Association between lifestyle factors and thyroid function in young euthyroid adults

Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:Energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).Energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.

The Use of Insulin Negatively Impacts the Mortality of Severe COVID-19 in Patients with Type 2 Diabetes—A Systematic Review

Obesity and type 2 diabetes are among the most important risk factors for severe coronavirus disease-19. Some studies have suggested that the use of insulin as a therapeutic agent to treat hyperglycemia and the metabolic abnormalities associated with type 2 diabetes during the acute phase of severe coronavirus disease-19 could have a negative impact on the disease’s progression;however, there is no consensus on this issue. Here, we performed a systematic review in an attempt to answer this important question. We included 29 articles published from December 2019 to August 2023, which reported the outcomes of 3,070,657 patients with severe coronavirus disease-19 that had the diagnosis of diabetes and were treated with either insulin or other glucose-reducing agents. The results show that using insulin as a pharmacological intervention to treat type 2 diabetes in patients with severe coronavirus disease-19 increases the likelihood of mortality by 193%.

Evaluation of brain tumor metabolism with [^(11)C] choline PET and ~1H-MRS.

BACKGROUND:The signal of choline containing compounds（Cho）in proton magnetic resonance spectroscopy（1H-MRS）is elevated in brain tumors.[11C]choline uptake as assessed using positron emission tomography（PET）has also been suggested to be higher in brain tumors than in the normal brain.We examined whetherquantitative analysis of choline accumulation and content using these 1wo novel techniques would be helpful innon-invasive,preoperative evaluation of suspected brain tumors and tumor malignancy grade.METHODS:12patients with suspected brain tumor were studied using[11C]choline PET,gadolinium enhanced 3-D magneticresonance imaging and1H-MRS prior to diagnostic biopsy or resection.Eleven normal subjects served as

Glutamine Metabolism: A New Target Pathway for PET Imaging and Cancer Therapy

Individuals with metabolic syndrome will have increased risk for cardiovascular disease, diabetes and cancer. Based on abnormal glucose metabolism, or called Warburg effect in cancer cells, positron emission tomography (PET) imaging using 18F-FDG has achieved a great success in diagnosis and monitoring therapeutic responds for cancer patients. Beyond glucose metabolism, resurgence of glutamine metabolism in cancer research has recently broadened interests. Observations of addiction to glutamine in cancer cells lead to considering contribution of glutaminolysis in cancer cell growth, differentiation and proliferation. Furthermore, oncogenes have been found to be major factors in modulating abnormal glutamine metabolism in cancer cells. PET imaging probes and therapeutic agents targeting glutamine metabolic and signaling pathways have been proposed and investigated.

Potential Value of Positron Emission Tomography(PET)in Evaluating the Ketogenic Diet as Anticancer Therapy

Positron Emission Tomography(PET)imaging is a noninvasive and extraordinarily sensitive imaging modality that provides a functional and metabolic assessment of normal or diseased tissue.[18F]-fluorodeoxyglucose PET imaging(FDG PET)is widely used clinically for tumor imaging,and has been proven to improve the diagnosis and subsequent treatment of cancer patients.The rationale behind FDG PET imaging is the Warburg effect,which states that there is increased glycolysis in cancer cells,even in the presence of oxygen,making it possible to detect cells exhibiting increased glycolysis,thus diagnosing even small tumors.The ketogenic diet(KD)with low carbohydrate and high fat intake has been used as an alternative treatment for cancer and other diseases,with nearly a century of use for reducing seizure onset in epileptics.The cellular mechanism underlying KD therapy is also based on the Warburg effect.The increased ketolysis stimulated by KD therapy inhibits the abnormally elevated glycolysis in cancer cells,leading to reduced tumor growth and metastasis.In this review,we first describe the Warburg effect as the common biological basis connecting PET and KD therapy.This paper also provides overviews of PET imaging and KD therapy.Two newly published papers,one regarding the molecular mechanism of KD therapy in the treatment of cancers,another on the in vivo PET imaging of cerebral metabolism of glucose and ketone bodes in humans after a moderate KD,are thoroughly reviewed.Furthermore,this review describes how PET imaging may be applied to study the effects of KD therapy in humans and animals,and which currently available PET tracers can be used to image glucose and ketone metabolic pathways.

Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease

Metabolic associated fatty liver disease(MAFLD),formerly named“nonalcoholic fatty liver disease”occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death,such as cardio-vascular,digestive,metabolic,neoplastic and neuro-degenerative diseases.However,progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation,which acts as disease accelerator.Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver,where insulin resistance has been assumed to play an important role.Special emphasis has been given to digital imaging studies and in particular to positron emission tomography,as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism.An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver,dysregulated endogenous glucose production and insulin resistance.

