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1.
Artigo em Inglês | MEDLINE | ID: mdl-33933586

RESUMO

OBJECTIVE: We aimed to provide a model to predict the prospective development of radiographic KOA (rKOA). METHOD: Baseline sera from 333 non-radiographic KOA subjects belonging to OA Initiative (OAI) who developed or not, rKOA during a follow-up period of 96 months were used in this study. The exploratory cohort included 200 subjects, whereas the replication cohort included 133. The levels of inter-alpha trypsin inhibitor heavy chain 1 (ITIH1), complement C3 (C3) and calcyclin (S100A6), identified in previous large proteomic analysis, were analyzed by using sandwich immunoassays on suspension bead arrays. The association of protein levels and clinical covariates with rKOA incidence was assessed by combining logistic regression analysis, Receiver Operating Characteristic analysis, Integrated Discrimination Improvement (IDI) analysis and Kaplan-Meier curves. RESULTS: Levels of ITIH1, C3 and S100A6 were significantly associated with the prospective development of rKOA, showing an area under the curve (AUC) of 0.713 (0.624-0.802), 0.708 (0.618-0.799) and 0.654 (0.559-0.749), respectively to predict rKOA in the replication cohort. The inclusion of ITIH1 in the clinical model (age, gender, BMI, previous knee injury and WOMAC pain) improved the predictive capacity of the clinical covariates (AUC=0.754 [0.670-0.838]) producing the model with the highest AUC (0.786 [0.705-0.867]) and the highest IDI index (9%). High levels of ITIH1 were also associated with an earlier onset of the disease. CONCLUSION: A clinical model including protein biomarkers that predicts incident rKOA has been developed. Among the tested biomarkers, ITIH1 showed potential to improve the capacity to predict rKOA incidence in clinical practice.

2.
Vaccines (Basel) ; 9(3)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806390

RESUMO

Immunological correlates of natural resistance to HIV have been identified in HIV-exposed seronegative (HESN) individuals and include a low-inflammatory genital mucosal status. The cervicovaginal epithelium has not been studied for such correlates despite constituting an important barrier against sexual HIV transmission. To fill this gap in knowledge, we collected samples of blood, cervical mononuclear cells, cervicovaginal lavage, and ectocervical tissue from Kenyan HESN sex workers (n = 29) and controls (n = 33). The samples were analyzed by flow cytometry, protein profiling, 16S rRNA gene sequencing, in situ image analysis, and tissue-based RNA sequencing. A significantly higher relative proportion of regulatory T cells in blood (B7+CD25hiFoxP3+CD127loCD4+ and B7+Helios+FoxP3+CD4+), and a significantly lower proportion of activated cervical T cells (CCR5+CD69+CD4+ and CCR5+CD69+CD8+), were found in the HESN group compared with the controls. In contrast, there were no statistically significant differences between the study groups in cervicovaginal protein and microbiome compositions, ectocervical epithelial thickness, E-cadherin expression, HIV receptor expression, and tissue RNA transcriptional profiles. The identification of an intact ectocervical microenvironment in HESN individuals add new data to current knowledge about natural resistance to sexual transmission of HIV.

3.
J Neurotrauma ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858214

RESUMO

The diagnosis and management of concussion is hindered by its diverse clinical presentation and assessment tools reliant upon subjectively-experienced symptoms. The biomechanical threshold of concussion is also not well understood and asymptomatic or 'subconcussive impacts' of variable magnitudes are common in contact sports. Concerns have risen because athletes returning to activity too soon have an increased risk of prolonged recovery or long-term adverse health consequences. To date, little is understood on a molecular level regarding concussion and subconcussive impacts. Recent research suggests that neuro-inflammatory mechanisms may serve an important role subsequent to concussion and possibly subconcussive impacts. These studies suggest that autoantibodies may be a feasible method of detection for acute concussion and monitoring for changes due to cumulative exposure to subconcussive impacts. Hence, we aimed to profile the IgA autoantibody repertoire in saliva by screening a unique sport-related head trauma biobank. Saliva samples (N=167) were donated by male and female participants enrolled in either the Concussion (24 to 48 hours post-injury) or Subconcussion (non-concussed participants having moderate or high cumulative subconcussive impact exposure) Cohorts. Study design included discovery and verification phases. Discovery aimed to identify new candidate autoimmune targets of IgA. Verification tested whether Concussion and Subconcussion Cohorts increased IgA reactivity and cohorts showed similarities. In each phase, sample testing was randomized. The results show a significant increase in the prevalence of IgA towards protein fragments representing HTR1A, SRRM4 and FAS after concussion and subconcussion. These results may suggest that concussion and subconcussion induce similar physiological effects, especially in terms of immune response. Our study demonstrates that saliva is a potential biofluid for autoantibody detection in concussion and subconcussion. After rigorous confirmation in much larger independent study sets, a validated salivary autoantibody assay could provide a non-subjective quantitative means of assessing concussive and subconcussive events.

