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Abstract Understanding how the traits of lineages are related to diversification is key for elucidating the origin of variation in species richness. Here, we test whether traits are related to species richness among lineages of trees from all major biogeographical settings of the lowland wet tropics. We explore whether variation in mortality rate, breeding system and maximum diameter are related to species richness, either directly or via associations with range size, among 463 genera that contain wet tropical forest trees. For Amazonian genera, we also explore whether traits are related to species richness via variation among genera in mean species-level range size. Lineages with higher mortality rates—faster life-history strategies—have larger ranges in all biogeographic settings and have higher mean species-level range sizes in Amazonia. These lineages also have smaller maximum diameters and, in the Americas, contain dioecious species. In turn, lineages with greater overall range size have higher species richness. Our results show that fast life-history strategies influence species richness in all biogeographic settings because lineages with these ecological strategies have greater range sizes. These links suggest that dispersal has been a key process in the evolution of the tropical forest flora.

The intensification of extreme climate events is already a reality throughout the world. In the Brazilian Amazon, the most frequent extreme events are linked to droughts and floods. This study expanded the documentation on extreme events of floods, water crisis, fires and forest fires in the state of Acre, in the southwestern Brazilian Amazon. We analyzed extreme weather events in state and municipal state-of-emergency and public-calamity decrees, reports of people who faced the impacts of these events, scientific articles, and press reports. The results show that the state of Acre recorded 202 extreme events between 1987 and 2023, with an increasing trend in the number and occurrence of various types of extreme events in the same year since 2010. Twenty-one state-of-emergency and public-calamity decrees were issued, with flood events being the most frequent. The cities of Rio Branco and Cruzeiro do Sul recorded 14 and 21 extreme events, respectively, or approximately one event every two years. These data show the urgency of implementing actions to adapt to climate extremes. Starting in 2005, the annual results indicate an increase in municipalities (counties) experiencing more than one type of extreme event, pointing to the need for effective public policies for adaptation and mitigation in the state of Acre.

Humans play an interconnecting role in social-ecological systems (SES), they are part of these systems and act as agents of their destruction and regulation. This study aims to provide an analytical framework, which combines the concept of SES with the concept of tipping dynamics. As a result, we propose an analytical framework describing relevant dynamics and feedbacks within SES based on two matrixes: the “tipping matrix” and the “cross-impact matrix.” We take the Southwestern Amazon as an example for tropical regions at large and apply the proposed analytical framework to identify key underlying sub-systems within the study region: the soil ecosystem, the household livelihood system, the regional social system, and the regional climate system, which are interconnected through a network of feedbacks. We consider these sub-systems as tipping elements (TE), which when put under stress, can cross a tipping point (TP), resulting in a qualitative and potentially irreversible change of the respective TE. By systematically assessing linkages and feedbacks within and between TEs, our proposed analytical framework can provide an entry point for empirically assessing tipping point dynamics such as “tipping cascades,” which means that the crossing of a TP in one TE may force the tipping of another TE. Policy implications: The proposed joint description of the structure and dynamics within and across SES in respect to characteristics of tipping point dynamics promotes a better understanding of human-nature interactions and critical linkages within regional SES that may be used for effectively informing and directing empirical tipping point assessments, monitoring or intervention purposes. Thereby, the framework can inform policy-making for enhancing the resilience of regional SES.

Tree mortality has been shown to be the dominant control on carbon storage in Amazon forests, but little is known of how and why Amazon forest trees die. Here the authors analyse a large Amazon-wide dataset, finding that fast-growing species face greater mortality risk, but that slower-growing individuals within a species are more likely to die, regardless of size.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20537-x

Climate, species composition, and soils are thought to control carbon cycling and forest structure in Amazonian forests. Here, we add a demographics scheme (tree recruitment, growth, and mortality) to a recently developed non-demographic model—the Trait-based Forest Simulator (TFS)—to explore the roles of climate and plant traits in controlling forest productivity and structure. We compared two sites with differing climates (seasonal vs. aseasonal precipitation) and plant traits. Through an initial validation simulation, we assessed whether the model converges on observed forest properties (productivity, demographic and structural variables) using datasets of functional traits, structure, and climate to model the carbon cycle at the two sites. In a second set of simulations, we tested the relative importance of climate and plant traits for forest properties within the TFS framework using the climate from the two sites with hypothetical trait distributions representing two axes of functional variation (“fast” vs. “slow” leaf traits, and high vs. low wood density). The adapted model with demographics reproduced observed variation in gross (GPP) and net (NPP) primary production, and respiration. However, NPP and respiration at the level of plant organs (leaf, stem, and root) were poorly simulated. Mortality and recruitment rates were underestimated. The equilibrium forest structure differed from observations of stem numbers suggesting either that the forests are not currently at equilibrium or that mechanisms are missing from the model. Findings from the second set of simulations demonstrated that differences in productivity were driven by climate, rather than plant traits. Contrary to expectation, varying leaf traits had no influence on GPP. Drivers of simulated forest structure were complex, with a key role for wood density mediated by its link to tree mortality. Modeled mortality and recruitment rates were linked to plant traits alone, drought-related mortality was not accounted for. In future, model development should focus on improving allocation, mortality, organ respiration, simulation of understory trees and adding hydraulic traits. This type of model that incorporates diverse tree strategies, detailed forest structure and realistic physiology is necessary if we are to be able to simulate tropical forest responses to global change scenarios.

Rural communities are important stewards of forests that provide valuable ecological services. This makes them vital allies to outside organizations seeking to support conservation and development initiatives. However, rural communities also have priorities and needs that may not align with the goals of conservation and development projects. This makes effective engagement of communities by outside organizations an important challenge. When rural communities lose traditional livelihood options, they prioritize economic benefits as a condition for participating in projects, and they exhibit "project fatigue" when many projects are imposed on their time. We reflect on our experience in seeking to align the goals of a conservation and development project with community priorities in the Chico Mendes Extractive Reserve in Acre, Brazil. Our project featured capacity building for monitoring forest health to foster participation in payments for ecosystem services programs. Although we pursued prior consultations and designed participatory activities, and although we combined knowledge transmission with skills training, participation declined. That prompted our team to consult with community members, which generated important insights about expectations of immediate economic remuneration, community political cultures, communicative practices, and differences among local constituencies. These insights motivated adaptation of our practices via several strategies, such as focusing on young adults and holding workshops as part of community assemblies, which aligned project goals with the priorities of community members to improve project outcomes.

