Subgrouping of facilitatory or inhibitory conditioned pain modulation responses in patients with chronic knee pain. Explorative analysis from a multicentre trial.

BACKGROUND: Facilitatory and inhibitory conditioned pain modulation (CPM) responses are observed in healthy volunteers and chronic pain patients, but the clinical implications for phenotyping are unknown. This study aimed to subgroup and compare chronic knee pain patients according to their CPM responses. METHODS: This explorative, cross-sectional study included 127 patients with chronic knee pain (osteoarthritis or following total knee arthroplasty). Individual CPM responses were categorized as facilitatory (test stimuli pain intensity increased when conditioning stimuli were applied), as inhibitory (test stimuli pain intensity decreased) or as no change (defined as less than 5.3% change in pain intensity). Outcomes were clinical pain intensities, temporal summation, widespread pain, self-reported physical function, PainDETECT questionnaire and Pain Quality Assessment Scale. Data were analysed as comparisons between the inhibitory and the facilitatory groups and using multivariate linear regression models. RESULTS: Fifty-four patients had facilitatory CPM responses, 49 had inhibitory CPM responses, and 24 showed no change in CPM response. A between-group difference was observed for self-reported physical function, with the facilitatory CPM group reporting better function (54.4 vs. 46.0, p = 0.028) and the facilitatory CPM group reported more deep pain sensations (3.2 vs. 2.0, p = 0.021). The remaining outcomes showed no between-group differences. Higher clinical pain intensity and facilitated temporal summation were associated in the facilitated CPM group but not in the inhibitory CPM group. CONCLUSION: These explorative findings indicated that quantitative clinical and experimental differences exist between facilitatory or inhibitory CPM responses in a chronic knee pain patient population. Differences in patients' CPM responses should be further investigated to unravel possible clinical importance. SIGNIFICANCE: Our findings confirm that conditioned pain modulation consist of inhibitory and facilitatory responders among a patient population with chronic knee pain. This explorative study indicates that patients with either facilitatory or inhibitory conditioned pain modulation could exhibit differences in pain outcomes. Subgrouping of chronic pain patients depending on individual conditioned pain modulation responses could be considered in phenotyping patients prior to inclusion in clinical trials or used for personalizing the management regime.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Recommendations for the delivery of therapeutic exercise for people with knee and/or hip osteoarthritis. An international consensus study from the OARSI Rehabilitation Discussion Group.

OBJECTIVE: To develop evidence-informed recommendations to support the delivery of best practice therapeutic exercise for people with knee and/or hip osteoarthritis (OA). DESIGN: A multi-stage, evidence-informed, international multi-disciplinary consensus process that included: 1) a narrative literature review to synthesise existing evidence; 2) generation of evidence-informed proposition statements about delivery of exercise for people with knee and/or hip OA by an international multi-disciplinary expert panel, with statements refined and analysed thematically; 3) an e-Delphi survey with the expert panel to gain consensus on the most important statements; 4) a final round of statement refinement and thematic analysis to group remaining statements into domains. RESULTS: The expert panel included 318 members (academics, health care professionals and exercise providers, patient representatives) from 43 countries. Final recommendations comprised 54 specific proposition statements across 11 broad domains: 1) use an evidence-based approach; 2) consider exercise in the context of living with OA and pain; 3) undertake a comprehensive baseline assessment with follow-up; 4) set goals; 5) consider the type of exercise; 6) consider the dose of exercise; 7) modify and progress exercise; 8) individualise exercise; 9) optimise the delivery of exercise; 10) focus on exercise adherence; and 11) provide education about OA and the role of exercise. CONCLUSION: The breadth of issues identified as important by the international diverse expert panel highlights that delivering therapeutic exercise for OA is multi-dimensional and complex.

Comparison of Intact Allergen Extracts and Allergoids For Subcutaneous Immunotherapy: The Effect of Chemical Modification Differs Both Between Species and Between Individual Allergen Molecules.

