Feasibility and acceptability of a technology-based, rural weight management intervention in older adults with obesity.

BACKGROUND: Older adults with obesity residing in rural areas have reduced access to weight management programs. We determined the feasibility, acceptability and preliminary outcomes of an integrated technology-based health promotion intervention in rural-living, older adults using remote monitoring and synchronous video-based technology. METHODS: A 6-month, non-randomized, non-blinded, single-arm study was conducted from October 2018 to May 2020 at a community-based aging center of adults aged ≥65 years with a body mass index (BMI) ≥30 kg/m2. Weekly dietitian visits focusing on behavior therapy and caloric restriction and twice-weekly physical therapist-led group strength, flexibility and balance training classes were delivered using video-conferencing to participants in their homes. Participants used a Fitbit Alta HR for remote monitoring with data feedback provided by the interventionists. An aerobic activity prescription was provided and monitored. RESULTS: Mean age was 72.9±3.9 years (82% female). Baseline anthropometric measures of weight, BMI, and waist circumference were 97.8±16.3 kg, 36.5±5.2 kg/m2, and 115.5±13.0 cm, respectively. A total of 142 participants were screened (n=27 ineligible), and 53 consented. There were nine dropouts (17%). Overall satisfaction with the trial (4.7+ 0.6, scale: 1 (low) to 5 (high)) and with Fitbit (4.2+ 0.9) were high. Fitbit was worn an average of 81.7±19.3% of intervention days. In completers, mean weight loss was 4.6±3.5 kg or 4.7±3.5% (p< 0.001). Physical function measures of 30-s sit-to-stand repetitions increased from 13.5±5.7 to 16.7±5.9 (p< 0.001), 6-min walk improved by 42.0±77.3 m (p=0.005) but no differences were observed in gait speed or grip strength. Subjective measures of late-life function improved (3.4±4.7 points, p< 0.001). CONCLUSIONS: A technology-based obesity intervention is feasible and acceptable to older adults with obesity and may lead to weight loss and improved physical function. CLINICAL TRIAL REGISTRATION: Registered on Clinicaltrials.gov # NCT03104205 . Registered on April 7, 2017. First participant enrolled on October 1st, 2018.

Driving phase slips in a superfluid atom circuit with a rotating weak link.

We have observed well-defined phase slips between quantized persistent current states around a toroidal atomic (23Na) Bose-Einstein condensate. These phase slips are induced by a weak link (a localized region of reduced superfluid density) rotated slowly around the ring. This is analogous to the behavior of a superconducting loop with a weak link in the presence of an external magnetic field. When the weak link is rotated more rapidly, well-defined phase slips no longer occur, and vortices enter into the bulk of the condensate. A noteworthy feature of this system is the ability to dynamically vary the current-phase relation of the weak link, a feature which is difficult to implement in superconducting or superfluid helium circuits.

Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.

BACKGROUND AND STUDY AIMS: Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. PATIENTS AND METHODS: The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 - 8.9, 9 - 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. RESULTS: In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (P < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (P < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. CONCLUSIONS: This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy.

Modelling the hierarchical structure in datasets with very small clusters: a simulation study to explore the effect of the proportion of clusters when the outcome is continuous.

In cluster-randomised trials, the problem of non-independence within clusters is well known, and appropriate statistical analysis documented. Clusters typically seen in cluster trials are large in size and few in number, whereas datasets of preterm infants incorporate clusters of size two (twins), size three (triplets) and so on, with the majority of infants being in 'clusters' of size one. In such situations, it is unclear whether adjustment for clustering is needed or even possible. In this paper, we compared analyses allowing for clustering (linear mixed model) with analyses ignoring clustering (linear regression). Through simulations based on two real datasets, we explored estimation bias in predictors of a continuous outcome in different size datasets typical of preterm samples, with varying percentages of twins. Overall, the biases for estimated coefficients were similar for linear regression and mixed models, but the standard errors were consistently much less well estimated when using a linear model. Non-convergence was rare but was observed in approximately 5% of mixed models for samples below 200 and percentage of twins 2% or less. We conclude that in datasets with small clusters, mixed models should be the method of choice irrespective of the percentage of twins. If the mixed model does not converge, a linear regression can be fitted, but standard error will be underestimated, and so type I error may be inflated.

Superflow in a toroidal Bose-Einstein condensate: an atom circuit with a tunable weak link.

