Continued Tumor Reduction of Metastatic Pheochromocytoma/Paraganglioma Harboring Succinate Dehydrogenase Subunit B Mutations with Cyclical Chemotherapy

Patients harboring germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene present with pheochromocytomas and paragangliomas (PPGL) that are more likely malignant and clinically aggressive. The combination chemotherapy cyclophosphamide, vincristine, and dacarbazine (CVD) was retrospectively evaluated in patients with SDHB-associated metastatic PPGL.Query Twelve metastatic PPGL patients harboring SDHB mutations/polymorphisms with undetectable SDHB immunostaining were treated with CVD. CVD therapy consisted of 750 mg/m² cyclophosphamide with 1.4 mg/m² vincristine on day 1 and 600 mg/m² dacarbazine on days 1 and 2, every 21–28 days. Treatment outcome was determined by RECIST criteria as well as determination of response duration and progression-free and overall survivals. A median of 20.5 cycles (range 4–41) was administered. All patients had tumor reduction (12–100% by RECIST). Complete response was seen in two patients, while partial response was observed in 8. The median number of cycles to response was 5.5. Median duration of response was 478 days, with progression-free and overall survivals of 930 and 1190 days, respectively. Serial [¹⁸F]-fluorodeoxyglucose positron emission tomography and computed tomography imaging demonstrated continued incremental reduction in maximal standardized uptake values (SUV_max) values in 26/30 lesions. During treatment administration, the median SUV decreased from?> 25 to?< 6, indicating the efficacy of chemotherapy over a prolonged period of time. Prolonged therapy results in continued incremental tumor reduction, and is consistent with persistent drug sensitivity. CVD chemotherapy is recommended to be considered part of the initial management in patients with metastatic SDHB-related PPGL.     

Rural Livelihood Variation and its Effects on Child Growth in Timor-Leste

Economic development introduces opportunities for subsistence households to diversify income sources. Timor-Leste is undergoing this transition; however, little is known about the patterns of household strategies and the effects of rural development on child wellbeing. We derive strategies from 190 households in two rural Timor-Leste communities and examine the links between resource strategies and child growth using linear mixed modeling. Children’s z-height, z-weight, and z-BMI are well below international standards. We find agriculture remains predominantly subsistence-based, with some reliance on cash flow from government pensions and salaries. Households with stable income sources are better able to accumulate wealth, and children living in salaried households have better z-height. However, child growth is best predicted by individual-level factors rather than household ecology. Substantial variation in household strategy and little association of strategy with growth indicates there is no ‘best’ strategy in this transitioning environment.     

Seasonal dynamics of agonistic behavior and hormones in an ex situ all‐male colony of large flying foxes

Large flying foxes (Pteropus vampyrus) are a socially complex species. In situ colonies typically comprise thousands of individuals in small harems of one male to many females. In ex situ environments, all‐male colonies are becoming more common due to a surplus of males in the population. There is limited information describing the hormonal and behavioral patterns of all‐male colonies during the breeding season. We assessed seasonal changes in hormones and behavior in an all‐male colony of 12 large flying foxes at Disney's Animal Kingdom^®. We validated hormone assays using morning urine and fecal samples to assess seasonal changes in excreted immunoreactive testosterone and glucocorticoid metabolites. We collected behavior data using an all‐occurrence method, recording agonistic behaviors related to territorial defense (hooking, biting, wing flexing, vocalizing, and wrestling), and sexual behavior (mounting and frontal grabbing). Results indicated that (i) we could reliably measure testosterone and glucocorticoid metabolites concentrations from fecal and urine samples collected from individual bats; (ii) there were distinct relationships between changes in levels of agonism and hormone concentrations throughout the year; and (iii) three agonistic behaviors (chasing, wrestling, and open‐mouth threat) peaked prior to the increase in testosterone and glucocorticoid hormones measured during the breeding season. These three behaviors could potentially be used as early indicators to signal the onset of the breeding season and allow time to implement ex situ management changes to reduce the incidence of agonism between individuals.     

Environmental DNA detection of rare and invasive fish species in two Great Lakes tributaries

The extraction and characterization of DNA from aquatic environmental samples offers an alternative, noninvasive approach for the detection of rare species. Environmental DNA, coupled with PCR and next‐generation sequencing (“metabarcoding”), has proven to be very sensitive for the detection of rare aquatic species. Our study used a custom‐designed group‐specific primer set and next‐generation sequencing for the detection of three species at risk (Eastern Sand Darter, Ammocrypta pellucida; Northern Madtom, Noturus stigmosus; and Silver Shiner, Notropis photogenis), one invasive species (Round Goby, Neogobius melanostomus) and an additional 78 native species from two large Great Lakes tributary rivers in southern Ontario, Canada: the Grand River and the Sydenham River. Of 82 fish species detected in both rivers using capture‐based and eDNA methods, our eDNA method detected 86.2% and 72.0% of the fish species in the Grand River and the Sydenham River, respectively, which included our four target species. Our analyses also identified significant positive and negative species co‐occurrence patterns between our target species and other identified species. Our results demonstrate that eDNA metabarcoding that targets the fish community as well as individual species of interest provides a better understanding of factors affecting the target species spatial distribution in an ecosystem than possible with only target species data. Additionally, eDNA is easily implemented as an initial survey tool, or alongside capture‐based methods, for improved mapping of species distribution patterns.     

Factors associated with a low prevalence of exclusive breastfeeding during hospital stay in urban and semi-rural areas of southern Vietnam

Background

There is a paucity of data regarding risk factors associated with suboptimal breastfeeding practices in urbanized areas of low-middle income countries (LMICs).

