Telehealth Availability for Cancer Care During the COVID-19 Pandemic: Cross-Sectional Study.

BACKGROUND: Telehealth was an important strategy for maintaining continuity of cancer care during the coronavirus pandemic and has continued to play a role in outpatient care; however, it is unknown whether services are equally available across cancer hospitals. OBJECTIVE: This study aimed to assess telehealth availability at cancer hospitals for new and established patients with common cancers to contextualize the impact of access barriers to technology on overall access to health care. METHODS: We conducted a national cross-sectional secret shopper study from June to November 2020 to assess telehealth availability at cancer hospitals for new and established patients with colorectal, breast, and skin (melanoma) cancer. We examined facility-level factors to determine predictors of telehealth availability. RESULTS: Of the 312 investigated facilities, 97.1% (n=303) provided telehealth services for at least 1 cancer site. Telehealth was less available to new compared to established patients (n=226, 72% vs n=301, 97.1%). The surveyed cancer hospitals more commonly offered telehealth visits for breast cancer care (n=266, 85%) and provided lower access to telehealth for skin (melanoma) cancer care (n=231, 74%). Most hospitals (n=163, 52%) offered telehealth for all 3 cancer types. Telehealth availability was weakly correlated across cancer types within a given facility for new (r=0.16, 95% CI 0.09-0.23) and established (r=0.14, 95% CI 0.08-0.21) patients. Telehealth was more commonly available for new patients at National Cancer Institute-designated facilities, medical school-affiliated facilities, and major teaching sites, with high total admissions and below-average timeliness of care. Telehealth availability for established patients was highest at Academic Comprehensive Cancer Programs, nongovernment and nonprofit facilities, medical school-affiliated facilities, Accountable Care Organizations, and facilities with a high number of total admissions. CONCLUSIONS: Despite an increase in telehealth services for patients with cancer during the COVID-19 pandemic, we identified differences in access across cancer hospitals, which may relate to measures of clinical volume, affiliation, and infrastructure.

Impact of an enhanced recovery after surgery program with a multimodal analgesia care pathway on opioid prescribing and clinical outcomes for patients undergoing colorectal surgery.

Background: Opioids are a mainstay for acute pain management, but their side effects can adversely impact patient recovery. Multimodal analgesia (MMA) is recommended for treatment of postoperative pain and has been incorporated in enhanced recovery after surgery (ERAS) protocols. The objective of this quality improvement study was to implement an MMA care pathway as part of an ERAS program for colorectal surgery and to measure the effect of this intervention on patient outcomes and costs. Methods: This pre-post study included 856 adult inpatients who underwent an elective colorectal surgery at three hospitals within an integrated healthcare system. The impact of ERAS program implementation on opioid prescribing practices, outcomes, and costs was examined after adjusting for clinical and demographic confounders. Results: Improvements were seen in MMA compliance (34.0% vs 65.5%, P < 0.0001) and ERAS compliance (50.4% vs 57.6%, P < 0.0001). Reductions in mean days on opioids (4.2 vs 3.2), daily (51.6 vs 33.4 mg) and total (228.8 vs 112.7 mg) morphine milligram equivalents given during hospitalization, and risk-adjusted length of stay (4.3 vs 3.6 days, P < 0.05) were also observed. Conclusions: Implementing ERAS programs that include MMA care pathways as standard of care may result in more judicious use of opioids and reduce patient recovery time.

Physical Activity Interventions to Alleviate Depressive Symptoms in Children and Adolescents: A Systematic Review and Meta-analysis.