We have created a long-lived (≈40 s) persistent current in a toroidal Bose-Einstein condensate held in an all-optical trap. A repulsive optical barrier across one side of the torus creates a tunable weak link in the condensate circuit, which can affect the current around the loop. Superflow stops abruptly at a barrier strength such that the local flow velocity at the barrier exceeds a critical velocity. The measured critical velocity is consistent with dissipation due to the creation of vortex-antivortex pairs. This system is the first realization of an elementary closed-loop atom circuit.

Intensive nutrition counseling as part of a multi-component weight loss intervention improves diet quality and anthropometrics in older adults with obesity.

BACKGROUND AND AIMS: Obesity significantly impacts older adults. Intensive nutrition counseling can aid in weight reduction and improve diet quality, but data are sparse in this population. The objective of this intervention is to determine how intensive nutrition counseling affects diet quality and anthropometric measures during a multi-component weight loss intervention in rural older adults with obesity. METHODS: A series of 12-week, single-arm feasibility pilots were conducted in fall 2017 and winter/spring 2018 in a community aging center in rural Northern New England. Adults were eligible if ≥ 65 years old with a Body Mass Index (BMI) ≥30 kg/m2. Exclusion criteria included dementia/cognitive impairment, uncontrolled psychiatric illness, weight-loss surgery, weight loss >5% in previous 6-months, life-threatening illness, palliative/hospice services, current participation in another weight-loss study/program, obesogenic medications, or presence of major chronic conditions. Participants received once-weekly nutrition counseling by a registered dietitian nutritionist (RDN), and twice-weekly exercise sessions by a physical therapist (PT). Primary outcomes were diet quality changes measured by total Rapid Eating and Activity Assessment for Patients-Short Version (REAP-S) and Automated Self-Administered 24-h dietary recall (ASA-24). Secondary outcome measures were changes in weight (kilograms) and waist circumference (centimeters). McNemar test was conducted for all paired categorical data while paired t-tests were conducted for all paired continuous data. All analyses were conducted in R; p-value<0.05 was significant. RESULTS: Total n = 23. Mean age was 72.2 (5.8) years (73.9% female); mean BMI was 35.9 ± 5.0 kg/m2. At 12 weeks, diet quality significantly improved. REAP-S scores increased by 3.53 ± 3.13 points (p < 0.001). Kilocalories, grams fat, grams saturated fat, milligrams sodium, grams added sugar, and grams alcohol via ASA-24 significantly decreased (all p < 0.05). Significant reductions in weight (-5.22 ± 3.13 kg) and waist circumference (-6.88 ± 5.67 cm) were observed (both p < 0.001). CONCLUSION: Intensive nutrition counseling significantly enhances diet quality and reduces weight and waist circumference in rural older adults with obesity.

Creation and detection of Skyrmions in a Bose-Einstein condensate.

We present the first experimental realization and characterization of two-dimensional Skyrmions and half-Skyrmions in a spin-2 Bose-Einstein condensate. The continuous rotation of the local spin of the Skyrmion through an angle of pi (and half-Skyrmion through an angle of pi/2) across the cloud is confirmed by the spatial distribution of the three spin states as parametrized by the bending angle of the l vector. The winding number w = (0,1,2) of the internal spin states comprising the Skyrmions is confirmed through matter-wave interference.

Stretched arc discharge in produced water.

The objective of the present study was to investigate the feasibility of stretching an arc discharge in produced water to increase the volume of produced water treated by plasma. Produced water is the wastewater generated by hydraulic fracturing of shale during the production phase in shale-oil or shale-gas exploration. The electric conductivity of produced water is in the range of 50-200 mS/cm, which provides both a challenge and opportunity for the application of plasmas. Stretching of an arc discharge in produced water was accomplished using a ground electrode and two high-voltage electrodes: one positioned close to the ground electrode and the other positioned farther away from the ground. The benefit of stretching the arc is that the contact between the arc and water is significantly increased, resulting in more efficient plasma treatment in both performance and energy cost.

Effects of various prostanoids on thyrotropin secretion by superfused anterior pituitary cells.

