Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain.

There are currently no drugs known to rescue the function of Kv1.1 voltage-gated potassium channels carrying loss-of-function sequence variants underlying the inherited movement disorder, Episodic Ataxia 1 (EA1). The Kwakwaka'wakw First Nations of the Pacific Northwest Coast used Fucus gardneri (bladderwrack kelp), Physocarpus capitatus (Pacific ninebark) and Urtica dioica (common nettle) to treat locomotor ataxia. Here, we show that extracts of these plants enhance wild-type Kv1.1 current, especially at subthreshold potentials. Screening of their constituents revealed that gallic acid and tannic acid similarly augment wild-type Kv1.1 current, with submicromolar potency. Crucially, the extracts and their constituents also enhance activity of Kv1.1 channels containing EA1-linked sequence variants. Molecular dynamics simulations reveal that gallic acid augments Kv1.1 activity via a small-molecule binding site in the extracellular S1-S2 linker. Thus, traditional Native American ataxia treatments utilize a molecular mechanistic foundation that can inform small-molecule approaches to therapeutically correcting EA1 and potentially other Kv1.1-linked channelopathies.

A retrospective assessment of fuel break effectiveness for containing rangeland wildfires in the sagebrush biome.

Escalated wildfire activity within the western U.S. has widespread societal impacts and long-term consequences for the imperiled sagebrush (Artemisia spp.) biome. Shifts from historical fire regimes and the interplay between frequent disturbance and invasive annual grasses may initiate permanent state transitions as wildfire frequency outpaces sagebrush communities' innate capacity to recover. Therefore, wildfire management is at the core of conservation plans for sagebrush ecosystems, especially critical habitat for species of conservation concern such as the greater sage-grouse (Centrocercus urophasianus; hereafter sage-grouse). Fuel breaks help facilitate wildfire suppression by modifying behavior through fuels modification and allowing safe access points for containment by firefighters. The Bureau of Land Management has proposed to roughly double the existing fuel break network in the western U.S., centered on the Great Basin. To our knowledge, no broad-scale examination of fuel break effectiveness or the environmental conditions under which fuel breaks are expected to be most effective has been conducted. We performed a retrospective assessment of probability of fuel break contributing to wildfire containment on recorded wildfire and fuel break interactions from 1985 to 2018 within the western U.S. We characterized environmental, fuels, and weather conditions within 500 m of wildfire contact, and within 5 km of the approaching wildfire. We used a binomial mixed model within a Bayesian framework to identify relationships between these variables and fuel break success. Fuel breaks were least successful in areas classified as having low resilience to disturbance and low resistance to invasion, in areas composed of primarily woody fuels, and when operating in high temperature and low precipitation conditions. Fuel breaks were most effective in areas where fine fuels dominated and in areas that were readily accessible. Maintenance history and fuel break type also contributed to the probability of containment. Overall results indicate a complex and sometimes paradoxical relationship between landscape characteristics that promote wildfire spread and those that impact fuel break effectiveness. Finally, we developed predictive maps of fuel break effectiveness by fuel break type to further elucidate these complex relationships and to inform urgently needed fuel break placement and maintenance priorities across the sagebrush biome.

Biomass valorization toward sustainable asphalt pavements: Progress and prospects.