BACKGROUND: Allergen products for subcutaneous immunotherapy (SCIT) contain intact allergen extracts or chemically modified allergoids. Chemical modification was introduced to reduce allergenicity while retaining immunogenicity and thereby enable safer and more efficient allergy immunotherapy. METHODS: Experimental allergoids were produced from intact allergen extract for birch, grass, and house dust mite (HDM) to evaluate the effects of chemical modification. Preparations were compared with commercial allergoids and analyzed using SDS-PAGE/immunoblotting, IgE-inhibition assays, and crossed immunoelectrophoresis (CIE). Dermatophagoides pteronyssinus (Der p) vaccines were also tested for protease activity and immunizing capacity in a mouse model. RESULTS: The composition of IgE-binding epitopes in allergoids differed from that of intact allergen vaccines. Birch and grass allergoids produced smears of protein aggregates on SDS-PAGE, whereas intact allergen preparations showed distinct protein bands as expected. Der p allergoid vaccines, however, showed a distinct protein band corresponding to major allergen Der p 1 in both SDS-PAGE and CIE analysis, and commercial Der p allergoid vaccines showed Der p 1-related cysteine protease activity. CONCLUSION: Allergoids and intact allergen preparations differ with respect to the composition of IgE-binding epitopes. However, chemical cross-linking does not affect every allergen molecule to the same degree. Der p 1, for example, remains largely unmodified. Furthermore, the investigational HDM allergoid vaccines showed reduced and delayed immune responses when used for immunization of mice.

Tamoxifen-independent Cre-activity in SMMHC-CreER T2 mice.

Background and aims: Recent technological advances have established vascular smooth muscle cells (SMCs) as central players in atherosclerosis. Increasingly complex genetic mouse models have unveiled that 30-70% of cells in experimentally induced atherosclerotic lesions derive from a handful of medial SMCs, and that these can adopt a broad range of plaque cell phenotypes. Most of these models are based on the SMMHC-CreER T2 mouse line as Cre-driver. Importantly, Cre-activation can be controlled in time (by administration of tamoxifen, TAM), which is critical to avoid unwanted effects of premature recombination events. The aim of this study was to scrutinize an unexpected observation of TAM-independent Cre-activity in this mouse line. Methods: Cre-activity was assessed by PCR in tissues from SMMHC-CreER T2 mice crossed with mice homozygous for loxP-flanked (floxed) exon 4 of Ccn2 (our gene-of-interest), and Ccn2 protein was measured in aortas by targeted mass spectrometry. Results: We observed spontaneous near-complete excision of floxed Ccn2 in aortas from adult mice that were not treated with TAM. As a result, Ccn2 protein was significantly reduced in aortas from these mice, but not to the same extent as TAM-treated littermates. Remarkably, most of the excision was completed in 4-week-old mice. Excision was Cre-dependent, as knockout bands were negligible in heart and liver (dominated by non-SMCs) of these mice, and undetectable in the aorta in the absence of Cre. Conclusion: Our observations warrant caution, and we advocate inclusion of appropriate controls (i.e., TAM-untreated mice) in future studies.

Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/-, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.

Direct measurement of the triple spin flip rate in dynamic nuclear polarization.

A previous study of the effect of Gadolinium doping on the dynamic polarization (DNP) of 13C using trityls showed that the rate at which the polarization builds up is almost independent of the Gadolinium concentration, while the electron spin-lattice relaxation rate varies over an order of magnitude. In this paper we analyze the polarization build-up in detail and show that in this case DNP is due to the cross-effect (CE) and that the build-up rate can be quantitatively interpreted as the rate of the triple spin flips responsible for the CE. Thus this build-up rate presents a direct measurement of this triple spin flip rate.

Use of Crotalidae equine immune F(ab')2 antivenom for treatment of an Agkistrodon envenomation.

