Changes In Weight Distribution Research Articles

PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.

Development of Electronic Flight Bag Application for Small Turboprop Aircraft Weight and Balance Calculation

Nowadays, many airlines in modern aviation utilize an Electronic Flight Bag (EFB) during flight to replace traditional paper-based systems. Considering the importance of aircraft weight and balance calculation to flight operations, the flight mission of X-123 (a small turboprop aircraft) and the current EFB market, research on weight and balance application development of X-123 on EFB in Indonesia is conducted. The research aimed to develop the application according to Indonesian regulations and to examine the weight and balance characteristics of X-123 through several simulations in a programming language, Python. Furthermore, Staff Instruction 8900 - 3.3 is analyzed to identify the factors that should be considered in EFB development. The global architecture design and substantial features are, then, proposed as an initial EFB development. In the global architecture design, the utilization of a gateway becomes important as a connection between the EFB developer and the client, providing aircraft data changes flexibility to the client. Moreover, the calculation formula is completely discussed in the calculation modules as a substantial feature and implemented in the simulation. According to simulation results, the payload weight and payload distribution changes can affect significantly the CG location. It is recommended to weigh and assign the payload before flight to ensure flight operation safety. In addition, the proposal of the architecture design and substantial features can be used as a reference and further developed by the Indonesian aviation companies.

Time-varying traffic load model of expressway based on long-term monitored data from multiple regions — A case in central and eastern China

Traffic load is one of the main loads borne by highway transportation infrastructure, which seriously impacts the safe operation of the bridge and road. Due to the change in the external environment and government policy, the traffic load has obvious time-varying characteristics, which is the key to establishing the real traffic load model. The two main time-varying factors of traffic load are the growth of traffic volume and the evolution of vehicle weight. In the long-term research work, there is a lack of research based on continuous monitoring data for the above two factors. Therefore, this paper carries out a study on the time-varying traffic load model of expressways based on long-term monitored data from multiple regions. Firstly, the data sources of monitored 18 expressways in central and eastern China are introduced. Secondly, the Logistic model is selected as the basic model to study the growth laws of expressways from different provinces; meanwhile, the evolution of vehicle weight distribution is also analyzed and a simplified model is established accordingly. Finally, a case study of a newly opened eight-lane expressway is operated to characterize the influence of time-varying vehicles. The results show that the traffic volume and vehicle weight distribution change significantly with the increase of service time. The Logistic model and liner model are appropriate to characterize the evolution model of the traffic volume and vehicle weight distribution separately. The time-varying characteristics of traffic load have a significant impact on the standard fatigue traffic load model and the cumulative equivalent axle loads. The research results could provide a reference for the establishment of time-varying traffic load standard models for highways and the revision of related standards. At the same time, it could provide technical support for the full life-cycle investigation and design of the road and bridge infrastructure.

Study on the Performance and Mechanism of Cold-Recycled Asphalt Based on Permeable Recycling Agent.

In order to investigate the influence of recycling agent composition on the recycling effect of aged asphalt in the cold recycling process, the design and optimization of cold recycling agent composition were performed through the central composite design-response surface method combined with the dynamic shear rheometer (DSR) test and the bending beam rheometer (BBR) test. The molecular weight distribution and component changes in aged asphalt before and after the addition of a cold recycling agent were also analyzed by gel permeation chromatography (GPC) and hydrogen-flame ionization test. The results showed that the permeable cold recycling agent has a recycling effect on the aged asphalt, but its effectiveness is greatly affected by recycling agent composition. The best recycling effect was achieved when the ratio of aromatic oil and penetrant in the cold recycling agent was 61.2:38.8, respectively. In terms of the recycling agent and aromatic functional groups in the aromatic oil, the aromatics in the recycling agent are derived from the aromatic oils, and the penetrant is only fused and permeated with the aromatic oils. After the admixture of the cold recycling agent, the penetrant in the recycling agent allows the aromatic oil to enter the aged asphalt at room temperature. The light components volatilized by aging are replenished, allowing the aged asphalt to recover some of its properties.

