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  1. Article ; Online: Multidisciplinary clinical guidelines in proactive monitoring, early diagnosis, and effective management of trastuzumab deruxtecan (T-DXd)-induced interstitial lung disease (ILD) in breast cancer patients.

    Wekking, D / Porcu, M / Pellegrino, B / Lai, E / Mura, G / Denaro, N / Saba, L / Musolino, A / Scartozzi, M / Solinas, C

    ESMO open

    2023  Volume 8, Issue 6, Page(s) 102043

    Abstract: Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC), has altered the treatment landscape in breast cancer (BC), irrespective of the HR-receptor status. The use of the agent is ... ...

    Abstract Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC), has altered the treatment landscape in breast cancer (BC), irrespective of the HR-receptor status. The use of the agent is increasing, despite the finding that exposure to T-DXd increases the risk of interstitial lung disease (ILD), particularly in BC patients. Although T-DXd-related ILD can be potentially severe and life-threatening, most low-grade cases can be treated safely using a multidisciplinary approach comprising early and accurate diagnosis, effective management, close monitoring, and the prompt administration of steroids. Additionally, increasing patients' education on ILD symptoms ensures close attention and enables prompt reporting, enhancing patient outcomes. It is recommended that predictive biomarkers are assessed in patients with risk factors for developing ILD. Currently, diagnostic criteria comprise newly identified pulmonary opacities, the relation of symptom onset to medication initiation, and the exclusion of other causes of ILD. The general condition of patients is weakened during the management of ILD (BC progression and corticosteroid treatment). Consequently, BC chemotherapy might be attenuated. This highlights the importance of preventing (high-grade) ILD, especially since its use is expanded. Identifying high-risk patients, diagnosing, and customizing treatment is, however, challenging and additional information on patient selection is often not fully clarified. In this paper, we provide updated multidisciplinary clinical guidance for patient selection, proactive monitoring, early diagnosis, and effectively management of T-DXd-induced ILD in HER2-positive BC patients. We describe the risk factors for developing ILD, patients' characteristics of ILD, and the histopathological and radiographic characteristics of ILD, including real-world clinical practice reports. These recommendations provide a structured step-by-step approach for managing each suspected BC-related ILD grade.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/complications ; Breast Neoplasms/drug therapy ; Early Detection of Cancer ; Immunoconjugates ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/drug therapy ; Lung Diseases, Interstitial/etiology
    Chemical Substances trastuzumab deruxtecan (5384HK7574) ; Immunoconjugates
    Language English
    Publishing date 2023-11-10
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2059-7029
    ISSN (online) 2059-7029
    DOI 10.1016/j.esmoop.2023.102043
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  2. Article: The Role of Cytokinome in the HNSCC Tumor Microenvironment: A Narrative Review and Our Experience.

    Denaro, Nerina / Solinas, Cinzia / Garrone, Ornella / Cauchi, Carolina / Ruatta, Fiorella / Wekking, Demi / Abbona, Andrea / Paccagnella, Matteo / Merlano, Marco Carlo / Lo Nigro, Cristiana

    Diagnostics (Basel, Switzerland)

    2022  Volume 12, Issue 11

    Abstract: ... definitive CRT is the mainstay of treatment. In recurrent metastatic (R/M), HNSCC immune checkpoint ... several improvements in the outcome of patients with R/M HNSCC, overall survival (OS) remains dismal, equaling a median ... targeted therapy (e.g., Cetuximab). The presence of cytokines indicates an immune response that might occur ...

    Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. In locally advanced (LA) HNSCC, a multidisciplinary approach consisting of surgery followed by chemoradiation (CRT) or definitive CRT is the mainstay of treatment. In recurrent metastatic (R/M), HNSCC immune checkpoint inhibitors (ICIs) with or without chemotherapy represent the new first-line option. However, cancer will recur in about two out of five patients with LA HNSCC. If progression occurs within six months from platin-radiotherapy treatment, anti-programmed cell death-1 (PD-1) may be prescribed. Otherwise, immunotherapy with or without chemotherapy might be considered if PD-L1 is expressed. Despite several improvements in the outcome of patients with R/M HNSCC, overall survival (OS) remains dismal, equaling a median of 14 months. In-depth knowledge of the tumor microenvironment (TME) would be required to change the course of this complex disease. In recent years, many predictive and prognostic biomarkers have been studied in the HNSCC TME, but none of them alone can select the best candidates for response to ICIs or targeted therapy (e.g., Cetuximab). The presence of cytokines indicates an immune response that might occur, among other things, after tumor antigen recognition, viral and bacterial infection, and physic damage. An immune response against HNSCC results in the production of some cytokines that induce a pro-inflammatory response and attract cells, such as neutrophils, macrophages, and T cell effectors, to enhance the innate and adaptive anti-tumor response. We revised the role of a group of cytokines as biomarkers for treatment response in HNSCC.
    Language English
    Publishing date 2022-11-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics12112880
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  3. Article ; Online: Facilitating Recovery of Daily Functioning in People With a Severe Mental Illness Who Need Longer-Term Intensive Psychiatric Services: Results From a Cluster Randomized Controlled Trial on Cognitive Adaptation Training Delivered by Nurses.

    Stiekema, Annemarie P M / van Dam, Michelle T / Bruggeman, Richard / Redmeijer, Jeroen E / Swart, Marte / Dethmers, Marian / Rietberg, Kees / Wekking, Ellie M / Velligan, Dawn I / Timmerman, Marieke E / Aleman, André / Castelein, Stynke / van Weeghel, Jaap / Pijnenborg, Gerdina M H / van der Meer, Lisette

    Schizophrenia bulletin

    2020  Volume 46, Issue 5, Page(s) 1259–1268

    Abstract: Background: Feasible and effective interventions to improve daily functioning in people with a severe mental illness (SMI), such as schizophrenia, in need of longer-term rehabilitation are scarce.: Aims: We assessed the effectiveness of Cognitive ... ...

    Abstract Background: Feasible and effective interventions to improve daily functioning in people with a severe mental illness (SMI), such as schizophrenia, in need of longer-term rehabilitation are scarce.
    Aims: We assessed the effectiveness of Cognitive Adaptation Training (CAT), a compensatory intervention to improve daily functioning, modified into a nursing intervention.
    Method: In this cluster randomized controlled trial, 12 nursing teams were randomized to CAT in addition to treatment as usual (CAT; n = 42) or TAU (n = 47). Daily functioning (primary outcome) was assessed every 3 months for 1 year. Additional follow-up assessments were performed for the CAT group in the second year. Secondary outcomes were assessed every 6 months. Data were analyzed using multilevel modeling.
    Results: CAT participants improved significantly on daily functioning, executive functioning, and visual attention after 12 months compared to TAU. Improvements were maintained after 24 months. Improved executive functioning was related to improved daily functioning. Other secondary outcomes (quality of life, empowerment, negative symptoms) showed no significant effects.
    Conclusions: As a nursing intervention, CAT leads to maintained improvements in daily functioning, and may improve executive functioning and visual attention in people with SMI in need of longer-term intensive psychiatric care. Given the paucity of evidence-based interventions in this population, CAT can become a valuable addition to recovery-oriented care.
    Language English
    Publishing date 2020-03-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 439173-1
    ISSN 1745-1701 ; 0586-7614
    ISSN (online) 1745-1701
    ISSN 0586-7614
    DOI 10.1093/schbul/sbz135
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  4. Article: Psychiatric symptoms in systemic lupus erythematosus: an update.

    Wekking, E M

    Psychosomatic medicine

    1993  Volume 55, Issue 2, Page(s) 219–228

    Abstract: ... e.g., rheumatoid arthritis) showed striking similarities between both patient groups with respect ...

