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AIMS: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). MATERIALS AND METHODS: Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated. RESULTS: Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46-50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). CONCLUSIONS: High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. REGISTRATION NUMBER TRIAL: ID NCT00700856 https://clinicaltrials.gov.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adulto , Humanos , Hemoglobinas Glicadas , Controle Glicêmico , Lipidômica , Ácidos Graxos , Tecido Adiposo , Ácidos Graxos não Esterificados , InsulinaRESUMO
A fatty liver index (FLI) greater than sixty (FLI ≥ 60) is an established score for metabolic dysfunction-associated steatotic liver disease (MASLD), which carries a high risk for diabetes and cardiovascular disease, while a FLI ≤ 20 rules out the presence of steatosis. Thus, we investigated whether FLI was associated with cardiometabolic risk factors, i.e., visceral (VAT), subcutaneous (SC), epicardial (EPI), extrapericardial (PERI), and total cardiac (CARD-AT) adipose tissue, hepatic fat ((by magnetic resonance imaging, MRI, and spectroscopy, MRS), and insulin resistance (IR, HOMA-IR and OGIS-index), and components of metabolic syndrome. All individuals with FLI ≥ 60 had MASLD, while none with FLI ≤ 20 had steatosis (by MRS). Subjects with FLI ≥ 60 had a higher BMI and visceral and cardiac fat (VAT > 1.7 kg, CARD-AT > 0.2 kg). FLI was positively associated with increased cardiac and visceral fat and components of metabolic syndrome. FLI, VAT, and CARD-AT were all associated with IR, increased blood pressure, cholesterol, and reduced HDL. For FLI ≥ 60, the cut-off values for fat depots and laboratory measures were estimated. In conclusion, FLI ≥ 60 identified not only subjects with steatosis but also those with IR, abdominal and cardiac fat accumulation, increased blood pressure, and hyperlipidemia, i.e., those at higher risk of cardiometabolic diseases. Targeted reduction of FLI components would help reduce cardiometabolic risk.
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Doenças Cardiovasculares , Fígado Gorduroso , Resistência à Insulina , Síndrome Metabólica , Humanos , Síndrome Metabólica/etiologia , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Doenças Cardiovasculares/metabolismo , Gordura Intra-Abdominal/metabolismoRESUMO
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disorder, but the factors that determine this heterogeneity remain poorly understood. Adipose tissue dysfunction is causally linked to NAFLD since it causes intrahepatic triglyceride (IHTG) accumulation through increased hepatic lipid flow, due to insulin resistance and pro-inflammatory adipokines release. While many studies in NAFLD have looked at total adiposity (i.e. mainly subcutaneous fat, SC-AT), it is still unclear the possible impact of visceral fat (VF). Thus, we investigated how VF versus SC-AT was related to NAFLD severity in lean, overweight and obese individuals versus lean controls. METHODS: Thirty-two non-diabetic NAFLD with liver biopsy (BMI 21.4-34.7 kg/m2 ) and eight lean individuals (BMI 19.6-22.8 kg/m2 ) were characterized for fat distribution (VF, SC-AT and IHTG by magnetic resonance imaging), lipolysis and insulin resistance by tracer infusion, free fatty acids (FFAs) and triglyceride (TAG) concentration and composition (by mass spectrometry). RESULTS: Intrahepatic triglyceride was positively associated with lipolysis, adipose tissue insulin resistance (Adipo-IR), TAG concentrations, and increased saturated/unsaturated FFA ratio. Compared to controls VF was higher in NAFLD (including lean individuals), increased with fibrosis stage and associated with insulin resistance in liver, muscle and adipose tissue, increased lipolysis and decreased adiponectin levels. Collectively, our results suggest that VF accumulation, given its location close to the liver, is one of the major risk factors for NAFLD. CONCLUSIONS: These findings propose VF as an early indicator of NAFLD progression independently of BMI, which may allow for evidence-based prevention and intervention strategies.