Long-Term Monoacylglycerol Lipase Inhibitor Treatment Decelerates Pathological Changes in APP/PS1-21 Mice, but Behavioral Improvements Require Early-Stage Treatment Onset—Short Report

The arachidonic acid (AA) pathway produces several essential proinflammatory eicosanoids. However, in many neurodegenerative diseases, e.g. Alzheimer’s disease (AD), this pathway is chronically hyperactivated. In brain, primarily monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to AA, which is further metabolized to generate many proinflammatory eicosanoids. MAGL inhibition, simultaneously reducing the level of eicosanoids and increasing those of neuroprotective endocannabinoids, has proved efficacious in some AD models, reducing neurotoxic β-amyloid (Aβ) levels and improving memory functions. Here, a MAGL inhibitor, JZL184 was chronically administered (16 mg/kg, i.p., 3 x/wk for 5 mo) for 1 - 1.5 mo and 7 - 8 mo old transgenic (TG) and wild-type (WT) APP/PS1-21 mice modelling cerebral amyloidosis. According to immunohistochemistry, JZL184 significantly increased the expression levels of cannabinoid receptor 1 in older WT and younger TG and WT mice, decreased cannabinoid receptor 2 and oligomeric Aβ in older and younger TG mice and decreased microglia-specific marker Iba1 in younger TG mice, compared to TG mice treated with vehicle only. However, in the Morris Water Maze test, spatial memory functions improved significantly only in younger TG and WT mice, compared to vehicle-treated littermates. These tentative results suggest that chronic, rather long-term MAGL inhibition can decelerate pathological changes in TG APP/PS1-21 mice but it improves memory functions only when administered at an early stage of the

游离脂肪酸的消耗可迅速降低心肌病性心力衰竭患者的心脏作功和效率

背景:通过抑制游离脂肪酸(FFA)代谢来增强心肌葡萄糖代谢的代谢调质可改善心力衰竭患者的心脏功能。作者探讨FFA迅速减少对原发性扩张型心肌病(IDCM)所致心力衰竭患者心脏功能的影响。

非痴呆性早期帕金森病患者海马和前额的萎缩与认知损害有关

Background: Early stage patients with Parkinsons disease (PD) show cognitive impairment in frontal lobe functions and memory tests. Hippocampal atrophy is s een in medicated patients with advanced PD. Objectives: To examine whether prefr ontal or hippocampal atrophy are already present in early stage PD, and whether such atrophy is associated with cognitive impairment. Methods: Twenty non medic ated, non demented patients with early stage PD and 22 neurologically healthy a ge matched controls were studied. All subjects underwent magnetic resonance imag ing to study hippocampal and prefrontal atrophy. Atrophy was evaluated by a neur oradiologist using a five point scale. In addition, the patients underwent a neu ropsychological test battery sensitive to frontal lobe functions and memory. Res ults: Patients with PD had atrophy in the right and the left prefrontal cortex. In the right hippocampus, the mean atrophy score was 1.15 in PD and 0.45 in cont rols. Corresponding figures for the left hippocampus were 1.05 for PD and 0.64 f or controls. In PD, the left hippocampus atrophy correlated with verbal memory a nd prefrontal atrophy correlated with impaired performance in a test measuring v igilance. Conclusions: Non medicated, non demented patients with early stage P D show hippocampal and prefrontal atrophy. Impaired memory is related to hippoca mpal atrophy, whereas sustained attention is related to prefrontal atrophy.

Imaging of Insulitis in NOD Mice with IL-2-Gd-DTPA and 1.5 T MRI

To explore the possibility to use 1.5 T MRI in imaging of accumulating gadolinium (Gd) into inflamed en- docrine pancreas (insulitis), we compared intravenously delivered IL-2-Gd-DTPA and Gd-DTPA (Magne- vist?) in phenotypically healthy 12 weeks old female non-obese diabetic (NOD) mice. At 1 to 48 h after the injection mice were sacrificed and the pancreas-to-background ratio was determined using MRI. In addition Gd concentration of the pancreas and plasma were measured. The pancreas-to-plasma ratio of Gd was 25-fold 24 h after the i.v. injection of IL-2-Gd-DTPA. At the same time the pancreas-to-background ratio measured with 1.5T MRI was 1.5-times higher in the NOD mice receiving IL-2-Gd-DTPA than Magnevist? (271 ± 37 vs. 183 ± 0,1, P = 0.04) indicating that sufficient differences may exist between IL-2-Gd-DTPA accumulating in the pancreas and in the surrounding tissues to support the use of MRI for imaging of pan- creatic insulitis.

ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific,brain-penetrating fusion protein

Background:Hijacking the transferrin receptor(TfR)is an effective strategy to transport amyloid-beta(Aβ)immuno-positron emission tomography(immunoPET)ligands across the blood-brain barrier(BBB).Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβpathology in mouse models of Alzheimer’s disease(AD).This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET radioligands.Methods:Two affinity variants of the rat TfR antibody,OX26,were chemically conjugated to a F(ab′)2 fragment of the anti-Aβantibody,bapineuzumab(Bapi),to generate two bispecific fusion proteins:OX265-F(ab′)2-Bapi and OX2676-F(ab′)2-Bapi.Pharmacokinetic analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type(WT)rats.[124I]I-OX265-F(ab′)2-Bapi was administered to TgF344-AD and WT rats for in vivo PET imaging.Ex vivo distribution of injected[124I]I-OX265-F(ab′)2-Bapi and Aβpathology were assessed.Results:More[125I]I-OX265-F(ab′)2-Bapi was taken up into the brain 4 h post-administration than[124I]I-OX2676-F(ab′)2-Bapi.[124I]I-OX265-F(ab′)2-Bapi PET visualized Aβpathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβpathology.The PET signals significantly correlated with Aβlevels in AD animals.Conclusion:Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB,such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently.Furthermore,bispecific immunoPET imaging of brain Aβpathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats,suggesting that this immunoPET strategy has the potential to be translated to higher species.

Neural mechanisms of top-down divided and selective spatial attention in visual and auditory perception

Top-down attention mechanisms require the selection of specificobjects or locations;however,the brain mechanism involved when attention is allocated across different modalities is not well understood.The aim of this study was to use functional magnetic resonance imaging to define the neural mechanisms underlyingdivided and selective spatial attention.A concurrent audiovisual stimulus was used,and subjects were prompted to focus on a visual,auditory and audiovisual stimulus in a Posner paradigm.Ourbehavioral results confirmed the better performance of selectiveattention compared to devided attention.We found differences in the activation level of the frontoparietal network,visual/auditorycortex,the putamen and the salience network under differentattention conditions.We further used Granger causality(GC)toexplore effective connectivity differences between tasks.Differences in GC connectivity between visual and auditory selective tasksreflected the visual dominance effect under spatial attention.In addition,our results supported the role of the putamen inredistributing attention and the functional separation of the saliencenetwork.In summary,we explored the audiovisual top-down allocation of attention and observed the differences in neuralmechanisms under endogenous attention modes,which revealedthe differences in cross-modal expression in visual and auditory attention under attentional modulation.

心率变异性在手术后不良心脏事件危险分层中的作用

越来越多的证据表明自主神经系统的功能紊乱与心源性猝死关系密切。心率变异性（HRV）测定已广泛用于自主神经系统功能变化的检测。数项关于心脏患者的研究显示，HRV减小及压力感受器功能障碍与现有的左室射血分数等临床预测因子相比，是更强的心源性猝死的预测因子。所有手术后并发症中的1／3和超过半数的死亡可归因于心脏并发症。几个风险指数仅在单个患者围手术期近期危险分层中有效，而在远期预后的危险分层中无效。目前临床上尚缺乏用于评估手术后远期危险性的类似方法。最近有少数研究显示手术前HRV减小可作为手术后远期病死率的独立预测因子，但还需要进行更多的关于手术患者的研究，以确立手术前压力感受器功能障碍（单独存在或与HRV合并存在）对手术后近期及远期预后的可能预测价值。

氙气麻醉对健康受试者大脑糖代谢与脑血流耦联关系的影响：采用正电子计算机断层显像技术的研究

背景全身麻醉药能够改变脑局部糖代谢（regionalcerebralglucosemetabolism，rCMRgk）和脑血流（cerebralbloodflow，CBF）之间的相互关系。本研究应用正电子计算机断层显像（positronemissiontomography，PET）研究技术评价氙气麻醉对健康受试者rCMRgk及rCBF的影响。方法采用纯氙气对5例男性健康受试者进行麻醉，分别用埔F标记的氟脱氧葡萄糖和^15O标记的水分子测量基础值（清醒时）及1个肺泡最低有效浓度（minimumalveolarconcentration，MAC）下的rCMRgk及rCBF值。采用兴趣区（region-of-interest，ROI）分析及体素定量分析测量rCMRgk及rCBF的变化。结果麻醉期间氙气平均浓度为67．2％±0．8％（均数±标准差）。氙气麻醉导致rCMRgk均一性降低，但仅导致rCBF在13个兴趣区中的7个降低。灰质区rCMR出及疋BF分别降低了32．4％±4．0％（P〈0．001）和14．8％±5．9％（P=0．007）；自质区rCMR出降低了10．9％±6．4％（P=0．030），而rCBF增加了9．2％±7．3％。在岛叶、扣带前回、扣带后回及躯体感觉皮质区rCBF／rCMR出比值增加最明显。结论在1MAC氙气麻醉时rCMR出的降低程度大于rCBF的降低，因而rCBF／rCMRgk比值增加。有趣的是氙气麻醉对脑代谢及脑血流的影响与挥发性麻醉药相似。