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While Effective Altruism helps influencers do good by supporting farmed animal causes, it has been woefully inadequate in guiding strategies within the farmed animal advocacy space. Moreover, Effective Altruist funding has generated troubling consequences. Focusing on short-term incremental improvements, advocates are taking their eyes off the prize: the end of factory farming. The farmed animal movement has more investments than ever going into corporate campaigns, but meaningful returns have been diminishing. While advocacy groups receive significant funding for incremental improvements, other promising strategies tied to a bolder vision for systemic change remain underfunded. We don’t need to accept the factory farm as an inevitable evil and content ourselves with making it “more humane.” Funders can do enormous good within their lifetimes, but only through a willingness to confront complex social challenges. The movement needs funders with fearlessness, an entrepreneurial spirit of experimentation, and the moral imagination to end industrial farming.

Serine is a nonessential amino acid generated by the sequential actions of phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1), and phosphoserine phosphatase (PSPH). Increased serine biosynthesis occurs in several cancers and supports tumor growth. In addition, cancer cells can harness exogenous serine to enhance their metabolism and proliferation. Here we tested the relative contributions of exogenous and endogenous sources of serine on the biology of colorectal cancer. In murine tumors, Apc status was identified as a determinant of the expression of genes controlling serine synthesis. In patient samples, PSAT1 was overexpressed in both colorectal adenomas and adenocarcinomas. Combining genetic deletion of PSAT1 with exogenous serine deprivation maximally suppressed the proliferation of colorectal cancer cells and induced profound metabolic defects including diminished nucleotide production. Inhibition of serine synthesis enhanced the transcriptional changes following exogenous serine removal as well as alterations associated with DNA damage. Both loss of PSAT1 and removal of serine from the diet were necessary to suppress colorectal cancer xenograft growth and enhance the antitumor activity of 5-fluorouracil (5-FU). Restricting endogenous and exogenous serine in vitro augmented 5-FU–induced cell death, DNA damage, and metabolic perturbations, likely accounting for the observed antitumor effect. Collectively, our results suggest that both endogenous and exogenous sources of serine contribute to colorectal cancer growth and resistance to 5-FU.Significance:These findings provide insights into the metabolic requirements of colorectal cancer and reveal a novel approach for its treatment.

This file contains methods and references for data presented in the supplement and legends for Supplementary Figures S1-S4

Resolving the electronic structure of a single atom within a molecule is of fundamental importance for understanding and predicting chemical and physical properties of functional molecules such as molecular catalysts. However, the observation of the orbital signature of an individual atom is challenging. We report here the direct identification of two adjacent transition-metal atoms, Fe and Co, within phthalocyanine molecules using high-resolution noncontact atomic force microscopy (HR-AFM). HR-AFM imaging reveals that the Co atom is brighter and presents four distinct lobes on the horizontal plane whereas the Fe atom displays a “square” morphology. Pico-force spectroscopy measurements show a larger repulsion force of about 5 pN on the tip exerted by Co in comparison to Fe. Our combined experimental and theoretical results demonstrate that both the distinguishable features in AFM images and the variation in the measured forces arise from Co’s higher electron orbital occupation above the molecular plane. The ability to directly observe orbital signatures using HR-AFM should provide a promising approach to characterizing the electronic structure of an individual atom in a molecular species and to understand mechanisms of certain chemical reactions.

We demonstrate a composite laser written 3D waveguide in boro-aluminosilicate glass, with an estimated index contrast of 1.7%, providing a 2.5x improvement of minimum bend radius down to 4.0 mm at 1550 nm.