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Resistência à Insulina , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Adiponectina , Tecido Adiposo , Ácidos Graxos não Esterificados , Humanos , Gordura Intra-Abdominal , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/complicações , TriglicerídeosRESUMO
BACKGROUND AND AIMS: Peroxisome proliferator-activated receptor (PPAR)-γ agonists decrease hepatic/visceral fat (VF) and improve necroinflammation despite subcutaneous (SC) fat weight-gain. Understanding the impact of changes in VF, VF-to-SC fat distribution (VF/SC) and adiponectin (ADPN) levels in relation to histological improvement after weight-loss or pioglitazone is relevant as novel PPAR-γ agonists are being developed for treating non-alcoholic steatohepatitis (NASH). METHODS: Fifty-five patients with NASH received a -500 kcal/d hypocaloric diet and were randomized (double-blind) to pioglitazone (45 mg/d) or placebo for 6-months. Before and after treatment patients underwent a liver biopsy and measurement of hepatic/peripheral glucose fluxes, hepatic/adipose tissue-IR and, in 35 patients, hepatic and VF/SC-fat was measured by magnetic resonance spectroscopy/imaging. Data were examined by multivariable statistical analyses combined with machine-learning techniques (partial least square discriminant analysis [PLS-DA]). RESULTS: Both pioglitazone (despite weight-gain) and placebo (if weight-loss) reduced steatosis but only pioglitazone ameliorated necroinflammation. Using machine-learning PLS-DA showed that the treatment differences induced by a PPAR-γ agonist vs placebo on metabolic variables and liver histology could be best explained by the increase in ADPN and a decrease in VF/SC, and to a lesser degree, improvement in oral glucose tolerance test-glucose concentrations and ALT. Decrease in steatosis and disease activity score (ballooning plus lobular inflammation) kept a close relationship with an increase in ADPN (r = -.71 and r = -.44, P < .007, respectively) and reduction in VF/SC fat (r = .41 and r = .37, P < .03 respectively). CONCLUSIONS: Reduction in VF and improved VF/SC-distribution, combined with an increase in ADPN, mediate the histological benefits of PPAR-γ action, highlighting the central role of fat metabolism and its distribution on steatohepatitis disease activity in patients with NASH.
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Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Tiazolidinedionas , Adiponectina , Dieta Redutora , Humanos , Hipoglicemiantes/uso terapêutico , Gordura Intra-Abdominal , Fígado , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade , PPAR gama , Tiazolidinedionas/uso terapêuticoRESUMO
BACKGROUND: Patients with suspected deep vein thrombosis (DVT) of the lower limb represent a diagnostic dilemma for general practitioners. Compression ultrasonography (US) is universally recognized as the best test of choice. We assessed the diagnostic accuracy of compression US performed by general practitioners given short training in the management of symptomatic proximal DVT. METHODS: From May 2014 to May 2016, we evaluated in a multicenter, prospective cohort study all consecutive outpatients with suspected DVT; bilateral proximal lower limb compression US was performed by general practitioners and by physicians expert in vascular US, each group blinded to the other's findings. In all examinations with a negative or nondiagnostic result, compression US was repeated by the same operator after 5 to 7 days. Inter-observer agreement and accuracy were calculated. RESULTS: We enrolled a total of 1,107 patients. The expert physicians diagnosed DVT in 200 patients, corresponding to an overall prevalence of 18.1% (95% CI, 15.8%-20.3%). The agreement between the trained general practitioners and the experts was excellent (Cohen κ = 0.86; 95% CI, 0.84-0.88). Compression US performed by general practitioners had a sensitivity of 90.0% (95% CI, 88.2%-91.8%) and a specificity of 97.1% (95% CI, 96.2%-98.1%) with a diagnostic accuracy for DVT of 95.8% (95% CI, 94.7%-97.0%). CONCLUSIONS: Our results suggest that, even in hands of physicians not expert in vascular US, compression US can be a reliable tool in the diagnosis of DVT. We found that the sensitivity achieved by general practitioners appeared suboptimal, however, so future studies should evaluate the implementation of proper training strategies to maximize skill.
