Feeding Soy Protein Concentrates with Low and High Isoflavones Alters 9 and 18 Weeks Serum Isoflavones and Inflammatory Protein Levels in Lean and Obese Zucker Rats.

Soy's anti-inflammatory properties contribute to the health benefits of soy foods. This study was designed to investigate the bioavailability of soy isoflavones and whether the isoflavone content of soy protein concentrate diet would affect serum inflammatory proteins in an obese (fa/fa) Zucker rat model. Six-week-old male lean (L) and obese (O) Zucker rats were fed a casein control diet (C), soy protein concentrate with low isoflavones (SPC-LIF), or soy protein concentrate with high isoflavones (SPC-HIF) (7 rats/dietary group) before being killed at 9 and 18 weeks. Serum samples were analyzed for isoflavones and inflammatory proteins. At both time points, serum total (aglycone + conjugates) genistein, daidzein, and equol concentrations were significantly higher in L-SPC-HIF and O-SPC-HIF groups compared with L-SPC-LIF and O-SPC-LIF groups, respectively, and were not detectable in either L-C or O-C groups. At week 9, serum C-reactive protein (CRP) concentration was significantly lower in O-SPC-HIF group compared with O-C and O-SPC-LIF group, whereas proteins tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels did not differ between any groups. At week 18, serum CRP levels in both O-SPC-HIF and O-SPC-LIF groups were significantly lower compared with the O-C group. TNF-α level was higher in the O-SPC-LIF group compared with both O-C and O-SPC-HIF groups, whereas IL-6 levels were not different between any groups. Taken together, feeding Zucker rats SPC-LIF and SPC-HIF diets led to different serum isoflavone concentrations in both L and O Zucker rats and altered CRP and TNF-α levels in obese Zucker rats compared with controls.

We Built it, But Did They Come: Veterans' Use of VA Healthcare System-Provided Complementary and Integrative Health Approaches.

BACKGROUND: Interest in complementary and integrative health (CIH) approaches, such as meditation, yoga, and acupuncture, continues to grow. The evidence of effectiveness for some CIH approaches has increased in the last decade, especially for pain, with many being recommended in varying degrees in national guidelines. To offer nonpharmacological health management options and meet patient demand, the nation's largest integrated healthcare system, the Veterans Health Administration (VA), greatly expanded their provision of CIH approaches recently. OBJECTIVE: This paper addressed the questions of how many VA patients might use CIH approaches and chiropractic care if they were available at modest to no fee, and would patients with some health conditions or characteristics be more likely than others to use these therapies. DESIGN: Using electronic medical records, we conducted a national, three-year, retrospective analysis of VA patients' use of eleven VA-covered therapies: chiropractic care, acupuncture, Battlefield Acupuncture, biofeedback, clinical hypnosis, guided imagery, massage therapy, meditation, Tai Chi/Qigong, and yoga. PARTICIPANTS: We created a national cohort of veterans using VA healthcare from October 2016-September 2019. KEY RESULTS: Veterans' use of these approaches increased 70% in three years. By 2019, use was 5.7% among all VA patients, but highest among patients with chronic musculoskeletal pain (13.9%), post-traumatic stress disorder (PTSD; 10.6%), depression (10.4%), anxiety (10.2%), or obesity (7.8%). The approach used varied by age and race/ethnicity, with women being uniformly more likely than men to use each approach. Patients having chronic musculoskeletal pain, obesity, anxiety, depression, or PTSD were more likely than others to use each of the approaches. CONCLUSIONS: Veterans' use of some approaches rapidly grew recently and was robust, especially among patients most in need. This information might help shape federal/state health policy on the provision of evidence-based CIH approaches and guide other healthcare institutions considering providing them.

Imaging of pre- and post-cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pediatric intraperitoneal malignancy.

Although rare, pediatric peritoneal carcinomatosis does occur in primary abdominopelvic tumors. Additionally, peritoneal carcinomatosis has been described to occur as metastatic disease where the primary tumor is outside the abdominopelvic cavity. Where amenable, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can be beneficial in disease management. However, favorable outcomes are predicated on specific tumor histology as well as proper patient selection, which significantly relies on preoperative imaging. This review gives a comprehensive, up-to-date summary on pediatric peritoneal carcinomatosis pre-surgical evaluation; where imaging is beneficial and limited; pediatric radiologists' role in helping to quantify disease; and how we, as pediatric radiologists, can help the surgeons and oncologists in the selection of patients for cytoreductive surgery and HIPEC.