Este estudo teve por objetivo detalhar aspectos climáticos relacionados ao período de seca que acarretou nos grandes incêndios ocorridos no Acre, durante a estação seca (junho a setembro) de 2005. Um aspecto original deste estudo foi a avaliação da variabilidade climática sub-sazonal. A avaliação dos padrões anômalos de variáveis climáticas relevantes mostrou que associações consistentes entre a superfície e a atmosfera que determinaram a severidade da estiagem de 2005. Primeiro, houve um pré-condicionamento dado que a estação chuvosa imediatamente anterior (2004-2005) foi deficiente. Segundo, os volumes de precipitação durante a estação seca de 2005 foram irrisórios, com a maior parte do estado experimentando menos de 50% da chuva esperada na estação, e algumas regiões, principalmente no leste acreano, com menos de 25%. Em uma perspectiva histórica, a estação seca de 2005 classificou-se como a menos chuvosa na série 1998 a 2014. Considerando-se uma média para toda a estação seca, a umidade relativa do ar apresentou anomalias negativas, devido a um transporte anômalo, contrário ao fluxo climatológico, de ar mais seco das latitudes mais ao sul para o sudoeste da Amazônia. De forma consistente com o déficit de umidade na atmosfera, a umidade do solo (modelo de balanço hídrico) também apresentou anomalias negativas durante a estação seca de 2005. O panorama sazonal de anomalias negativas de umidade relativa, foi resultante de dois ciclos sub-sazonais nos quais a umidade relativa do ar apresentou declínio acentuado e posterior recuperação, intercalados por um período de aproximadamente 20 dias de relativa normalidade. Em cada um destes ciclos foram atingidos valores mínimos extremos (inferiores a 1% dos mínimos da série de 1998 a 2014). Estes mínimos extremos de umidade relativa aparentam estar associados a condições mais persistentes de estiagem, condições estas que são sucedidas por um aumento de queimadas e/ou maior alastramento de incêndios. Os dois ciclos sub-sazonais mostraram associação com os movimentos de subsidência atmosférica de grande escala. Este mecanismo de subsidência mostrou-se associado com pulsos de atividade inibidora intensificada que se propagaram do Oceano Pacífico para a região do estado do Acre, de forma análoga à Oscilação de Madden-Julian.

A Amazônia vem sofrendo o aumento de intensidade e de ocorrência de eventos climáticos extremos. A ocorrência de secas nesta região aumenta a susceptibilidade das florestas a incêndios florestais, com diversas consequências para o meio ambiente, economia e saúde da população. O objetivo deste estudo foi fornecer uma análise espaço-temporal do uso do fogo no Estado do Acre, e assim auxiliar a Sala de Situação do Estado na tomada de decisão para priorizar o monitoramento de áreas com risco de incêndios. Para isso, foram utilizados dados de focos de calor oriundos de múltiplos satélites, dados de unidades fundiárias e análises estatísticas para gerar um ordenamento de áreas prioritárias para monitoramento de incêndios. O satélite AQUA, desde o início de sua operação em 2002, foi responsável por 40% a 75% dos totais de detecção de focos. Com o lançamento do satélite S-NPP em 2013, este vem sendo responsável pela maioria das detecções de focos de calor devido melhores em suas resoluções espaciais e radiométricas. Trinta e nove por cento do total de focos de calor detectados, foram localizados em projetos de assentamentos, 26% em áreas particulares, 10% em unidades de conservação e menos de 2% em terras indígenas. Um mapa de risco de incêndios baseado em análises de tendência e número de ocorrências de focos de calor foi proposto para auxiliar a deï¬nição de áreas prioritárias para monitoramento e ï¬scalização. Conclui-se que as informações geradas com base nos dados históricos de focos de calor podem ser incorporadas aos modelos de risco de incêndios que operam com dados puramente climáticos de forma a melhorar a espacialização do risco e assim apoiar o planejamento e a tomada de decisão.

Tree species in tropical forests provide economically important goods and ecosystem services. In submontane forests of southwestern Amazonia, we investigated the degree to which tree species important for subsistence and trade contribute to aboveground carbon storage (AGC). We used 41 1-hectare plots to determine the species abundance, basal area, and AGC of stems > 10 cm diameter at breast height (dbh). Economically important taxa were classified using ethnobotanical studies and according to their stem density. These taxa (n = 263) accounted for 45% of total stems, 53% of total basal area, and 56% of total AGC, significantly more than taxa with minor or unknown uses (Welch test at p < 0.05). Taxa with 1-2 stems per hectare, or with fewer than 1 stem per hectare (common and rare) accounted for 35% of total AGC, more than the 22% accounted for by dominant taxa. High basal area had a greater impact on AGC than abundance in economic taxa because their populations are skewed to adult trees. Size in these taxa had a median dbh > 40 cm and few stems in regeneration classes of dbh < 10 to 20 cm (e.g., Bertholletia excelsa, Cariniana spp., Cedrelinga spp., Ceiba spp., Dipteryx spp.), whereas dominant Tetragastris spp., and Pseudolmedia spp. had most stems in low diameter classes and a median diameter of < 30 cm. Bertholletia excelsa, with 1.5 stems per hectare, showed the highest basal area of any species and accounted for 9% of AGC (11 Mg/ha), twice that of the second-ranking species. Our study shows that economic importance and carbon stocks in trees are closely linked in southwestern Amazonia. Unplanned harvests can disrupt synergistic dual roles altering carbon stocks temporally or permanently. Precautionary measures based on species ecology, demography, and regeneration traits should be at the forefront of REDD+ to reconcile maximum harvesting limits, biodiversity conservation, and sustainable forest management.

The light environment underwater can vary dramatically over space and time, challenging the visual systems of aquatic organisms. To meet these challenges, many species shift their spectral sensitivities through changes in visual pigment chromophore composition and opsin expression. The red shiner (Cyprinella lutrensis) is a North American cyprinid minnow species that inhabits waters ranging widely in turbidity and temperature. We hypothesized that the visual system of the red shiner is plastic with chromophore composition and opsin expression varying in response to the environment. To test this hypothesis, we collected red shiners throughout the year from three Oklahoma creeks that vary in turbidity. We characterized the light environment by spectroradiometry, measured chromophore composition of the eyes with high performance liquid chromatography, characterized the mechanisms of chromophore metabolism, and examined ocular gene expression by RNA sequencing and de novo transcriptome assembly. We observed significantly higher proportions of the long-wavelength shifted A2 chromophore in the eyes of fish from the turbid site and in samples collected in winter, suggesting that there may be a temperature-dependent trade-off between chromophore-based spectral tuning and chromophore-related noise. Opsin expression varied between turbid and clear creeks, but did not align with light environment as expected, and the magnitude of these differences was limited compared to the differences in chromophore composition. We confirmed that red shiner CYP27C1 catalyzes the conversion of A1 to A2, but the ocular expression of CYP27C1 was not well correlated with A2 levels in the eye, suggesting conversion may be occurring outside of the eye., (© 2025. Published by The Company of Biologists.)