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Clínicos Gerais , Perna (Membro)/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia , Adulto JovemRESUMO
The liver is central in regulating glucose homeostasis, being the major contributor to endogenous glucose production and the greatest reserve of glucose as glycogen. It is both a target and regulator of the action of glucoregulatory hormones. Hepatic metabolic functions are altered in and contribute to the highly prevalent steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). In this Review, we describe the dysregulation of hepatic glucose metabolism in MASLD and MASH and associated metabolic comorbidities, and how advances in techniques and models for the assessment of hepatic glucose fluxes in vivo have led to the identification of the mechanisms related to the alterations in glucose metabolism in MASLD and comorbidities. These fluxes can ultimately increase hepatic glucose production concomitantly with fat accumulation and alterations in the secretion and action of glucoregulatory hormones. No pharmacological treatment has yet been approved for MASLD or MASH, but some antihyperglycaemic drugs approved for treating type 2 diabetes have shown positive effects on hepatic glucose metabolism and hepatosteatosis. A deep understanding of how MASLD affects glucose metabolic fluxes and glucoregulatory hormones might assist in the early identification of at-risk individuals and the use or development of targeted therapies.
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Fígado Gorduroso , Glucose , Fígado , Humanos , Glucose/metabolismo , Fígado/metabolismo , Fígado Gorduroso/metabolismoRESUMO
Background/Objectives: Several psychological conditions, including stress and depression, can adversely affect oral health; in fact, antidepressants, commonly used to treat depressive disorders, may have conflicting effects on the periodontal status of individuals. The aim of this review was to determine the effects of antidepressants on the periodontium. Methods: A literature search was conducted using electronic databases, Pubmed/MEDLINE, Cochrane Library, focusing on the use of antidepressants and their effects on periodontal health in animals or humans. Results: Seventeen articles have been included with the use of amitriptyline (two studies), desipramine (one study), imipramine (two studies), desvenlafaxine (one study), fluoxetine (six studies), venlafaxine (three studies) and tianeptine (two studies). One study evaluated several categories of antidepressants, such as selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic, atypical and monoamine oxidase inhibitors (MAO). Most trials showed improvements in periodontal health, especially with fluoxetine, but also with imipramine, desipramine, desvenlafaxine and tianeptine; on the contrary, worsening of clinical periodontal indices and increased loss of alveolar bone were reported with venlafaxine. Conclusions: This review suggests that in the presence of comorbidity between periodontitis and depression, pharmacological treatment with SNRIs, SSRIs and mixed antidepressants is associated with improvement in periodontal parameters, except for venlafaxine. Healthcare professionals (especially oral and mental health professionals) should investigate proper adherence to medication therapy in patients with a history of periodontitis and depression. Further clinical trials are needed to confirm these results.
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Treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduces liver steatosis and cardiometabolic risk (CMR). Only few data are available on lipid metabolism and no information on the postprandial lipidomic profile. Thus, we investigated how exenatide treatment changes lipid metabolism and composition during fasting and after a meal tolerance test (MTT) in adults with severe obesity without diabetes. Thirty individuals (26F/4M, 30-60 years old, BMI>40 kg/m2, HbA1c=5.76%) were assigned (1:1) to diet with exenatide treatment (EXE, n=15, 10 µg twice-daily) or without treatment as control (CT, n=15) for 3 months. Fasting and postprandial lipidomic profile (by LC/MS-QTOF) and fatty acid metabolism (following a 6-hour MTT/tracer study) and composition (by GC/MS) were evaluated before and after treatment. Both groups had slight weight loss (EXE: -5.5% vs CT: -1.9%, p=0.052). During fasting, exenatide, compared to CT, reduced some ceramides (CER) and lysophosphocholines (LPC) previously associated with CMR, while relatively increasing unsaturated phospholipid species (PC, LPC) with protective effects on CMR, although concentrations of total lipid species were unchanged. During MTT, both groups suppressed lipolysis equally to baseline, but EXE exenatide significantly lowered free fatty acid clearance and postprandial triacyclglycerols (TAG) concentrations, particularly saturated TAGs with 44-54 carbons. Exenatide also reduced some postprandial CERs, PCs, LPCs previously linked to cardiometabolic risk. These changes in lipidomic profile remained statistically significant after adjusting for weight loss. Exenatide improved fasting and postprandial lipidomic profile associated with CMR mainly by reducing saturated postprandial TAGs and CERs, independently of weight loss and diabetes.