4.
Nat Med ; 27(4): 640-646, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33859435

RESUMO

Apart from well-defined factors in neuronal cells1, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia2,3 and blood vessels4. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response. Notably, during the presymptomatic stage, perivascular fibroblast cells showed the strongest gene enrichments, and their marker proteins SPP1 and COL6A1 accumulated in enlarged perivascular spaces in patients with sporadic ALS. Moreover, in plasma of 574 patients with ALS from four independent cohorts, increased levels of SPP1 at disease diagnosis repeatedly predicted shorter survival with stronger effect than the established risk factors of bulbar onset or neurofilament levels in cerebrospinal fluid. We propose that the activity of the recently discovered perivascular fibroblast can predict survival of patients with ALS and provide a new conceptual framework to re-evaluate definitions of ALS etiology.

6.
Proteomics Clin Appl ; : e2000038, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830667

RESUMO

PURPOSE: Little is known about the longitudinal development of different plasma protein levels during early childhood and particularly in relation to lifestyle factors. This study aimed to monitor the plasma proteome early in life and the influence of different lifestyles. EXPERIMENTAL DESIGN: A multiplex bead-based immunoassay was used to analyze plasma levels of 97 proteins in 280 blood samples longitudinally collected in children at 6, 12, 24, and 60 months of age living in families with an anthroposophic (n = 15), partly anthroposophic (n = 27), or non-anthroposophic (n = 28) lifestyle. RESULTS: A total of 68 proteins (70%) showed significantly altered plasma levels between 6 months and 5 years of age. In lifestyle stratified analysis, 59 of 97 (61%) proteins were altered over time within one or more of the three lifestyle groups. Nearly half of these proteins (28 out of 59) changed irrespective of lifestyle. The temporal changes represented four longitudinal trends of the plasma proteins during development, also following stratification of lifestyle. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings contribute to understand the development of the plasma proteome under the influence of lifestyle exposures in early childhood.

8.
Proteomics Clin Appl ; : e2000089, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33682349

RESUMO

PURPOSE: The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatinC /eGFRcreatinine -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure. EXPERIMENTAL DESIGN: Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9 ± 11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10-4 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFRcystatinC ≤ 60% of eGFRcreatinine . RESULTS: SPS presented with significant associations (p < 5.4 × 10-4 ) in age and sex-adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments. CONCLUSIONS AND CLINICAL RELEVANCE: In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation.

9.
Biology (Basel) ; 10(2)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670473

RESUMO

Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer's disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer's and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 ± 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitiveexe-func); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitiveexe-func control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitiveexe-func control and neuronal glia injury (Adjusted R2 0.30; p ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitiveexe-func, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; p ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke.

10.
Alzheimers Res Ther ; 13(1): 54, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653397

RESUMO

BACKGROUND: Increased knowledge of the evolution of molecular changes in neurodegenerative disorders such as Alzheimer's disease (AD) is important for the understanding of disease pathophysiology and also crucial to be able to identify and validate disease biomarkers. While several biological changes that occur early in the disease development have already been recognized, the need for further characterization of the pathophysiological mechanisms behind AD still remains. METHODS: In this study, we investigated cerebrospinal fluid (CSF) levels of 104 proteins in 307 asymptomatic 70-year-olds from the H70 Gothenburg Birth Cohort Studies using a multiplexed antibody- and bead-based technology. RESULTS: The protein levels were first correlated with the core AD CSF biomarker concentrations of total tau, phospho-tau and amyloid beta (Aß42) in all individuals. Sixty-three proteins showed significant correlations to either total tau, phospho-tau or Aß42. Thereafter, individuals were divided based on CSF Aß42/Aß40 ratio and Clinical Dementia Rating (CDR) score to determine if early changes in pathology and cognition had an effect on the correlations. We compared the associations of the analysed proteins with CSF markers between groups and found 33 proteins displaying significantly different associations for amyloid-positive individuals and amyloid-negative individuals, as defined by the CSF Aß42/Aß40 ratio. No differences in the associations could be seen for individuals divided by CDR score. CONCLUSIONS: We identified a series of transmembrane proteins, proteins associated with or anchored to the plasma membrane, and proteins involved in or connected to synaptic vesicle transport to be associated with CSF biomarkers of amyloid and tau pathology in AD. Further studies are needed to explore these proteins' role in AD pathophysiology.