Continuously superfused rat anterior pituitary cells were used to study the effects of prostaglandins (PGs) and a thromboxane (TX) on the secretion of TSH. Indomethacin, a blocker of PG synthetase, inhibited the amount of TSH secreted in response to TRH. This reduction in TRH responsiveness was overcome by administration of PGE2 in combination with the TRH. Arachidonic acid, a prostanoid precursor, increased the amount of TSH released by TRH. Superfusion with TXB2 or imadazole, an inhibitor of TX synthetase, did not change TSH secretion. PGs A2, B2, D2, F1 alpha, F2 alpha, and endoperoxide analogs U-44069 and U-46619 had no effect on hormone release. PGE1 and E2 both increased TRH-stimulated TSH, but neither compound affected basal output; PGI2 was found to stimulate TSH release. Somatostatin inhibited TRH-induced TSH, but failed to block the effects of the PGs. These studies demonstrate that PGs, but no TXs, play a role in TSH secretion. PGE1 and PGE2 appear to modulate TRH responsiveness, while PGI2 directly stimulates hormone output.

Pharmacological studies of the involvement of hypothalamic prostaglandins in the regulation of thyrotropin secretion.

A case is made for the involvement of pituitary prostaglandins (PGs) in the regulation of thyrotropin (TSH) secretion by citing recent evidence that TSH release in vivo and in vitro is enhanced by treatment with exogenous PGs and is inhibited by drugs (e.g., indomethacin) that block PG synthesis. Pharmacological studies were then performed to test the hypothesis that hypothalamic PGs also affect TSH secretion indirectly via the appropriate hypothalamic hormones that regulate pituitary secretion. The inhibition of thyroidectomy-induced TSH secretion was used as an endpoint in choosing the best of several drugs purported to inhibit PG synthesis. The established effectiveness of indomethacin and aspirin were used for reference in testing the following drugs: naproxen, mefenamic acid, tranylcypromine, and phenelzine. Only naproxen was found to be effective, but since it was no more potent than indomethacin, the latter drug was used for subsequent work. Indomethacin was stereotaxically implanted into several hypothalamic regions known to regulate TSH secretion, and sequential plasma samples were analyzed for TSH by radioimmunoassay. Bilateral implants of indomethacin in the anterior hypothalamic area increased TSH secretion throughout the 72 hr period of study. Sham inplants at this site and indomethacin implants in other nearby sites were ineffective. These findings suggest that endogenous PGs play an inhibitory role in the hypothalamic regulation of pituitary secretion.

Factors modulating the secretion of thyrotropin and other hormones of the thyroid axis.

The first portion of this paper is devoted to an overview of the normal function of the hypothalamo-pituitary-thyroid axis. This section emphasizes areas of current research interest and it identifies several sites and mechanisms that are potentially important interfaces with toxins or toxic mechanisms. We then describe an in vitro technique for the continuous superfusion of enzymatically dispersed pituitary cells; this approach is particularly valuable in studying the dynamics of the TSH responses to the factors known (or suspected) to regulate TSH secretion in vivo. Using this technique, we have found that 10(-5)M prostaglandin (PG)I2 stimulates TSH secretion without altering the response to TRH (10(-8)M), and that this stimulation is not due to its rapid conversion to 6-keto PGF1 alpha. In contrast PGs of the E series (PGE1 and PGE2, 10(-5)M) increase responsiveness to TRH but have no effect alone. We found no effects of any of the other prostanoids tested (PGs A2, B2, F1 alpha, F2 alpha, thromboxanes A2 and B2, and the endoperoxide analog, U-44069. Somatostain (10(-9)M inhibits TRH-induced TSH secretion, but does not alter the responsiveness to PGI2. These findings suggest that somatostatin blocks TSH secretion at a point that is functionally prior to the involvement of the PGs, and perhaps does so by blocking synthesis or limiting availability of selected PGs.

Role of Kupffer cells in iodized oil embolization.

RATIONALE AND OBJECTIVES: Iodized oil is a common oily embolic agent used in chemoembolization for treating hepatic tumors. However, how the iodized oil is cleared from the liver has been an unsettled and controversial issue. In this study, the authors attempt to clarify whether Kupffer cells are involved in the clearance of iodized oil and to evaluate the effect of hepatic arterial injection of iodized oil on the functional status of Kupffer cells. METHODS: Iodized oil was injected into the proper hepatic artery in 42 Fischer 344 rats. In vivo microscopy was performed immediately after and 1, 3, 7, 15, 30, and 60 days after injection. Electron microscopy was performed after in vivo microscopy. RESULTS: Kupffer cells actively captured and phagocytosed iodized oil droplets in the hepatic circulation. The number and functional status of Kupffer cells in the liver were significantly increased after the injection of the iodized oil and returned to normal when the liver was cleared of the oil. CONCLUSIONS: Kupffer cells play an important role in clearing iodized oil from the liver. Iodized oil activates the immune defense system in the liver, which may have a synergistic effect in tumor treatment.