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BACKGROUND: Weight loss and lifestyle intervention improve glucose tolerance delaying the onset of type 2 diabetes (T2D), but individual responses are highly variable. Determining the predictive factors linked to the beneficial effects of weight loss on glucose tolerance could provide tools for individualized prevention plans. Thus, the aim was to investigate the relationship between pre-intervention values of insulin sensitivity and secretion and the improvement in glucose metabolism after weight loss. METHODS: In the DEXLIFE cohort (373 individuals at high risk of T2D, assigned 3:1 to a 12-week lifestyle intervention or a control arm, Trial Registration: ISRCTN66987085), K-means clustering and logistic regression analysis were performed based on pre-intervention indices of insulin sensitivity, insulin secretion (AUC-I), and glucose-stimulated insulin response (ratio of incremental areas of insulin and glucose, iAUC I/G). The response to the intervention was evaluated in terms of reduction of OGTT-glucose concentration. Clusters' validation was done in the prospective EGIR-RISC cohort (n = 1538). RESULTS: Four replicable clusters with different glycemic and metabolomic profiles were identified. Individuals had similar weight loss, but improvement in glycemic profile and ß-cell function was different among clusters, highly depending on pre-intervention insulin response to OGTT. Pre-intervention high insulin response was associated with the best improvement in AUC-G, while clusters with low AUC-I and iAUC I/G showed no beneficial effect of weight loss on glucose control, as also confirmed by the logistic regression model. CONCLUSIONS: Individuals with preserved ß-cell function and high insulin concentrations at baseline have the best improvement in glucose tolerance after weight loss.
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Glicemia , Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Insulina , Fenótipo , Redução de Peso , Humanos , Redução de Peso/fisiologia , Células Secretoras de Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Masculino , Feminino , Insulina/sangue , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/sangue , Estudos Prospectivos , Glicemia/metabolismo , Glicemia/análise , Adulto , Resistência à Insulina/fisiologia , Teste de Tolerância a Glucose , Intolerância à Glucose , Secreção de Insulina , Estilo de Vida , IdosoRESUMO
BACKGROUND: The effectiveness of different types of electric toothbrushes in terms of removing bacterial plaque is still a debated issue. The aim of the study was to compare the plaque removal after a single use of two types of electric toothbrushes, sonic and roto-oscillating, in patients with fixed orthodontics. METHODS: Twenty-five subjects with fixed multibrackets appliances were randomly selected. Plaque scores were detected using a fluorescein-based detector. After using the sonic toothbrush with a surfactant-free toothpaste, the plaque scores were detected again. After 3 months, the procedure is performed again following the same methods, using the roto-oscillating toothbrush. For the statistical analysis a Student's t-test using Microsoft Excel 2021 (Microsoft Corp., Redmond, WA, USA) was performed. The differences were considered statistically significant for probability values P<0.05. RESULTS: It can be seen that the brushing carried out with a sonic technology is more effective than the roto-oscillating technology. However, the FMPS, MOPI and OPI indexes do not show differences between the use of the two toothbrushes. The OHI-S index shows a statistically significant difference using the sonic toothbrush with a significance level of 0.05%. CONCLUSIONS: It can be said that both electric toothbrushes are effective for maintaining a good home oral hygiene in patients with fixed orthodontics.
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Assistência Odontológica , Escovação Dentária , Humanos , Fluoresceína , Aparelhos Ortodônticos Fixos , PacientesRESUMO
PURPOSE: To address the paucity of data in patients with historically poor outcomes, we conducted the single-arm phase IIIb CheckMate 401 study to evaluate the safety and efficacy of nivolumab plus ipilimumab followed by nivolumab monotherapy in clinically diverse patient populations with advanced melanoma. METHODS: Treatment-naive patients with unresectable stage III-IV melanoma received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg (240 mg following a protocol amendment) once every 2 weeks for ≤24 months. The primary end point was the incidence of grade 3-5 select treatment-related adverse events (TRAEs). Overall survival (OS) was a secondary end point. Outcomes were evaluated in subgroups defined by Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastasis status, and melanoma subtype. RESULTS: In total, 533 patients received at least one dose of study drug. Grade 3-5 select TRAEs affecting the GI (16%), hepatic (15%), endocrine (11%), skin (7%), renal (2%), and pulmonary (1%) systems occurred in the all-treated population; similar incidence rates were observed across all subgroups. At 21.6 months' median follow-up, 24-month OS rates were 63% in the all-treated population, 44% in the ECOG PS 2 subgroup (including patients with cutaneous melanoma only), 71% in the brain metastasis subgroup, 36% in the ocular/uveal melanoma subgroup, and 38% in the mucosal melanoma subgroup. CONCLUSION: Nivolumab plus ipilimumab followed by nivolumab monotherapy was tolerable in patients with advanced melanoma and poor prognostic characteristics. Efficacy was similar between the all-treated population and patients with brain metastases. Reduced efficacy was observed in patients with ECOG PS 2, ocular/uveal melanoma, and/or mucosal melanoma, highlighting the continued need for novel treatment options for these difficult-to-treat patients.