Infants born with low or high ("at-risk") birthweights are at greater risk of adverse health outcomes across the life course. Our objective was to examine whether geographic hotspots of low and high birthweight prevalence in New York City had different patterns of neighborhood risk factors. We performed census tract-level geospatial clustering analyses using (1) birthweight prevalence and maternal residential address from an all-payer claims database and (2) domains of neighborhood risk factors (socioeconomic and food environment) from national and local datasets. We then used logistic regression analysis to identify specific neighborhood risk factors associated with low and high birthweight hotspots. This study examined 2088 census tracts representing 419,025 infants. We found almost no overlap (1.5%) between low and high birthweight hotspots. The majority of low birthweight hotspots (87.2%) overlapped with a socioeconomic risk factor and 95.7% overlapped with a food environment risk factor. Half of high birthweight hotspots (50.0%) overlapped with a socioeconomic risk factor and 48.8% overlapped with a food environment risk factor. Low birthweight hotspots were associated with high prevalence of excessive housing cost, unemployment, and poor food environment. High birthweight hotspots were associated with high prevalence of uninsured persons and convenience stores. Programs and policies that aim to prevent disparities in infant birthweight should examine the broader context by which hotspots of at-risk birthweight overlap with neighborhood risk factors. Multi-level strategies that include the neighborhood context are needed to address prenatal pathways leading to low and high birthweight outcomes.

Objective To identify differences in healthcare expenditures and utilization by race in patients treated for common benign urologic conditions. Materials and Methods A retrospective secondary data analysis was conducted of patients with common benign urologic conditions using 2016-2018 Medical Expenditure Panel Survey data. Benign conditions included urolithiasis, cystitis, erectile dysfunction (ED), pelvic organ prolapse (POP), urinary incontinence (UI), and benign prostatic hyperplasia (BPH). Generalized linear models were used to evaluate the relationship between total healthcare expenditures and utilization and race for each condition. Adjusted analyses accounted for age, sex, number of chronic conditions, poverty status, self-reported health status, marital status, highest degree of educational attainment, and insurance status. Results The weighted analysis sample consisted of 27,110,416 patients, of whom 80.9% were Non-Hispanic white, 6.9% Non-Hispanic black, and 12.2% other minority races. After adjustment, total healthcare expenditures were significantly lower for Non-Hispanic blacks (incidence rate ratio [IRR] = 0.19, 95% confidence interval [CI]: 0.06-0.61) and other minority races (IRR = 0.30, 95% CI: 0.10-0.88) compared to Non-Hispanic whites treated for ED. Similarly, compared to Non-Hispanic whites, healthcare expenditures were significantly lower for Non-Hispanic blacks treated for UI (IRR = 0.56, 95% CI: 0.35-0.90). Conclusion Healthcare expenditures are significantly lower for Non-Hispanic black patients treated for ED and UI in the US Future research is needed to determine if these differences represent an inequality in the delivery of urologic care for patients with these conditions.

Although the number of countries participating in pivotal trials submitted to enable drug registration has nearly doubled over the past 25 years, there has not been a substantial increase in the diversity of clinical trial populations. In parallel, our understanding of factors that influence medicine response and variability has continued to evolve. The notion of intrinsic and extrinsic sources of variability has been embedded into different regulatory guidelines, including the recent guideline on the importance of enhancing the diversity of clinical trial populations. In addition to presenting the clinical and scientific reasons for ensuring that clinical trial populations represent the demographics of patient populations, this overview outlines the efforts of regulatory agencies, patient advocacy groups and clinical researchers to attain this goal through strategies to meet representation in recruitment targets and broaden eligibility criteria. Despite these efforts, challenges to participation in clinical trials remain, and certain groups continue to be underrepresented in development programmes. These challenges are amplified when the representativeness of specific groups may vary across countries and regions in a global clinical programme. Whilst enhanced trial diversity is a critical step towards ensuring that results will be representative of patient populations, a concerted effort is required to characterise further the factors influencing interindividual and regional differences in response for global populations. Quantitative clinical pharmacology principles should be applied to allow extrapolation of data across groups or regions as well as provide insight into the effect of patient-specific characteristics on a medicine's dose rationale and efficacy and safety profiles.