Diagnostic multiparametric MRI of the prostate has steadily evolved over the last three decades and can now reliably depict the dominant tumor in most men with prostate cancer. In response, several methods of targeted biopsy to direct tissue sampling of suspected tumor foci seen at multiparametric MRI have been developed and successfully tested in recent years, including software-assisted MRI-ultrasound (US) fusion biopsy and direct MRI-guided in-bore biopsy. These advances are leading to a sea change in the approach to prostate cancer diagnosis, with the traditional approach of blind systematic biopsy increasingly being replaced by MRI directed targeted biopsy. This review aims to describe the current status of targeted biopsy, with an emphasis on the relative accuracy of different techniques. The results of several critical large multicenter trials are presented, while unanswered questions that require more research are highlighted., Competing Interests: Declarations. Competing interests: Founder and shareholder in and consultant to OmnEcoil Instruments, Inc., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The bacterial pathogen, Staphylococcus aureus, grows by dividing in two alternating orthogonal planes. How these cell division planes are positioned correctly is not known. Here we used chemical genetic screening to identify PcdA as a division plane placement factor. Molecular biology and imaging approaches revealed non-orthogonal division plane selection for pcdA mutant bacteria. PcdA is a structurally and functionally altered member of the McrB AAA+ NTPase family, which are often found as restriction enzyme subunits. PcdA interacts with the tubulin-like divisome component, FtsZ, and the structural protein, DivIVA; it also localizes to future cell division sites. PcdA multimerization, localization and function are NTPase activity-dependent. We propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Although pcdA deletion did not affect S. aureus growth in several laboratory conditions, its clustered growth pattern was disrupted, sensitivity to cell-wall-targeting antibiotics increased and virulence in mice decreased. We propose that the characteristic clustered growth pattern of S. aureus, which emerges from dividing in alternating orthogonal division planes, might protect the bacterium from host defences., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Abstract: We describe early ex vivo proof-of-concept testing of a novel system composed of a disposable endorectal coil and converging multichannel needle guide with a reusable clamp stand, embedded electronics, and baseplate to allow for endorectal magnetic resonance (MR) imaging and in-bore MRI-targeted biopsy of the prostate as a single integrated procedure. Using prostate phantoms imaged with standard T 2 -weighted sequences in a Siemens 3T Prisma MR scanner, we measured the signal-to-noise ratio in successive 1-cm distances from the novel coil and from a commercially available inflatable balloon coil and measured the lateral and longitudinal deviation of the tip of a deployed MR compatible needle from the intended target point. Signal-to-noise ratio obtained with the novel system was significantly better than the inflatable balloon coil at each of five 1-cm intervals, with a mean improvement of 78% ( P < 0.05). In a representative sampling of 15 guidance channels, the mean lateral deviation for MR imaging-guided needle positioning was 1.7 mm and the mean longitudinal deviation was 2.0 mm. Our ex vivo results suggest that our novel system provides significantly improved signal-to-noise ratio when compared with an inflatable balloon coil and is capable of accurate MRI-guided needle deployment., Competing Interests: F.V.C. is a founder and shareholder in and consultant to OmnEcoil Instruments, Inc. The other authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

When faced with starvation, the bacterium Bacillus subtilis transforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor σ F is exclusively activated in the smaller daughter cell. Compartment-specific activation of σ F requires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates σ F in both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that the core components of the redeployed cell division machinery drive the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program., Competing Interests: Competing interests statement:The authors declare no competing interest.

Radiologists across many imaging modalities commonly encounter gallbladder adenomyomatosis. The classic imaging appearances of gallbladder adenomyomatosis are well described and confirm benignity. However, in clinical practice, adenomyomatosis can be challenging to differentiate from other gallbladder pathologies that require cholecystectomy. In this article, we describe the common and uncommon appearances of gallbladder adenomyomatosis on multimodality imaging, helping differentiate adenomyomatosis from non-benign gallbladder abnormalities. Accurately differentiating adenomyomatosis from its mimics provides the surgical team with important clinical and surgical management information, improving patient outcomes., Competing Interests: Declaration of competing interest There are no financial or personal interests to report on behalf of all authors regarding this publication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The spherical bacterium Staphylococcus aureus , a leading cause of nosocomial infections, undergoes binary fission by dividing in two alternating orthogonal planes, but the mechanism by which S. aureus correctly selects the next cell division plane is not known. To identify cell division placement factors, we performed a chemical genetic screen that revealed a gene which we termed pcdA . We show that PcdA is a member of the McrB family of AAA+ NTPases that has undergone structural changes and a concomitant functional shift from a restriction enzyme subunit to an early cell division protein. PcdA directly interacts with the tubulin-like central divisome component FtsZ and localizes to future cell division sites before membrane invagination initiates. This parallels the action of another McrB family protein, CTTNBP2, which stabilizes microtubules in animals. We show that PcdA also interacts with the structural protein DivIVA and propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Deletion of pcdA conferred abnormal, non-orthogonal division plane selection, increased sensitivity to cell wall-targeting antibiotics, and reduced virulence in a murine infection model. Targeting PcdA could therefore highlight a treatment strategy for combatting antibiotic-resistant strains of S. aureus .

When faced with starvation, the bacterium Bacillus subtilis transforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor σ F is exclusively activated in the smaller daughter cell. Compartment specific activation of σ F requires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates σ F in both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that a unique feature of the sporulation septum, defined by the cell division machinery, drives the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program., Competing Interests: The authors declare no competing interests.

Purpose: Investigate the intermediate-term oncological outcome after negative multiparametric MRI (mpMRI) of the prostate in patients without biopsy proven prostate cancer (PCa)., Methods: The retrospective study included 121 patients with negative mpMRI (Prostate Imaging Reporting and Data System version 2.1 category<3) performed at our institution between 2012 and 2017 without known biopsy proven PCa. Clinical and pathological data were collated including post-MRI prostatic tissue diagnoses with highest Grade Group and most recent prostate specific antigen (PSA) levels up to any definitive prostate cancer treatment. Mean PSA velocities between patients with and without a subsequent diagnosis of Grade Group 2 or higher (GG2+) PCa were compared, and an optimal threshold value was calculated., Results: Outcome data available included PSA values in 117 patients and prostate tissue sampling in 52 patients. Over a median follow up interval of 49.8 months, only 11 of 121 patients (9.1%) were diagnosed with GG2+ PCa, 10 patients (8.3%) with GG1 PCa, and 31 patients (25.6%) had negative prostate tissue samples. Mean PSA velocity was significantly higher in the patients diagnosed with GG2+ PCa (3.87 ng/mL/year) compared to those not diagnosed with GG2+ PCa (-0.71 ng/mL/year, p < 0.001). A threshold PSA velocity of 0.27 ng/mL/year had a 100% sensitivity and 69.8% specificity for GG2+ PCa (AUC: 0.898)., Conclusion: <10% of patients with negative mpMRI without prior biopsy proven PCa were diagnosed with GG2+ PCa over median follow up of over four years and were associated with PSA velocity of ≥0.27 ng/mL/year. PSA monitoring may be a reasonable management strategy in patients with a negative mpMRI without biopsy proven PCa., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cholecystectomy is one of the most common surgeries performed in the United States. Although complications are uncommon, the high incidence of this surgery means that a radiologist will likely encounter these complications in practice. Complications may arise in the immediate postoperative period or can be delayed for weeks, months, or years after surgery. Vague and nonspecific symptoms make clinical diagnosis challenging. As a result, multimodality imaging is important in postoperative evaluation. US and multidetector CT are the usual first-line imaging modalities. Hepatobiliary scintigraphy, SPECT/CT, and MRI with conventional or gadoxetate hepatobiliary contrast material are important and complementary modalities that are used for workup. The authors begin with a brief discussion of surgical technique and expected postoperative findings and then describe complications organized into four groups: (a) biliary complications, (b) stone-related complications, (c) iatrogenic complications, and (d) gallbladder complications. Biliary complications include bile leaks and bilomas, acute biliary obstruction, and biliary stricture. Stone-related complications include retained and recurrent stones and spillage of stones into the peritoneum. Iatrogenic complications include hemorrhage, vasculobiliary injury, arterial pseudoaneurysms, duodenal injury, and migration of clips. Gallbladder complications include recurrent cholecystitis after subtotal reconstituting cholecystectomy and unexpected gallbladder cancer. An invited commentary by Mullens and Ibrahim is available online. Online supplemental material is available for this article . © RSNA, 2022.

Despite advances in diagnosis and treatment, prostate cancer remains the second leading cause of cancer related mortality in men. Prognosis is variable and dependent on several clinical and genetic factors, including BRCA gene mutations. Recent clinical studies have reported that BRCA-associated prostate cancer is a more aggressive subtype with a higher probability of nodal involvement and distant metastases at the time of diagnosis, but radiological findings have not been described. Accurate recognition of those tumors could help guide clinical management and prompt testing and counseling for BRCA mutations. We have recently encountered four patients with BRCA-associated prostate cancer who underwent multiparametric MRI. The MRI appearances of these tumors, which were generally locally advanced and aggressive in appearance, are presented to facilitate recognition of BRCA-associated prostate cancer and guide potential genetic testing and counseling., (Copyright © 2022 Elsevier Inc. All rights reserved.)