Impact of Pregnancy on Papilledema and Vision Loss in Idiopathic Intracranial Hypertension Patients: A Chart Review and Case Series of 13 Patients.

Studies suggest that weight gain is a prominent risk factor for recurrence of papilledema in idiopathic intracranial hypertension (IIH). Given this information, the significant weight gain that occurs during pregnancy, and the fact that pharmacologic therapy is many times discontinued, raises concerns for worsening edema and vision loss. To examine the impact of pregnancy weight gain on IIH, a retrospective chart review of patients with IIH and pregnancy was performed. Compared with previous studies, we 1) quantified findings with optical coherence tomography (OCT) and Humphrey visual field (HVF) data, 2) Included baseline data before pregnancy, 3) determined excess pregnancy weight gain using body mass index-adjusted weight gain goals, and 4) correlated worsening in IIH symptoms with changes in papilledema. Charts were reviewed for patients with diagnoses of IIH who had at least 2 visits with neuro-ophthalmology during pregnancy. Thirteen patients met inclusion criteria. Data were compared from baseline visits before pregnancy, pregnancy visits, and postpregnancy visits. Comparisons of HVF mean deviation (MD), OCT retinal nerve fiber layer (RNFL), and Max OCT RNFL during pregnancy were not significant compared with baseline ( P = 0.51, 0.41, and 0.25). Three patients were found to have increased papilledema during pregnancy (Max Avg OCT RNFL of 152.5, 129, and 123.5 μm) of which 2 developed new reproducible mild visual field defects (HVF ∆MD -1.78 and -4.49). All patients showed more than the 6% weight gain, typically observed in recurrent IIH. Eleven patients gained more than their weight from initial diagnosis. Eight patients had excess pregnancy weight gain. Six patients discontinued pharmacologic therapy for IIH. Weight gain seems to carry a lower risk in IIH patients when associated with pregnancy. This is suggested by the high rate of stable or even decreased disc edema in patients despite medication discontinuation and excess pregnancy weight gain. We postulate these findings may be related to changes in weight distribution or endocrine changes during pregnancy.

Advanced Dynamic Weight Bearing as an Observer-independent Measure of Hyperacute Hypersensitivity in Mice

ABSTRACT Background Standard methods assessing pain in rodents are often observer dependent, potentially resulting in biased outcomes. Advanced dynamic weight bearing (ADWB) offers an observer-independent approach that can provide objective, reliable data in preclinical pain research. Aims The aim of this study was to characterize the use of ADWB in assessing murine responses to allyl isothiocyanate (AITC)-induced hyperacute hypersensitivity and identify best practices for use of the device. Methods Male C57BL/6J mice received intraplantar injections of saline or 0.1% AITC solution and were assessed using the ADWB system; simultaneous observer-dependent durations of paw licking and biting were measured. ADWB data were analyzed using the proprietary software from Bioseb and correlated to observer-dependent results, with parameters assessed to optimize data collected. Results ADWB detected pain-directed changes in weight and surface area distribution in AITC-treated mice, with paw weight and surface area placement correlating to paw licking and biting. Optimization of adjustable threshold parameters allowed for reduced coefficients of variability and increased duration of validated data. Conclusions The ADWB assay provides an efficient and unbiased measure of chemical-induced hyperacute hypersensitivity in mice. ADWB detection parameters influence amount of validated data and variability, a consideration for data analysis in future studies.

The Effect of Aging on the Molecular Distribution of Crumb Rubber Modified Asphalt Based on the Gel Permeation Chromatography Test