Importance: Depression is the second most prevalent mental disorder among children and adolescents, yet only a small proportion seek or receive disorder-specific treatment. Physical activity interventions hold promise as an alternative or adjunctive approach to clinical treatment for depression. Objective: To determine the association of physical activity interventions with depressive symptoms in children and adolescents. Data Sources: PubMed, CINAHL, PsycINFO, EMBASE, and SPORTDiscus were searched from inception to February 2022 for relevant studies written in English, Chinese, or Italian. Study Selection: Two independent researchers selected studies that assessed the effects of physical activity interventions on depressive symptoms in children and adolescents compared with a control condition. Data Extraction and Synthesis: A random-effects meta-analysis using Hedges g was performed. Heterogeneity, risk of bias, and publication bias were assessed independently by multiple reviewers. Meta-regressions and sensitivity analyses were conducted to substantiate the overall results. The study followed the PRISMA reporting guideline. Main Outcomes and Measures: The main outcome was depressive symptoms as measured by validated depression scales at postintervention and follow-up. Results: Twenty-one studies involving 2441 participants (1148 [47.0%] boys; 1293 [53.0%] girls; mean [SD] age, 14 [3] years) were included. Meta-analysis of the postintervention differences revealed that physical activity interventions were associated with a reduction in depressive symptoms compared with the control condition (g = -0.29; 95% CI, -0.47 to -0.10; P = .004). Analysis of the follow-up outcomes in 4 studies revealed no differences between the physical activity and control groups (g = -0.39; 95% CI, -1.01 to 0.24; P = .14). Moderate study heterogeneity was detected (Q = 53.92; df = 20; P < .001; I2 = 62.9% [95% CI, 40.7%-76.8%]). The primary moderator analysis accounting for total physical activity volume, study design, participant health status, and allocation and/or assessment concealment did not moderate the main treatment effect. Secondary analyses demonstrated that intervention (ie, <12 weeks in duration, 3 times per week, unsupervised) and participant characteristics (ie, aged ≥13 years, with a mental illness and/or depression diagnosis) may influence the overall treatment effect. Conclusions and Relevance: Physical activity interventions may be used to reduce depressive symptoms in children and adolescents. Greater reductions in depressive symptoms were derived from participants older than 13 years and with a mental illness and/or depression diagnosis. The association with physical activity parameters such as frequency, duration, and supervision of the sessions remains unclear and needs further investigation.

The Beneficial Effect of an Intra-articular Injection of Losartan on Microfracture-Mediated Cartilage Repair Is Dose Dependent.

BACKGROUND: A previous publication demonstrated that the oral intake of losartan promoted microfracture-mediated hyaline-like cartilage repair in osteochondral defects of a rabbit knee model. However, an intra-articular (IA) injection of losartan may have direct beneficial effects on cartilage repair and has not been studied. PURPOSE: To determine the dosage and beneficial effects of an IA injection of losartan on microfracture-mediated cartilage repair and normal cartilage homeostasis. STUDY DESIGN: Controlled laboratory study. METHODS: Rabbits were divided into 5 groups (n = 6 each): a microfracture group (MFX group) and 4 different losartan treatment groups that received varying doses of IA losartan (0.1, 1, 10, and 100 mg per knee). An osteochondral defect (5 mm) was created in the trochlear groove cartilage of 1 limb in each rabbit, and 5 microfracture perforations were made in the osteochondral defect. Both the injured and the contralateral knee joints were injected with IA losartan immediately after microfracture and at 2 and 4 weeks after surgery. Rabbits were sacrificed at 6 weeks after surgery for analysis including gross observation, micro-computed tomography, histology, and reverse transcription quantitative polymerase chain reaction. RESULTS: Micro-computed tomography and gross observation demonstrated comparable subchondral bone healing and hyaline-like cartilage morphology in the 0.1-, 1-, and 10-mg losartan groups relative to the MFX group. Conversely, the 100-mg losartan group showed neither bony defect healing nor cartilage repair. Histology revealed higher O'Driscoll scores and hyaline-like cartilage regeneration in the 1-mg losartan group compared with the MFX group. In contrast, the 100-mg losartan group showed the lowest histology score and no cartilage repair. An IA injection of losartan at the doses of 0.1, 1, and 10 mg did not cause adverse effects on uninjured cartilage, while the 100-mg dose induced cartilage damage. Quantitative polymerase chain reaction results showed downregulation of the transforming growth factor ß (TGF-ß) signaling pathway after IA losartan injection. CONCLUSION: An IA injection of losartan at the dose of 1 mg was most effective for the enhancement of microfracture-mediated cartilage repair without adversely affecting uninjured cartilage. Conversely, a high dose (100 mg) IA injection of losartan inhibited cartilage repair in the osteochondral defect and was chondrotoxic to normal articular cartilage. CLINICAL RELEVANCE: An IA injection of losartan at an optimal dosage represents a novel microfracture enhancement therapy and warrants a clinical trial for future clinical applications.