BACKGROUND. Few published studies have compared in-bore and fusion MRI-targeted prostate biopsy, and the available studies have had conflicting results. OBJECTIVE. The purpose of this study was to compare the target-specific cancer detection rate of in-bore prostate biopsy with that of fusion MRI-targeted biopsy. METHODS. The records of men who underwent in-bore or fusion MRI-targeted biopsy of PI-RADS category 4 or 5 lesions between August 2013 and September 2019 were retrospectively identified. PI-RADS version 2.1 assessment category, size, and location of each target were established by retrospective review by a single experienced radiologist. Patient history and target biopsy results were obtained by electronic medical record review. Only the first MRI-targeted biopsy of the dominant lesion was included for patients with repeated biopsies or multiple targets. In-bore and fusion biopsy were compared by propensity score weights and multivariable regression to adjust for imbalances in patient and target characteristics between biopsy techniques. The primary endpoint was target-specific prostate cancer detection rate. Secondary endpoints were detection rate after application of propensity score weighting for cancers in International Society of Urological Pathology (ISUP) grade group 2 (GG2) or higher and detection rate with the use of off-target systematic sampling results. RESULTS. The study sample included 286 men (in-bore biopsy, 191; fusion biopsy, 95). Compared with fusion biopsy, in-bore biopsy was associated with significantly greater likelihood of detection of any cancer (odds ratio, 2.28 [95% CI, 1.04-4.98]; p = .04) and nonsignificantly greater likelihood of detection of ISUP GG2 or higher cancer (odds ratio, 1.57 [95% CI, 0.88-2.79]; p = .12) in a target. When off-target sampling was included, in-bore biopsy and combined fusion and systematic biopsy were not different for detection of any cancer (odds ratio, 1.16 [95% CI, 0.54-2.45]; p = .71) or ISUP GG2 and higher cancer (odds ratio, 1.15 [95% CI, 0.66-2.01]; p = .62). CONCLUSION. In this retrospective study in which propensity score weighting was used, in-bore MRI-targeted prostate biopsy had a higher target-specific cancer detection rate than did fusion biopsy. CLINICAL IMPACT. Pending a larger prospective randomized multicenter comparison between in-bore and fusion biopsy, in-bore may be the preferred approach should performing only biopsy of a suspicious target, without concurrent systematic biopsy, be considered clinically appropriate.

MRI features are presented in a multicenter retrospective series of five patients with a unilateral masslike lesion seen in the genitourinary diaphragm at MRI performed for known or suspected prostate cancer. In all cases, the lesion appeared as an encapsulated 1.3 to 3.0 cm mass of heterogeneous low or intermediate T2 signal intensity in the genitourinary diaphragm, and targeted biopsy demonstrated benign Cowper's gland tissue. This entity is a potential imaging pitfall that could result in a diagnosis of an exophytic nodule of benign prostatic hyperplasia or local spread of prostate cancer. We present these cases to facilitate correct identification of Cowper's gland hyperplasia as an occasional finding at MRI of the prostate., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To retrospectively study the performance of CT-guided biopsy of target prostate lesions at a single institution., Methods: Between May 2016 and February 2021, we retrospectively identified all men without rectal access who underwent transgluteal CT-guided biopsy of PIRADS 4 or 5 targets detected on multiparametric MRI (n = 9). Clinical, radiological, and pathological details were collected by review of the electronic medical record, and included age, pre-biopsy prostate specific antigen (PSA) value, prior biopsy history, biopsy targeting technique and procedural details, complications, and final histologic diagnosis. Two targeting techniques were used: Localizing with anatomic landmarks or localizing with contrast enhancement., Results: Mean patient age was 69 years (range, 49-74) and mean PSA was 14.6 ng/mL (range 7-23). Four lesions were targeted using anatomic landmarks and 5 were targeted using contrast enhancement. All biopsies were technically successful and all resulted as prostate cancer. Three biopsies showed Gleason 6 cancer and 6 biopsies showed clinically significant prostate cancers with Gleason 7 or above. There were no major complications. 7 patients went on to definitive treatment with surgery or radiation., Conclusion: Transgluteal CT-guided biopsy of MRI detected prostate lesions diagnoses clinically significant prostate cancer without complication and therefore should be considered for patients without a rectum., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Adenomyosis is a common benign uterine disorder in which ectopic endometrial glands extend into the myometrium. Adenomyosis is increasingly diagnosed in young women, affecting 20%-35% of women of reproductive age. Features of adenomyosis can be seen with either US or MRI, especially with newer imaging technology. With advances in reproductive endocrinology as well as a trend toward later maternal age, adenomyosis is increasingly noted during pregnancy, often while performing imaging for other reasons. Hormonal changes during pregnancy alter the appearance of adenomyosis, which includes diffuse, focal, and cystic adenomyosis. Recognizing these imaging changes in pregnancy proves essential for accurately diagnosing adenomyosis as a benign condition, as it mimics serious placental and myometrial abnormalities. Using a lower-frequency US transducer or MRI can be helpful in distinguishing among these entities. Describing the location of adenomyosis in relationship to the site of placentation is also important. Diagnosing adenomyosis is crucial because it can be associated with poor pregnancy outcomes, including spontaneous abortion, preterm birth, and fetal growth restriction. Adenomyosis is also a risk factor for preeclampsia. Intramural ectopic pregnancy is a rare but serious condition that can mimic cystic adenomyosis, and comparison with prepregnancy images can help differentiate the two conditions. The authors review the unique imaging characteristics of adenomyosis in pregnancy, focusing on accurate diagnosis of an underrecognized benign condition that can mimic myometrial and placental pathologic conditions. © RSNA, 2021.

We report the case of a 66-year-old previously healthy man presenting with blood and mucus in his urine. Cystoscopy revealed a mass in the prostatic urethra, and endoscopic biopsy showed adenocarcinoma in situ with mucinous features. Endorectal multiparametric prostate MRI demonstrated a 1.9 cm T2 hyperintense mass in the peripheral zone of the left prostatic apex with extension into the urethral lumen. No diffusion restriction or early enhancement was seen in the mass. Radical prostatectomy was performed, and final pathology demonstrated a mucin-producing urothelial adenocarcinoma arising from the prostatic urethra. The peripheral zone T2 hyperintense abnormality correlated with abundant pools of mucin extending into the prostatic stroma and surrounded by neoplastic prostatic glandular cells. We conclude prostatic urethral mucinous urothelial carcinoma should be included in the differential diagnosis for T2 hyperintense prostatic masses., (Copyright © 2020. Published by Elsevier Inc.)

Background: The use of electricity to mediate bacterial growth is unique in providing spatial control, but requires a more detailed understanding. Methods: We use two gold wires on a glass coverslip with an overlayer of agar to image Escherichia coli cells with brightfield and fluorescence microscopy while simultaneously applying a voltage. Cells outside of the wires provide a control population to measure cell growth as a function of voltage, rather than any difference in culture conditions or growth phase. Results: An applied voltage suppresses the fraction of E. coli undergoing elongation and division with recovery to control values when the voltage is removed. Depolarization is observed over the same voltage range suggesting a membrane potential-mediated response. Conclusions: Our experiments identify and use subcytotoxic voltages to measure differences in the fraction of E. coli cells elongating and dividing as a function of applied voltage. It is hoped that this research will inform the developing field of bacterial electrophysiology., Competing Interests: No competing financial interests exist., (Copyright 2020, Mary Ann Liebert, Inc., publishers.)