Nuclear actin has been implicated in dynamic chromatin rearrangements in diverse eukaryotes. In mammalian cells, it is required to reposition double-strand DNA breaks to enable homologous recombination repair and to enhance transcription by facilitating RNA Pol II recruitment to gene promoters. In the yeast Saccharomyces cerevisiae, nuclear actin modulates interphase chromosome dynamics and is required to reposition the induced INO1 gene to the nuclear periphery. Here, we have investigated the role of actin in driving intergenic interactions between Heat Shock Factor 1 (Hsf1)-regulated Heat Shock Protein (HSP) genes in budding yeast. These genes, dispersed on multiple chromosomes, dramatically reposition following exposure of cells to acute thermal stress, leading to their clustering within dynamic biomolecular condensates. Using an auxin-induced degradation strategy, we found that conditional depletion of nucleators of either linear or branched F-actin (Bni1/Bnr1 and Arp2, respectively) had little or no effect on heat shock-induced HSP gene coalescence or transcription. In addition, we found that pretreatment of cells with latrunculin A, an inhibitor of both filamentous and monomeric actin, failed to affect intergenic interactions between activated HSP genes and their heat shock-induced intragenic looping and folding. Moreover, latrunculin A pretreatment had little effect on HSP gene expression at either RNA or protein levels. In notable contrast, we confirmed that repositioning of activated INO1 to the nuclear periphery and its proper expression do require actin. Collectively, our work suggests that transcriptional activation and 3D genome restructuring of thermally induced, Hsf1-regulated genes can occur in the absence of actin.

Not available.

Poverty-related disparities appear early in life in cognitive, language, and social-emotional development, and in growth, especially obesity, and have long-term consequences across the life course. It is essential to develop effective strategies to promote healthy behaviors in pregnancy and the early years of parenthood that can mitigate disparities. Primary preventive interventions within the pediatric primary care setting offer universal access, high engagement, and population-level impact at low cost. While many families in poverty or with low income would benefit from preventive services related to both development and growth, most successful interventions have tended to focus on only one of these domains. In this manuscript, we suggest that it may be possible to address both development and growth simultaneously and effectively. In particular, current theoretical models suggest alignment in mechanisms by which poverty can create barriers to parent-child early relational health (i.e., parenting practices, creating structure, and parent-child relationship quality), constituting a final common pathway for both domains. Based on these models and related empirical data, we propose a strength-based, whole child approach to target common antecedents through positive parenting and prevent disparities in both development and growth; we believe this approach has the potential to transform policy and practice. Achieving these goals will require new payment systems that make scaling of primary prevention in health care feasible, research funding to assess efficacy/effectiveness and inform implementation, and collaboration among early childhood stakeholders, including clinicians across specialties, scientists across academic disciplines, and policy makers.

Alcohol abuse reduces hepatic vitamin A (retinoids), reductions that are associated with progression of alcohol liver disease (ALD). Restoring hepatic retinoids through diet is contraindicated in ALD due to the negative effects of alcohol on retinoid metabolism. There are currently no drugs that can both mitigate alcohol-driven hepatic retinoid losses and progression of ALD. Using a mouse model of alcohol intake, we examined if an agonist for the retinoic acid (RA) receptor β2 (RARβ2), AC261066 (AC261) could prevent alcohol-driven hepatic retinoid losses and protect against ALD. Our results show that mice co-treated with AC261 and alcohol displayed mitigation of ALD, including reduced macro, and microvesicular steatosis, and liver damage. Alcohol intake led to increases in hepatic centrilobular levels of ALDH1A1, a rate-limiting enzyme in RA synthesis, and co-localization of ALDH1A1 with the alcohol-metabolizing enzyme CYP2E1, and 4-HNE, a marker of oxidative stress; expression of these targets was abrogated in mice co-treated with AC261 and alcohol. By RNA sequencing technology, we found that AC261 treatments opposed alcohol modulation of 68 transcripts involved in canonical retinoid metabolism. Alcohol modulation of these transcripts, including CES1D, CES1G, RBP1, RDH10, and CYP26A1, collectively favor hepatic retinoid hydrolysis and catabolism. However, despite this, co-administration of AC261 with alcohol did not mitigate alcohol-mediated depletions of hepatic retinoids, but did reduce alcohol-driven increases in serum retinol. Our data show that AC261 protected mice against ALD, even though AC261 did not prevent alcohol-mediated reductions in hepatic retinoids. These data warrant further studies of the anti-ALD properties of AC261.