Development and Preclinical Evaluation of New Inhaled Lipoglycopeptides for the Treatment of Persistent Pulmonary Methicillin-Resistant Staphylococcus aureus Infections.

Chronic pulmonary methicillin-resistant Staphylococcus aureus (MRSA) disease in cystic fibrosis (CF) has a high probability of recurrence following treatment with standard-of-care antibiotics and represents an area of unmet need associated with reduced life expectancy. We developed a lipoglycopeptide therapy customized for pulmonary delivery that not only demonstrates potent activity against planktonic MRSA, but also against protected colonies of MRSA in biofilms and within cells, the latter of which have been linked to clinical antibiotic failure. A library of next-generation potent lipoglycopeptides was synthesized with an emphasis on attaining superior pharmacokinetics (PK) and pharmacodynamics to similar compounds of their class. Our strategy focused on hydrophobic modification of vancomycin, where ester and amide functionality were included with carbonyl configuration and alkyl length as key variables. Candidates representative of each carbonyl attachment chemistry demonstrated potent activity in vitro, with several compounds being 30 to 60 times more potent than vancomycin. Selected compounds were advanced into in vivo nose-only inhalation PK evaluations in rats, where RV94, a potent lipoglycopeptide that utilizes an inverted amide linker to attach a 10-carbon chain to vancomycin, demonstrated the most favorable lung residence time after inhalation. Further in vitro evaluation of RV94 showed superior activity to vancomycin against an expanded panel of Gram-positive organisms, cellular accumulation and efficacy against intracellular MRSA, and MRSA biofilm killing. Moreover, in vivo efficacy of inhaled nebulized RV94 in a 48 h acute model of pulmonary MRSA (USA300) infection in neutropenic rats demonstrated statistically significant antibacterial activity that was superior to inhaled vancomycin.

'TB or not TB': the conundrum of pre-European contact tuberculosis in the Pacific.

Tuberculosis (TB) is a major global health threat, infecting one-third of the world's population. Despite this prominence, the age, origin and spread of the disease have been topics of contentious debate. Molecular studies suggest that Mycobacterium tuberculosis 'sensu stricto', the most common strain of TB infecting humans today, originated in Africa and from there spread into Europe and Asia. The M. tuberculosis strains most commonly found across the Pacific and the Americas today are most closely related to European strains, supporting a hypothesis that the disease only reached these regions relatively recently via European sailors or settlers. However, this hypothesis is inconsistent with palaeopathological evidence of TB-like lesions in human remains from across the Pacific that predate European contact. Similarly, genetic evidence from pre-European South American mummies challenges the notion of a European introduction of the disease into the Pacific. Here, we review the complex evidence for the age and origin of TB in the Pacific, and discuss key gaps in our knowledge and how these may be addressed. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

Forms of selenium in vitamin-mineral mixes differentially affect serum alkaline phosphatase activity, and serum albumin and blood urea nitrogen concentrations, of steers grazing endophyte-infected tall fescue.