To cope with the global climate crisis and assist in achieving the carbon neutrality, the use of biomass materials to fully or partially replace petroleum-based products and unrenewable resources is expected to become a widespread solution. Based on the analysis of the existing literature, this paper firstly classified biomass materials with potential application prospects in pavement engineering according to their application and summarized their respective preparation methods and characteristics. The pavement performance of asphalt mixtures with biomass materials was analyzed and summarized, and the economic and environmental benefits of bio-asphalt binder were evaluated. The analysis shows that pavement biomass materials with potential for practical application can be divided into three categories: bio-oil, bio-fiber, and bio-filler. Adding bio-oil to modify or extend the virgin asphalt binder can mostly improve the low temperature performance of asphalt binder. Adding styrene-butadienestyrene (SBS) or other preferable bio-components for composite modification will have a further improved effect. Most of the asphalt mixtures prepared by using bio-oil modified asphalt binders have improved the low temperature crack resistance and fatigue resistance of asphalt mixtures, but the high temperature stability and moisture resistance may decrease. As a rejuvenator, most bio-oils can restore the high and low temperature performance of aged asphalt and recycled asphalt mixture, and improve fatigue resistance. Adding bio-fiber could significantly improve the high temperature stability, low temperature crack resistance and moisture resistance of asphalt mixtures. Biochar as a bio-filler can slow down the asphalt aging process and some other bio-fillers can improve the high temperature stability and fatigue resistance of asphalt binders. Through calculation, it is found that the cost performance of bio-asphalt has the ability to surpass conventional asphalt and has economic benefits. The use of biomass materials for pavements not only reduces pollutants, but also reduces the dependence on petroleum-based products. It has significant environmental benefits and development potential.

Perspectives on the Use of Proprietary Blends in Dietary Supplements.

This paper discusses the rationale for use of proprietary blends on dietary supplement labels, and their implications for researchers and consumers. The Dietary Supplement Health Education Act of 1994 allows the listing of nonnutrient dietary ingredients as proprietary blends on dietary supplement labels for companies to protect their unique formulas. The weight of the blend and names of the ingredients within the blends must be declared, but not the amounts of the individual ingredients within the proprietary blend. Thus, from label information, the amount of a dietary ingredient in a proprietary blend is not available for calculating exposures in assessments of intakes or for determining doses in clinical trials.

Importance of diet in amphibian metamorphosis-based studies designed to assess the risk of thyroid active substances.

The present study evaluated the hypothesis that dietary quality used in historical studies may impact the effects of chemical stressors on premetamorphic development and metamorphosis due to suboptimal nutritional quality. A modified Amphibian Metamorphosis Assay (AMA) was performed in which Nieuwkoop and Faber (NF) Stage 47 tadpoles of Xenopus laevis were exposed for 32 days to iodide (I- )-deficient FETAX solution supplemented with <0.025, 0.17, 0.52, 1.58, and 4.80 µg I- /L (measured concentrations 0.061, 0.220, 0.614, 1.65, and 4.73 µg I- /L) and fed a pureed Frog Brittle (FB) diet. An AMA guideline benchmark group (four replicates) exposed to dechlorinated tap water and fed standard Sera Micron Nature® (SMN) diet was evaluated concurrently. Developmental delay, observed as changes in stage distribution or median developmental stage, occurred in FB treatments with 0.061, 0.220, and 0.614 µg/L I- , respectively. Developmental rates and hind limb length of the 1.65 and 4.73 µg/L I- groups were similar to each other, but both treatments fell short of the developmental rate achieved by the SMN benchmark. Iodide supplementation also had no impact on nonthyroidal growth endpoints, which were markedly reduced in FB-fed frogs compared with their SMN-fed counterparts. All larvae that received the FB diet had mildly to severely hypoplastic/atrophic thyroids, a condition for which iodine supplementation had little if any ameliorative effect. Collectively, these results suggested that nutritional deficiencies in the FB diet negatively affected both growth and metamorphic development, the latter of which was only compensated to a limited extent by iodine supplementation.

Developmental trajectories of thalamic progenitors revealed by single-cell transcriptome profiling and Shh perturbation.

The thalamus is the principal information hub of the vertebrate brain, with essential roles in sensory and motor information processing, attention, and memory. The complex array of thalamic nuclei develops from a restricted pool of neural progenitors. We apply longitudinal single-cell RNA sequencing and regional abrogation of Sonic hedgehog (Shh) to map the developmental trajectories of thalamic progenitors, intermediate progenitors, and post-mitotic neurons as they coalesce into distinct thalamic nuclei. These data reveal that the complex architecture of the thalamus is established early during embryonic brain development through the coordinated action of four cell differentiation lineages derived from Shh-dependent and -independent progenitors. We systematically characterize the gene expression programs that define these thalamic lineages across time and demonstrate how their disruption upon Shh depletion causes pronounced locomotor impairment resembling infantile Parkinson's disease. These results reveal key principles of thalamic development and provide mechanistic insights into neurodevelopmental disorders resulting from thalamic dysfunction.