Asphalt aging is one of the main causes of asphalt pavement cracking, loosening and other issues. On a macro level, the asphalt hardens and becomes more brittle, while on a micro level, the chemical composition and molecular weight distribution change. This is a very complicated physicochemical process. Gel permeation chromatography (GPC) is a powerful technical tool for understanding the mechanism of asphalt aging and expressing the asphalt aging process. GPC can be used to measure the distribution and content of each component in the asphalt aging process. The mechanism of action of crumb rubber modified asphalt has not been fully elucidated due to its complex composition. This study investigated the molecular weight of crumb rubber modified asphalt before and after aging, and filtered asphalt based on gel permeation chromatography. The results indicated that crumb rubber itself experiences severe degradation following PAV aging and that a significant number of macromolecular materials are incorporated into the asphalt phase, causing changes in key parameters. The average molecular weight (Mw) and dispersion (D) of crumb rubber modified asphalt are directly related. At the same time, the Mw of crumb rubber modified asphalt has a positive correlation with LMS content, while SMS content has a negative correlation with Mw. The increase in crumb rubber content has a positive impact on the material interaction, and the molecular weight distribution of crumb rubber modified asphalt is affected by the reaction degree of the crumb rubber in asphalt. The complex physical and chemical reaction of crumb rubber in asphalt has a direct impact on the external macro rheological properties of asphalt.

Does a shorter residual first metatarsal length after first ray amputation in diabetic patients leads to poorer outcomes – A risk factor study

BackgroundThe first ray plays a vital role in the normal function of the foot and the gait cycle where in its absence can lead to abnormal changes in weight distribution to the residual first metatarsal stump and lesser metatarsals with predisposition to developing lesser toe deformities reulcerations and reamputations particularly in diabetic patients. This study aims to characterise the outcomes after first ray amputation and its associated risk factors with focus on the impact of residual first metatarsal length. MethodsAll diabetic patients with first ray amputations from January 2012 to December 2016 were reviewed. Residual first metatarsal length was measured using postoperative radiographs. Risk factors for outcomes such as readmission, reulceration and/or reamputation, transfer ulceration and/or amputation of lesser toes, proximal amputations, ulcer-free duration (UFD) and mortality were analysed using bivariate logistic/linear regression followed by multiple logistic/linear regression models adjusting for confounding factors. ResultsAmong 89 patients with first ray amputations, 65.3 % needed readmission for further treatment. Although only 10.1 % had reulceration at the first ray which all led to reamputation, there were 56.2 % with transfer ulceration and 40.4 % with transfer amputation of the lesser toes in this cohort. The prevalence of transmetatarsal amputation was 18 % and proximal amputations at 12.4 % while the average UFD was 27 months. Mortality rate was 31.5 % with an average of 3-year survival. Preservation of the first metatarsal length via metatarsophalangeal joint disarticulation independently reduced likelihood of readmissions and residual metatarsal length of > one third when compared to < one third after first ray amputations had lower likelihood of transfer amputation of lesser toes. ConclusionFirst ray amputation in diabetic patients leads to significant morbidities and mortality. Preservation of the residual first metatarsal length independently reduced the likelihood of readmissions and transfer amputation to the lesser toes.

Pathological Detection of Micro and Fuzzy Gastric Cancer Cells Based on Deep Learning

In recent years, with the increasing incidence of cancer, regular physical examination is an important way to find cancer. Nuclear screening is an important method for the diagnosis of gastrointestinal diseases, but it is challenging in the face of small and fuzzy gastrointestinal images. Different from traditional medical objects, pathological slice images are mostly blurry and tiny, which is somewhat difficult to detect and segment. The traditional diagnostic method lacks rapid quantitative analysis and has a certain delay in medical diagnosis, and traditional image processing uses morphological features and pixel distribution to extract features; it is often difficult to achieve the desired effect on small blurry images. This paper proposes a small, microfuzzy pathology detection algorithm based on the attention mechanism; the YOLOv5 is improved under small and micro fuzzy scenarios of the detection of cancer cells in the full field of digital pathology and tests it in the gastric cancer slice dataset. The network structure is improved, and the ability to learn features on small and micro targets is enhanced according to the law of feature distribution. Spatial and channel changes in network attention and attention weight distribution. In the deep blur scenario, the attention mechanism is added to optimize its recognition ability, and the test result shows F1_score is 0.616, and the mAP is 0.611, which can provide the decision support for clinical judgment.

Chemical Changes Over Time Associated with Protein Drying.