The goal of this study was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral mix would differentially affect serological and hepatic parameters of growing steers grazing toxic endophyte-infected tall fescue-mixed forage pasture. Predominately Angus steers (BW = 183 ± 34 kg) were randomly selected from herds of fall-calving cows grazing endophyte-infected tall fescue-mixed pasture and consuming vitamin-mineral mixes that contained 35 ppm Se as ISe, OSe, and MIX forms. Steers were weaned, depleted of Se for 98 d, and subjected to summer-long common grazing of an endophyte-infected tall fescue-mixed pasture (0.51 ppm total ergovaline + ergovalinine; 10.1 ha). Steers were assigned (n = 8 per treatment) to the same Se form treatments upon which they were raised. Se treatments were administered by daily top-dressing 85 g of vitamin-mineral mix onto 0.23 kg soyhulls, using in-pasture Calan gates. The PROC MIXED procedure of SAS was used to assess the effect of Se form treatments on serum parameters at day 0, 22, 43, 64, and 86. After slaughter, the effect of Se treatment on hepatic alkaline phosphatase (tissue nonspecific isoform, TNALP) mRNA, protein, and albumin protein content was assessed using the PROC GLM procedure of SAS. Fisher's protected LSD procedure was used to separate treatment means. Partial correlation analysis was used to evaluate the relationship among whole blood Se concentration and serum parameters, accounting for the effect of time. Across periods, MIX steers had more (P ≤ 0.04) serum albumin than OSe and ISe steers, respectively. However, the relative hepatic bovine serum albumin protein content was not affected (P = 0.28) by Se treatments. Serum alkaline phosphatase activity was greater (P ≤ 0.01) in MIX and OSe steers. Similarly, hepatic TNALP protein content in MIX steers was greater (P = 0.01) than ISe steers. Partial correlation analysis revealed that serum albumin, blood urea nitrogen, and alkaline phosphatase activity were correlated (r ≥ 0.23, P ≤ 0.02) with whole blood Se concentration. In summary, consumption of 3 mg Se/d as OSe or MIX forms of Se in vitamin-mineral mixes increased serum albumin concentration and alkaline phosphatase activity, the reduction of which is associated with fescue toxicosis. We conclude that the organic forms of Se ameliorated the depression of 2 of known serological biomarkers of fescue toxicosis.

Forms of selenium in vitamin-mineral mixes differentially affect the expression of genes responsible for prolactin, ACTH, and α-MSH synthesis and mitochondrial dysfunction in pituitaries of steers grazing endophyte-infected tall fescue.

The goal of this study was to test the hypothesis that sodium selenite (inorganic Se, ISe), SEL-PLEX (organic forms of Se, OSe), vs. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially alter pituitary transcriptome profiles in growing beef steers grazing an endophyte-infected tall fescue (E+) pasture. Predominately Angus steers (BW = 183 ± 34 kg) were randomly selected from fall-calving cows grazing E+ pasture and consuming VM mixes that contained 35 ppm Se as ISe, OSe, or MIX forms. Steers were weaned, depleted of Se for 98 d, and subjected to summer-long common grazing of a 10.1 ha E+ pasture containing 0.51 ppm ergot alkaloids. Steers were assigned (n = 8 per treatment) to the same Se-form treatments on which they were raised. Selenium treatments were administered by daily top-dressing 85 g of VM mix onto 0.23 kg soyhulls, using in-pasture Calan gates. As previously reported, serum prolactin was greater for MIX (52%) and OSe (59%) steers vs. ISe. Pituitaries were collected at slaughter and changes in global and selected mRNA expression patterns determined by microarray and real-time reverse transcription PCR analyses, respectively. The effects of Se treatment on relative gene expression were subjected to one-way ANOVA. The form of Se affected the expression of 542 annotated genes (P < 0.005). Integrated pathway analysis found a canonical pathway network between prolactin and pro-opiomelanocortin (POMC)/ACTH/α-melanocyte-stimulating hormone (α-MSH) synthesis-related proteins and that mitochondrial dysfunction was a top-affected canonical pathway. Targeted reverse transcription-PCR analysis found that the relative abundance of mRNA encoding prolactin and POMC/ACTH/α-MSH synthesis-related proteins was affected (P < 0.05) by the form of Se, as were (P ≤ 0.05) mitochondrial dysfunction-related proteins (CYB5A, FURIN, GPX4, and PSENEN). OSe steers appeared to have a greater prolactin synthesis capacity (more PRL mRNA) vs. ISe steers through decreased dopamine type two receptor signaling (more DRD2 mRNA), whereas MIX steers had a greater prolactin synthesis capacity (more PRL mRNA) and release potential by increasing thyrotropin-releasing hormone concentrations (less TRH receptor mRNA) than ISe steers. OSe steers also had a greater ACTH and α-MSH synthesis potential (more POMC, PCSK2, CPE, and PAM mRNA) than ISe steers. We conclude that form of Se in VM mixes altered expression of genes responsible for prolactin and POMC/ACTH/α-MSH synthesis, and mitochondrial function, in pituitaries of growing beef steers subjected to summer-long grazing an E+ pasture.

Inhaled Treprostinil-Prodrug Lipid Nanoparticle Formulations Provide Long-Acting Pulmonary Vasodilation.