    Abstract Twenty-one studies on the prevalence and type of psychiatric symptoms in systemic lupus erythematosus (SLE) are reviewed and evaluated. Substantial differences in prevalence of psychiatric symptoms in SLE-patients (from 17%-71%) have been reported. Of the investigated methodological aspects, differences in assessment techniques appeared to be the main source of the variability in findings. Although various types of psychiatric symptoms have been observed, depression is most frequently reported. There was no consistent relationship between the occurrence of psychiatric symptoms and other symptoms of SLE. However, the data suggest an association with (the patient's perception of) illness severity and with the experience of psychosocial stressors. Studies applying control groups (patients with other chronic diseases (e.g., rheumatoid arthritis) showed striking similarities between both patient groups with respect to prevalence and type of psychiatric symptoms. There is some evidence, however, indicating that a small proportion of the psychiatric symptomatology, in particular psychosis, is related to neurological dysfunction in SLE.
    MeSH term(s) Adrenal Cortex Hormones/therapeutic use ; Comorbidity ; Female ; Humans ; Inpatients/psychology ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/psychology ; Male ; Mental Disorders/etiology ; Outpatients/psychology ; Prevalence
    Chemical Substances Adrenal Cortex Hormones
    Language English
    Publishing date 1993-03
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Review
    ZDB-ID 3469-1
    ISSN 1534-7796 ; 0033-3174
    ISSN (online) 1534-7796
    ISSN 0033-3174
    DOI 10.1097/00006842-199303000-00011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice.

    Jacobs, Sophie A H / Gart, Eveline / Vreeken, Debby / Franx, Bart A A / Wekking, Lotte / Verweij, Vivienne G M / Worms, Nicole / Schoemaker, Marieke H / Gross, Gabriele / Morrison, Martine C / Kleemann, Robert / Arnoldussen, Ilse A C / Kiliaan, Amanda J

    Nutrients

    2019  Volume 11, Issue 8

    Abstract: Background: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile ... ...

    Abstract Background: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity.
    Methods: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI.
    Results: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity.
    Conclusions: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.
    MeSH term(s) Adipose Tissue/metabolism ; Animals ; Brain/pathology ; Diet, High-Fat/adverse effects ; Female ; Lipid Metabolism ; Liver/pathology ; Male ; Mice ; Mice, Obese ; Non-alcoholic Fatty Liver Disease/etiology ; Obesity/complications ; Obesity/metabolism ; Obesity/pathology ; Receptors, LDL/deficiency ; Sex Factors
    Chemical Substances Receptors, LDL
    Language English
    Publishing date 2019-08-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu11081861
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  6. Article ; Online: Hersenschade door blootstelling aan oplosmiddelen; diagnostiek en beloop van chronische toxische encefalopathie.

    van Valen, Evelien / van Hout, Evelien S E / Wekking, Ellie M / Lenderink, Annet F / van der Laan, Gert / Hageman, Gerard

    Nederlands tijdschrift voor geneeskunde

    2015  Volume 159, Page(s) A9431

    Abstract: ... and (e) impairment on neuropsychological assessment. Exposure to organic solvents can cause chronic ...

    Title translation Brain damage caused by exposure to organic solvents; diagnostics and disease course of chronic solvent-induced encephalopathy.
    Abstract Since 1997 more than 3,000 patients have been referred to one of the two Dutch Solvent Teams with health problems that may have been caused by long-term occupational exposure to organic solvents. A diagnosis of 'chronic solvent-induced encephalopathy' was made in approximately 500 patients. The diagnostics of this disease is based on five elements: (a) symptoms in line with the diagnosis; (b) relevant exposure to an organic solvent with neurotoxic effects; (c) a clear temporal relationship between the onset of symptoms and exposure to a solvent with neurotoxic effects; (d) exclusion of other causes for the symptoms; and (e) impairment on neuropsychological assessment. Exposure to organic solvents can cause chronic health effects, which may even persist years after exposure has ceased. In general, no more serious deterioration of health is observed after exposure has ceased.
    MeSH term(s) Brain/drug effects ; Brain Injuries/chemically induced ; Disease Progression ; Humans ; Neuropsychological Tests ; Neurotoxicity Syndromes/diagnosis ; Occupational Exposure ; Solvents/toxicity
    Chemical Substances Solvents
    Language Dutch
    Publishing date 2015
    Publishing country Netherlands
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 82073-8
    ISSN 1876-8784 ; 0028-2162
    ISSN (online) 1876-8784
    ISSN 0028-2162
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  7. Article ; Online: Chronic solvent-induced encephalopathy: course and prognostic factors of neuropsychological functioning.

    van Valen, Evelien / Wekking, Ellie / van Hout, Moniek / van der Laan, Gert / Hageman, Gerard / van Dijk, Frank / de Boer, Angela / Sprangers, Mirjam

    International archives of occupational and environmental health

    2018  Volume 91, Issue 7, Page(s) 843–858

    Abstract: Purpose: Working in conditions with daily exposure to organic solvents for many years can result in a disease known as chronic solvent-induced encephalopathy (CSE). The aims for this study were to describe the neuropsychological course of CSE after ... ...