A new device for transcatheter closure of the patent ductus arteriosus. A feasibility study in dogs.

A new device for transcatheter closure of the patent ductus arteriosus was developed and initially evaluated in the vasculature of adult mongrel dogs. The device consists of a nylon sack that can be made in various sizes and shapes. A small flexible crossbar attached to the distal end maintains the position of the sack while it is filled with a segment of modified guide wire. The device is delivered coaxially through a 10-Fr Teflon catheter and is easily repositioned or retrieved before release. The expansile force of the sack against the vessel wall can be varied, and its stability is easily checked prior to detachment. The device produced immediate and permanent vascular occlusion without inflammation or erosion. Over time, the entire unit became incorporated into the vessel wall by neointimal encasement. Nylon sacks offer a simple, unique method of closing virtually any ductus arteriosus without general anesthesia and major surgery.

Injection of a silicone prepolymer system into the gallbladder of rabbits.

The aim of this study was to assess the feasibility of a new nonsurgical treatment for cholelithiasis. This involved injecting a liquid prepolymer into the gallbladder which would polymerize in situ, entrapping existing gallstones and permanently filling the gallbladder so as to prevent subsequent gallstone formation. Initially, several silicone prepolymer mixtures were tested in vitro for viscosity, cure time, radiopacity, and consistency when polymerized. The optimal system with regard to these parameters consisted of two room temperature vulcanizing silicones (3110 and 200), a catalyst (F), and barium sulfate. This mixture was then injected into beakers containing human gallstones alone and in combination with bile, and was periodically evaluated over six months. It was also injected into the gallbladder of six rabbits and left for 12 weeks. No clinical complications were noted in any of the animals. The cured silicone system maintained its original shape and did not fragment. At necropsy, the casts were free in the rabbits' gallbladders, with small accumulations of biliary sludge adhered to their surfaces. No mucocele of the gallbladder was found in any of the rabbits. Cholecystic histology was normal in all cases, and only one animal exhibited a mild chronic portal triaditis. These promising results indicate the need for further studies of the technique and refinement of the silicone formulation.

Alteration in starch microsphere degradation following contrast angiography in the dog kidney.

Six adult mongrel dogs received bilateral sequential renal arterial injections of degradable starch microspheres following preadministration arteriograms. Renal arterial flow was measured using electromagnetic flow probes, and microspheres were administered until flow was blocked completely. One kidney in each dog was subjected to immediate postembolization arteriography, while the contralateral kidney served as a control. In the control kidneys, arterial flow returned to 90-95% of baseline within 30 minutes of embolization, and angiography at this time revealed a normal nephrogram. Blood flow in the kidneys that received postembolization arteriography returned to only 60-65% of baseline, even when followed up to 1 hour. Angiography at this time revealed persistent defects in the nephrogram. The effect of heparin, Renografin-60, and distilled deionized water on amylase activity was evaluated in vitro. No change in enzyme activity was noted.

Preparation, characterization, and evaluation of ioxilan carbonate particles for computed tomography contrast enhancement of liver.

RATIONALE AND OBJECTIVES: To prepare and characterize a new particulate contrast medium, cyclic carbonate of ioxilan (IX-C) particles, as a macrophage imaging agent for computed tomography (CT) enhancement of the liver. METHODS: Cyclic carbonate of ioxilan was synthesized from ioxilan, a nonionic water-soluble contrast agent. The IX-C particles prepared by a solvent extraction-evaporation method were characterized by size distribution, degradability, suspension stability, and median lethal dose. Pharmacokinetics of IX-C particles and their effectiveness in enhancing liver attenuation and in detecting hepatic tumors were evaluated using normal and VX2-tumor-bearing rabbits. RESULTS: The IX-C particles were biodegradable, with ioxilan and carbon dioxide as the degradation products. The particles had an average size of 1 to 2 microns and were stable in saline suspension. The median lethal dose determined for IX-C particles was 2.6 and 3.1 g/kg body weight for female and male rabbits, respectively. A dose of 200 mg iodine/kg body weight caused an increase of 38 Hounsfield units in liver attenuation. In rabbit, hepatic clearance of the contrast medium occurred in 2 days. A tumor barely visible in precontrast scans could be detected after contrast injection. CONCLUSIONS: Development of particulate contrast medium from nonionic contrast agents represents a new approach. Ioxilan carbonate particles have suitable physicochemical properties that warrant further studies before clinical evaluation.