Treprostinil (TRE), a prostanoid analogue approved in the USA for the treatment of pulmonary arterial hypertension, requires continuous infusion or multiple dosing sessions per day for inhaled and oral routes of administration due to its short half-life. The inhaled drug is known to induce adverse systemic and local effects including headache, nausea, cough, and throat irritation which may be due at least in part to transiently high drug concentrations in the lungs and plasma immediately following administration [1]. To ameliorate these side effects and reduce dosing frequency we designed an inhaled slow-release TRE formulation. TRE was chemically modified to be an alkyl prodrug (TPD) which was then packaged into a lipid nanoparticle (LNP) carrier. Preclinical screening in a rat model of hypoxia-induced pulmonary vasoconstriction led to selection of a 16-carbon alkyl ester derivative of TRE. The TPD-LNP demonstrated approximately 10-fold lower TRE plasma Cmax compared to inhaled TRE solution while maintaining an extended vasodilatory effect. The favorable PK profile is attributed to gradual dissociation of TPD from the LNP and subsequent conversion to TRE. Together, this sustained presentation of TRE to the lungs and plasma is consistent with a once- or twice-daily dosing schedule in the absence of high Cmax-associated adverse events which could provide patients with an improved treprostinil therapy.

Yoga for Heart Failure: A Review and Future Research.

BACKGROUND: Complementary and alternative medicine is a rapidly growing area of biomedical inquiry. Yoga has emerged in the forefront of holistic medical care due to its long history of linking physical, mental, and spiritual well-being. Research in yoga therapy (YT) has associated improved cardiovascular and quality of life (QoL) outcomes for the special needs of heart failure (HF) patients. AIM: The aim of this study is to review yoga intervention studies on HF patients, discuss proposed mechanisms, and examine yoga's effect on physiological systems that have potential benefits for HF patients. Second, to recommend future research directions to find the most effective delivery methods of yoga to medically stable HF patients. METHODS: The authors conducted a systematic review of the medical literature for RCTs involving HF patients as participants in yoga interventions and for studies utilizing mechanistic theories of stretch and new technologies. We examined physical intensity, mechanistic theories, and the use of the latest technologies. CONCLUSIONS: Based on the review, there is a need to further explore yoga mechanisms and research options for the delivery of YT. Software apps as exergames developed for use at home and community activity centers may minimize health disparities and increase QoL for HF patients.

Electrochemical surface engineering of magnesium metal by plasma electrolytic oxidation and calcium phosphate deposition: biocompatibility and in vitro degradation studies.

In this study, the surface of magnesium metal was electrochemically engineered for enhanced biocompatibility and controlled degradation in body fluid. Firstly, a plasma electrolytic oxidation (PEO) coating was formed on magnesium, followed by electrochemical deposition of calcium phosphate (CaP) using an unconventional electrolyte. Cytocompatibility tests using L929 cells revealed that the PEO-CaP coating significantly improved the biocompatibility of magnesium. In vitro electrochemical degradation experiments in simulated body fluid (SBF) showed that the PEO-CaP coating improved the degradation resistance of magnesium significantly. The corrosion current density (i corr) of the PEO-CaP coated magnesium was ∼99% and ∼97% lower than that of bare magnesium and the PEO-only coated magnesium, respectively. Similarly, electrochemical impedance spectroscopy (EIS) results showed that the polarisation resistance (R P) of the PEO-CaP coated magnesium was one-order of magnitude higher as compared to the PEO-only coated magnesium and two-orders of magnitude higher than the bare magnesium, after 72 h immersion in SBF. Scanning electron microscopy (SEM) analysis revealed no localized degradation in the PEO-CaP coated magnesium. The study demonstrated that the PEO-CaP coating is a promising combination for enhancing the biocompatibility and reducing the degradation of magnesium for potential biodegradable implant applications.

Preclinical Pharmacology and Pharmacokinetics of Inhaled Hexadecyl-Treprostinil (C16TR), a Pulmonary Vasodilator Prodrug.

