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In a randomized trial, optical coherence tomography–guided PCI resulted in a larger minimum stent area than angiography-guided PCI, but there was no between-group difference in target-vessel failure at 2 years.

In a randomized trial, patients with tricuspid regurgitation who were treated with transcatheter edge-to-edge repair had more favorable clinical outcomes at 1 year than did patients who received medical therapy.

Background Polypoid cystitis (PoC) in dogs is associated with chronic inflammatory bladder conditions and is discovered during evaluation for signs of lower urinary tract disease, or incidentally. Objective To describe PoC in dogs evaluated in an academic practice. Animals Dogs with confirmed (n = 59) or presumptive (n = 53) PoC were evaluated between January 2004 and October 2020. Methods For this retrospective study, medical records were searched for PoC. Results The most common presenting signs of 112 dogs with PoC were hematuria (n = 42; 38%), stranguria (n = 28; 25%), and pollakiuria (n = 25; 22%). Polyps were found incidentally (n = 13; 12%). Urinary tract infection (UTI; n = 61; 54%) or urolithiasis (n = 38; 34%) was a common presumptive cause. Escherichia coli (n = 39; 53%), Enterococcus faecalis (n = 14; 19%) and Staphylococcus pseudintermedius (n = 5; 7%) were isolated from dogs with UTI. Ultrasonographic findings (n = 101) included polypoid structures (n = 44; 44%), broad‐based masses (n = 16; 26%), and bladder wall thickening (n = 25; 25%); mostly in the cranioventral bladder apex (n = 56; 80%). Of 41 specimens tested, none had evidence of the BRAF V595E mutation. Urinary tract neoplasia was not reported in any dog during follow‐up (range 1 month–8.4 years; median 8 months). Interventions included antibiotic or anti‐inflammatory administration, and surgical or cystoscopic ablation. During follow‐up, recurrent signs of lower urinary tract disease were reported in 23 (20%) dogs. Conclusions and Clinical Importance History of either UTI or urolithiasis, compatible imaging findings, and absence of detectable BRAF V595E mutation support the presumptive diagnosis of PoC in dogs. Affected dogs have a good prognosis, warranting differentiation from other urinary tract diseases.

The treatment of conduct problems among children and adolescents with callous-unemotional (CU) traits has been subject to much speculation; however, treatment outcome research has been surprisingly limited and findings have been mixed. This review examines the research to date in this field as it pertains to two key questions. First, are CU traits associated with clinical outcomes and processes in the family based treatment of child and adolescent conduct problems? Second, can family based intervention produce change in CU traits? Using a systematic search strategy, we identified 16 treatment outcomes studies that can be brought to bear on these questions. These studies provide strong evidence of unique associations between CU traits and risk for poor treatment outcomes, while at the same time indicating that social-learning-based parent training is capable of producing lasting improvement in CU traits, particularly when delivered early in childhood. We discuss the potential for this emerging evidence base to inform the planning and delivery of treatments for clinic-referred children with CU traits, and detail an ongoing program of translational research into the development of novel interventions for this high-risk subgroup.

Breast cancer poses a significant health challenge in Sub-Saharan Africa, particularly in Ghana, where late-stage diagnoses and limited healthcare access contribute to elevated mortality rates. This study focuses on the crucial role of pathology and laboratory medical (PALM) services in the timely diagnosis of breast cancer within Ghana. A cross-sectional survey of hospitals was completed from November 2020 to October 2021, with 94.8% of identified in-country hospitals participating. Pathology service-related parameters assessed included whether pathology was available for the diagnosis of breast cancer on-site or via external referral, the number of pathology personnel, additional breast cancer diagnostic capabilities including estrogen and progesterone and/or HER2 testing, and the time from biopsy to patients receiving their results. Geospatial mapping was used to identify areas of limited access. Of the 328 participating hospitals, 136 (41%) reported breast cancer pathology services, with only 6 having on-site capabilities. Pathology personnel, comprising 15 consultants and 15 specialists, were concentrated in major referral centers, particularly in Greater Accra and Kumasi. An assessment of referral patterns suggested that 75% of the population reside within an hour of breast cancer pathology services. Among the 136 hospitals with access to breast cancer pathology, only a limited number reported that results included ER/PR (38%) and HER2 testing (33%). Ghana has been able to ensure significant pathology service availability through robust referral pathways with centralized labs. Despite this, difficulties persist with the majority of pathology results not including hormone receptor testing which is important in providing tumor specific treatment.

A majority of adults in the United States are exposed to a potentially traumatic event but only a handful go on to develop impairing mental health conditions such as posttraumatic stress disorder (PTSD). Identifying those at elevated risk shortly after trauma exposure is a clinical challenge. The aim of this study was to develop computational methods to more effectively identify at-risk patients and, thereby, support better early interventions. We proposed machine learning (ML) induction of models to automatically predict elevated PTSD symptoms in patients 1 month after a trauma, using self-reported symptoms from data collected via smartphones. We show that an ensemble model accurately predicts elevated PTSD symptoms, with an area under the curve (AUC) of .85, using a bag of support vector machines, naive Bayes, logistic regression, and random forest algorithms. Furthermore, we show that only 7 self-reported items (features) are needed to obtain this AUC. Most importantly, we show that accurate predictions can be made 10 to 20 days posttrauma. These results suggest that simple smartphone-based patient surveys, coupled with automated analysis using ML-trained models, can identify those at risk for developing elevated PTSD symptoms and thus target them for early intervention.