The intestinal pathogen Clostridioides difficile exhibits heterogeneity in motility and toxin production. This phenotypic heterogeneity is achieved through phase variation by site-specific recombination via the DNA recombinase RecV, which reversibly inverts the "flagellar switch" upstream of the flgB operon. A recV mutation prevents flagellar switch inversion and results in phenotypically locked strains. The orientation of the flagellar switch influences expression of the flgB operon post-transcription initiation, but the specific molecular mechanism is unknown. Here, we report the isolation and characterization of spontaneous suppressor mutants in the non-motile, non-toxigenic recV flg OFF background that regained motility and toxin production. The restored phenotypes corresponded with increased expression of flagellum and toxin genes. The motile suppressor mutants contained single-nucleotide polymorphisms (SNPs) in rho, which encodes the bacterial transcription terminator Rho factor. Analyses using transcriptional reporters indicate that Rho contributes to heterogeneity in flagellar gene expression by preferentially terminating transcription of flg OFF mRNA within the 5' leader sequence. Additionally, Rho is important for initial colonization of the intestine in a mouse model of infection, which may in part be due to the sporulation and growth defects observed in the rho mutants. Together these data implicate Rho factor as a regulator of gene expression affecting phase variation of important virulence factors of C. difficile., Competing Interests: The authors have declared that no competing interests exist.

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

OBJECTIVE. The purpose of this study is to investigate the impact of direct MRI-guided biopsy of the prostate on clinical management in practice. MATERIALS AND METHODS. We retrospectively identified 127 patients with unknown ( n = 98) or untreated prostate cancer with a Gleason score of 6 ( n = 29) who underwent direct MRI-guided biopsy of the prostate at our institution between August 2013 and January 2018, after initial multiparametric endorectal MRI examination revealed one or more Prostate Imaging Reporting and Data System (PI-RADS or PI-RADSv2) category 4 or 5 target lesion. All available medical and imaging records were reviewed to determine pertinent clinical details, biopsy findings, and postbiopsy management. RESULTS. The mean patient age was 68 years (interquartile range, 63-73 years). Findings from MRI-guided biopsy were positive for 93 of 127 patients (73%), with prostate cancer of Gleason score of 7 or higher diagnosed in 84 of these 93 patients (90%). When stratified by clinical scenario, the rate of positive biopsy findings was 66% (57/86) for patients who had negative findings from one or more prior transrectal ultrasound-guided biopsies, 83% (10/12) for biopsy-naive patients, and 90% (26/29) for patients undergoing active surveillance. Overall, 90 of 127 patients (71%) received a new ( n = 67) or upgraded ( n = 23) diagnosis of prostate cancer, and 57 of these 90 patients (63%) proceeded to receive treatment with prostatectomy, radiation, or androgen deprivation therapy. CONCLUSION. The results of this study suggest that direct MRI-guided biopsy is associated with high rates of significant prostate cancer detection and subsequent definitive treatment across common clinical scenarios and should be considered an important supplementary diagnostic tool in the appropriate setting.

Clostridioides difficile infection (CDI) is a toxin-mediated diarrheal disease. Several factors have been identified that influence the production of the two major C. difficile toxins, TcdA and TcdB, but prior published evidence suggested that additional unknown factors were involved in toxin regulation. Previously, we identified a C. difficile regulator, RstA, that promotes sporulation and represses motility and toxin production. We observed that the predicted DNA-binding domain of RstA was required for RstA-dependent repression of toxin genes, motility genes, and rstA transcription. In this study, we further investigated the regulation of toxin and motility gene expression by RstA. DNA pulldown assays confirmed that RstA directly binds the rstA promoter via the predicted DNA-binding domain. Through mutational analysis of the rstA promoter, we identified several nucleotides that are important for RstA-dependent transcriptional regulation. Further, we observed that RstA directly binds and regulates the promoters of the toxin genes tcdA and tcdB , as well as the promoters for the sigD and tcdR genes, which encode regulators of toxin gene expression. Complementation analyses with the Clostridium perfringens RstA ortholog and a multispecies chimeric RstA protein revealed that the C. difficile C-terminal domain is required for RstA DNA-binding activity, suggesting that species-specific signaling controls RstA function. Our data demonstrate that RstA is a transcriptional repressor that autoregulates its own expression and directly inhibits transcription of the two toxin genes and two positive toxin regulators, thereby acting at multiple regulatory points to control toxin production. IMPORTANCE Clostridioides difficile is an anaerobic, gastrointestinal pathogen of humans and other mammals. C. difficile produces two major toxins, TcdA and TcdB, which cause the symptoms of the disease, and forms dormant endospores to survive the aerobic environment outside the host. A recently discovered regulatory factor, RstA, inhibits toxin production and positively influences spore formation. Herein, we determine that RstA directly binds its own promoter DNA to repress its own gene transcription. In addition, our data demonstrate that RstA directly represses toxin gene expression and gene expression of two toxin gene activators, TcdR and SigD, creating a complex regulatory network to tightly control toxin production. This study provides a novel regulatory link between C. difficile sporulation and toxin production. Further, our data suggest that C. difficile toxin production is regulated through a direct, species-specific sensing mechanism., (Copyright © 2019 Edwards et al.)

The SecA2 protein export system is critical for the virulence of Mycobacterium tuberculosis . However, the mechanism of this export pathway remains unclear. Through a screen for suppressors of a secA2 mutant, we identified a new player in the mycobacterial SecA2 pathway that we named SatS for S ec A 2 ( t wo) S uppressor. In M. tuberculosis , SatS is required for the export of a subset of SecA2 substrates and for growth in macrophages. We further identify a role for SatS as a protein export chaperone. SatS exhibits multiple properties of a chaperone, including the ability to bind to and protect substrates from aggregation. Our structural studies of SatS reveal a distinct combination of a new fold and hydrophobic grooves resembling preprotein-binding sites of the SecB chaperone. These results are significant in better defining a molecular pathway for M. tuberculosis pathogenesis and in expanding our appreciation of the diversity among chaperones and protein export systems., Competing Interests: BM, RH, LL, NR, SM, BA, JS, MB No competing interests declared, (© 2019, Miller et al.)

There are differences in renal biopsy yield related to on-site evaluation, tissue division, and operator, among others. To understand these variations, we collected adequacy-associated data (%cortex, glomeruli, arteries, length) from consecutive native and allograft kidney biopsies over a 22-month period. In total, 1332 biopsies (native: 873, allograft: 459) were included, 617 obtained by nephrologists, 663 by radiologists, and 559 with access to on-site division. Proceduralists with access to on-site evaluation had significantly lower inadequacy rates and better division of tissue for light microscopy (LM), immunofluorescence, and electron microscopy than those without access to on-site evaluation. Radiologists in our region were significantly less likely to have access to on-site evaluation than nephrologists. On multivariate analysis for native kidney biopsies, the effect of having a radiologist perform the biopsy and having access to on-site division were both significant predictors of obtaining greater calculated amount of cortex for LM. Despite the trend for radiologists to obtain more tissue in general, biopsies from nephrologists contained a greater percentage of cortex and were more likely to be considered adequate for LM (native kidney inadequacy rate for LM: 1.11% vs. 5.41%, P=0.0086). Biopsies in which inadequate or marginal cortical tissue was submitted for LM had only minor decreases in the amount of cortex submitted for immunofluorescence and electron microscopy, revealing an opportunity for improved specimen triaging when limited tissue is obtained. In conclusion, both on-site evaluation/division and proceduralist significantly affect quantitative kidney biopsy metrics, which in turn affects the pathologist's ability to render an accurate diagnosis with appropriate prognostic information for the patient and treating nephrologist.