This article describes the preclinical pharmacology and pharmacokinetics (PK) of hexadecyl-treprostinil (C16TR), a prodrug of treprostinil (TRE), formulated in a lipid nanoparticle (LNP) for inhalation as a pulmonary vasodilator. C16TR showed no activity (>10 µM) in receptor binding and enzyme inhibition assays, including binding to prostaglandin E2 receptor 2, prostaglandin D2 receptor 1, prostaglandin I2 receptor, and prostaglandin E2 receptor 4; TRE potently bound to each of these prostanoid receptors. C16TR had no effect (up to 200 nM) on platelet aggregation induced by ADP in rat blood. In hypoxia-challenged rats, inhaled C16TR-LNP produced dose-dependent (0.06-6 µg/kg), sustained pulmonary vasodilation over 3 hours; inhaled TRE (6 µg/kg) was active at earlier times but lost its effect by 3 hours. Single- and multiple-dose PK studies of inhaled C16TR-LNP in rats showed proportionate dose-dependent increases in TRE Cmax and area under the curve (AUC) for both plasma and lung; similar results were observed for dog plasma levels in single-dose PK studies. In both species, inhaled C16TR-LNP yielded prolonged plasma TRE levels and a lower plasma TRE Cmax compared with inhaled TRE. Inhaled C16TR-LNP was well tolerated in rats and dogs; TRE-related side effects included cough, respiratory tract irritation, and emesis and were seen only after high inhaled doses of C16TR-LNP in dogs. In guinea pigs, inhaled TRE (30 µg/ml) consistently produced cough, but C16TR-LNP (30 µg/ml) elicited no effect. These results demonstrate that C16TR-LNP provides long-acting pulmonary vasodilation, is well tolerated in animal studies, and may necessitate less frequent dosing than inhaled TRE with possibly fewer side effects.

Role of cathepsins D in the midgut of Dysdercus peruvianus.

Hemipteran ancestors probably lost their digestive serine peptidases on adapting to a plant sap diet. On returning to protein ingestion, these insects start using cathepsin (lysosomal) peptidases as digestive enzymes, from which the less known is cathepsin D. Nine of the ten cathepsin D transcribing genes found in Dysdercus peruvianus midgut are expressed exclusively in this tissue and only DpCatD10 is also expressed in other tissues. The main action of cathepsins D is in the first (V1) (from three, V1-3) midgut regions, where 40% of the total proteolytic activity was assigned to aspartic peptidases with an optimum pH of 3.5. The most expressed cathepsins D were identified in the midgut luminal contents by proteomics. The data indicate that D. peruvianus have kept a lysosomal gene expressed in all tissues and evolved another set of genes with a digestive function restricted to midgut. Digestive cathepsins D apparently complement the action of digestive cathepsin L and they are arguably responsible for the hydrolysis of cysteine peptidase inhibitors known to be present in the cotton seeds eaten by the insect, before they meet cathepsin L.

Pulmonary Deposition and Elimination of Liposomal Amikacin for Inhalation and Effect on Macrophage Function after Administration in Rats.

Pulmonary nontuberculous mycobacterial (PNTM) infections represent a treatment challenge. Liposomal amikacin for inhalation (LAI) is a novel formulation currently in development for the treatment of PNTM infections. The pulmonary deposition and elimination of LAI and its effect on macrophage function were evaluated in a series of preclinical studies in healthy rats. The pulmonary deposition of LAI was evaluated in female rats (n = 76) treated with LAI by nebulizer at 10 mg/kg of body weight per day or 90 mg/kg per day for 27 days, followed by dosing of dually labeled LAI (LAI with a lipid label plus an amikacin label) on day 28 with subsequent lung histological and amikacin analyses. In a separate study for assessment of alveolar macrophage function, rats (n = 180) received daily treatment with LAI at 90 mg/kg per day or 1.5% saline over three 30-day treatment periods followed by 30-day recovery periods; phagocytic and Saccharomyces cerevisiae (yeast) killing capabilities and inflammatory mediator release were assessed at the end of each period. LAI demonstrated equal dose-dependent deposition across all lung lobes and regions. Lipid and amikacin labels showed diffuse extracellular colocalization, followed by macrophage uptake and gradual amikacin elimination. Macrophages demonstrated accumulation of amikacin during treatment periods and nearly complete elimination during recovery periods. No evidence of an inflammatory response was seen. No differences in microsphere uptake or yeast killing were seen between LAI-treated and control macrophages. Neither LAI-treated nor control macrophages demonstrated constitutive inflammatory mediator release; however, both showed normal mediator release on lipopolysaccharide stimulation. LAI is readily taken up by macrophages in healthy rats without compromising macrophage function.