    Abstract Purpose: Working in conditions with daily exposure to organic solvents for many years can result in a disease known as chronic solvent-induced encephalopathy (CSE). The aims for this study were to describe the neuropsychological course of CSE after first diagnosis and to detect prognostic factors for neuropsychological impairment after diagnosis.
    Methods: This prospective study follows a Dutch cohort of CSE patients who were first diagnosed between 2001 and 2011 and underwent a second neuropsychological assessment 1.5-2 years later. Cognitive subdomains were assessed and an overall cognitive impairment score was calculated. Paired t tests and multivariate linear regression analyses were performed to describe the neuropsychological course and to obtain prognostic factors for the neuropsychological functioning at follow-up.
    Results: There was a significant improvement on neuropsychological subdomains at follow-up, with effect sizes between small and medium (Cohen's d 0.27-0.54) and a significant overall improvement of neuropsychological impairment with a medium effect size (Cohen's d 0.56). Prognostic variables for more neuropsychological impairment at follow-up were a higher level of neuropsychological impairment at diagnosis and having a comorbid diagnosis of a psychiatric disorder at diagnosis.
    Conclusions: Results are in line with previous research on the course of CSE, stating that CSE is a non-progressive disease after cessation of exposure. However, during follow-up the percentage patients with permanent work disability pension increased from 14 to 37%. Preventive action is needed in countries where exposure to organic solvents is still high to prevent new cases of CSE.
    MeSH term(s) Adult ; Attention ; Brain Damage, Chronic/chemically induced ; Brain Damage, Chronic/physiopathology ; Brain Damage, Chronic/psychology ; Cognitive Dysfunction/chemically induced ; Cognitive Dysfunction/physiopathology ; Cognitive Dysfunction/psychology ; Female ; Follow-Up Studies ; Humans ; Linear Models ; Male ; Memory ; Multivariate Analysis ; Netherlands ; Occupational Diseases/chemically induced ; Occupational Diseases/physiopathology ; Occupational Diseases/psychology ; Occupational Exposure/adverse effects ; Prognosis ; Prospective Studies ; Solvents/toxicity
    Chemical Substances Solvents
    Language English
    Publishing date 2018-06-25
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 129038-1
    ISSN 1432-1246 ; 0340-0131 ; 0367-9977
    ISSN (online) 1432-1246
    ISSN 0340-0131 ; 0367-9977
    DOI 10.1007/s00420-018-1328-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Does the MMPI-168 exaggerate psychotic pathology?

    Dingemans, P M / Wekking, E M

    Journal of clinical psychology

    1996  Volume 52, Issue 3, Page(s) 297–301

    Abstract: Three scoring versions of the MMPI, scored on the same protocol, were compared in a multivariate design with 198 psychiatric patients. The MMPI-168 schizophrenia scale had a statistically higher elevation than the Dutch and American scoring versions. ... ...

    Abstract Three scoring versions of the MMPI, scored on the same protocol, were compared in a multivariate design with 198 psychiatric patients. The MMPI-168 schizophrenia scale had a statistically higher elevation than the Dutch and American scoring versions. This makes MMPI-168 profiles more often "schizophrenic" than other scoring versions. The MMPI-168 systematically overscores the presence of "psychotic" code types, 45% of all protocols. Implications of the findings are discussed.
    MeSH term(s) Cross-Cultural Comparison ; Humans ; MMPI/statistics & numerical data ; Netherlands ; Patient Admission ; Personality Disorders/classification ; Personality Disorders/diagnosis ; Personality Disorders/psychology ; Psychometrics ; Psychotic Disorders/classification ; Psychotic Disorders/diagnosis ; Psychotic Disorders/psychology ; Reproducibility of Results ; Schizophrenia/classification ; Schizophrenia/diagnosis ; Schizophrenic Psychology ; United States
    Language English
    Publishing date 1996-05
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 219160-x
    ISSN 1097-4679 ; 0021-9762
    ISSN (online) 1097-4679
    ISSN 0021-9762
    DOI 10.1002/(SICI)1097-4679(199605)52:3<297::AID-JCLP6>3.0.CO;2-P
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  9. Article ; Online: Treatment effect modifiers for the patient education programme for Parkinson's disease.