Upon drying, physical changes of the characteristics of proteins are observed by coagulation, but the nature and chronology of these changes have not been well studied. Coagulation changes the structure of protein from liquid to a solid or a thicker liquid by heat, mechanical action, or acids. Changes may have implications regarding the cleanability of reusable medical devices; therefore, an understanding of the chemical phenomena associated with drying of proteins is essential to ensuring adequate cleaning and mitigation of retained surgical soils. Using a high-performance gel permeation chromatography analysis with right-angle light-scattering detector at 90°, it was demonstrated that as soils dry, the molecular weight distribution changes. From the experimental evidence, the molecular weight distribution trends over time with drying to higher values. This is interpreted as a combination of oligomerization, degradation, and entanglement. As water is removed through evaporation, the distance between proteins decreases and their interactions increase. Albumin will polymerize into higher-molecular-weight oligomers, decreasing its solubility. Mucin, commonly found in the gastrointestinal tract to prevent infection, will degrade in the presence of enzymes releasing low-molecular-weight polysaccharides and leaving behind a peptide chain. The research described in this article investigated this chemical change.

Study of the Effect and Underlying Mechanism of Clove Extract on Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Objective: The aim of this study was to identify the efficacy and underlying mechanism of cloves as an osteoarthritis (OA) treatment in a monosodium iodoacetate (MIA)-induced rat OA model. Osteoarthritis (OA) is nowadays one of the most prevalent degenerative joint diseases.Methods: Sprague-Dawley rats treated with MIA (50 μL; 80 mg/mL) were used as in vivo OA models. Cloves (100 and 200 mg/kg b.w.) were administered orally once daily for 2 weeks from 7 days after MIA injection. Changes in hindpaw weight distribution (HWD) were measured as a joint discomfort index. Activation markers related to inflammatory responses and cartilage degeneration in the right knee joints were evaluated by serum analysis and western blotting.Results: HWD decreased in the MIA control group but showed a dose-dependent elevation after clove treatment. Clove treatment inhibited inflammatory factors by PI3K/Akt/NF-κB signaling pathways, while also activating antioxidant factors through Sirt1/AMPK signaling pathways. Clove treatment also suppressed matrix metalloproteinase (MMP) overexpression and significantly increased the levels of tissue inhibitors of metalloproteinases (TIMPs).Conclusions: Treatment with cloves effectively reversed MIA-induced effects. Therefore, clove treatment could have the potential to protect against or treat OA.

Modeling the Coal Tar Pitch Primary Carbonization Process

The properties of the carbon materials obtained as the final product of coal tar pitch carbonization process are a consequence of the type of chemical and physical phenomena occurring through the process. A new simplified approach for modeling of the primary carbonization is presented to provide the semi-quantitative knowledge about the process useful for improving the efficiency of the industries that deal with this process. The proposed approach is based on defining thermodynamic and kinetic equations simply representing numerous phenomena happening during primary carbonization. Partial pressures of emitted volatiles in a simple pitch system are studied. The model enables estimating the mass and enthalpy changes of pitch through thermal treatment consistent with experimental data for mass losses of pitch heat treated up to 550 °C. Application of the model to describe molecular weight distribution changes of pitch during primary carbonization is demonstrated, showing a good agreement between the presented results and the investigations reported by Greinke. For the first time, the effect of important parameters in pitch carbonization, such as the heating rate of the pitch and the carrier gas flow rate, on the emission rate of volatiles is successfully modeled. The present model is well able to estimate the energy requirement for thermal treatment of pitch up to 350 °C.

Objective and Quantitative Evaluation of Spontaneous Pain-Like Behaviors Using Dynamic Weight-Bearing System in Mouse Models of Postsurgical Pain.