Interstitial Mycosis Fungoides: An Unusual Mimic of Interstitial Granuloma Annulare Not to Miss.

Interstitial mycosis fungoides is a rare histopathologic variant of mycosis fungoides that may resemble interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Reported is a case of a 62-year-old African American female who presented with an asymptomatic, progressive rash of the left underarm and abdomen with histologic features suggestive of granuloma annulare. Biopsies revealed an interstitial pattern of cells in the dermis with prominent small aggregates of atypical lymphocytes, a few atypical lymphocytes in the lower epidermis, and a mild increase in dermal mucin. Immunohistochemistry staining revealed the atypical lymphocytes to be positive for CD3 and CD8 and negative for CD4 and CD7, an aberrant immunoprofile. Mixed in the dermis with the atypical lymphoid cells were a few CD68 positive histiocytes and S100 protein positive dermal dendritic cells. T-cell receptor beta gene rearrangement studies showed nearly the same clonal peaks for TCRB rearrangement in two biopsy specimens from separate sites, all supporting a diagnosis of interstitial mycosis fungoides. The patient is undergoing treatment with full body narrowband UVB (nbUVB) phototherapy with notable improvement in skin discoloration and resolution of several abdominal lesions. A diagnosis of interstitial mycosis fungoides is challenging to make based on clinical features alone and is often clinically misdiagnosed. Awareness of histopathologic features is critical to make an accurate diagnosis and thus patient management.

Ancient DNA reveals five streams of migration into Micronesia and matrilocality in early Pacific seafarers.

Micronesia began to be peopled earlier than other parts of Remote Oceania, but the origins of its inhabitants remain unclear. We generated genome-wide data from 164 ancient and 112 modern individuals. Analysis reveals five migratory streams into Micronesia. Three are East Asian related, one is Polynesian, and a fifth is a Papuan source related to mainland New Guineans that is different from the New Britain-related Papuan source for southwest Pacific populations but is similarly derived from male migrants ~2500 to 2000 years ago. People of the Mariana Archipelago may derive all of their precolonial ancestry from East Asian sources, making them the only Remote Oceanians without Papuan ancestry. Female-inherited mitochondrial DNA was highly differentiated across early Remote Oceanian communities but homogeneous within, implying matrilocal practices whereby women almost never raised their children in communities different from the ones in which they grew up.

Genomes from Verteba cave suggest diversity within the Trypillians in Ukraine.

The transition to agriculture occurred relatively late in Eastern Europe, leading researchers to debate whether it was a gradual, interactive process or a colonisation event. In the forest and forest-steppe regions of Ukraine, farming appeared during the fifth millennium BCE, associated with the Cucuteni-Trypillia cultural complex (CTCC, ~ 5000-3000 BCE). Across Europe, the Neolithisation process was highly variable across space and over time. Here, we investigate the population dynamics of early agriculturalists from the eastern forest-steppe region based on the analyses of 20 ancient genomes from the site of Verteba Cave (3935-825 cal BCE). Results reveal that the CTCC individuals' ancestry is related to both western hunter-gatherers and Near Eastern farmers, has no local ancestry associated with Ukrainian Neolithic hunter-gatherers and has steppe ancestry. An Early Bronze Age individual has an ancestry profile related to the Yamnaya expansions but with 20% of ancestry related to the other Trypillian individuals, which suggests admixture between the Trypillians and the incoming populations carrying steppe-related ancestry. A Late Bronze Age individual dated to 980-825 cal BCE has a genetic profile indicating affinity to Beaker-related populations, detected close to 1000 years after the end of the Bell Beaker phenomenon during the third millennium BCE.