OBJECTIVE Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue. METHODS We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss. CONCLUSION Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.

Material hardship and stress, associated with poor infant outcomes, increased during the Coronavirus Disease 2019 pandemic. Chinese American families were vulnerable to racism-driven disparities. Little is known about maternal perceptions of pandemic impacts on their infants, family, and community. Purposive sampling of low-income Chinese American mothers (n = 25) with infants (1-15 months). Semi-structured qualitative interviews conducted in Mandarin, Cantonese, or English were audio-recorded, transcribed, and translated. Transcripts coded using applied thematic analysis in an iterative process of textual analysis until thematic saturation. Three themes emerged: (1) Heightened family hardship included financial strain, disruption of transnational childcare, experiences of racism; (2) Altered infant routines/developmental consequences included using protective equipment on infants, concerns about infant socio-emotional development; (3) Coping strategies included stockpiling essentials, adapting family diets. Strategies to mitigate disparities include expanding social needs screening, correcting misinformation, strengthening support networks, and including low-income Chinese Americans in these efforts.

Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed medications. They are among the first-line medications for several chronic or relapsing-remitting psychiatric conditions, including major depressive disorder and anxiety disorders. The advantages of SSRI use include ease of titration and their tolerability and safety profile. Guidelines for the short-term use of SSRIs are widely available, but there is no well-organized guidance on how and whether to maintain a patient on SSRIs for the long-term. In this article, we discuss the benefits and possible adverse consequences of long-term SSRI use, as well as clinical practice considerations when using SSRIs chronically. The major benefit of long-term SSRI use is relapse prevention. The current literature suggests that the general health risks of long-term SSRI use are low; however, further research, particularly in special populations including youth and the elderly, is needed. Long-term SSRI use increases the risk of tachyphylaxis and discontinuation syndrome. Recognizing that many patients may remain on SSRIs for many years, there are several factors that prescribers should consider if they choose to use an SSRI when initiating treatment and during long-term monitoring. The decision to continue or to discontinue an SSRI should be an active one, involving both the patient and prescriber, and should be revisited periodically. Patients who remain on SSRIs for the long-term should also have periodic monitoring to reassess the risk-benefit ratio of remaining on the SSRI, as well as to assess the safety, tolerability, and efficacy of the medication.

INTRODUCTION: Routine prenatal screening ultrasounds primarily serve to diagnose major fetal anomalies which may prompt further testing and inform clinical decision-making, including possible pregnancy termination. Meanwhile, expectant parents may view the ultrasound experience and information gained differently from their clinicians. In this setting, how to best counsel patients, especially regarding the increasing findings of indeterminant clinical significance, is unclear. Greater understanding of women’s views before undergoing their ultrasound may help to guide anticipatory counseling about the purpose of screening and interpretation of results. METHODS: We surveyed 289 patients presenting for scheduled prenatal ultrasounds at an academic tertiary care center. Discrete and open-ended questions assessed views surrounding the receipt of abnormal results and management of the pregnancy once fetal anomalies are detected. Qualitative responses were analyzed using thematic analysis. RESULTS: Most (95%) desired information about abnormal sonographic findings, although only half would consider pregnancy termination for anomalies. Reasons for wanting return of abnormal results included preparedness, valuing knowledge, and to a lesser extent, informing decision-making. When considering potential termination as a result of ultrasound findings, participants’ rationales demonstrated deontological (seeing termination as inherently impermissible or permissible), relational (duties arising from the role of being a mother), and consequentialist (weighing harms and benefits) reasoning. CONCLUSION: This study highlights women’s perceptions of prenatal ultrasounds as an inherently valuable source of information and preparedness, beyond their role in informing clinical decision-making. Identifying the ethical constructs underpinning patients’ perspectives may help direct development of counseling tools responsive to individual needs and values regarding prenatal ultrasound findings.