    A'Campo, L E I / Wekking, E M / Spliethoff-Kamminga, N G A / Stijnen, T / Roos, R A C

    International journal of clinical practice

    2012  Volume 66, Issue 1, Page(s) 77–83

    Abstract: Aim: A recent randomised controlled trial showed significant benefits for Parkinson's disease (PD) caregivers' psychosocial problems and need for help and a trend towards significant improvement of patients' quality of life after participation in the ... ...

    Abstract Aim: A recent randomised controlled trial showed significant benefits for Parkinson's disease (PD) caregivers' psychosocial problems and need for help and a trend towards significant improvement of patients' quality of life after participation in the Patient Education Programme for Parkinson's disease (PEPP). Large variations in change scores were found, indicating variation in benefit. The aim of this study was to search for treatment effect modifiers.
    Methods: Outcome measures were patients' quality of life [Parkinson's Disease Questionnaire (PDQ)-39] and caregivers' psychosocial burden [Belastungsfragebogen Parkinson Angehörigen kurzversion (BELA-A-k)]. Candidate treatment effect modifiers were participants' characteristics and baseline scores on psychological questionnaires (BELA-P/A-k, PDQ-39, EQ-5D, Self-rating Depression Scale) and patients' neuropsychological test scores (Mini Mental State Examination, National Adult Reading Test, Dutch version, Word Test, Behavioural Assessment of the Dysexecutive Syndrome rule shift, Trail Making Test, Stroop). Secondary analyses of data from a randomised controlled trial with 64 patients and 46 caregivers were performed using regression analyses with treatment group interaction terms.
    Results: No significant modifiers were found for the patients. In the caregiver group, a higher MMSE score of the patient at baseline was found to be a significant predictor of a lower BELA-A-k Bothered by score post-intervention of the caregiver.
    Conclusions: A potential predictor of treatment benefit was found for caregivers of PD patients with better cognitive functioning. This study did not find treatment effect modifiers for PD patients: demographics, disease stage and time of diagnosis, cognitive functioning, level of baseline psychosocial burden, participating with or without a caregiver, and caregiver changes did not influence treatment outcome. The PEPP seems suitable for the majority of patients.
    MeSH term(s) Aged ; Caregivers/psychology ; Cognition Disorders/rehabilitation ; Cost of Illness ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/rehabilitation ; Patient Education as Topic/methods ; Quality of Life ; Treatment Outcome
    Language English
    Publishing date 2012-01
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 1386246-7
    ISSN 1742-1241 ; 1368-5031
    ISSN (online) 1742-1241
    ISSN 1368-5031
    DOI 10.1111/j.1742-1241.2011.02791.x
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  10. Article ; Online: Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice

    Jacobs, Sophie A.H. / Gart, Eveline / Vreeken, Debby / Franx, Bart A.A. / Wekking, Lotte / Verweij, Vivienne G.M. / Worms, Nicole / Schoemaker, Marieke H. / Gross, Gabriele / Morrison, Martine C. / Kleemann, Robert / Arnoldussen, Ilse A.C. / Kiliaan, Amanda J.

    Nutrients

    2019  Volume 11, Issue 8

    Abstract: BACKGROUND: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile ... ...

    Abstract BACKGROUND: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity. METHODS: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI. RESULTS: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity. CONCLUSIONS: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.
    Keywords juvenile ; obesity ; sex
    Language English
    Publishing country nl
    Document type Article ; Online
    ZDB-ID 2518386-2
    ISSN 2072-6643
    ISSN 2072-6643
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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