11.
Crit Care ; 25(1): 103, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712077

RESUMO

BACKGROUND: Severe traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls. METHODS: We conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Score, was collected after 6-12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (QA), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses. Key findings were validated in blood samples from an independent TBI cohort. RESULTS: TBI patients had an upregulation of structural CNS and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated with QA, among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained ~ 10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, ΔR2 = 7.4%) and complement factor B in serum (p = 0.003, ΔR2 = 9.2%) were independent outcome predictors also following step-down modelling. CONCLUSIONS: This represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.

12.
Clin Exp Dent Res ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33754493

RESUMO

OBJECTIVES: The impact of dental occlusion on the experiences of head and neck cancer patients and their oral, social and psychological functioning has been sparsely investigated. There is a lack of knowledge regarding the experience of tooth loss and dentures among patients treated for head and neck cancer. The aim of this study was to describe the experiences of head and neck cancer patients of prophylactic tooth extractions and temporary removable dentures, 6 months after radiotherapy treatment. MATERIAL AND METHODS: An individual interview with 25 patients 6 months after radiotherapy was subjected to a qualitative content analysis. RESULTS: Two categories, Impaired oral function and Belief in the future, and seven subcategories described the patients' experiences of temporary removable dentures during the first 6 months after prophylactic tooth extractions. The temporary removable dentures affected the patients' ability to chew, swallow and speak, caused pain, and were experienced as an enemy. Despite that, the patients were hopeful and had a wish for recovery, which gave them the energy to live. CONCLUSION: Prophylactic tooth extractions and temporary removable dentures 6 months after radiotherapy treatment affect head and neck cancer patients' recovery and everyday life. However, they have the will to take on these challenges, pertaining not only to themselves, but also to relatives and health professionals. At the individual level, the patient needs individualized professional support to get through the arduous procedure, from the acute situation until the end of the rehabilitation phase.

14.
Sci Rep ; 11(1): 5160, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664279

RESUMO

The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n = 15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43-1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98-3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.


Assuntos
Anticorpos Antivirais/sangue , /imunologia , Licença Médica/estatística & dados numéricos , Adulto , Anticorpos Antivirais/imunologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia
16.
Methods Mol Biol ; 2259: 143-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33687712

RESUMO

The versatility of protein microarrays provides researchers with a wide variety of possibilities to address proteomic studies. Therefore, protein microarrays are becoming very useful tools to identify candidate biomarkers in human body fluids for disease states such as rheumatoid arthritis (RA). In RA serum, there is a high prevalence of rheumatoid factor (RF), which is an antibody with high specificity against Fc portion of IgG. The presence of RF, in particular RF-IgM, has the great potential to interfere with antibody-based immunoassays by nonspecifically binding capture antibodies. Because of this concern, we describe a procedure to reduce the interference of RF-IgM on RA serum protein profiling approaches based on multiplexed antibody suspension bead arrays.


Assuntos
Artrite Reumatoide/sangue , Proteômica/métodos , Anticorpos Imobilizados/química , Artrite Reumatoide/diagnóstico , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Imunoglobulina M/análise , Imunoglobulina M/sangue , Fator Reumatoide/análise , Fator Reumatoide/sangue
17.
J Infect Dis ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33580261

RESUMO

BACKGROUND: Whether SARS-CoV-2 positivity among symptomatic subjects reflects past or future disease may be difficult to ascertain. METHODS: We tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the testing results to sick leave records and determined associations with past or future sick leave using multinomial logistic regression. ClinicalTrials.gov NCT04411576. RESULTS: Subjects with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11.97 (CI 95% 6.29-22.80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR 6.31 (4.38-9.08)). Only 2.5% of employees were SARS-CoV-2 positive while 10.5% were positive by serology and 1.2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR 1.06 (95% CI, 0.71-1.57)). CONCLUSIONS: High amounts of SARS-CoV-2 virus, as determined using PCR Ct values, associates with development of sickness in the next few weeks. The results support the concept that PCR Ct may be informative when testing for SARS-CoV-2 is performed.