Methods

Through a large prospective birth cohort, which enrolled 6706 infants in Vietnam between 2009 and 2013, we investigated the practice of exclusive breastfeeding during hospital stay in urban and semi-rural populations and aimed to identify factors associated with suboptimal breastfeeding practices. Univariate and multivariable logistic regression were performed to determine factors associated with not exclusive breastfeeding during hospital stay.

Results

Of 6076 mothers, 33% (2187) breastfed their infant exclusively before hospital discharge; 9% (364/4248) in urban and 74% (1823/2458) in semi-rural areas. Exclusive breastfeeding up to 4 months was recorded in 15% (959/6210) of participants; this declined to <?1% (56/6093) at 6 months. Delivery by Caesarean section (Odds Ratio [OR] 0.07; 95% Confidence Interval [CI] 0.04, 0.11 and OR 0.05; 95% CI 0.03, 0.08) and neonatal complications (OR 0.2; 95% CI 0.07, 0.47 and OR 0.25; 95% CI 0.14, 0.46) were common and highly significant risk factors associated with a lack of exclusive breastfeeding during hospital stay in urban and semi-rural settings, respectively.

Conclusions

To our knowledge, this is the first large-scale investigation aimed at identifying factors associated with exclusive breastfeeding during hospital stay in Vietnam. Breastfeeding promotion strategies should prioritize common risk factors in hospital, such as Caesarean section and neonatal complications, and other location specific factors associated with socioeconomics.

     

The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration

Integrin β3 is seen as a key anti‐angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro‐ or anti‐angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3‐dependent adhesome. We show that depletion of β3‐integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3‐integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2‐driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3‐integrin levels are reduced.     

The effect of warmer winters on the demography of an outbreak insect is hidden by intraspecific competition

Warmer climates are predicted to increase bark beetle outbreak frequency, severity, and range. Even in favorable climates, however, outbreaks can decelerate due to resource limitation, which necessitates the inclusion of competition for limited resources in analyses of climatic effects on populations. We evaluated several hypotheses of how climate impacts mountain pine beetle reproduction using an extensive 9‐year dataset, in which nearly 10,000 trees were sampled across a region of approximately 90,000 km², that was recently invaded by the mountain pine beetle in Alberta, Canada. Our analysis supports the hypothesis of a positive effect of warmer winter temperatures on mountain pine beetle overwinter survival and provides evidence that the increasing trend in minimum winter temperatures over time in North America is an important driver of increased mountain pine beetle reproduction across the region. Although we demonstrate a consistent effect of warmer minimum winter temperatures on mountain pine beetle reproductive rates that is evident at the landscape and regional scales, this effect is overwhelmed by the effect of competition for resources within trees at the site level. Our results suggest that detection of the effects of a warming climate on bark beetle populations at small spatial scales may be difficult without accounting for negative density dependence due to competition for resources.     

Multi‐model comparison highlights consistency in predicted effect of warming on a semi‐arid shrub

A number of modeling approaches have been developed to predict the impacts of climate change on species distributions, performance, and abundance. The stronger the agreement from models that represent different processes and are based on distinct and independent sources of information, the greater the confidence we can have in their predictions. Evaluating the level of confidence is particularly important when predictions are used to guide conservation or restoration decisions. We used a multi‐model approach to predict climate change impacts on big sagebrush (Artemisia tridentata), the dominant plant species on roughly 43 million hectares in the western United States and a key resource for many endemic wildlife species. To evaluate the climate sensitivity of A. tridentata, we developed four predictive models, two based on empirically derived spatial and temporal relationships, and two that applied mechanistic approaches to simulate sagebrush recruitment and growth. This approach enabled us to produce an aggregate index of climate change vulnerability and uncertainty based on the level of agreement between models. Despite large differences in model structure, predictions of sagebrush response to climate change were largely consistent. Performance, as measured by change in cover, growth, or recruitment, was predicted to decrease at the warmest sites, but increase throughout the cooler portions of sagebrush's range. A sensitivity analysis indicated that sagebrush performance responds more strongly to changes in temperature than precipitation. Most of the uncertainty in model predictions reflected variation among the ecological models, raising questions about the reliability of forecasts based on a single modeling approach. Our results highlight the value of a multi‐model approach in forecasting climate change impacts and uncertainties and should help land managers to maximize the value of conservation investments.     

Perfusion‐based fluorescence imaging method delineates diverse organs and identifies multifocal tumors using generic near‐infrared molecular probes

Rapid detection of multifocal cancer without the use of complex imaging schemes will improve treatment outcomes. In this study, dynamic fluorescence imaging was used to harness differences in the perfusion kinetics of near‐infrared (NIR) fluorescent dyes to visualize structural characteristics of different tissues. Using the hydrophobic nontumor‐selective NIR dye cypate, and the hydrophilic dye LS288, a high tumor‐to‐background contrast was achieved, allowing the delineation of diverse tissue types while maintaining short imaging times. By clustering tissue types with similar perfusion properties, the dynamic fluorescence imaging method identified secondary tumor locations when only the primary tumor position was known, with a respective sensitivity and specificity of 0.97 and 0.75 for cypate, and 0.85 and 0.81 for LS288. Histological analysis suggests that the vasculature in the connective tissue that directly surrounds the tumor was a major factor for tumor identification through perfusion imaging. Although the hydrophobic dye showed higher specificity than the hydrophilic probe, use of other dyes with different physical and biological properties could further improve the accuracy of the dynamic imaging platform to identify multifocal tumors for potential use in real‐time intraoperative procedures.