Inhibitors of the Hippo Pathway Kinases STK3/MST2 and STK4/MST1 Have Utility for the Treatment of Acute Myeloid Leukemia.

Serine/threonine-protein kinases 3 and 4 (STK3 and STK4, respectively) are key components of the Hippo signaling pathway, which regulates cell proliferation and death and provides a potential therapeutic target for acute myeloid leukemia (AML). Herein, we report the structure-based design of a series of pyrrolopyrimidine derivatives as STK3 and STK4 inhibitors. In an initial screen, the compounds exhibited low nanomolar potency against both STK3 and STK4. Crystallization of compound 6 with STK4 revealed two-point hinge binding in the ATP-binding pocket. Further characterization and analysis demonstrated that compound 20 (SBP-3264) specifically inhibited the Hippo signaling pathway in cultured mammalian cells and possessed favorable pharmacokinetic and pharmacodynamic properties in mice. We show that genetic knockdown and pharmacological inhibition of STK3 and STK4 suppress the proliferation of AML cells in vitro. Thus, SBP-3264 is a valuable chemical probe for understanding the roles of STK3 and STK4 in AML and is a promising candidate for further advancement as a potential therapy.

Dairying enabled Early Bronze Age Yamnaya steppe expansions.

During the Early Bronze Age, populations of the western Eurasian steppe expanded across an immense area of northern Eurasia. Combined archaeological and genetic evidence supports widespread Early Bronze Age population movements out of the Pontic-Caspian steppe that resulted in gene flow across vast distances, linking populations of Yamnaya pastoralists in Scandinavia with pastoral populations (known as the Afanasievo) far to the east in the Altai Mountains1,2 and Mongolia3. Although some models hold that this expansion was the outcome of a newly mobile pastoral economy characterized by horse traction, bulk wagon transport4-6 and regular dietary dependence on meat and milk5, hard evidence for these economic features has not been found. Here we draw on proteomic analysis of dental calculus from individuals from the western Eurasian steppe to demonstrate a major transition in dairying at the start of the Bronze Age. The rapid onset of ubiquitous dairying at a point in time when steppe populations are known to have begun dispersing offers critical insight into a key catalyst of steppe mobility. The identification of horse milk proteins also indicates horse domestication by the Early Bronze Age, which provides support for its role in steppe dispersals. Our results point to a potential epicentre for horse domestication in the Pontic-Caspian steppe by the third millennium BC, and offer strong support for the notion that the novel exploitation of secondary animal products was a key driver of the expansions of Eurasian steppe pastoralists by the Early Bronze Age.

Monoacylglycerol Lipase Inhibitor MJN110 Reduces Neuronal Hyperexcitability, Restores Dendritic Arborization Complexity, and Regulates Reward-Related Behavior in Presence of HIV-1 Tat.

While current therapeutic strategies for people living with human immunodeficiency virus type 1 (HIV-1) suppress virus replication peripherally, viral proteins such as transactivator of transcription (Tat) enter the central nervous system early upon infection and contribute to chronic inflammatory conditions even alongside antiretroviral treatment. As demand grows for supplemental strategies to combat virus-associated pathology presenting frequently as HIV-associated neurocognitive disorders (HAND), the present study aimed to characterize the potential utility of inhibiting monoacylglycerol lipase (MAGL) activity to increase inhibitory activity at cannabinoid receptor-type 1 receptors through upregulation of 2-arachidonoylglycerol (2-AG) and downregulation of its degradation into proinflammatory metabolite arachidonic acid (AA). The MAGL inhibitor MJN110 significantly reduced intracellular calcium and increased dendritic branching complexity in Tat-treated primary frontal cortex neuron cultures. Chronic MJN110 administration in vivo increased 2-AG levels in the prefrontal cortex (PFC) and striatum across Tat(+) and Tat(-) groups and restored PFC N-arachidonoylethanolamine (AEA) levels in Tat(+) subjects. While Tat expression significantly increased rate of reward-related behavioral task acquisition in a novel discriminative stimulus learning and cognitive flexibility assay, MJN110 altered reversal acquisition specifically in Tat(+) mice to rates indistinguishable from Tat(-) controls. Collectively, our results suggest a neuroprotective role of MAGL inhibition in reducing neuronal hyperexcitability, restoring dendritic arborization complexity, and mitigating neurocognitive alterations driven by viral proteins associated with latent HIV-1 infection.