Child obesity is widely prevalent, and general pediatricians play an important role in identifying and caring for patients with obesity. Appropriate evaluation and treatment require an understanding of the complex etiology of child obesity, its intergenerational transmission, and its epidemiologic trends, including racial/ethnic and socioeconomic disparities. The American Academy of Pediatrics has published screening, evaluation, and treatment guidelines based on the best available evidence. However, gaps in evidence remain, and implementation of evidence-based recommendations can be challenging. It is important to review optimal care in both the primary care and multidisciplinary weight management settings. This allows for timely evaluation and appropriate referrals, with the pediatrician playing a key role in advocating for patients at higher risk. There is also a role for larger-scale prevention and policy measures that would not only aid pediatricians in managing obesity but greatly benefit child health on a population scale.

This study evaluated the collateral, or unanticipated, impacts of Smart Beginnings (SB), a two-site, tiered intervention designed to promote responsive parenting and school readiness, on breastfeeding intensity in a low-income sample. Impact analyses for the SB intervention were conducted using an intent-to-treat design leveraging a two-arm random assignment structure. Mothers assigned to the SB intervention group were more than three times more likely to give breastmilk as the only milk source at infant age 6 months than mothers assigned to the control group at one site, an effect not evident at the other study site. As development and growth are the two most salient domains of child health, understanding how interventions impact subsequent parenting practices across both domains is critical to address long-term economic and racial/ethnic disparities. Implications of the findings are discussed for improving the efficacy of interventions based on paediatric primary care.

Objective Circulating cellular communication network factor 1 (CCN1) improves risk stratification in ACS patients and, as we have recently shown, predicts all-cause mortality in patients with dilated cardiomyopathy (DCM). It was the aim of this study to evaluate whether the prognostic role of CCN1 is influenced by an inflammatory phenotype. Methods Patients with a primary diagnosis of DCM, defined as LVEF 117%), were included in this single-center study. Exclusion criteria comprised primary valvular diseases (≥second degree), acute myocarditis, active infectious diseases, pulmonary diseases, cancer, chronic alcoholism, and heart failure of other origins. CCN1 levels were determined in serum at study inclusion using an enzyme-linked immunosorbent assay. The primary endpoint was all-cause mortality during follow-up. An adjusted multivariable cox regression model was used to assess the association between CCN1 and all-cause mortality. We further analysed potential effect modifications by adding either an interaction term between CCN1 and DCMi diagnosis (DCMi vs. DCM). The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score to predict all-cause mortality in HF patients was used as a reference model. The performance of CCN1 in combination with the MAGGIC score and NT-proBNP to predict all-cause mortality was assessed using Cox's proportional-hazards models Results A total of 283 predominantly male DCM patients (78.5% males) with a median age of 55.7 (interquartile range [IQR 48.2, 65.7]) years and predominantly recent onset of disease (3.8 [IQR 1.1, 20.5] months) with a severely reduced LVEF (31 [IQR 25, 37] %), increased LVEDD (67.0 [IQR 62.8, 72.0] mm), and normal eGFR (CKD-EPI) (90.9 [IQR73.9, 102.4] ml/min) were analyzed. During a median follow-up of 12.4 [IQR 10.5, 14.0] years, a total of 107 (37.8%) patients died. Patients in the highest CCN1 tertile had a significantly higher mortality risk than those in the lower tertile (HR 1.82; 95% CI 1.06, 3.14; P=0.030) in adjusted multivariable Cox regression models. Adding CCN1 to the MAGGIC risk score improved c-statistics for prognostic accuracy of all-cause mortality at 6 years (0.624 to 0.645, p=0.012), unlike NT-proBNP (0.624 to 0.630, p=0.123). Patients classified as DCMi (n=128) had significantly lower CCN1 levels compared with classical DCM (n=155) (154.9 (115.4–191.7) vs. 174.7 (130.0–241.0) pg/ml, P=0.022). Inflammation status (DCMi vs DCM) had no significant impact (P interaction = 0.28) on the association of CCN1 and all-cause mortality (Fig. 1). Conclusion CCN1 independently predicts all-cause mortality in DCM patients and improves risk stratification beyond the MAGGIC score. In this pilot cohort, the inflammatory phenotype had no impact on prognostic discrimination. Data are currently analyzed in a validation cohort. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Kerckhoff Research Foundation