Exon 2-mediated deletion of Trem2 does not worsen metabolic function in diet-induced obese mice.

Triggering receptor expressed on myeloid cells 2 (Trem2) is highly expressed on myeloid cells and is involved in cellular lipid homeostasis and inflammatory processes. Trem2 deletion in mice (Trem2-/- ) evokes adipose tissue dysfunction, but its role in worsening obesity-induced metabolic dysfunction has not been resolved. Here we aimed to determine the causal role of Trem2 in regulating glucose homeostasis and insulin sensitivity in mice. Nine-week-old male and female littermate wild-type (WT) and Trem2-/- mice were fed a low- or high-fat diet for 18 weeks and phenotyped for metabolic function. Diet-induced weight gain was similar between genotypes, irrespective of sex. Consistent with previous reports, we find that loss of Trem2 causes massive adipocyte hypertrophy and an attenuation in the lipid-associated macrophage transcriptional response to obesity. In contrast to published data, we find that loss of Trem2 does not worsen metabolic function in obese mice. No differences in intraperitoneal glucose tolerance (ipGTT), oral GTT or mixed meal substrate control, including postprandial glucose, non-esterified fatty acids, insulin or triglycerides, were found between WT and Trem2-/- animals. Similarly, no phenotypic differences existed when animals were challenged with stressors on metabolic demand (i.e. acute exercise or environmental temperature modulation). Collectively, we report a disassociation between adipose tissue remodelling caused by loss of Trem2 and whole-body metabolic homeostasis in obese mice. The complementary nature of experiments conducted gives credence to the conclusion that loss of Trem2 is unlikely to worsen glucose homeostasis in mice.

Large group differences in binaural sensitivity are represented in preattentive responses from auditory cortex.

Correlated sounds presented to two ears are perceived as compact and centrally lateralized, whereas decorrelation between ears leads to intracranial image widening. Though most listeners have fine resolution for perceptual changes in interaural correlation (IAC), some investigators have reported large variability in IAC thresholds, and some normal-hearing listeners even exhibit seemingly debilitating IAC thresholds. It is unknown whether or not this variability across individuals and outlier manifestations are a product of task difficulty, poor training, or a neural deficit in the binaural auditory system. The purpose of this study was first to identify listeners with normal and abnormal IAC resolution, second to evaluate the neural responses elicited by IAC changes, and third to use a well-established model of binaural processing to determine a potential explanation for observed individual variability. Nineteen subjects were enrolled in the study, eight of whom were identified as poor performers in the IAC-threshold task. Global scalp responses (N1 and P2 amplitudes of an auditory change complex) in the individuals with poor IAC behavioral thresholds were significantly smaller than for listeners with better IAC resolution. Source-localized evoked responses confirmed this group effect in multiple subdivisions of the auditory cortex, including Heschl's gyrus, planum temporale, and the temporal sulcus. In combination with binaural modeling results, this study provides objective electrophysiological evidence of a binaural processing deficit linked to internal noise, that corresponds to very poor IAC thresholds in listeners that otherwise have normal audiometric profiles and lack spatial hearing complaints.NEW & NOTEWORTHY Group differences in the perception of interaural correlation (IAC) were observed in human adults with normal audiometric sensitivity. These differences were reflected in cortical-evoked activity measured via electroencephalography (EEG). For some participants, weak representation of the binaural cue at the cortical level in preattentive N1-P2 cortical responses may be indicative of a potential processing deficit. Such a deficit may be related to a poorly understood condition known as hidden hearing loss.

Change in plasma α-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation.

BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV1)] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGAex). We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV1 decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4-mL/y attenuated FEV1 decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564). CONCLUSIONS: Greater response to vitE supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.

Selenomelanin: An Abiotic Selenium Analogue of Pheomelanin.

Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments and as radiation protection agents. There exist five multifunctional yet structurally and biosynthetically incompletely understood varieties of melanin: eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin. Although eumelanin and allomelanin have been the focus of most radiation protection studies to date, some research suggests that pheomelanin has a better absorption coefficient for X-rays than eumelanin. We reasoned that if a selenium enriched melanin existed, it would be a better X-ray protector than the sulfur-containing pheomelanin because the X-ray absorption coefficient is proportional to the fourth power of the atomic number (Z). Notably, selenium is an essential micronutrient, with the amino acid selenocysteine being genetically encoded in 25 natural human proteins. Therefore, we hypothesize that selenomelanin exists in nature, where it provides superior ionizing radiation protection to organisms compared to known melanins. Here we introduce this novel selenium analogue of pheomelanin through chemical and biosynthetic routes using selenocystine as a feedstock. The resulting selenomelanin is a structural mimic of pheomelanin. We found selenomelanin effectively prevented neonatal human epidermal keratinocytes (NHEK) from G2/M phase arrest under high-dose X-ray irradiation. Provocatively, this beneficial role of selenomelanin points to it as a sixth variety of yet to be discovered natural melanin.

Effects of dietary electrolytes, osmolytes, and energetic compounds on body temperature indices in heat-stressed lactating cows.

Objectives were to determine the effects of a product containing electrolytes, osmolytes, and energetic compounds (EOEC) on body temperature indices in heat-stressed (HS) Holstein cows. Lactating cows were assigned to 1 of 2 treatments: 1) a control diet (n = 10) or 2) a control diet supplemented with 113 g/d of EOEC (n = 10; Bovine BlueLite® Pellets; TechMix LLC, Stewart, MN). The trial consisted of 2 experimental periods (P). During P1 (4 d), cows were fed their respective treatments and housed in thermoneutral conditions. During P2 (4 d), HS was artificially induced using an electric heat blanket (EHB). Overall, HS markedly increased vaginal temperature (Tv), rectal temperature (Tr), skin temperature (Ts), and respiration rate (RR) (P < .01). There were no dietary treatment differences in Tv, Tr, or RR; however, during P2 EOEC-supplemented cows had increased Ts (0.8 °C; P = .04). Compared to P1, HS decreased DMI and milk yield (45 and 27%, respectively, P < .01) similarly amongst treatments. Relative to P1, circulating insulin decreased (41%; P = .04) in CON cows, whereas it remained unaffected in EOEC-supplemented cows, resulting in a 2-fold increase in EOEC compared with CON-fed cows (P < .01) during P2. Relative to P1, HS increased circulating non-esterified fatty acids (NEFA; 63%; P < .01). During P2, there tended to be a treatment by day interaction on circulating NEFA, as concentrations decreased from d 2 to 4 of P2 in EOEC-fed cows but continued to increase in CON cows. In summary, feeding EOEC altered some key aspects of energetic metabolism and increased Ts.

Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.

This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 µg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 µg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).

Effects of an oral supplement containing calcium and live yeast on post-absorptive metabolism, inflammation and production following intravenous lipopolysaccharide infusion in dairy cows.

Objectives were to evaluate the effects of an oral supplement containing soluble Ca, and live yeast in LPS-challenged dairy cows. The trial consisted of 2 experimental periods (P). During P1 (3 d), cows (n = 12) were fed ad libitum and baseline data was collected. At the beginning of P2 (which lasted 96 h), all cows were i.v. challenged with 0.375 µg/kg BW LPS. Cows were assigned randomly to 1 of 2 treatments: 1) control (CON; no bolus; n = 6) or 2) an oral bolus containing Ca and live yeast (CLY; YMCP Vitall® 44.718 g of elemental Ca; TechMix, LLC., Stewart, MN; n = 6), administered -0.5 and 6.5 h relative to LPS infusion. Following LPS administration, circulating Ca decreased in both treatments but supplemental CLY ameliorated the hypocalcemia (48 h area under the curve: -10.8 vs. -1.9 mmol/L × h; P < .01). Lipopolysaccharide decreased dry matter intake (DMI; 60%) similarly for both treatments on d 1, but overall (d 1-4) DMI tended to be reduced less (14 vs. 30%; P = .06) in CLY supplemented vs CON cows. Lipopolysaccharide reduced milk yield (70%; P < .01) from 12 to 24 h, but throughout P2, milk yield from CLY supplemented cows was increased (38%; P = .03) relative to CON cows. Overall during P2, circulating LPS-binding protein and serum amyloid A increased post LPS (3- and 4-fold, respectively, P < .01), but were unaffected by treatment (P ≥ .68). In conclusion, providing an oral supplement containing Ca and live yeast prior to and following LPS administration markedly ameliorated LPS-induced hypocalcemia and improved DMI and milk yield.