BackgroundThe paucity of objective and reliable measurements of pain-like behaviors has impeded the translatability of mouse models of postsurgical pain. The advanced dynamic weight-bearing (DWB) system enables evaluation of spontaneous pain-like behaviors in pain models. This study investigated the suitability and efficiency of the DWB system for assessing spontaneous pain-like behaviors and analgesic therapies in murine models of postsurgical pain.MethodsMale adult C57BL/6JJcl mice were subjected to multiple surgical pain models with distinct levels of invasiveness, including a superficial incisional pain model involving only hind paw skin incision, deep incisional pain model that also involved incision and elevation of the underlying hind paw muscles, and orthopedic pain model involving tibial bone fracture and fixation with a pin (fracture and pinning [F/P] model). Spontaneous pain-like behaviors post-surgery were evaluated using weight distribution, pawprint area of the operated paw in the DWB system, and guarding pain score. Mechanical hypersensitivity was assessed using the von Frey test. The therapeutic effects of analgesics (diclofenac and buprenorphine for the deep incision model and diclofenac for the F/P model) were evaluated using the DWB system and von Frey test.ResultsThe von Frey test demonstrated contradictory results between superficial and deep incisional pain models. The DWB system captured weight distribution changes in the operated hind paw, in accordance with the invasiveness and time course of wound healing in these surgical pain models. The reduction in weight-bearing on the operated paw correlated with guarding score, degree of paw swelling, and local expression of inflammatory mediators. DWB enabled accurate evaluation of the pharmacological effects of analgesics for detecting attenuation of surgery-induced weight-bearing changes in these models.ConclusionThe DWB system serves as an objective and reliable method for quantifying pain-like behaviors and evaluating the therapeutic effects of analgesics in mouse models of postsurgical pain models.

Examination of the Blank Error on Mirror Accuracy of Lightweight SiC Mirror and a Compensation Method

Due to excellent characteristics of specific stiffness and thermal stability, silicon carbide-based (SiC) material is commonly selected to construct large-scale lightweight mirror. In general, the fabrication process of SiC mirror is similar to the casting process. The blank error of SiC mirror is 0~1 mm. Due to the high hardness of SiC, only the mirror surface and some positioning surface will be milled. The mirror surface accuracy will be degraded due to the fact that the blank error can cause significant changes in weight distribution. In this paper, Monte Carlo analysis is firstly performed to examine the blank error on gravity center, stiffness and mirror accuracy of a SiC mirror. It is found that according to the designed mount location, the amount of degradation is more than 2.5 nm of which the probability is 40.3%. It is known that the error of gravity center can be compensated by optimizing the axial mount location. Then inverse modeling and testing of gravity center for the SiC mirror is carried out in order to determine the optimal axial mount location. Based on the proposed method, the mirror degradation introduced by the blank error has been eliminated to the greatest extend.

Stem Cell Therapy in the Treatment of Elbow Joint Osteoarthritis in Dogs

Osteoarthritis is a common disease in dogs that cause chronic pain, stiffness and can greatly reduce the quality of life. Standard treatment mostly is still symptomatic and is based on pain relief, without any disease-modifying effect and the side effects of painkillers can occur relatively common. The aim of this study was to determine do single intra-articular allogeneic stem cell injection gives improvement on patient well-being and have disease remodeling effects. Ten dogs with unilateral elbow osteoarthritis were selected. In osteoarthritic joint single stem cell intra-articular injection was made. Treatment was assessed by using stance analyzer to detect weight distribution, goniometry to measure range of motion, radiological examination to assess osteophyte size and size of subtrochlear sclerosis, joint fluid and blood sample analysis was made before and six months after treatment and once a month animal owner questionnaires were made. There was beneficial changes in weight distribution, range of motion, in size of osteophyte and subtrochlear sclerosis but not statistically significant. But in patient well-being observations from animal owner questionnaires there was significant improvements.

OSTEOCALCIN ROLE IN THE REGULATION OF INSULIN SECRETION AND OSTEOTROPIC EFFECTS OF DIFFERENT CLASSES OF ANTI-DIABETIC DRUGS (LITERATURE REVIEW AND OWN RESEARCH)

