that have been cultured. One of the unique features of heliobacteria is that they have properties of both the photosynthetic green sulfur bacteria (containing the type I reaction center) and Clostridia (forming heat-resistant endospores). Most of the previous studies of heliobacteria, which are strict anaerobes and have the simplest known photosynthetic apparatus, have focused on energy and electron transfer processes. It has been assumed that like green sulfur bacteria, the major carbon flow in heliobacteria is through the (incomplete) reductive (reverse) tricarboxylic acid cycle, whereas the lack of CO(2)-enhanced growth has not been understood. Here, we report studies to fill the knowledge gap of heliobacterial carbon metabolism. We confirm that the CO(2)-anaplerotic pathway is active during phototrophic growth and that isoleucine is mainly synthesized from the citramalate pathway. Furthermore, to our surprise, our results suggest that the oxidative (forward) TCA cycle is operative and more active than the previously reported reductive (reverse) tricarboxylic acid cycle. Both isotopomer analysis and activity assays suggest that citrate is produced by a putative (Re)-citrate synthase and then enters the oxidative (forward) TCA cycle. Moreover, in contrast to (Si)-citrate synthase, (Re)-citrate synthase produces a different isomer of 2-fluorocitrate that is not expected to inhibit the activity of aconitase.


Recombinant Rotaviruses Rescued by Reverse Genetics Reveal the Role of NSP5 Hyperphosphorylation in the Assembly of Viral Factories.
Rotavirus (RV) replicates in round-shaped cytoplasmic viral factories, although how they assemble remains unknown. During RV infection, NSP5 undergoes hyperphosphorylation, which is primed by the phosphorylation of a single serine residue. The role of this posttranslational modification in the formation of viroplasms and its impact on virus replication remain obscure. Here, we investigated the role of NSP5 during RV infection by taking advantage of a modified fully tractable reverse-genetics system. A trans-complementing cell line stably producing NSP5 was used to generate and characterize several recombinant rotaviruses (rRVs) with mutations in NSP5. We demonstrate that an rRV lacking NSP5 was completely unable to assemble viroplasms and to replicate, confirming its pivotal role in rotavirus replication. A number of mutants with impaired NSP5 phosphorylation were generated to further interrogate the function of this posttranslational modification in the assembly of replication-competent viroplasms. We showed that the rRV mutant strains exhibited impaired viral replication and the ability to assemble round-shaped viroplasms in MA104 cells. Furthermore, we investigated the mechanism of NSP5 hyperphosphorylation during RV infection using NSP5 phosphorylation-negative rRV strains, as well as MA104-derived stable transfectant cell lines expressing either wild-type NSP5 or selected NSP5 deletion mutants. Our results indicate that NSP5 hyperphosphorylation is a crucial step for the assembly of round-shaped viroplasms, highlighting the key role of the C-terminal tail of NSP5 in the formation of replication-competent viral factories. Such a complex NSP5 phosphorylation cascade may serve as a paradigm for the assembly of functional viral factories in other RNA viruses.IMPORTANCE The rotavirus (RV) double-stranded RNA genome is replicated and packaged into virus progeny in cytoplasmic structures termed viroplasms. The nonstructural protein NSP5, which undergoes a complex hyperphosphorylation process during RV infection, is required for the formation of these virus-induced organelles. However, its roles in viroplasm formation and RV replication have never been directly assessed due to the lack of a fully tractable reverse-genetics (RG) system for rotaviruses. Here, we show a novel application of a recently developed RG system by establishing a stable trans-complementing NSP5-producing cell line required to rescue rotaviruses with mutations in NSP5. This approach allowed us to provide the first direct evidence of the pivotal role of this protein during RV replication. Furthermore, using recombinant RV mutants, we shed light on the molecular mechanism of NSP5 hyperphosphorylation during infection and its involvement in the assembly and maturation of replication-competent viroplasms.


How Does Implant Survivorship Vary with Different Corail Femoral Stem Variants? Results of 51,212 Cases with Up to 30 Years Of Follow-up from the Norwegian Arthroplasty Register.