Biocompatibility and in Vitro Degradation Behavior of Magnesium-Calcium Alloy Coated with Calcium Phosphate Using an Unconventional Electrolyte.

Calcium phosphate (CaP) was electrochemically coated on a magnesium-calcium (Mg-Ca) alloy using an unconventional electrolyte and a pulse-potential method. The CaP particles of the coating were relatively large, flat, and irregularly oriented; however, they covered the entire alloy surface with a coating thickness of 5 µm. Cytocompatibility tests using L929 cells inoculated in Eagle minimum essential medium supplemented with 10% (v/v) fetal bovine serum (E-MEM+FBS) revealed that CaP coating improved the cytocompatibility of the alloy. It also showed effective suppression of Mg2+ ion release from the substrate of the coated alloy and consequently reduced the pH increase of the medium. In vitro degradation experiments using electrochemical techniques in simulated body fluid (SBF) also suggested significant enhancement of the alloy degradation resistance by CaP coating. Potentiodynamic polarization results showed that the corrosion current density of the coated alloy was ∼95% lower than that of the bare metal. Electrochemical impedance spectroscopy results revealed that the polarization resistance (RP) of the coated alloy was more than an order of magnitude higher than that of the bare metal after 2 h of immersion in SBF. Interestingly, after 72 h of immersion, the measured RP had decreased by ∼82%, and the coating appeared cracked and damaged. The results suggest that SBF is more aggressive than E-MEM+FBS cell culture medium.

Form of supplemental selenium fed to cycling cows affects systemic concentrations of progesterone but not those of estradiol.

In areas where soils are deficient in selenium (Se), dietary supplementation of this trace mineral directly to cattle is recommended. Selenium status affects fertility, and the form of Se supplemented to cows affects tissue-specific gene expression profiles. The objective of this study was to determine whether the form of Se consumed by cows would affect follicular growth and the production of steroids. Thirty-three Angus-cross cows that had ad libitum access of a mineral mix containing 35 ppm of Se in free-choice vitamin-mineral mixes as either inorganic (ISe), organic (OSe), or a 50/50 mix of ISe and OSe (MIX) for 180 days were used. After 170 days of supplementation, all cows were injected with 25-mg PGF2α to induce regression of the CL and then monitored for behavioral estrus (Day 0). From Day 4 to Day 8 after estrus, follicular growth was determined by transrectal ultrasonography. On Day 6, cows were injected with PGF2α (20 then 15 mg, 8-12 hours apart) to induce regression of the developing CL and differentiation of the dominant follicle of the first follicular wave into a preovulatory follicle. On Day 8, 36 hours after PGF2α (20 mg), the contents of the preovulatory follicle were aspirated by ultrasound-guided follicular puncture. Blood collected on Days 6 and 8 and follicular fluid collected on Day 8 was analyzed for concentrations of progesterone and estradiol. Form of Se supplemented to cows affected (P = 0.04) the systemic concentration of progesterone on Day 6, but not on Day 8. Form of Se did not affect the systemic concentration of estradiol on Day 6 or Day 8. Form of Se tended to affect (P = 0.07) the concentration of progesterone, but not that of estradiol, in the follicular fluid. Form of Se did not affect diameter of the dominant ovarian follicle on Days 4 to 6, but tended to affect (P = 0.08) the diameter of the preovulatory follicle on Day 8. Our results suggest that form of Se fed to cows affects the production of progesterone but not that of estradiol. Further investigation of organic Se-induced increases in progesterone and potentially the effects of increased progesterone on the establishment of pregnancy, especially in cows of lower fertility, is warranted.

Experiments Testing the Causes of Namibian Fairy Circles.