Endoscopic interventions play an important role in the modern management of pancreatic fluid collections. Successful management of pancreatitis is dependent on proper classification of the disease and its local complications. The 2012 revised Atlanta classification divides acute pancreatitis into subtypes of necrotizing pancreatitis and interstitial edematous pancreatitis (IEP) on the basis of the radiologic presence or absence of necrosis, respectively. Local complications of IEP include acute pancreatic fluid collections and pseudocysts, which contain fluid only and are differentiated by the time elapsed since the onset of symptoms. Local complications of necrotizing pancreatitis include acute necrotic collections and walled-off necrosis, which contain nonliquefied necrotic debris and are differentiated by the time elapsed since the onset of symptoms. Endoscopic techniques are used to treat local complications of pancreatitis, often in a step-up approach, by which less invasive techniques are preferred initially with potential subsequent use of more invasive procedures, dependent on the patient's clinical response and collection evolution. Common interventions performed by the advanced endoscopist include endoscopic transmural drainage and endoscopic transmural necrosectomy. However, some collections require a multimodal approach with adjunctive placement of percutaneous drainage catheters or the use of videoscopic-assisted retroperitoneal débridement. Additional endoscopic interventions may be required in the setting of pancreatic or biliary duct stones or strictures. Common complications of endoscopic intervention in the setting of pancreatitis include bleeding, infection, perforation, and stent migration. This article reviews the classification of acute pancreatitis, familiarizes radiologists with the common endoscopic techniques used in its management, and improves identification of the clinically relevant imaging findings and procedural complications related to endoscopic interventions in pancreatitis. © RSNA, 2018.

Purpose: To investigate the concordance between dominant intraprostatic cancer seen on endorectal multiparametric MRI and confirmed by MRI-targeted biopsy with histopathological findings at radical prostatectomy, since existing literature has emphasized the miss rather than the concordance rate of MRI., Materials and Methods: We retrospectively identified 20 patients who underwent radical prostatectomy after a dominant intraprostatic cancer focus was identified at endorectal multiparametric MRI and confirmed by MRI-targeted biopsy. Concordance was determined by comparing the location and Gleason grade group of dominant tumor at MRI with the location and Gleason grade group determined at histopathological review., Results: Mean patient age was 65 years (range, 48 to 76) and median serum prostatic specific antigen level was 9.4 ng/mL (range, 4.6 to 58.0). In all 20 patients, the location of dominant tumor based on MRI and targeted biopsy corresponded with the dominant tumor location at histopathology. In 9 patients, Gleason grade group was the same at targeted biopsy and final histopathology. In 9 patients, final Gleason grade group was higher and in two patients it was lower., Conclusion: Our preliminary results suggest dominant tumor as determined by endorectal multiparametric MRI and confirmed by a positive MRI-targeted biopsy has high concordance with histopathological findings at radical prostatectomy for location, and reasonable concordance for Gleason grade group., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The biological mechanisms regulating physical activity patterns appear to be linked to the sex hormones. Elucidation of these regulatory mechanisms may enhance individual physical activity patterns producing positive gains in health., Purpose: The purpose of this study was to evaluate the prolonged effects of estrogen on wheel running distance, duration, and speed in orchidectomized mice., Methods: The physical activity patterns of 9-wk-old C57BL/6j male mice (n = 28) were observed. Wheel running distance, duration, and speed were assessed under physiological conditions for 7 d. Next, physical activity patterns were evaluated after bilateral orchidectomy (n = 14) or sham orchidectomy (n = 14) for an additional 7 d. Orchidectomized mice were provided estrogen containing capsules for three additional weeks; control mice were provided estrogen-free capsules. Wheel running distance, duration, and speed were analyzed by three two-way (treatment group-phase of study) analysis of variance tests., Results: Wheel running speed was unaffected by sex hormone status. Distance (mean ± SD = 6.74 ± 2.13 km at baseline) decreased significantly after orchidectomy (2.27 ± 1.55 km) and remained low after initial estrogen treatment (3.04 ± 1.05 km). Prolonged estrogen exposure sustained a significant elevation of daily distance (4.47 ± 1.87 km). Prolonged estrogen exposure recovered and significantly sustained wheel running duration (baseline, 248 ± 60 min; postorchidectomy, 102 ± 53 min; prolonged exposure, 170 ± 63 min)., Conclusions: Wheel running behavior was reduced significantly after orchidectomy and remained low after initial treatment with estrogens, but recovered to near control levels after 2 wk of exposure to estrogens. The estrogenic mechanism regulating wheel running behavior in male mice appears to induce an extensive but slow acting biological mechanism. Understanding the biological drive behind this mechanism may aid in developing useful therapeutic strategies to combat health issues related to physical inactivity.

Objective: To evaluate the length of contact between dominant tumor foci and the prostatic capsule as a sign of extracapsular extension at endorectal multiparametric MR imaging., Materials and Methods: We retrospectively identified 101 patients over a three-year interval who underwent endorectal multiparametric prostate MR imaging prior to radical prostatectomy for prostate cancer. Two readers identified the presence of dominant tumor focus (largest lesion with PI-RADS version 2 score of 4 or 5), and measured the length of tumor capsular contact and likelihood of extracapsular extension by standard criteria (1-5 Likert scale). Results were analyzed using histopathological review as reference standard., Results: Extracapsular extension was found at histopathological review in 27 patients. Reader 1 (2) identified dominant tumor in 79 (73) patients, with mean tumor capsular contact length of 18.2 (14.0) mm. The area under the receiver operating characteristic curve for identification of extracapsular extension by tumor capsular contact length was 0.76 for reader 1 and 0.77 for reader 2, with optimal discrimination at values of 18 mm and 21 mm, respectively. In the subset of patients without obvious extracapsular extension by standard criteria (Likert scores 1-3), corresponding values were 0.74 and 0.66 with optimal thresholds of 24 and 21 mm., Conclusion: Length of contact between the dominant tumor focus and the capsule is a moderately useful sign of extracapsular extension at endorectal multiparametric prostate MR imaging, including the subset of patients without obvious extracapsular extension by standard criteria, with optimal discrimination at threshold values of 18 to 24 mm., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Clostridioides difficile causes diarrheal diseases mediated in part by the secreted toxins TcdA and TcdB. C. difficile produces flagella that also contribute to motility and bacterial adherence to intestinal cells during infection. Flagellum expression and toxin gene expression are linked via the flagellar alternative sigma factor, SigD. Recently, we identified a flagellar switch upstream of the early flagellar biosynthesis operon that mediates phase variation of both flagellum and toxin production in C. difficile strain R20291. However, we were unable to detect flagellar switch inversion in C. difficile strain 630, a ribotype 012 strain commonly used in research labs, suggesting that the strain is phase locked. To determine whether a phase-locked flagellar switch is limited to 630 or present more broadly in ribotype 012 strains, we assessed the frequency and phenotypic outcomes of flagellar switch inversion in multiple C. difficile ribotype 012 isolates. The laboratory-adapted strain JIR8094, a derivative of strain 630, and six clinical and environmental isolates were all found to be phase-off, nonmotile, and attenuated for toxin production. We isolated low-frequency motile derivatives of JIR8094 with partial recovery of motility and toxin production and found that additional changes in JIR8094 impact these processes. The clinical and environmental isolates varied considerably in the frequency by which flagellar phase-on derivatives arose, and these derivatives showed fully restored motility and toxin production. Taken together, these results demonstrate heterogeneity in flagellar and toxin phase variation among C. difficile ribotype 012 strains and perhaps other ribotypes, which could impact disease progression and diagnosis. IMPORTANCE C. difficile produces flagella that enhance bacterial motility and secretes toxins that promote diarrheal disease symptoms. Previously, we found that production of flagella and toxins is coregulated via a flippable DNA element termed the flagellar switch, which mediates the phase-variable production of these factors. Here, we evaluate multiple isolates of C. difficile ribotype 012 strains and find them to be primarily flagellar phase off ( flg -off state). Some, but not all, of these isolates showed the ability to switch between flg -on and -off states. These findings suggest heterogeneity in the ability of C. difficile ribotype 012 strains to phase-vary flagellum and toxin production, which may broadly apply to pathogenic C. difficile ., (Copyright © 2018 American Society for Microbiology.)