The Corail® cementless stem (DePuy Synthes) has been used in Norway since 1987 and is one of the most frequently used stems in THA worldwide. Although the published survival results of the standard Corail stem have been good, little is known about the long-term (more than 20 years) survival of other stem design variants. Further, some changes were made to the extramedullary part of the stem in 2003, and the effect of these changes on survival is unknown. (1) What is the survival up to 30 years of the standard collarless Corail femoral stem, and were extramedullary changes (slimmer, polished and rectangular neck, shorter taper) associated with differences in survivorship? (2) How does the 10-year survival and the risk of revision of other Corail stem variants, including the standard collared stem, coxa vara collared stem, and high offset collarless stem, compare with those of the standard collarless stem? (3) Which factors are associated with an increased risk of revision of the Corail stem, and are there any differences in those factors among the four stem variants? Data for this study were drawn from the Norwegian Arthroplasty Register. Since 1987, THAs have been registered in the Norwegian Arthroplasty Register with completeness of data greater than 97% for primary THAs and 93% for revisions. To study survivorship with up to 30 years of follow-up (1987 to 2018; median 7.7-year follow-up), and to compare the original stem with stems with extramedullary modifications, we included 28,928 standard collarless Corail stems in 24,893 patients (mean age at time of implantation 62 years; 66% [16,525 of 24,893] were women). To compare the newer stem variants with the standard collarless stem (2008 to 2018), we included 20,871 standard collarless, 10,335 standard collared, 6760 coxa vara collared, and 4801 high offset collarless stems. Survival probabilities were estimated using the Kaplan-Meier method with endpoints of stem revision, revision due to aseptic stem loosening, and periprosthetic fracture. The endpoint of all noninfectious causes of THA revision (including cup revision) was additionally analyzed for the long-term comparison. The proportion of patients who died was limited, and there was no difference in death rate between the groups compared. Therefore, we believe that competing events were not likely to influence survivorship estimates to a large degree. To compare different stem variants and evaluate factors that could be associated with the risk of revision, we calculated hazard ratios using Cox regression analyses with adjustments for gender, age group, surgical approach, diagnosis, and stem size. The 30-year Kaplan-Meier survival of the standard collarless stem was 88.4% (95% confidence interval 85.4% to 91.4%), 93.3% (95% CI 91.1% to 95.5%), and 94.4% (95% CI 92.0% to 96.8%) using stem revision for any noninfectious cause, aseptic loosening, and periprosthetic fracture of the femur as endpoints, respectively. There was no difference in survival between the original stem and the modified stem. The 10-year Kaplan-Meier survivorship free of stem revision (all causes including infection) was 97.6% (95% CI 97.2% to 98.0%) for the standard collarless stem, 99.0% (95% CI 98.8% to 99.2%) for the standard collared stem, 97.3% (95% CI 96.3% to 98.3%) for the coxa vara collared stem, and 95.0% (95% CI 93.6% to 96.4%) for the high offset collarless stem. Compared with the standard collarless stem, the standard collared stem performed better (HR 0.4 [95% CI 0.3 to 0.6]; p < 0.001) and the high offset collarless stem performed more poorly (HR 1.4 [95% CI 1.1 to 1.7]; p = 0.006) with any stem revision as the endpoint, and similar results were found with revision for aseptic stem loosening and periprosthetic fracture as endpoints. Controlling for the noted confounders, the standard collared stem had a lower revision risk. The high offset collarless stem had an increased stem revision risk for any reason (HR 1.4 [95% CI 1.1 to 1.7]; p = 0.006) and aseptic loosening (HR 1.6 [95% CI 1.1 to 2.3]; p = 0.022). Other factors associated with an increased risk of stem revision for all stem variants were being a man (HR 1.7 [95% CI 1.4 to 2.0]; p < 0.001), age 70 to 79 years and 80 years and older compared with the age group of 50 to 59 years (HR 1.6 [95% CI 1.2 to 2.0]; p < 0.001 and HR 1.9 [95% CI 1.4 to 2.6]; p < 0.001, respectively), the anterior approaches (direct anterior Smith-Petersen and anterolateral Watson-Jones combined) compared with the posterior approach (HR 1.4 [95% CI 1.1 to 1.7]; p = 0.005), as well as a preoperative nonosteoarthritis diagnosis (HR 1.3 [95% CI 1.0 to 1.6]; p = 0.02) and small stem sizes (sizes 8-11) compared with the medium sizes (sizes 12-15) (HR 1.4 [95% CI 1.1 to 1.6]; p = 0.001). The very small sizes (8 and 9) were associated with a 2.0 times higher risk of revision (95%. CI 1.4 to 2.6; p < 0.01) compared with all other sizes combined. When using the uncemented Corail stem, surgeons can expect good results with up to 30 years of follow-up. Our results should be generalizable to the typical surgeon at the average hospital in a comparable setting. From our results, using a collared variant would be preferable to a collarless one. Due to an increased risk of periprosthetic fracture, caution with the use of the uncemented Corail stem in patients older than 70 years, especially in women, is warranted. Poorer stem survival should also be expected with the use of small stem sizes. The risk of periprosthetic fractures for the Corail uncemented stem versus cemented stems in different age categories has not been extensively examined, nor has the use of a collar for different age groups and genders, and both should be subjects for further investigation. Level III, therapeutic study.