Management of Melanoma Patients by Non-Dermatologists in the Military Health System: A Retrospective Observational Study.

INTRODUCTION: Compared to their civilian counterparts, military personnel can have more exposure to sunlight and, as recent studies have shown, do have an increased incidence of melanoma. Given the inherent challenges service members may face in getting appropriate care whether because of operational tempo, deployments, and/or austere locations, many are initially diagnosed by specialties other than dermatology. In this study, we sought to determine if patients within the military health system were receiving appropriate follow-up management after biopsies by non-dermatologists led to the diagnosis of melanoma by pathology. MATERIALS AND METHODS: Using the Co-Path system, 1,000 patients were identified who had first time biopsies positive for melanoma. Of these, 73 were originally biopsied by non-dermatologists. Retrospective medical record review was performed to determine specialties of the non-dermatologists, staging of melanoma at diagnosis, referrals to specialists and dermatologists, and adherence to National Comprehensive Cancer Network guidelines. The study protocol was approved by the Walter Reed National Military Medical Center Institutional Review Board, protocol number WRNMMC-EDO-2017-0030, in compliance with all applicable federal regulations governing the protection of human subject research. RESULTS: Family medicine physicians made up the majority of non-dermatologists involved in performing biopsies that led to the diagnosis of melanoma in this study. Most patients were Stage I (pT1a), and the average time from initial biopsy to further wide excision biopsy was 18 days. Sixty-seven of the 73 patients biopsied by non-dermatologists received referrals to dermatologists, and 55 of the 67 patients followed through with being seen. Follow-up full body skin exams were performed on 55 of the 73 patients, with dermatologists conducting the majority of them. National Comprehensive Cancer Network guidelines were followed in 45 of the 73 patients, with an additional 24 patients having insufficient evidence to determine if guidelines were adhered to. CONCLUSION: Our study demonstrated that a number of different specialties outside of dermatology are involved in performing biopsies on patients in which melanoma is a concern. Although the results show that the majority of patients biopsied by non-dermatologists received appropriate follow-up care, there is still room to improve to ensure that all melanoma patients receive referrals to and are seen by dermatologists after a diagnosis of melanoma.

Engineering Magnetic Phases in Two-Dimensional Non-van der Waals Transition-Metal Oxides.

The family of 2D magnetic materials is continuously expanding because of the rapid discovery of exfoliable van der Waals magnetic systems. Recently, the synthesis of non-van der Waals magnetic "hematene" from common iron ore has opened an unconventional route to 2D material discovery. These non-van der Waals 2D systems are chemically stable and easily available and may have different or enhanced properties compared to their van der Waals counterparts. In this work, we have investigated and explained the nature of magnetic ordering in non-van der Waals 2D metal oxides. Two-dimensional hematene is found to be fully oxygen-passivated and stable under ambient conditions. It exhibits a striped ferrimagnetic ground state with a small net magnetic moment. Superexchange interactions are predicted to control the magnetic ground state of hematene, where pressure-induced spin crossover results in an observable net magnetic moment. Modulating the superexchange by alloying hematenes alters the magnetic ordering, tuning the system to a ferromagnetic ground state. Extending this strategy to the design of a new 2D material, we propose 2D chromia (α-Cr2O3) or "chromene", which, because of larger inter-transition metal distances and suppressed AFM superexchange, has a ferromagnetic ground state. We also show that tuning the magnetic ordering in these materials controls the transport properties by modulating the band gap, which may be of use in spintronic or catalytic applications.

Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension.