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML), but patients still experience treatment-limiting toxicities or therapeutic failure. To investigate the real-world use and outcomes of imatinib in patients with CML in Australia, a retrospective cohort study of patients with CML commencing imatinib (2001-2018) was conducted across two sites. Prescribing patterns, tolerability outcomes, and survival and molecular response were evaluated. 86 patients received 89 imatinib treatments. Dose modifications were frequently observed (12-month rate of 58%). At last follow-up, 62 patients (5-year rate of 55%) had permanently discontinued imatinib treatment, of which 44 switched to another TKI (5-year rate of 46%). Within 3 months of starting imatinib, 43% (95% CI, 32%-53%) of patients experienced imatinib-related grade ≥3 adverse drug reactions (ADRs). Higher comorbidity score, lower body weight, higher imatinib starting dose, and Middle Eastern or North African ancestry were associated with a higher risk of grade ≥3 ADR occurrence on multivariable analysis (MVA). Estimated overall survival and event-free survival rates at 3 years were 97% (95% CI, 92%-100%) and 81% (95% CI, 72%-92%), respectively. Cumulative incidence of major molecular response (MMR) at 3 years was 63% (95% CI, 50%-73%). On MVA, imatinib starting dose, ELTS score, BCR-ABL1 transcript type, pre-existing pulmonary disease, and potential drug-drug interactions were predictive of MMR. In conclusion, imatinib induced deep molecular responses that translated to good survival outcomes in a real-world setting, but was associated with a higher incidence of ADRs, dose modifications and treatment discontinuations than in clinical trials.

Background: Maternal social support promotes healthy infant feeding practices, which influence healthy growth and development. Less is known about how the interplay of social support networks and multicultural health beliefs may influence infant feeding practices, particularly among immigrant Chinese American mothers with economic disadvantage and low breastfeeding rates. Research Aim: To explore the role of social support networks in the development of infant feeding practices in immigrant Chinese American mothers with infants. Methods: This was a prospective, cross-sectional qualitative study where we conducted semi-structured interviews in Mandarin, Cantonese, or English with Chinese American mothers of infants ( N = 25) at a federally qualified health center in the Sunset Park neighborhood of Brooklyn, New York. Data were analyzed by a multicultural, multidisciplinary team using qualitative thematic analysis and the constant comparative method to identify and iteratively refine emerging codes. Results: Three themes emerged describing how broad transnational communities and close family and friends influence maternal-infant feeding practices: (1) Gathering and processing infant feeding information from broad transnational resources (i.e., from both the mother’s country of residence and the mother’s country of origin); (2) aligning maternal feeding attitudes with cultural health beliefs of local social networks; and (3) gaining confidence with transactional maternal–infant feeding interactions. Conclusions: Strategies to promote healthy infant feeding should consider how family supports and culturally-relevant coaching can help align multilevel transnational social networks with healthy infant feeding practices.

Our current legal protections and ethical oversight have been insufficient for guarding against ethical violations involving our health data in the modern age. Concerns regarding the governance and privacy of health data are growing in tandem with calls for updated ethical guidelines for data-driven research. In this piece we discuss how blockchain technology and privacy preserving forms of computation may be foundational for new ethical guidelines given their potential to resolve the fundamental tensions between our concurrent obligations to protect individuals’ health data rights and to promote learning from health data for the good of society.