INTRODUCTION: Anavip (F(ab')2AV) is a lyophilized F(ab')2 immunoglobulin fragment derived from horses immunized with venom from Bothrops asper and Crotalus durissus. It was approved by the FDA in 2015 for treatment of North American rattlesnake envenomation but not for Agkistrodon envenomation. Published data regarding the efficacy and safety of Anavip in treating Agkistrodon envenomations is limited. We present a case of a patient treated with Anavip after confirmed Agkistrodon laticinctus envenomation. CASE DETAILS: A 77 year-old man was bitten on his fifth finger by a captive A. laticinctus. He was taken to a local emergency department where he received a 10 vial initial dose of F(ab')2AV for pain and swelling and was transferred. At the receiving facility, his pain had improved and his swelling had not progressed. Over the next 30 h, his platelets declined to 132,000/mm3 and he received an additional 4 vials of F(ab')2AV. The remainder of his course was unremarkable with complete recovery by 3 months. DISCUSSION: This case provides an additional published datapoint on the use of this F(ab')2AV in the treatment of envenomation by Agkistrodon.

Deep muscle-proteomic analysis of freeze-dried human muscle biopsies reveals fiber type-specific adaptations to exercise training.

Skeletal muscle conveys several of the health-promoting effects of exercise; yet the underlying mechanisms are not fully elucidated. Studying skeletal muscle is challenging due to its different fiber types and the presence of non-muscle cells. This can be circumvented by isolation of single muscle fibers. Here, we develop a workflow enabling proteomics analysis of pools of isolated muscle fibers from freeze-dried human muscle biopsies. We identify more than 4000 proteins in slow- and fast-twitch muscle fibers. Exercise training alters expression of 237 and 172 proteins in slow- and fast-twitch muscle fibers, respectively. Interestingly, expression levels of secreted proteins and proteins involved in transcription, mitochondrial metabolism, Ca2+ signaling, and fat and glucose metabolism adapts to training in a fiber type-specific manner. Our data provide a resource to elucidate molecular mechanisms underlying muscle function and health, and our workflow allows fiber type-specific proteomic analyses of snap-frozen non-embedded human muscle biopsies.

The role of interleukin-18 in the diagnosis and monitoring of hemophagocytic lymphohistiocytosis/macrophage activation syndrome - a systematic review.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of HLH and its subtype Macrophage Activation Syndrome (MAS) remains a challenge. Interleukin 18 (IL-18) is emerging as a potential biomarker for HLH/MAS but is currently not a part of diagnostic criteria. This systematic review aimed to assess the potential role of IL-18 in the diagnosis and monitoring of HLH and MAS, and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase were searched on 30 January 2020. Studies included all subtypes of HLH and a range of underlying disorders in both children and adults. A total of 14 studies were included. Generally, serum IL-18 was elevated in both primary and secondary HLH (> 1000 pg/ml) compared with other inflammatory conditions and with healthy individuals; thus, serum IL-18 may be able to discriminate between HLH and other inflammatory conditions. Significantly increased IL-18 (> 10 000 pg/ml) was also consistently described in MAS compared with other subtypes of HLH. The ability of IL-18 to distinguish MAS from systemic juvenile idiopathic arthritis (JIA) is less unambiguous, as IL-18 levels > 100 000 pg/ml were described in sJIA patients both with and without MAS. IL-18 may help to differentiate between HLH subtypes and other inflammatory conditions. As HLH and MAS are rare disorders, only few and relatively small studies exist on the subject. Larger, prospective multi-center studies are called for to assess the diagnostic precision of IL-18 for HLH and MAS.

Long-term outcomes after in-hospital cardiac arrest: 30-day survival and 1-year follow-up of mortality, anoxic brain damage, nursing home admission and in-home care.

AIMS: Long-term functional outcomes after in-hospital cardiac arrest (IHCA) are scarcely studied. However, survivors are at risk of neurological impairment from anoxic brain damage which could affect quality of life and lead to need of care at home or in a nursing home. METHODS: We linked data on ICHAs in Denmark with nationwide registries to report 30-day survival as well as factors associated with survival. Furthermore, among 30-day survivors we reported the one-year cumulative risk of anoxic brain damage or nursing home admission with mortality as the competing risk. RESULTS: In total, 517 patients (27.3%) survived to day 30 out of 1892 eligible patients; 338 (65.9%) were men and median age was 68 (interquartile range 58-76). Lower age, witnessed arrest by health care personnel, monitored arrest and presumed cardiac cause of arrest were associated with 30-day survival. Among 454 30-day survivors without prior anoxic brain damage or nursing home admission, the risk of anoxic brain damage or nursing home admission within the first-year post-arrest was 4.6% (n = 21; 95% CI 2.7-6.6%) with a competing risk of death of 15.6% (n = 71; 95% CI 12.3-19.0%), leaving 79.7% (n = 362) alive without anoxic brain damage or nursing home admission. When adding the risk of need of in-home care among 343 30-day survivors without prior home care needs, 68.8% (n = 236) were alive without any of the composite events one-year post-arrest. CONCLUSION: The majority of 30-day survivors of IHCA are alive at one-year follow-up without anoxic brain damage, nursing home admission or need of in-home care.