BACKGROUND: Obesity-related hypertension is a common disorder, and attempts to combat the underlying obesity are often unsuccessful. We previously revealed that mice globally deficient in the inhibitory immunoglobulin G (IgG) receptor FcγRIIB are protected from obesity-induced hypertension. However, how FcγRIIB participates is unknown. Studies were designed to determine if alterations in IgG contribute to the pathogenesis of obesity-induced hypertension. METHODS: Involvement of IgG was studied using IgG µ heavy chain-null mice deficient in mature B cells and by IgG transfer. Participation of FcγRIIB was interrogated in mice with global or endothelial cell-specific deletion of the receptor. Obesity was induced by high-fat diet (HFD), and blood pressure (BP) was measured by radiotelemetry or tail cuff. The relative sialylation of the Fc glycan on mouse IgG, which influences IgG activation of Fc receptors, was evaluated by Sambucus nigra lectin blotting. Effects of IgG on endothelial NO synthase were assessed in human aortic endothelial cells. IgG Fc glycan sialylation was interrogated in 3442 human participants by mass spectrometry, and the relationship between sialylation and BP was evaluated. Effects of normalizing IgG sialylation were determined in HFD-fed mice administered the sialic acid precursor N-acetyl-D-mannosamine (ManNAc). RESULTS: Mice deficient in B cells were protected from obesity-induced hypertension. Compared with IgG from control chow-fed mice, IgG from HFD-fed mice was hyposialylated, and it raised BP when transferred to recipients lacking IgG; the hypertensive response was absent if recipients were FcγRIIB-deficient. Neuraminidase-treated IgG lacking the Fc glycan terminal sialic acid also raised BP. In cultured endothelial cells, via FcγRIIB, IgG from HFD-fed mice and neuraminidase-treated IgG inhibited vascular endothelial growth factor activation of endothelial NO synthase by altering endothelial NO synthase phosphorylation. In humans, obesity was associated with lower IgG sialylation, and systolic BP was inversely related to IgG sialylation. Mice deficient in FcγRIIB in endothelium were protected from obesity-induced hypertension. Furthermore, in HFD-fed mice, ManNAc normalized IgG sialylation and prevented obesity-induced hypertension. CONCLUSIONS: Hyposialylated IgG and FcγRIIB in endothelium are critically involved in obesity-induced hypertension in mice, and supportive evidence was obtained in humans. Interventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break the link between obesity and hypertension.

State of deworming coverage and equity in low-income and middle-income countries using household health surveys: a spatiotemporal cross-sectional study.

BACKGROUND: Mass deworming against soil-transmitted helminthiasis, which affects 1 billion of the poorest people globally, is one of the largest public health programmes for neglected tropical diseases, and is intended to be equitable. However, the extent to which treatment programmes for deworming achieve equitable coverage across wealth class and sex is unclear and the public health metric of national deworming coverage does not include representation of equity. This study aims to measure both coverage and equity in global, national, and subnational deworming to guide future programmatic evaluation, investment, and metric design. METHODS: We used nationally representative, geospatial, household data from Demographic and Health Surveys that measured mother-reported deworming in children of preschool age (12-59 months). Deworming was defined as children having received drugs for intestinal parasites in the previous 6 months before the survey. We estimated deworming coverage disaggregated by geography, wealth quintile, and sex, and computed an equity index. We examined trends in coverage and equity index across countries, within countries, and over time. We used a regression model to compute the household correlates of deworming and ecological correlates of equitable deworming. FINDINGS: Our study included 820 883 children living in 50 countries from Africa, the Americas, Asia, and Europe that are endemic for soil-transmitted helminthiasis using 77 Demographic and Health Surveys from December, 2003, to October, 2017. In these countries, the mean deworming coverage in preschool children was estimated at 33·0% (95% CI 32·9-33·1). The subnational coverage ranged from 0·5% to 87·5%, and within-country variation was greater than between-country variation. Of the 31 countries reporting that they reached the WHO goal of more than 75% national coverage, 30 had inequity in deworming, with treatment concentrated in wealthier populations. We did not detect systematic differences in deworming equity by sex. INTERPRETATION: Substantial inequities in mass deworming programmes are common as wealthier populations have consistently higher coverage than that of the poor, including in countries reporting to have reached the WHO goal of more than 75% national coverage. These inequities seem to be geographically heterogeneous, modestly improving over time, with no evidence of sex differences in inequity. Future reporting of deworming coverage should consider disaggregation by geography, wealth, and sex with incorporation of an equity index to complement the conventional public health metric of national deworming coverage. FUNDING: Bill & Melinda Gates Foundation, Stanford University Medical Scientist Training Program.