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Neoplasias Encefálicas , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Nivolumabe/uso terapêutico , Ipilimumab , Neoplasias Cutâneas/patologia , Neoplasias Encefálicas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Adjuvant trastuzumab therapy improves the outcome of patients with early breast cancer (EBC) and overexpression of human epidermal growth factor receptor 2 (HER2). However, it is potentially cardiotoxic. This study aims to evaluate the relationship between the use of angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARBs) and/or ß-blockers and development of heart failure (HF) and/or left ventricular dysfunction during 1 year of adjuvant trastuzumab therapy. METHODS: A total of 499 women receiving adjuvant trastuzumab therapy for EBC entered in a multicenter registry and were divided into four subgroups according to treatment with ACEi/ARBs and/or ß-blockers. Occurrence of HF and decrease of left ventricular ejection fraction (LVEF; minimum 10 percentage points) were recorded. RESULTS: HF occurred in 2% of patients who did not take either ACEi/ARBs or ß-blockers, 8% of patients receiving ACEi/ARBs alone, 8% receiving ß-blockers alone (p = .03), and 19% receiving both medications (p < .01). The prevalence of patients with LVEF that decreased by at least 10 percentage points was similar in all groups. Combined ACEi/ARBs and ß-blocker therapy was independently associated with hypertension and a significant reduction of LVEF from baseline to 3-month evaluation. The use of ACEi/ARBs alone or ß-blockers alone was predicted only by hypertension. Combined therapy of ACEi/ARBs plus ß-blockers predicted LVEF recovery from the 3-month to 12-month evaluation. CONCLUSIONS: In clinical practice, the degree of hypertension and decrease in LVEF during the first 3 months of adjuvant trastuzumab therapy for EBC are associated with the use of ACEi/ARBs and ß-blockers. The combined use of these two medications is associated with a recovery of LVEF during months 3-12 of adjuvant trastuzumab therapy.
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Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Cardiotônicos/uso terapêutico , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/uso terapêutico , Cardiotônicos/efeitos adversos , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , TrastuzumabRESUMO
PURPOSE: To reach a consensus on a consistent strategy to adopt when screening patients for the clinical management of dentin hypersensitivity. MATERIALS AND METHODS: A panel consisting of members of the Advanced Technology in Oral Hygiene Sciences Academy (ATASIO) was formed to start a review process on dentin hypersensitivity (DH) and subsequently elaborate a decision tree to manage DH, from diagnosis to prognosis. The panel employed the RAND in their deliberations. After an initial systematic literature review, it became evident that a consensually validated protocol for the management of patients affected by dentin hypersensitivity has to be considered mandatory by all dental professionals. However, the outcome of the systematic review made it evident that the treatment options to be provided, as well as their prognosis and timing, had never been defined. The panel produced documents that addressed the topic and were subsequently used to generate a questionnaire. A workshop of expert dental professionals was organised to reach consensus on the main steps of the decision tree. Each member completed the questionnaire independently, and then a panel discussion was held to reach a consensus. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated was answered. A clinical decision threshold was created. CONCLUSIONS: The dissemination of the information to a wide dental audience should commence upon publication of this consensus document. The authors hope that this consensus will become a model for the development of a dedicated protocol to manage DH.