Isolation of Mycoplasma hominis using the BACTEC 9000 series blood culture system.

Mycoplasma hominis has been implicated as an important cause of septicaemia. There have been reported variances in the ability of blood culture systems to support the growth of this organism. In this study the ability of the BACTEC 9000 series automated system to grow and detect M hominis was assessed. Three of five wild M hominis strains grew in the BACTEC Anaerobic Plus/F medium but growth was not flagged by the detection mechanism of the system. It is recommended that users of the BACTEC 9000 series should use a seven day protocol and perform terminal subculture for suspected cases of M hominis septicaemia.

Hepatic arterial infusion of verapamil and doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration: pharmacological evaluation of reduction in systemic drug exposure and assessment of hepatic toxicity.

Tumour resistance to chemotherapeutic drugs through expression of the multidrug resistance phenotype is a major impediment in the treatment of hepatic malignancies. We performed hepatic arterial infusion of verapamil (at a dose known to block P-glycoprotein activity) and doxorubicin combined with complete hepatic venous isolation and extracorporeal chemofiltration in non-tumour-bearing pigs with normal livers to evaluate the pharmacology and toxicology of this drug combination. The complete hepatic venous isolation-chemofiltration system significantly reduced system exposure to both verapamil and doxorubicin (P < 0.01). Hepatic arterial infusion of verapamil (2 mg/kg) alone did not result in hepatocellular toxicity. However, the combination of verapamil and doxorubicin (3 mg/kg or 5 mg/kg) produced significant elevations in liver enzymes (P < 0.01), and gross histological evidence of liver damage in 90% of the treated animals. The results of this study indicate that hepatic arterial infusion of verapamil and doxorubicin, in an attempt to improve treatment response in unresectable liver tumours expressing the multidrug resistance phenotype, may not be tolerated by patients with limited hepatic reserve.

The bacteriological screening of donated human milk: laboratory experience of British Paediatric Association's published guidelines.

This study was undertaken to assess the application of the British Paediatric Association's (BPA) published guidelines to the bacteriological screening of breast milk donated to a District General Hospital milk bank. Samples of donated milk were subjected to bacterial counts and provisional identification after both 24 and 48 h incubation on cysteine lactose electrolyte-deficient (CLED) and Columbia blood agar. 21.8% (76 out of 348) donations of milk failed to reach the BPA acceptable criteria. The organisms responsible for the rejection of these samples were all evident within 24 h incubation, and were not significantly confined to one medium. A large percentage of rejected samples originated from a small number of donor mothers; 63.2% came from one donor. In applying BPA guidelines, both CLED and Columbia blood agar were found to be equally effective in screening for unacceptable organisms in prepasteurization donated breast milk. The 24 h period allowed for bacteriological screening, prior to pasteurization of milk samples, was sufficient to allow the growth of all potentially pathogenic bacteria in this study. To prevent the donation of consistently contaminated milk, more active communication between the milk bank staff and the donor is recommended.

Halogenated analogues of tamoxifen: synthesis, receptor assay, and inhibition of MCF7 cells.

This study was conducted to develop a ligand for imaging estrogen-receptor-positive breast tumors by positron emission tomography or single photon emission computed tomography. We synthesized fluoro and iodo analogues of tamoxifen, and these halogenated analogues produced greater affinity for binding to the receptor than tamoxifen. Values of the inhibition affinity constants were as follows: tamoxifen, 15,000 nM; fluoromethyl-N,N-diethyltamoxifen, 2500 nM for the cis isomer and 500 nM for the trans isomer; and iodomethyl-N,N-diethyltamoxifen, 1500 nM for the cis isomer and 1000 nM for the trans isomer. In studies of human MCF7 breast tumor cell growth, concentrations that inhibited tumor growth in 50% of the cases were as follows: tamoxifen, 11 microM; fluoromethyl-N,N-diethyltamoxifen, 4.5 and 11.8 microM for the cis and trans isomers, respectively; and iodomethyl-N,N-diethyltamoxifen, 2.4 and 6.3 microM for the cis and trans isomers, respectively. These studies suggest that both fluoro and iodo analogues of tamoxifen may be useful diagnostic compounds for predicting the response of estrogen-receptor-positive breast tumors to tamoxifen analogues used in chemotherapy.