Bacterial Model Membranes Deform ( resp. Persist) upon Ni2+ Binding to Inner Core ( resp. O-Antigen) of Lipopolysaccharides.

The surface charge densities, apparent equilibrium binding constants, and free energies of binding of nickel ions to supported and suspended lipid membranes prepared from POPC and two types of lipopolysaccharide (LPS) are reported. Second- and third-order nonlinear optical mixing shows that rough LPS (rLPS)-incorporated bilayers carry the highest charge density and provide the most binding sites for nickel ions while LPS-free bilayers exhibit the lowest charge density and fewest binding sites. Ni2+ binding is almost fully reversible at low concentrations but less so at higher Ni2+ concentrations. Ni2+ adsorption isotherms exhibit hysteresis loops. The role of interfacial depth on the observed second harmonic generation (SHG) responses is discussed in the context of complementary dynamic light scattering, X-ray spectroscopy, and cryogenic transmission electron microscopy experiments. The latter reveal considerable Ni2+-induced structural deformations to the bacterial membrane models containing the short, O-antigen-free rLPS, consistent with complex formation on the vesicle surfaces that involve Ni2+ ions and carboxylate groups in the inner core of rLPS. In contrast, Ni2+ ion complexation to the charged groups (phosphates and carboxylate) of the considerably longer O-antigen units in sLPS appears to protect the phospholipid backbone against metal binding and thus preserve the vesicle structure.

Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training.

CONTEXT: The combination of two beneficial antidiabetes interventions, regular exercise and pharmaceuticals, is intuitively appealing. However, metformin, the most commonly prescribed diabetes medication, attenuates the favorable physiological adaptations to exercise; in turn, exercise may impede the action of metformin. OBJECTIVE: We sought to determine the influence of an alternative diabetes treatment, sodium glucose cotransporter 2 (SGLT2) inhibition, on the response to endurance exercise training. DESIGN, PARTICIPANTS, AND INTERVENTION: In a randomized, double-blind, repeated measures parallel design, 30 sedentary overweight and obese men and women were assigned to 12 weeks of supervised endurance exercise training, with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: ≤10 mg/day). OUTCOME MEASUREMENTS AND RESULTS: Endurance exercise training favorably modified body mass, body composition (dual-energy x-ray absorptiometry), peak oxygen uptake (graded exercise with indirect calorimetry), responses to standardized submaximal exercise (indirect calorimetry, heart rate, and blood lactate), and skeletal muscle (vastus lateralis) citrate synthase activity (main effects of exercise training, all P < 0.05); SGLT2 inhibition did not influence any of these physiological adaptations (exercise training × treatment interaction, all P > 0.05). However, after endurance exercise training, fasting blood glucose was greater with SGLT2 inhibition, and increased insulin sensitivity (oral glucose tolerance test/Matsuda index) was abrogated with SGLT2 inhibition (exercise training × treatment interaction, P < 0.01). CONCLUSION: The efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training-induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition.

Exploring Different Approaches in Measuring EHR-based Adherence to Best Practice - A Case Study with Order Sets and Associated Outcomes.

In connection with a recent enterprise-wide rollout of a new electronic health record, Intermountain Healthcare is investing significant effort in building a central library of best-practice order sets. These order sets represent best practice guidelines for specific clinical scenarios and are deployed with the intent of standardizing care, reducing variation, and consistently delivering good clinical outcomes to the populations we serve. The importance of measuring their use and the level to which caregivers adhere to these standards becomes an important factor in understanding and characterizing the impact that they deliver. Notwithstanding the importance of these metrics, well- defined methods for measuring adherence to a given clinical guideline as delivered through an order set are not fully characterized in the medical literature. In this paper, we describe initial efforts at measuring compliance to a defined 'best practice' standard by means of content utilization analysis, a calculated adherence model, and relevant clinical key performance indicators. The degree to which specified clinical outcomes vary across these measurement models are compared for a group of order sets tied to treating coronary artery bypass graft patients and heart failure patients. While the patterns derived from this analysis show some uncertainty, more granular methods that look at line-item, or 'order level' detail reveal more significant differences in the corresponding set of outcomes than higher-level adherence surrogates.