The grasslands on the sandy soils of the eastern edge of the Namib Desert of Namibia are strikingly punctuated by millions of mostly regularly-spaced circular bare spots 2 to 10 m or more in diameter, generally with a margin of taller grasses. The causes of these so called fairy circles are unknown, but several hypotheses have been advanced. In October 2009, we set up experiments that specifically tested four hypothesized causes, and monitored these 5 times between 2009 and 2015. Grass exclusion in circles due to seepage of subterranean vapors or gases was tested by burying an impermeable barrier beneath fairy circles, but seedling density and growth did not differ from barrier-less controls. Plant germination and growth inhibition by allelochemicals or nutrient deficiencies in fairy circle soils were tested by transferring fairy circle soil to artificially cleared circles in the grassy matrix, and matrix soil to fairy circles (along with circle to circle and matrix to matrix controls). None of the transfers changed the seedling density and growth from the control reference conditions. Limitation of plant growth due to micronutrient depletion within fairy circles was tested by supplementing circles with a micronutrient mixture, but did not result in differences in plant seedling density and growth. Short-range vegetation competitive feedbacks were tested by creating artificially-cleared circles of 2 or 4 m diameter located 2 or 6 m from a natural fairy circle. The natural circles remained bare and the artificial circles revegetated. These four experiments provided evidence that fairy circles were not caused by subterranean vapors, that fairy circle soil per se did not inhibit plant growth, and that the circles were not caused by micronutrient deficiency. There was also no evidence that vegetative feedbacks affected fairy circles on a 2 to 10 m scale. Landscape-scale vegetative self-organization is discussed as a more likely cause of fairy circles.

Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication.

Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios. Efforts to discover and develop poliovirus antiviral agents have been ongoing in earnest since the formation in 2007 of the Poliovirus Antivirals Initiative. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has recently demonstrated activity in an oral poliovirus vaccine human challenge model. Additional antiviral candidates with differing mechanisms of action continue to be profiled and evaluated preclinically with the goal of having 2 antivirals available for use in combination to treat iVDPV excreters.

Individual intake of free-choice mineral mix by grazing beef cows may be less than typical formulation assumptions and form of selenium in mineral mix affects blood Se concentrations of cows and their suckling calves.

The objectives of this study were to determine (1) the individual ad libitum intake of mineral mix by beef cows managed under a year-long, fall-calving, forage-based production regimen and (2) if Se form in the mineral mix affected the blood Se concentrations of cows and suckling calves. Twenty-four late-gestation (6 to 8 months) Angus-cross cows (2.7 ± 0.8 years; body weight [BW] = 585 ± 58 kg) were blocked by BW and randomly assigned (n = 8) to a mineral supplement treatment (TRT) containing 35 ppm Se as either inorganic (ISe; sodium selenite), organic (OSe; Sel-Plex®), or a 1:1 combination of ISe/OSe (MIX). Cows commonly grazed a 10.1-ha predominately tall fescue pasture and had individual ad libitum access to TRT using in-pasture Calan gates. Cows calved from August to November and calves had common ad libitum access to creep feed and a mineral supplement that lacked Se. Cow jugular blood was taken at 28-day intervals (13 periods) and calf blood was taken with cows from birth through weaning. Individual cow mineral mix (mean = 54.0 ± 7.0 g/day, range = 97.3 to 27.9 ± 7.4 g/day) and Se (mean = 1.82 ± 0.25 mg/day, range = 3.31 to 0.95 ± 0.25 mg/day) intakes were affected by period (P < 0.0001), but not by cow Se TRT (P > 0.30). Cow blood Se (0.109 to 0.229 ± 0.01 µg/mL) was affected (P < 0.002) by period, Se form, and their interaction, with ISe < MIX for periods 8 and 11, ISe < OSe for all periods except period 1, and MIX < OSe for periods 2 to 4, 7, 8, 10, and 12. Calf blood Se (in micrograms Se per milliliter) was correlated with cow blood Se and affected (P < 0.0001) by cow Se TRT, with ISe (0.07 to 0.11) < MIX (0.10 to 0.15) = OSe (0.16 to 0.19). These data reveal that (1) mean supplemental ad libitum cow mineral intake was 36% less than the typical formulation intake expectations (85 g/day) and, correspondingly, mean supplemental Se intake was 33% less than that allowed by the FDA and (2) cow Se TRT differentially affected both cow and calf blood Se concentrations, resulting in adequate concentrations for all cows but inadequate concentrations for ISe calves.