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans.

BACKGROUND: Transcutaneous stimulation of the external ear is thought to recruit afferents of the auricular vagus nerve, providing a means to activate noradrenergic pathways in the central nervous system. Findings from human studies examining the effects of auricular stimulation on noradrenergic biomarkers have been mixed, possibly relating to the limited and variable parameter space explored to date. OBJECTIVE: We tested the extent to which brief pulse trains applied to locations of auricular innervation (canal and concha) elicit acute pupillary responses (PRs) compared to a sham location (lobe). Pulse amplitude and frequency were varied systematically to examine effects on PR features. METHODS: Participants (n = 19) underwent testing in three separate experiments, each with stimulation applied to a different external ear location. Perceptual threshold (PT) was measured at the beginning of each experiment. Pulse trains (∼600 ms) consisting of different amplitude (0.0xPT, 0.8xPT, 1.0xPT, 1.5xPT, 2.0xPT) and frequency (25 Hz, 300 Hz) combinations were administered during eye tracking procedures. RESULTS: Stimulation to all locations elicited PRs which began approximately halfway through the pulse train and peaked shortly after the final pulse (≤1 s). PR size and incidence increased with pulse amplitude and tended to be greatest with canal stimulation. Higher pulse frequency shortened the latency of PR onset and peak dilation. Changes in pupil diameter elicited by pulse trains were weakly associated with baseline pupil diameter. CONCLUSION: (s): Auricular stimulation elicits acute PRs, providing a basis to synchronize neuromodulator release with task-related neural spiking which preclinical studies show is a critical determinant of therapeutic effects. Further work is needed to dissociate contributions from vagal and non-vagal afferents mediating activation of the biomarker.

Patient perspectives on how to demonstrate respect: Implications for clinicians and healthcare organizations.

OBJECTIVE: Clinicians and healthcare organizations are ethically obligated to treat patients with respect, yet it is not clear what actions best demonstrate respect to patients. This exploratory qualitative study aimed to understand what actions on both an individual and organizational level effectively demonstrate respect for primary care patients. METHODS: We conducted semi-structured telephone interviews with primary care patients in an integrated healthcare delivery system in Oregon and an integrated safety net health system in Colorado who were participating in a genomics implementation research study of a hereditary cancer screening program. We systematically coded interview transcripts using a coding framework developed based on iterative review of the interview guide and transcripts. We further analyzed the data coded with sub-codes relating to patients' experiences with respect in healthcare using a descriptive content analysis approach. RESULTS: We interviewed 40 English-speaking (n = 30, 75%) and Spanish-speaking (n = 10, 25%) patients. Most interviewees identified as female (n = 35, 88%) and either Hispanic/Latino(a) (n = 17, 43%) or White or European American (n = 15, 38%). Interviewees identified two categories of efforts by individual clinicians that demonstrate respect: engaging with patients and being transparent. They identified five efforts by healthcare organizations: promoting safety and inclusivity, protecting patient privacy, communicating about scheduling, navigating financial barriers to care, and ensuring continuity of care. CONCLUSIONS: Our findings suggest that patients' experiences of respect depend on efforts by individual clinicians as well as healthcare organizations. Our findings offer insight into how clinicians can build stronger partnerships with patients and how organizations can seek to promote access to care and patient safety and comfort. They also illustrate areas for future research and quality improvement to more effectively respect patients.

Investigating the (in)visible: Piloting an integrated methodology to explore multiple forms of violence.