Background. Current data suggest that bone tissue produces hormonally active factors - modulators of metabolic processes throughout the body. The most significant osteoproteins is osteocalcin, the non-collagen structural protein of the bone matrix, which is synthesized by osteoblasts and enters the bloodstream during the resorption of bone tissue. Osteocalcin is involved in the regulation of energy balance, insulin secretion, peripheric insulin sensitivity, and adipocyte’s function, while being an important marker of bone remodeling. The aim of this study was to investigate the relationship between osteocalcin levels and metabolic parameters in 97 patients with type 2 diabetes over 50 years of age, in the course of pharmacotherapy using different classes of antidiabetic drugs, namely human insulin, glucagon-like peptide-1 agonists (aGLP), and sodium-glucose co-transporter 2 (SGLT2) inhibitors, depending on presence of obesity. Results. There was found the highest serum osteocalcin level in patients without obese who received a metabolically active therapy with insulin or aGLP-1, comparing to nonobese subjects of SGLT2 inhibitors therapy group. The lowest level of HbA1c and triglycerides observed in non-obese patients on the background of taking aGLP-1. Conclusion. It can be assumed that the factor determining the hypoglycemic efficacy of investigated drugs may be the pathogenesis of type 2 diabetes which depends on the degree of obesity, while the type of antidiabetic therapy has a corrective effect, probably mediated by changes in body weight and fat distribution.

Static Body Weight Distribution and Girth Measurements Over Time in Dogs After Acute Thoracolumbar Intervertebral Disc Extrusion.

Dogs with thoracolumbar intervertebral disc extrusion (TL-IVDE) can exhibit variable neurologic deficits after decompressive surgery. The objectives of this study were to quantify changes in static weight distribution (SWD) and limb and body circumference over time in dogs recovering from surgery for TL-IVDE. Dogs with acute TL-IVDE were prospectively evaluated at baseline (48–72 h post-operatively), 2, 4, 8, and 12 weeks post-operatively. Commercially-available digital scales were used to measure weight distributed to the pelvic limbs (PL%) and asymmetry between left and right pelvic limbs (LRA), each expressed as a percentage of total body weight. Trunk and thigh circumference measurements were performed using a spring-loaded tape measurement device. Measurements were performed in triplicate, compared to neurologically normal small breed control dogs and analyzed for changes over time. P <0.05 was significant. Twenty-one dogs were enrolled; 18 regained ambulation and 3 did not by study completion. PL% increased from 27.6% at baseline to 30.7% at 12 weeks but remained lower than in control dogs (37%) at all time points (p < 0.0001), even excluding dogs still non-ambulatory at 12 weeks (p < 0.025). LRA was similar to the control dogs, and did not have an association with surgical side. Caudal trunk girth decreased over time to 95% of baseline (p = 0.0002), but this was no longer significant after accounting for reductions in body weight (p = 0.30). Forward shifting of body weight persisted in dogs with TL-IVDE 12 weeks after surgery even among ambulatory dogs. SWD and circumference measurements could provide additional objective measures to monitor recovery.

Sleep Disturbance and Changes in Energy Intake and Body Composition During Weight Loss in the POUNDS Lost Trial.

To examine associations between sleep disturbance and changes in weight and body composition and the mediating role of changes of appetite and food cravings in the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) 2-year weight-loss diet intervention trial, this study included 810 overweight or obese individuals with baseline sleep disturbance assessment who were randomly assigned one of four diets varying in macronutrient composition. Changes in body weight and fat distribution were assessed by DEXA and computed tomography during the 2-year intervention. Participants were asked to provide sleep disturbance levels (no, slight, moderate, or great) at baseline and to recall their sleep disturbances since last visit at 6, 12, 18, and 24 months. Weight loss during the first 6 months was followed by 1.5 years of steady weight regain. Participants with greater sleep disturbance from baseline to 6 months showed significant losses of body weight (Ptrend <0.001) and waist circumference (Ptrend = 0.002) at 6 months, after multivariate adjustment. Compared with individuals without sleep disturbance at all from baseline to 6 months, those with slight, moderate, or great sleep disturbance showed an elevated risk of failure to lose weight (-5% or more loss) at 6 months, when the maximum weight loss was achieved, with an odds ratio of 1.24 (95% CI 0.87, 1.78), 1.27 (95% CI 0.75, 2.13), or 3.12 (95% CI 1.61, 6.03), respectively. In addition, we observed that the repeatedly measured levels of sleep disturbance over 2 years were inversely associated with the overall weight loss rate (weight changes per 6 months) (Ptrend <0.001). Further, sleep disturbances during weight loss from baseline to 6 months and weight regain from 6 months to 24 months were significantly predictive of total fat, total fat mass percent, and trunk fat percent changes during the 2 years. Our results also indicated that food cravings for carbohydrates/starches, fast food fats, and sweets; cravings, prospective consumption, hunger of appetite measurements; and dietary restraint, disinhibition, and hunger subscales measured at 6 months significantly mediated the effects of sleep disturbance on weight loss. In conclusion, our results suggested that more severe sleep disturbance during weight loss was associated with an elevated risk of failure to lose weight during the dietary intervention. Food cravings and eating behaviors may partly mediate these associations.