Characteristics of bruises in carcasses of cows sourced from farms or from livestock markets.
Bruises in cattle develop after the application of force, and they provide evidence for sub-optimal animal welfare. The aim of this study was to describe the gross characteristics of bruises in cows arriving at the slaughterhouse directly from farms or through the livestock market. The number of bruises and their distribution on the carcass as well as their severity, shape, size and colour were assessed post mortem in a slaughterhouse in Chile. A total of 258 cow carcasses were evaluated, and a total of 846 bruises were found on 243 of the carcasses. Cows that had passed through a livestock market (M-carcasses) had in total 563 bruises (mean 3.8 bruises/carcass, s.d. 2.0), whereas cows transported directly from farms (F-carcasses) had in total 283 bruises (mean 2.5 bruises/carcass, s.d. 1.8). The backs of F-carcasses had twice as many bruises as M-carcasses (32.9% and 16.2%, respectively), whereas bruises in the rib area were more frequently observed in M-carcasses (13.1%) than in F-carcasses (8.1%). Superficial bruises (grade 1) were the most frequently observed (66.2% of all bruises). Regarding the size of the bruises, 64 (7.6%) were classified as large, 271 (32.0%) as medium and 511 (60.4%) as small. Irregularly shaped bruises were the most frequent (91.1%, n = 771), followed by linear (3.8%, n = 32), circular (3.1%, n = 26) and tramline-shaped bruises (1.9%, n = 16). The latter were noticed only in M-carcasses, which may indicate that these animals were beaten more frequently with sticks or other rod-shaped objects. Fresh, bright red-coloured bruises were found more frequently on all the animals (69.5% from farms and 70.5% from market) compared with bluish (29.7% and 29.3%, respectively) and yellow bruises (0.4% and 0.2%, respectively). The method of selling was significantly associated with the number of bruises on the carcass (P < 0.001) and the anatomical site (P < 0.05), but not with the severity, shape and colour of the bruises. Increased fat coverage reduced the severity of bruises (P < 0.001). This study shows that, in Chile, market animals have more bruises than those sourced directly from farms, and their distribution is different. More information about the causes of infliction may help reduce bruises and it may also improve their welfare. Further studies are required to elucidate whether the causes of the high bruising in the case of animals passing through markets are related only to extra handling (repeated loading, unloading, transportation, eventual mixing) or to the way of handling by personnel and inadequate design.


[Validation of the DTP-3 system for noninvasive spinal shape measurement by comparison with X-ray examination].
Repeated measurements of the spine are absolutely necessary in children and adolescents affected by spinal deformities especially during their growing-up periods. To avoid risks of tissue damage from x-ray exposure, several methods for non-invasive measurement of the spinal curvature have been developed. One of them is the DTP-3 position system allowing for a three-dimensional measurement of anatomical landmarks (spinous processes) and the calculation of curvature angles in both the frontal and sagittal planes. We were interested to know whether the DTP-3 was precise enough to determine the true spinal curvature. To determine the precision of the DTP-3 system, we constructed a model of the spine. The model was then repeatedly investigated by both the noninvasive and x-ray methods. The distortion of x-ray images caused by the central projection mechanism was considered and included in the calculation. In addition, a group of patients with scoliosis up to 40° was evaluated by both the DTP-3 system and x-ray (the latter according to Cobb's method). Differences in spatial coordinates between DTP-3 and x-ray examinations reached 20.9 mm in the frontal plane and 67.3 mm in the sagittal plane without distortion correction of x-ray images. The differences decreased below 1.5 mm after image distortion correction in each plane. Distortion correction had not the same effect for angle parameters as for coordinates. Differences between the DTP-3 angle parameters and Cobb's x-ray angles were below 4.7°, both without correction and after correction. The difference between DTP-3 angle parameters and Cobb's x-ray angles was -1.8° ± 3.0° (mean ± standard deviation) when measurement was performed on the patients with scoliosis. The goal of any clinical examination is to obtain data applicable to decision-making analysis. In the case of scoliosis it is necessary to report results in terms of Cobb's angle, which is the problem for all surface-dependent methods, especially in patients with double curves. A solution may be to define the maximal difference between noninvasive and x-ray methods that could be acceptable for good clinical practice. In this study we report good concordance between noninvasive and x-ray examinations of a modeled spinal deformity in terms of both angle and linear measurements. The same results were obtained for angle measurements in a group of patients with scoliosis up to 40°. Based on this study and our previous data we believe that the DTP-3 system can be introduced into clinical practice.