Traditional research methods typically utilize singular forms of data to conceptualize and measure violence. Methodologies designed to examine the impact of violence have been structured to primarily examine the interpersonal. However, scholars in community psychology, anthropology, and social work, and so forth, have recognized additional dimensions of violence that impact marginalized populations by restricting agency and negatively affecting physical and mental health, such as structural violence. Given growing interest in multiple forms of violence, new methodologies are required to holistically capture the full impact of violence on individuals. This article will discuss a unique methodology designed to investigate multiple forms of violence by melding semi-structured place-based interviews, family history interviews, walking interviews, and physiological data on heart rate coordinated with GPS data. This novel combination of methods allowed the researcher to deepen understanding of the relationship between place and violence while also highlighting the voices and experiences of young adults. Challenges to data collection, limitations of technology, and insights gained from the methodology will be discussed.

Carbohydrate Supplementation and the Influence of Breakfast on Fuel Use in Hypoxia.

PURPOSE: This study investigated the effect of carbohydrate supplementation on substrate oxidation during exercise in hypoxia after preexercise breakfast consumption and omission. METHODS: Eleven men walked in normobaric hypoxia (FiO2 ~11.7%) for 90 min at 50% of hypoxic V˙O2max. Participants were supplemented with a carbohydrate beverage (1.2 g·min-1 glucose) and a placebo beverage (both enriched with U-13C6 D-glucose) after breakfast consumption and after omission. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate carbohydrate (exogenous and endogenous [muscle and liver]) and fat oxidation. RESULTS: In the first 60 min of exercise, there was no significant change in relative substrate oxidation in the carbohydrate compared with placebo trial after breakfast consumption or omission (both P = 0.99). In the last 30 min of exercise, increased relative carbohydrate oxidation occurred in the carbohydrate compared with placebo trial after breakfast omission (44.0 ± 8.8 vs 28.0 ± 12.3, P < 0.01) but not consumption (51.7 ± 12.3 vs 44.2 ± 10.4, P = 0.38). In the same period, a reduction in relative liver (but not muscle) glucose oxidation was observed in the carbohydrate compared with placebo trials after breakfast consumption (liver, 7.7% ± 1.6% vs 14.8% ± 2.3%, P < 0.01; muscle, 25.4% ± 9.4% vs 29.4% ± 11.1%, P = 0.99) and omission (liver, 3.8% ± 0.8% vs 8.7% ± 2.8%, P < 0.01; muscle, 19.4% ± 7.5% vs 19.2% ± 12.2%, P = 0.99). No significant difference in relative exogenous carbohydrate oxidation was observed between breakfast consumption and omission trials (P = 0.14). CONCLUSION: In acute normobaric hypoxia, carbohydrate supplementation increased relative carbohydrate oxidation during exercise (>60 min) after breakfast omission, but not consumption.

Time to Authorized Clearance From Sport-Related Concussion: The Influence of Health Care Provider and Medical Facility.