18.
Psychoneuroendocrinology ; 126: 105162, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33578084

RESUMO

Growing evidence implies interactions between infections, the immune system and vulnerability for psychiatric disease. This study applies an affinity proteomic-based method to investigate potential disease associated autoantibody signatures in serum from patients from the "Young Adults" section of the Department of General Psychiatry at Uppsala University Hospital (n = 395) and population-based controls (n = 102). We found serum levels of antibodies against Lipopolysaccharide Binding Protein (LBP), a protein that is important for mediating innate immune responses involving the toll-like receptor-4 (TLR-4), to be higher in patients compared to controls (Mann Whitney U-test p = 5.248 × 10-10). The patients were divided into three groups based on their relative levels of autoantibodies against LBP. The distribution of autism spectra disorders (p = 2.0 × 10-4) and hospital care for an infection as adults (p = 0.036) differed between the anti-LBP groups, with low incidence in the group of patients with the highest levels of anti-LBP who were diagnosed with primarily affective and anxiety disorders. In a sub-group analysis, the controls who screened positive for current or previous psychiatric diagnosis (n = 20) had higher anti-LBP compared to non-psychiatric controls with negative screening for psychiatric disorders (Mann Whitney U-test p = 0.006). Inflammatory markers were found to differ across anti-LBP groups and several pro-inflammatory markers, including IL-1ß, were low in patients with high anti-LBP and serum LBP levels were lowest in patients with the highest levels of antibodies against LBP (p = 3.5 × 10-5). A cell-based model showed that polyclonal rabbit anti-LBP, obtained through purification via the same protein fragment used in the initial autoantibody analysis, could interfere with LBP signaling since addition of anti-LBP to the assay reduced both IL-1ß and IL-6 release from activated monocytes in response to LBP and LPS (p = 0.0001 and p = 0.02). This novel finding of antibodies against LBP, where high levels were only found in young adults with psychiatric disease, merits further study. Our results suggest that these antibodies may have relevance for TLR4 based immune responses and vulnerability for both infection and psychiatric disorders.

19.
Scand J Urol ; 55(2): 125-128, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33615988

RESUMO

Based on a nationwide register data we recently reported a link between male infertility and increased risk of early onset prostate cancer. However, mortality due to prostate cancer, which can be regarded as the ultimate proxy for its clinical significance, especially in the context of over-diagnosis and over-treatment, could not be explored in the previous study, since the follow-up period in most cases was too short. Data therefore must be retrieved from other cohorts, with longer follow-up. We sourced data from a population-based prospective cohort including 11,343 men aged over 45 years, enrolled in the 1970s. The results showed that childless men have higher risk for prostate cancer related mortality (HR: 1.49, 95% CI: 1.09-2.03, p = 0.01) compared to men with children, in particular when only married men, who most probably are involuntary childless, were considered (HR 1.54, 95% CI 1.13 - 2.10, p = 0.006). However, the prostate cancer incidence did not differ (HR = 1.04, 95% CI: 0.88-1.24). In conclusion, our results show that childless men are at higher risk for dying from prostate cancer, probably due to a more aggressive form of the disease.

20.
Intern Emerg Med ; 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33515187

RESUMO

Mediterranean diet protects from both cardiovascular disease (CVD) and cancer. In the 1960s, Ancel Keys defined the concept of Mediterranean diet in the South Italian region of Cilento and proposed it as a key factor for healthy ageing in the region. The aim of the current study was to compare the prevalence of CVD and cancer between a middle-aged population from Cilento and those of a Northern European population from Malmö, Sweden. We clinically characterized two middle-aged (50-67 years of age) population-based samples from Cilento (n = 809) and Malmö (n = 1025), Sweden, respectively. Logistic regression was used to calculate odds ratios (95% confidence interval) for disease prevalence in Malmö versus Cilento inhabitants adjusted for age and sex (model 1) and adjusted for all cardiometabolic risk factors (model 2). The prevalence of hypertension, current smoking, diabetes mellitus and levels of body mass index and triglycerides were lower, whereas HDL-cholesterol was higher in Malmö than in Cilento. LDL-cholesterol was higher and estimated glomerular filtration rate was lower in Malmö than in Cilento. The odds ratio for cardiovascular disease in Malmö versus Cilento inhabitants was 1.13 (0.69-1.87) (P = 0.62) in model 1, whereas it was significantly elevated in model 2 [2.03 (1.14-3.60) (P = 0.016)]. Moreover, the odds ratio for cancer in Malmö versus Cilento was 2.78 (1.81-4.27) (P < 0.001) in model 1 and 3.11 (1.97-4.92) (P < 0.001) in model 2. The higher odds of CVD and cancer in Malmö versus Cilento, when risk factors were accounted for, suggests the existence of unknown protective factors in Cilento.

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