Physical inactivity is a leading cause of hypokinetic diseases - obesity, heart disease, diabetes, and certain types of cancers. Increased city walkability, better access to fitness facilities, and remediation of socioeconomic barriers prove successful for limited populations within the confines of stringently controlled environments; however, these strategies fail to reverse the ever-increasing physical inactivity epidemic on a global scale indicating the existence of other unidentified factors. These purported biological factors remain critical targets to understand the regulation of this complex phenotype. An estrogenic mechanism that incompletely or slowly adjusts physical activity levels following reintroduction of estrogenic compounds to surgically gonadectomized mice has been postulated to exist. Currently, this mechanism remains scrutinized due to concerns that elevated estrogen levels induce urinary bladder distension. The distension of the urinary bladder may mechanically disrupt physical activity, masking any physiological effects estrogen has on physical activity. The purpose of this study was to evaluate the effects of estrogen on physical activity levels while employing dose-related strategies to alleviate distension in mice. Wheel running data were collected under normal physiological conditions, following removal of endogenous sex steroids via orchidectomy, and during estrogen replacement at various doses (0%, 10%, 50% or 100% estrogen-containing implants) to induce varying degrees of urinary bladder distension. Wheel running distance (P = 0.005) and duration (P = 0.006) decreased after orchidectomy, but slowly increased following estrogen replacement. During the study, wheel running did not return to the levels observed in physiologically intact mice. Significant distension was not observed between estrogen treatment groups indicating that a slow-responding estrogen effect exists in male mice that prevents wheel running from returning to normal levels immediately following steroid reintroduction. The limited increase in wheel running during estrogen treatment following orchidectomy is not an artifact of induced urinary bladder distension., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Clostridium difficile is a leading cause of nosocomial infections, causing disease that ranges from mild diarrhea to potentially fatal colitis. A variety of surface proteins, including flagella, enable C. difficile colonization of the intestine. Once in the intestine, toxigenic C. difficile secretes two glucosylating toxins, TcdA and TcdB, which elicit inflammation and diarrheal disease symptoms. Regulation of colonization factors and TcdA and TcdB is an intense area of research in C. difficile biology. A recent publication from our group describes a novel regulatory mechanism that mediates the ON/OFF expression of co-regulated virulence factors of C. difficile, flagella and toxins. Herein, we review key findings from our work, present new data, and speculate the functional consequence of the ON/OFF expression of these virulence factors during host infection.

Ultrasonography (US) is frequently the first imaging modality used to examine women with symptoms involving the pelvis. It is widely available and involves no exposure to ionizing radiation. Images can be acquired with a transabdominal, endovaginal, or translabial approach, and the use of video clips and three-dimensional reconstructions can be helpful. US is excellent for assessment of the uterus, ovaries, and adnexa. Occasionally, nongynecologic pelvic diseases arising from the gastrointestinal, genitourinary, and musculoskeletal systems and the pelvic peritoneal and extraperitoneal spaces may be detected and can be a source of diagnostic dilemma. US can be helpful not only in the detection but also occasionally in the characterization of such entities. Computed tomography and magnetic resonance imaging are useful in complicated cases. In this article, the normal US appearance of the bowel and US signs of bowel disease and specific entities, including appendicitis, diverticular disease, bowel obstruction, appendiceal mucocele, and intestinal tumors, are reviewed. The lower urinary tract is included in the field of view in every pelvic US examination; commonly encountered entities related to the urinary bladder, distal ureter, and urethra are illustrated. In addition to arising in the gastrointestinal and genitourinary tracts, pathologic conditions in the pelvis can arise in the peritoneal or extraperitoneal space. Although conditions of the pelvic peritoneal and extraperitoneal spaces are rare, it is important to recognize these entities and distinguish them from the more common gynecologic diseases. Owing to the implications for diagnosis and management, radiologists and other physicians who perform pelvic US should be aware of the spectrum of nongynecologic pathologic entities that can be detected. © RSNA, 2017.

Background: Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated., Objective: To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis., Materials and Methods: We included patients ages 4-18 years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy., Results: Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7 mm and ≥2 mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (P<0.01), with sensitivities of 91% and 97% and specificities of 60% and 50%. For examinations in which the appendix was not identified by one or both reviewers (23/98), the clinical outcome was negative., Conclusion: Rapid MRI without contrast agents or sedation is accurate for diagnosis of pediatric appendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7 mm for diameter and ≥2 mm for wall thickness demonstrate high sensitivities but relatively low specificities. Nonvisualization of the appendix favors a negative diagnosis.

MRI-targeted biopsy of the prostate appears to have the potential to reduce the high rates of underdiagnosis and overdiagnosis associated with the current diagnostic standard of transrectal ultrasound guided systematic biopsy. Direct or "in bore" MRI-guided biopsy is one of the three methods for MRI-targeted core needle sampling of suspicious, generally Pi-RADS 4 or 5, foci within the prostate, and our early experience suggests the approach demonstrates substantial utility and promise in the care of patients with prostate cancer. We performed direct MRI-guided biopsies in 50 patients within 19 months of establishing the first referral center for this service in our region. Our preliminary results indicate the service can be easily grown due to unmet demand, primarily in patients with a negative traditional systematic biopsy but with a concerning focus at MRI (30 of 50; 60%). Other applications include evaluation of patients who are on active surveillance (n=14; ten upgraded to higher Gleason score at MRI-guided biopsy), who are biopsy naïve (n=5; all positive at MRI-guided biopsy), or post focal therapy (n=1; positive for recurrent tumor at MRI-guided biopsy). With careful patient selection and technique, we have achieved a favorable overall positive biopsy rate of 73% (37 of 50), with 84% (31 of 37) positive biopsies demonstrating Gleason score 7 or greater disease. Large multicenter comparative trials will be required to determine the relative accuracy and appropriate utilization of direct MRI guided biopsy in the care pathway of patients with known or suspected prostate cancer., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

In the human intestinal pathogen Clostridium difficile, flagella promote adherence to intestinal epithelial cells. Flagellar gene expression also indirectly impacts production of the glucosylating toxins, which are essential to diarrheal disease development. Thus, factors that regulate the expression of the flgB operon will likely impact toxin production in addition to flagellar motility. Here, we report the identification a "flagellar switch" that controls the phase variable production of flagella and glucosylating toxins. The flagellar switch, located upstream of the flgB operon containing the early stage flagellar genes, is a 154 bp invertible sequence flanked by 21 bp inverted repeats. Bacteria with the sequence in one orientation expressed flagellum and toxin genes, produced flagella, and secreted the toxins ("flg phase ON"). Bacteria with the sequence in the inverse orientation were attenuated for flagellar and toxin gene expression, were aflagellate, and showed decreased toxin secretion ("flg phase OFF"). The orientation of the flagellar switch is reversible during growth in vitro. We provide evidence that gene regulation via the flagellar switch occurs post-transcription initiation and requires a C. difficile-specific regulatory factor to destabilize or degrade the early flagellar gene mRNA when the flagellar switch is in the OFF orientation. Lastly, through mutagenesis and characterization of flagellar phase locked isolates, we determined that the tyrosine recombinase RecV, which catalyzes inversion at the cwpV switch, is also responsible for inversion at the flagellar switch in both directions. Phase variable flagellar motility and toxin production suggests that these important virulence factors have both advantageous and detrimental effects during the course of infection.