CONTEXT: Return to play after sport-related concussion (SRC) requires authorized clearance from a health care provider (HCP). The variability in HCPs and facilities where athletes seek care may influence return time. OBJECTIVE: To identify the initial examiner, HCPs who authorize clearance to return to play, and medical facilities that authorize clearance to return to play for high school student-athletes after SRC and compare authorized clearance time by HCPs and medical facilities. DESIGN: Prospective cohort study. SETTING: High school. PATIENTS OR OTHER PARTICIPANTS: Student-athletes (n = 16 001) with SRC participating in athletics sponsored by the Michigan High School Athletic Association. MAIN OUTCOME MEASURE(S): Frequencies of initial examiner and authorized clearance for each HCP (doctor of osteopathic medicine, medical doctor, nurse practitioner, physician assistant) and medical facility (neurologist's office; team physician, primary care physician or pediatrician's office [PCP]; hospital; urgent/ready care) for each case of SRC. We calculated Kaplan-Meier curves and Peto tests to evaluate differences in the median time to authorized clearance between HCPs and facilities. Only cases with a date on which clearance to return to play was authorized (80.3%; n = 12 856) were included in the authorized clearance and time-to-return analyses. RESULTS: An athletic trainer was at least 1 of the initial examiners in 71.3% (n = 11 404) of SRC cases; 81.2% (n = 12 990) had only 1 initial examiner. We observed an association between the initial examiner and the medical facility providing clearance for athletic director (χ2 = 52.6, P < .001, V = .06), athletic trainer (χ2 = 172.0, P < .001, V = .12), coach (χ2 = 161.5, P < .001, V = .11), doctor of osteopathic medicine (χ2 = 59.4, P < .001, V = .07), and nurse practitioner (χ2 = 10.0, P = .04, V = .12). Clearance was authorized most frequently by a medical doctor (63.9%, n = 8218) and at a PCP (70.8%, n = 9099). Median (interquartile range) time to authorized clearance varied by facility (urgent/ready care = 7 days [4-11 days], hospital = 9 days [6-14 days], PCP = 10 days [6-14 days], team physician = 12 days [8-16 days], neurologist's office = 13 days [9-20 days]; P < .001). An athletic trainer was the initial examiner more often for males (74.1%) than for females (65.8%). The medical facility where clearance to return to play was authorized also differed between males (PCP = 69.3%, team physician = 11.3%, neurologist's office = 8.4%) and females (PCP = 73.6%, team physician = 8.5%, neurologist's office = 8.3%). CONCLUSIONS: Clearance to return to play after SRC was frequently provided by a medical doctor and at a PCP. The median time to return to unrestricted participation after SRC varied by HCP and medical facility. Future researchers should elucidate the reasons for these differences and determine why athletes seek care at different types of medical facilities.

Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial.

Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D3 (4000 IU) or standard-dose (400 IU) vitamin D3. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks). As compared with standard-dose vitamin D3, high-dose vitamin D3 did not significantly change body weight [-0.7 kg; (95% CI: -3.5, 2.0)], body mass index [-0.2 kg/m2; (95% CI: -1.2, 0.7)], muscle area [-1.7 cm2; (95% CI: -9.6, 6.3)], muscle attenuation [-0.4 HU; (95% CI: -4.2, 3.2)], visceral adipose tissue area [-7.5 cm2; (95% CI: -24.5, 9.6)], or subcutaneous adipose tissue area [-8.3 cm2; (95% CI: -35.5, 18.9)] over the first 8 cycles of chemotherapy. Among patients with advanced or metastatic colorectal cancer, the addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy did not result in any changes in body composition.

Effect of Neighborhood Food Environment and Socioeconomic Status on Serum Phosphorus Level for Patients on Chronic Dialysis.

BACKGROUND: Elevated blood phosphorus levels are common and associated with a greater risk of death for patients receiving chronic dialysis. Phosphorus-rich foods are prevalent in the American diet, and low-phosphorus foods, including fruits and vegetables, are often less available in areas with more poverty. The relative contributions of neighborhood food availability and socioeconomic status to phosphorus control in patients receiving dialysis are unknown. METHODS: Using longitudinal data from a national dialysis provider, we constructed hierarchical, linear mixed-effects models to evaluate the relationships between neighborhood food environment or socioeconomic status and serum phosphorus level among patients receiving incident dialysis. RESULTS: Our cohort included 258,510 patients receiving chronic hemodialysis in 2005-2013. Median age at dialysis initiation was 64 years, 45% were female, 32% were Black, and 15% were Hispanic. Within their residential zip code, patients had a median of 25 "less-healthy" food outlets (interquartile range, 11-40) available to them compared with a median of four "healthy" food outlets (interquartile range, 2-6). Living in a neighborhood with better availability of healthy food was not associated with a lower phosphorus level. Neighborhood income also was not associated with differences in phosphorus. Patient age, race, cause of ESKD, and mean monthly dialysis duration were most closely associated with phosphorus level. CONCLUSIONS: Neither neighborhood availability of healthy food options nor neighborhood income was associated with phosphorus levels in patients receiving chronic dialysis. Modifying factors, such as nutrition literacy, individual-level financial resources, and adherence to diet restrictions and medications, may be more powerful contributors than food environment to elevated phosphorus.