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Sensibilidade da Dentina , Consenso , Árvores de Decisões , Sensibilidade da Dentina/diagnóstico , Sensibilidade da Dentina/tratamento farmacológico , Humanos , Programas de Rastreamento , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: The COVID-19 pandemic has seriously affected young people. The present study aims to explore the effects of COVID-19 on lifestyle in 500 undergraduate students both during the acute phase of the pandemic (so-called "first wave") and during the second spread of infections (so-called "second wave"). Gender differences were also explored. Methods and results. During the first wave we found weight gain in 48.6% of subjects, a switch to an unhealthy diet (43%), and an increase in the amount of food introduced (35%). Interestingly, women showed higher intake of food in order to cope, while men privileged higher wine consumption as a coping mechanism. We observed a sharp reduction in physical activity, increased sedentary behaviours and deterioration in sleep quality. Stress correlates with eating to cope (r=0.86; p<0.001); drinking to cope (r=0.83; p<0.001). Contrary to expectations, the second wave led to a situation similar to the first. We have detected a further deterioration in quality of sleep (67% vs 77%; p<0.01) and also a reduction in sleeping time (68.6% vs 77.7; p<0.01). CONCLUSIONS: The long pandemic has led to unhealthy lifestyle changes in the student population of our municipality in Northern Italy. There are gender differences in lifestyle modifications developed during the pandemic that suggest a different response to stress. Moreover, the persistence of pandemic-related stress due to the "second wave" has severely affected the lifestyle habits of undergraduate student.
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COVID-19 , Estudantes de Medicina , Masculino , Feminino , Humanos , Adolescente , Pandemias , Fatores Sexuais , Estilo de VidaRESUMO
BACKGROUND & AIMS: The I148M Patatin-like Phospholipase Domain-containing 3 (PNPLA3), the rs641738 in the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) locus, and the E167K Transmembrane 6 Superfamily Member 2 (TM6SF2) polymorphisms represent the main predisposing factors to nonalcoholic fatty liver disease (NAFLD) development and progression. We previously generated a full knockout of MBOAT7 in HepG2 cells (MBOAT7-/-), homozygous for I148M PNPLA3. Therefore, we aimed to investigate the synergic impact of the 3 at-risk variants on liver injury and hepatocellular carcinoma (HCC) in a large cohort of NAFLD patients, and create in vitro models of genetic NAFLD by silencing TM6SF2 in both HepG2 and MBOAT7-/- cells. METHODS: NAFLD patients (n = 1380), of whom 121 had HCC, were stratified with a semiquantitative score ranging from 0 to 3 according to the number of PNPLA3, TM6SF2, and MBOAT7 at-risk variants. TM6SF2 was silenced in HepG2 (TM6SF2-/-) and MBOAT7-/- (MBOAT7-/-TM6SF2-/-) through Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). RESULTS: In NAFLD patients, the additive weight of these mutations was associated with liver disease severity and an increased risk of developing HCC. In HepG2 cells, TM6SF2 silencing altered lipid composition and induced the accumulation of microvesicular lipid droplets (LDs), whereas the MBOAT7-/-TM6SF2-/- cells showed a mixed microvesicular/macrovesicular pattern of LDs. TM6SF2 deletion strongly affected endoplasmic reticulum and mitochondria ultrastructures, thus increasing endoplasmic reticulum/oxidative stress. The mitochondrial number was increased in both TM6SF2-/- and MBOAT7-/-TM6SF2-/- models, suggesting an unbalancing in mitochondrial dynamics, and the silencing of both MBOAT7 and TM6SF2 impaired mitochondrial activity with a shift toward anaerobic glycolysis. MBOAT7-/-TM6SF2-/- cells also showed the highest proliferation rate. Finally, the re-overexpression of MBOAT7 and/or TM6SF2 reversed the metabolic and tumorigenic features observed in the compound knockout model. CONCLUSIONS: The co-presence of the 3 at-risk variants impacts the NAFLD course in both patients and experimental models, affecting LD accumulation, mitochondrial functionality, and metabolic reprogramming toward HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Aciltransferases/genética , Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Genótipo , Humanos , Lipase/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosfolipases A2 Independentes de Cálcio , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Differential network analysis has become a widely used technique to investigate changes of interactions among different conditions. Although the relationship between observed interactions and biochemical mechanisms is hard to establish, differential network analysis can provide useful insights about dysregulated pathways and candidate biomarkers. The available methods to detect differential interactions are heterogeneous and often rely on assumptions that are unrealistic in many applications. To address these issues, we develop a novel method for differential network analysis, using the so-called disparity filter as network reduction technique. In addition, we propose a classification model based on the inferred network interactions. The main novelty of this work lies in its ability to preserve connections that are statistically significant with respect to a null model without favouring any resolution scale, as a hard threshold would do, and without Gaussian assumptions. The method was tested using a published metabolomic dataset on colorectal cancer (CRC). Detected hub metabolites were consistent with recent literature and the classifier was able to distinguish CRC from polyp and healthy subjects with great accuracy. In conclusion, the proposed method provides a new simple and effective framework for the identification of differential interaction patterns and improves the biological interpretation of metabolomics data.