The standard treatment of atropine and oximes is insufficiently effective against all organophosphorus nerve agents. Bispyridinium non-oxime nicotinic antagonists are promising components to add to treatments. One of these, MB327, improves the survival of guinea-pigs after intoxication with tabun, sarin or soman. We extend our previous study of unsubstituted bispyridinium non-oximes with C1 to C10 alkane linkers to analogues having 4- tert- butylpyridinium rings and the same linker range. We report their effects on nicotinic-mediated calcium responses in muscle-derived (CN21) cells where nicotinic responses were inhibited in a concentration-dependent manner. A clear structure-activity relationship resulted: the inhibitory potency increased as the linker lengthened. Previous data showed the inhibition of human acetylcholinesterase in vitro increased similarly and that in general the toxicity to mice increased accordingly. However, the shorter analogues MB327 (4- tert- butyl C3) and MB442 (unsubstituted C5) compared favourably in toxicity to some oximes used to treat nerve agent poisoning. Like MB327, the non-oxime MB442, selected by the process described, improved the survival of guinea-pigs intoxicated with soman when combined with hyoscine and physostigmine or atropine and avizafone. Our research has now afforded two compounds able to protect guinea-pigs against nerve agent toxicity through a mechanism not previously exploited deliberately for this purpose.

HIV-1 infection is characterized by varying degrees of chronic immune activation and disruption of T-cell homeostasis, which impact the rate of disease progression. A deeper understanding of the factors that influence HIV-1–induced immunopathology and subsequent CD4 ⁺ T-cell decline is critical to strategies aimed at controlling or eliminating the virus. In an analysis of 127 acutely infected Zambians, we demonstrate a dramatic and early impact of viral replicative capacity (vRC) on HIV-1 immunopathogenesis that is independent of viral load (VL). Individuals infected with high-RC viruses exhibit a distinct inflammatory cytokine profile as well as significantly elevated T-cell activation, proliferation, and CD8 ⁺ T-cell exhaustion, during the earliest months of infection. Moreover, the vRC of the transmitted virus is positively correlated with the magnitude of viral burden in naive and central memory CD4 ⁺ T-cell populations, raising the possibility that transmitted viral phenotypes may influence the size of the initial latent viral reservoir. Taken together, these findings support an unprecedented role for the replicative fitness of the founder virus, independent of host protective genes and VL, in influencing multiple facets of HIV-1–related immunopathology, and that a greater focus on this parameter could provide novel approaches to clinical interventions. Significance HIV infection is associated with elevated inflammation and aberrant cellular immune activation. Indeed, the activation status of an HIV-infected individual is often more predictive of disease trajectory than viral load. Here, we highlight the importance of the replicative fitness of the transmitted viral variant in driving an early inflammatory state, characterized by T-cell activation and immune dysfunction. This impact on T-cell homeostasis is independent of protective host immune response genes and viral load. Highly replicating transmitted variants were also significantly more efficient at infecting memory CD4 ⁺ T cells, a population important for maintaining the latent viral reservoir. Together, these data provide a mechanism whereby viral replicative fitness acts as a major determinant of disease progression and persistence.

For mid‐ocean ridge basalts and ocean island basalts, measurements of Pb isotope ratios show broad linear correlations with a certain degree of scatter. In 207Pb/204Pb—206Pb/204Pb space, the best fit line defines a pseudo‐isochron age (τPb) of ∼1.9 Gyr. Previous modeling suggests a relative change in the behaviors of U and Pb between 2.25 and 2.5 Ga, resulting in net recycling of HIMU (high U/Pb) material in the latter part of Earth's history, to explain the observed τPb. However, simulations in which fractionation is controlled by a single set of partition coefficients throughout the model runs fail to reproduce τPb and the observed scatter in Pb isotope ratios. We build on these models with 3D mantle convection simulations including parameterizations for melting, U recycling from the continents and preferential removal of Pb from subducted oceanic crust. We find that both U recycling after the great oxygenation event and Pb extraction after the onset of plate tectonics, are required in order to fit the observed gradient and scatter of both the 207Pb/204Pb—206Pb/204Pb and 208Pb/204Pb—206Pb/204Pb arrays. Unlike much previous work, our model does not require accumulations of subducted oceanic crust to persist at the core‐mantle boundary for long periods of time in order to match geochemical observations. Plain Language Summary Lead isotope ratios measured within volcanic rocks which originate from deep within Earth (the mantle) define characteristic ages, which geodynamic modelers have previously explained by a global change in the relative behavior of uranium, thorium and lead at some time 2.25–2.5 billion years ago. A shortfall of previous modeling is that it fails to represent all of the different processes which can separate the elements of interest. As well as melting, our simulations feature methods for modeling non magmatic processes which ultimately alter Pb isotope ratios. These are the transportation of U from the continents into the mantle and the preferential loss of Pb from oceanic crust as it descends into the mantle (subduction). We find that a combination of these processes are required to best reproduce the range of Pb isotope ratios measured in rocks from mid‐ocean ridges. Contrary to previous work, we do not require subducted oceanic crust to accumulate in large piles at the base of the mantle. Key Points We present numerical geodynamic models with new parameterizations for U recycling and preferential Pb removal from subducted oceanic crust A combination of these processes provides a good fit to both Pb pseudo‐isochron and observed scatter of Pb isotope ratios measured in oceanic basalts Our models do not require long term accumulation of subducted oceanic crust to fit geochemical constraints