Gestational trophoblastic disease (GTD) is a spectrum of both benign and malignant gestational tumors, including hydatidiform mole (complete and partial), invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The latter four entities are referred to as gestational trophoblastic neoplasia (GTN). These conditions are aggressive with a propensity to widely metastasize. GTN can result in significant morbidity and mortality if left untreated. Early diagnosis of GTD is essential for prompt and successful management while preserving fertility. Initial diagnosis of GTD is based on a multifactorial approach consisting of clinical features, serial quantitative human chorionic gonadotropin (β-hCG) titers, and imaging findings. Ultrasonography (US) is the modality of choice for initial diagnosis of complete hydatidiform mole and can provide an invaluable means of local surveillance after treatment. The performance of US in diagnosing all molar pregnancies is surprisingly poor, predominantly due to the difficulty in differentiating partial hydatidiform mole from nonmolar abortion and retained products of conception. While GTN after a molar pregnancy is usually diagnosed with serial β-hCG titers, imaging plays an important role in evaluation of local extent of disease and systemic surveillance. Imaging also plays a crucial role in detection and management of complications, such as uterine and pulmonary arteriovenous fistulas. Familiarity with the pathogenesis, classification, imaging features, and treatment of these tumors can aid in radiologic diagnosis and guide appropriate management. © RSNA, 2017.

Purpose: Metastatic castration-resistant prostate cancer (CRPC) is the lethal form of the disease. Many groups have performed mutational or immunohistochemistry (IHC) testing in metastatic CRPC to identify treatment targets. However, the frequency with which mutational or IHC data have an impact on clinical decision making and the outcomes of molecularly guided therapy in CRPC are largely unknown. We report our institution's experience with mutational and IHC testing in patients with metastatic CRPC and its impact on clinical decision making and patient outcomes., Methods: Between 2012 and 2015, 59 patients with CRPC underwent metastatic tissue biopsies and were genotyped with a 37-cancer gene panel in a Clinical Laboratory Improvement Amendments-certified laboratory. PTEN expression by IHC testing was also measured in 35 of these samples. A retrospective chart review was performed to determine whether the genomic information was acted upon and the outcome of patients whose treatment was guided by molecular testing., Results: Forty-six of 59 patients with CRPC (78.0%) had biopsies with adequate tumor for mutational testing. Thirty-one of 46 subjects (67.4%) had mutations identified by sequencing. Of the 35 patients with CRPC whose biopsies were evaluated for PTEN expression by IHC testing, 13 had PTEN loss. Two patients had treatment on the basis of molecular testing, and one of these subjects had greater tumor control with molecularly guided therapy than his immediate prior therapy., Conclusion: Targeted sequencing and IHC can identify clinically informative molecular abnormalities in CRPC. Despite this, a small minority of patients in our series underwent therapies guided by mutational or IHC testing. Actionability of abnormalities identified in metastatic CRPC may be improved with access to clinical trials, insurance approval for unapproved uses of existing anticancer drugs, and larger gene sequencing panels that include more frequently mutated genes., Competing Interests: AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Molecular Testing in Patients With Castration-Resistant Prostate Cancer and Its Impact on Clinical Decision Making The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or po.ascopubs.org/site/ifc. Derrick L. Tao No relationship to disclose Shawna Bailey Research Funding: Janssen Research & Development (Inst), Medivation (Inst), Millennium (Inst), Aragon Pharmaceuticals (Inst), Bristol-Myers Squibb (Inst), OncoGenex (Inst), Astellas Scientific & Medical Affairs (Inst), Bayer (Inst), Myriad Genetics (Inst), SOTIO (Inst), Sanofi (Inst), Zenith Epigenetics (Inst), Boehringer Ingelheim Pharmaceuticals (Inst), Merck (Inst) Tomasz M. Beer Stock and Other Ownership Interests: Salarius Pharmaceuticals Consulting or Advisory Role: AstraZeneca, Churchill Pharmaceuticals, Dendreon, Janssen Biotech, Janssen Oncology, Janssen Research & Development, Johnson & Johnson, Janssen Japan, Roche Research Funding: Astellas Pharma (Inst), Bristol-Myers Squibb (Inst), Dendreon (Inst), Janssen Research & Development (Inst), Medivation (Inst), OncoGenex (Inst), SOTIO (Inst), SOTIO, Theraclone Sciences (Inst), Boehringer Ingelheim (Inst) Erik Foss Research Funding: Coinvestigator for a research grant from Moximed for magnetic resonance imaging of potential and postoperative patients undergoing KineSpring knee implant surgery (an orthopedic implant designed to alleviate degenerative joint pain). Brooke Beckett No relationship to disclose Alice Fung Speakers’ Bureau: Guerbet Bryan R. Foster Honoraria: CIVCO Medical Solutions Alexander Guimaraes Honoraria: Philips Healthcare 2015 ($1,500); Siemens Medical Solutions 2014 ($2,000) Speakers’ Bureau: Siemens Medical Solutions 2014 Travel, Accommodations, Expenses: Siemens Medical Solutions 2014, Philips Healthcare 2015 Jeremy P. Cetnar No relationship to disclose Julie N. Graff Honoraria: Bayer, Astellas Medivation, Janssen Oncology Consulting or Advisory Role: Exelixis Research Funding: Sanofi (Inst), Medivation (Inst), Bristol-Myers Squibb (Inst), Merck Sharp & Dohme (Inst), Janssen Oncology (Inst) Patents, Royalties, Other Intellectual Property: OncoResponse: Exceptional responders Travel, Accommodations, Expenses: Bayer, Merck Sharp & Dohme, Clovis Oncology Kristine M. Eilers No relationship to disclose Eric J. Small Stock and Other Ownership Interests: Fortis Therapeutics, Harpoon Therapeutics Honoraria: Janssen-Cilag Consulting or Advisory Role: Fortis Therapeutics, Gilead Sciences Research Funding: Janssen (Inst) Christopher L. Corless Honoraria: Roche Consulting or Advisory Role: Roche, Thermo Fisher Scientific Biomarkers Travel, Accommodations, Expenses: Roche, Thermo Fisher Scientific George V. Thomas No relationship to disclose Joshi J. Alumkal Consulting or Advisory Role: Astellas Pharma, Bayer Research Funding: Aragon Pharmaceuticals (Inst), Astellas Pharma (Inst), Millennium (Inst), Novartis (Inst), Zenith Epigenetics (Inst)