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Neoplasias Colorretais , Biomarcadores , Neoplasias Colorretais/diagnóstico , Humanos , MetabolômicaRESUMO
The present letter to editor comments the manuscript "Caliskan SG, Kilic MA, Bilgin MD. Acute effects of energy drink on hemodynamic and electrophysiologic parameters in habitual and non-habitual caffeine consumers. Clin Nutr ESPEN. 2021 Apr; 42:333-338. https://doi.org/10.1016/j.clnesp.2021.01.011. Epub 2021 Feb 4. PMID: 33745602." presenting some data on consumption of energy drinks among medical students during COVID-19 pandemic.
Assuntos
COVID-19 , Bebidas Energéticas , Bebidas Energéticas/efeitos adversos , Humanos , Pandemias , Quarentena , SARS-CoV-2RESUMO
The primary aim of this observational survey study was to assess patients' attitudes toward clinical dental practice during the COVID-19 pandemic; the secondary aim was to evaluate patients' attitudes towards oral health by maintaining an appropriate lifestyle and oral hygiene at home. The questionnaire was developed using Google Forms. The questionnaire consisted of three parts: Part A-geographic, demographic, and personal data; Part B-patients' attitude toward oral health selfcare and lifestyle; Part C-patients' attitude toward dental practice. This survey, conducted during the months of November and December 2020, enrolled 1135 subjects throughout Italy. All data were statistically analyzed. COVID-19 has changed patients' approach to dental procedures. Most of the people interviewed lived in families, and their greatest fear was infecting a family member. Restrictive measures forced people to stay at home, which led to an increased consumption of various types of food, including cariogenic foods. People said they felt safe when they went to the dentist, but they also paid special attention to measures to prevent contagion. Among the measures that should be introduced in similar situations in the future, people wanted telemedicine, a phone recall, and the possible use of video clips for home oral care instructions.
Assuntos
Fibrinolíticos/uso terapêutico , Hemorragia/etiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/efeitos adversos , Hemorragia/mortalidade , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Estudos Retrospectivos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/mortalidadeRESUMO
BACKGROUND/OBJECTIVE: The clinical conditions that lead to an alteration of the enamel structure are numerous. The diet high in sugars and acidifying substances, psychological stress that triggers parafunctional behaviors, the reduced intake of fiber-rich foods or alkalizing substances, together with other factors, contribute to demineralization of the tooth enamel. Dental mineralizing products on the current market are distinguished according to the dosage form, the active ingredient, the release technology, clinical indications and patient choice. Currently, it is necessary to propose to oral health professionals a guide to orient themselves in this chaotic choice, in order to prefer the most effective product for their own clinical target. METHODS: Italian Society of Oral Hygiene Sciences-S.I.S.I.O. is one of the leading scientific Italian societies representing those dental hygienists working with high-quality standards and in agreement with scientific evidence: in the last year, the SISIO working group has carried out a study focused on remineralizing agents in dentistry, in order to give an authoritative point of view to indicate a guideline in the decision process of the choice of a remineralizing agent. We will report the results pointed out from the last consensus meeting in 2017. RESULTS: We have reported the good the bad and the ugly have been discussed in a critical discussion of such topic. CONCLUSION: The SISIO experience has been reported in this position paper with the aim to serve as a useful aid in the daily choice of the clinical steps to perform, when dental professionals need to treat demineralized teeth.