We report the design and characterization of Fe-containing soft materials that respond to, interface with, and/or sequester Fe-chelating ‘siderophores’ that bacteria use to scavenge for iron and regulate iron homeostasis. We demonstrate that metal-organic network coatings fabricated by crosslinking tannic acid with iron(III) are stable in bacterial growth media, but erode upon exposure to biologically relevant concentrations of enterobactin and deferoxamine B, two siderophores produced by Gram-negative and Gram-positive bacteria, respectively. Our results are consistent with changes in network stability triggered by the extraction of iron(III) and reveal rates of siderophore-induced disassembly to depend upon both siderophore concentration and affinity for iron(III). These coatings also disassemble when incubated in the presence of cultures of wild-type Escherichia coli. Assays using genetically modified strains of E. coli reveal the erosion of these materials by live cultures to be promoted by secretion of enterobactin and not from other factors resulting from bacterial growth and metabolism. This stimuli-responsive behavior can also be exploited to design coatings that release the Fe-chelating antibiotic ciprofloxacin into bacterial cultures. Finally, we report the discovery of Fe-containing polymer hydrogels that avidly sequester and scavenge enterobactin from surrounding media. The materials reported here are (i) capable of interfacing or interfering with mechanisms that bacteria use to maintain iron homeostasis, either by yielding iron to or by sequestering iron-scavenging agents from bacteria, and can (ii) respond dynamically to or report on the presence of populations of iron-scavenging bacteria. Our results thus provide new tools that could prove useful for microbiological research and enable new stimuli-responsive strategies for interfacing with or controlling the behaviors of communities of iron-scavenging bacteria.

In 1994, American outdoor adventurers Ray and Jenny Jardine completed the Pacific Crest Trail, a long-distance hiking trail in Washington, Oregon, and California, carrying remarkably light packs. R...

To evaluate the influence of sarcopenia on survival in patients with hepatocellular carcinoma (HCC) treated with 90Y radioembolization. This single-center retrospective cohort study analyzed 82 consecutive patients (65 men and 17 women, mean age 65 years, range 31–83 years) with HCC treated with 90Y radioembolization between December 2013 and December 2017. Sarcopenia was assessed on pre-procedure MRI performed within 100 days prior to 90Y radioembolization by segmenting the paraspinal musculature at the level of the superior mesenteric artery origin and subtracting fat-intensity pixels to yield fat-free muscle area (FFMA). Sarcopenia was defined as FFMA ≤31.97 cm2 for men and ≤28.95 cm2 for women. Survival at 90 days, 180 days, 1 year, and 3 years following initial treatment was assessed using medical and public obituary records. Sarcopenia was identified in 30% (25/82) of patients. Death was reported for 49% (32/65) of males and 71% (8/17) of females (mean follow-up 19.6 months, range 21 days–58 months). Patients with sarcopenia were found to have increased mortality at 180 days (31.8% vs. 8.9%) and 1 year (68.2% vs. 21.2%). Sarcopenia was an independent predictor of mortality adjusted for BCLC stage and sub-analysis demonstrated that sarcopenia independently predicted increased mortality for patients with BCLC stage B disease. Sarcopenia was associated with increased 180-day and 1-year mortality in HCC patients undergoing 90Y radioembolization. Sarcopenia was an independent predictor of survival adjusted for BCLC stage with significant deviation in the survival curves of BCLC stage B patients with and without sarcopenia.

Defining risks associated with diabetes mellitus (DM) in patients undergoing penile prosthesis (PP) implantation remains controversial. This systematic review seeks to assess whether preoperative hemoglobin a1c (HbA1c) or serum glucose have been shown to predict infection following PP implantation in diabetic men. A stepwise literature search was performed. Eight and four studies assessing HbA1c and serum glucose respectively were included. Overall, data exploring HbA1c and serum glucose on PP infection were heterogeneous in time period, study design, and patient populations. Contemporary studies did not support either HbA1c nor blood glucose as predictors of PP infection in diabetic men.