Performance and outcome evaluation of emergency resuscitative thoracotomy in a Norwegian trauma centre: a population-based consecutive series with survival benefits.

BACKGROUND: Emergency resuscitative thoracotomy (ERT) is a lifesaving procedure for select indications in severely injured patients. The main body of the literature stem from regions with a high prevalence of penetrating injuries, while data from European institutions remain scarce. We aimed to evaluate a decade of ERT in a Norwegian trauma centre. METHODS: A prospectively collected series from the institutional trauma registry of all consecutive trauma patients who had an ERT at Stavanger University Hospital (SUH) from 2006 to 2018. Data were extracted using both registry and electronic patient record (EPR) data, including injury profile, demographics and outcomes. Comparison of groups were done by descriptive statistics. RESULTS: A total of 26 ERTs were performed during the study period, of which 20 were men (75%) and 6 women (25%). Five patients (19%) survived to hospital discharge, of which 3 men and 2 women with a median age of 46 years (range 24-68). All survivors had thoracic injury as location of major injury (LOMI.). Of the five survivors, four suffered blunt injury and one patient penetrating injury. At one-year of follow-up of the survivors, three patients scored 8/8 on Glasgow outcome scale-extended, 1 patient scored 7/8 and one patient 5/8. CONCLUSION: In this study, ERT conferred good outcome with survival in one of every five procedures. Performing ERT in severely injured patients presenting in extremis appears to be justified even in low-volume centres and in blunt trauma.

Closing the methane mass balance for an old closed Danish landfill.

In this study, a methane (CH4) mass balance was established for Hedeland landfill. CH4 generation rates were modelled using a multiphase first-order decay model (The Afvalzorg model) and determined at between 57 and 79 kg h-1. The CH4 emission rate was quantified at between 2 and 14 kg h-1, using the tracer gas dispersion method and the CH4 gas recovery efficiency was between 8 and 21%. At three places along the perimeter of the landfill, gas remediation systems have been installed to protect the residential houses from any risk of migrating landfill gas. About 0.76 kg h-1 of CH4 was extracted from these three remediation systems. Using a carbon mass balance for the lateral migrating landfill gas showed a fractional oxidation of about 78%, which corresponded to a CH4 flux of 3.5 kg h-1 from the three remediation systems, including the oxidised CH4. The total lateral CH4 flux (un-oxidised) from the total landfill perimeter was estimated at between 6.9 and 10.4 kg h-1. CH4 oxidation efficiency in the landfill cover soil, determined from stable carbon isotope analyses, was found to be between 12% and 92%. This resulted in an average CH4 oxidation rate of 32 kg h-1, using an average CH4 emission rate of 8 kg h-1. CH4 surface screenings and surface flux measurements supported the hypothesis that oxidation efficiency was in the higher range and that oxidation could close the CH4 mass balance.

Biofiltration of diluted landfill gas in an active loaded open-bed compost filter.