Changes in pedometer-measured physical activity are associated with weight loss and changes in body composition and fat distribution in response to reduced-energy diet interventions: The POUNDS Lost trial.

To examine whether changes in objectively measured physical activity (PA) are associated with weight loss and changes in body composition and fat distribution in response to weight-loss diet interventions. This study included 535 participants with overweight/ obesity, who were randomly assigned to four weight-loss diets varying in macronutrients. PA was measured objectively with pedometers, and body composition and fat distribution were measured using dual-energy X-ray absorptiometry and computed tomography scans at baseline, 6months and 24 months. From baseline to 6months, when the maximum weight loss was achieved, each 1000-steps/d increment in PA was associated with a greater reduction in body weight (β[SE]=-0.48[0.11]) and waist circumference (β[SE]=-0.49[0.12]). Similar inverse associations were found in changes in body composition and fat distribution (P < 0.05 and false discovery rate qvalue < 0.1 for all). The trajectory of the above adiposity measures across the 24-month intervention period differed between the patterns of PA change. Participants with the largest increase in PA maintained their weight loss from 6months to 24 months, while those with a smaller increase in PA regained their weight. In addition, dietary fat or protein intake significantly modified the associations between changes in PA and changes in body weight and waist circumference over 24 months (P∆PA*diet < 0.05). Changes in objectively measured PA were inversely related to changes in body weight, body composition and fat distribution in response to weight-loss diets, and such associations were more evident in people on a high-fat or average-protein diet compared with a low-fat or high-protein diet.

Concentration-response relationships of dolutegravir and efavirenz with weight change after starting antiretroviral therapy.

AimDolutegravir is associated with more weight gain than efavirenz in people starting antiretroviral therapy (ART). We investigated the concentration-response relationships of efavirenz and dolutegravir with weight gain.MethodsWe determined concentration-response relationships of dolutegravir and efavirenz (both combined with tenofovir disoproxil fumarate and emtricitabine) with changes in weight and fat distribution, derived from dual-energy x-ray absorptiometry scans, in a nested study of ART-naïve participants from a randomised controlled trial. Pharmacokinetic parameters used in analyses were efavirenz mid-dosing interval (MDI) concentrations and estimated dolutegravir area under the concentration-time curve (AUC0-24) using a population pharmacokinetic model developed in the study population. Study outcomes were percentage changes from baseline to week 48 in weight, and visceral and subcutaneous adipose tissue (VAT and SAT) mass.ResultsPharmacokinetic data were available for 158 and 233 participants in the efavirenz arm and dolutegravir arms respectively; 57.0% were women. On multivariable linear regression there were independent negative associations between efavirenz concentrations and changes in both weight (P <0.001) and SAT mass (P = 0.002). Estimated dolutegravir AUC0-24 was not associated with change in weight (P = 0.109) but was negatively associated with change in VAT mass (P = 0.025).ConclusionWe found an independent negative concentration-response relationship between efavirenz concentrations and weight change in ART-naïve participants. Dolutegravir concentrations were not independently associated with weight change. These findings suggest that weight gain differences between efavirenz and dolutegravir are driven by efavirenz toxicity impairing weight gain rather than by off-target effects of dolutegravir causing weight gain.