Pediatric ileocolic intussusception: new observations and unexpected implications.

BACKGROUND: Ileocolic intussusception occurs when the terminal ileum "telescopes" into the colon. We observed that ileocolic intussusception lengths are similar regardless of location in the colon. OBJECTIVE: To examine the uniformity of ileocolic intussusception length and its relationship to colon location, symptom duration and reducibility. MATERIALS AND METHODS: We retrospectively reviewed ultrasound-diagnosed pediatric ileocolic intussusceptions initially treated with pneumatic reduction at the Mayo Clinic or Texas Children's Hospital. We recorded demographic, imaging and surgical findings including age, gender, symptom duration, location of the ileocolic intussusception, reducibility with air enema and, if fluoroscopically irreducible, surgical findings. RESULTS: We identified 119 ileocolic intussusceptions (64% boys), with 81% in the right colon. There was no significant relationship between ileocolic intussusception length and colon location (P=0.15), nor ileocolic intussusception length and symptom duration (P=0.36). Ileocolic intussusceptions were more distal with increasing symptom duration (P=0.016). Successful reductions were unrelated to symptom duration (P=0.84) but were more likely with proximal versus distal locations (P=0.02). CONCLUSION: Ileocolic intussusception lengths are relatively uniform regardless of location along the course of the colon where they present. Our findings suggest that most of the apparent distal propagation of ileocolic intussusceptions is not caused by increasing telescoping of small bowel across the ileocecal valve but rather by foreshortening of the right colon. This implies poor cecal fixation and confirms fluoroscopic and surgical observations of cecal displacement from the right lower quadrant with ileocolic intussusceptions. The movement of the leading edge of the ileocolic intussusception during reduction is first due to "relocating" the cecum into the right lower quadrant after which the reduction of small bowel back across the ileocecal valve then occurs.

Radioactive iodine uptake in hyperthyroid cats after administration of recombinant human thyroid stimulating hormone.

BACKGROUND: Radioactive iodine therapy is considered the treatment of choice for hyperthyroidism in cats, but the availability of this modality is limited by costs and hospitalization requirements. Administration of recombinant human thyroid stimulating hormone (rh-TSH) to humans with thyroid neoplasia or nodular goiter can increase thyroidal iodine uptake, thereby allowing the use of lower radioactive iodine doses for treatment. Veterinary studies of this subject are limited, and results are conflicting. OBJECTIVE: To investigate the effects of rh-TSH administration on thyroidal iodine uptake in hyperthyroid cats. ANIMALS: Ten client-owned hyperthyroid cats. METHODS: In this prospective clinical study, cats were administered saline (placebo), 50 µg rh-TSH (low-dose), and 100 µg rh-TSH (high-dose) in randomized crossover design with treatments separated by 7-10 days. After each treatment, thyroid scintigraphy was performed by administering 300 µCi 123 I and assessing radionuclide uptake 8 and 24 hours later. Serum thyroid hormone concentrations were measured at each visit. RESULTS: Thyroidal percent iodine uptakes (mean ± SD at 8 and 24 hours) in cats treated with placebo (25.2 ± 13.4%, 30.0 ± 12.8%), low-dose (24.1 ± 12.5%, 29.4 ± 13.7%), and high-dose rh-TSH (24.2 ± 16.3%, 30.8 ± 15.3%) were not different (P = .76). Independent of rh-TSH administration, percent iodine uptakes were positively correlated with serum thyroid hormone concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: One-time administration of rh-TSH, even at high doses, would not be expected to lower radioactive iodine doses needed for treatment of hyperthyroidism in cats. Investigations of alternate strategies to increase thyroidal uptake of radioactive iodine are warranted.