Microbial oxidation in a biofilter is a treatment solution for diluted landfill gas (LFG), for instance at old landfills, where LFG recovery is no longer feasible, or from remediation systems designed to cut off laterally migrating LFG. In this study, an actively loaded open-bed compost filter, designed for the treatment of diluted LFG, was tested at an old landfill in Denmark. An 18 m3 biofilter was constructed in a 30 m3 container loaded with LFG mixed with air, in order to obtain diluted LFG. The inlet concentration of methane (CH4) fluctuated between 4.4 and 9.2 vol% during the five tested flow campaigns, resulting in CH4 loads of 106-794 g CH4 m-2 d-1. The maximum identified CH4 oxidation rate was 460 g m-2 d-1, with an overall CH4 oxidation efficiency of 58%. Due to preferential flows, especially along the edges of the filter at the transition points between the compost and the container wall, an overall CH4 oxidation efficiency of 100% was never achieved. However, pore gas profiles in selected areas in the filter material showed oxidation efficiencies close to 100%. The results were supported by tracer gas tests showing average oxidation efficiency in the nine measuring points of 89% at a CH4 load of 487 ± 64 g CH4 m-2 d-1.

Magnetic resonance imaging with optical preamplification and detection.

Magnetic resonance (MR) imaging relies on conventional electronics that is increasingly challenged by the push for stronger magnetic fields and higher channel count. These problems can be avoided by utilizing optical technologies. As a replacement for the standard low-noise preamplifier, we have implemented a new transduction principle that upconverts an MR signal to the optical domain and imaged a phantom in a clinical 3 T scanner with signal-to-noise comparable to classical induction detection.

PIN diode driver for NMR and MRI.

Designing custom coils for magnetic resonance systems, such as nuclear magnetic resonance (NMR) spectrometers and magnetic resonance imaging (MRI) scanners, often entails using non-standard configurations of the transmit-receive (T/R) switch and Q-spoiling circuits. The built-in drivers of commercial NMR and MRI systems are, typically, only reconfigurable within a narrow application range (if at all). Thus, the built-in driver may not be able to properly control the custom T/R switches and Q-spoiling circuits when using custom built coils. We present a PIN diode driver which functions in both an MRI scanner and NMR spectrometer. The PIN diode driver is based on readily available discrete components and achieves switching times for the reverse and forward bias states (transmit on and off) of 2 µs and 0.4 µs respectively. Hence, this work enables a higher degree of customization of the RF switching circuits in an MR system and is potentially of interest for designers of custom coils for both NMR spectrometers and MRI scanners.

Assessment of a landfill methane emission screening method using an unmanned aerial vehicle mounted thermal infrared camera - A field study.

An unmanned aerial vehicle (UAV)-mounted thermal infrared (TIR) camera's ability to delineate landfill gas (LFG) emission hotspots was evaluated in a field test at two Danish landfills (Hedeland landfill and Audebo landfill). At both sites, a test area of 100 m2 was established and divided into about 100 measuring points. The relationship between LFG emissions and soil surface temperatures were investigated through four to five measuring campaigns, in order to cover different atmospheric conditions along with increasing, decreasing and stable barometric pressure. For each measuring campaign, a TIR image of the test area was obtained followed by the measurement of methane (CH4) and carbon dioxide (CO2) emissions at each measuring point, using a static flux chamber. At the same time, soil temperatures measured on the surface, at 5 cm and 10 cm depths, were registered. At the Hedeland landfill, no relationship was found between LFG emissions and surface temperatures. In addition, CH4 emissions were very limited, on average 0.92-4.52 g CH4 m-2 d-1, and only measureable on the two days with decreasing barometric pressure. TIR images from Hedeland did not show any significant temperature differences in the test area. At the Audebo landfill, an area with slightly higher surface temperatures was found in the TIR images, and the same pattern with slightly higher temperatures was found at a depth of 10 cm. The main LFG emissions were found in the area with the higher surface temperatures. LFG emissions at Audebo were influenced significantly by changes in barometric pressure, and the average CH4 emissions varied between 111 g m-2 d-1 and 314 g m-2 d-1, depending on whether the barometric pressure gradient had increased or decreased, respectively. The temperature differences observed in the TIR images from both landfills were limited to between 0.7 °C and 1.2 °C. The minimum observable CH4 emission for the TIR camera to identify an emission hotspot was 150 g CH4 m-2 d-1 from an area of more than 1 m2.

One-year follow-up on liraglutide treatment for prediabetes and overweight/obesity in clozapine- or olanzapine-treated patients.

OBJECTIVE: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period. METHOD: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels. RESULTS: From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide. CONCLUSION: The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels.