Medicina

12 pages, 318 KiB

Open AccessEditor’s ChoiceReview

Telepharmacy Services: Present Status and Future Perspectives: A Review

by Simone Baldoni, Francesco Amenta and Giovanna Ricci

Medicina 2019, 55(7), 327; https://doi.org/10.3390/medicina55070327 - 01 Jul 2019

Cited by 88 | Viewed by 13338

Background and Objectives: The term “telepharmacy” indicates a form of pharmaceutical care in which pharmacists and patients are not in the same place and can interact using information and communication technology (ICT) facilities. Telepharmacy has been adopted to provide pharmaceutical services to [...] Read more.

Background and Objectives: The term “telepharmacy” indicates a form of pharmaceutical care in which pharmacists and patients are not in the same place and can interact using information and communication technology (ICT) facilities. Telepharmacy has been adopted to provide pharmaceutical services to underserved areas and to address the problem of pharmacist shortage. This paper has reviewed the multi-faceted phenomenon of telepharmacy, summarizing different experiences in the area. Advantages and limitations of telepharmacy are discussed as well. Materials and Methods: A literature analysis was carried out on PubMed, using as entry term “telepharmacy” and including articles on the topic published between 2012 and 2018. Results: The studies reviewed were divided into three categories of pharmacy practice, namely (1) support to clinical services, (2) remote education and handling of “special pharmacies”, and (3) prescription and reconciliation of drug therapies. In general, different telepharmacy services were effective and accompanied by a satisfaction of their targets. Conclusions: Nowadays, the shortage of health personnel, and in particular pharmacists, is a challenging issue that the health systems have to face. The use of a new technology such as telepharmacy can represent a possible option to solve these problems. However, there are unsolved limitations (e.g., legal implications) that make greater diffusion of telepharmacy difficult. Stronger data on the effectiveness of this area of pharmacy care, together with a critical evaluation of its limits, can make actors involved aware about the potentialities of it and could contribute to a larger diffusion of telepharmacy services in the interest of communities and citizens. Full article

20 pages, 1401 KiB

Open AccessEditor’s ChoiceArticle

Qualitative Assessment of Vaccine Hesitancy in Romania

by David Miko, Carmen Costache, Horațiu Alexandru Colosi, Vlad Neculicioiu and Ioana Alina Colosi

Medicina 2019, 55(6), 282; https://doi.org/10.3390/medicina55060282 - 17 Jun 2019

Cited by 32 | Viewed by 6224

Abstract

Background and objectives: Health systems all over the world are confronted with an alarming rise of cases in which individuals hesitate, delay, and even refuse vaccination, despite availability of quality vaccine services. In order to mitigate and combat this phenomenon, which are now [...] Read more.

Background and objectives: Health systems all over the world are confronted with an alarming rise of cases in which individuals hesitate, delay, and even refuse vaccination, despite availability of quality vaccine services. In order to mitigate and combat this phenomenon, which are now defined by the World Health Organization (WHO) as vaccine hesitancy (VH), we must first understand the factors that lead to its occurrence in an era characterized by wide access to safe and effective vaccines. To achieve this, we conducted field testing of the Vaccine Hesitancy Scale (VHS), as it was developed by the Strategic Advisory Group of Experts Working Group (SAGE WG), in Cluj-Napoca city, Cluj County, Romania. The scale is designed to quantify VH prevalence in a population, establish which vaccines generate the highest percentage of hesitancy, and allow a qualitative assessment of the individual’s reasons for hesitance. Materials and Methods: We conducted an observational cross-sectional survey, which was comprised of descriptive, analytical, and qualitative elements regarding VH. The necessary sample size was 452 individuals. The VHS and Matrix of Determinants (recommended by SAGE WG) for reasons people gave to justify their hesitance, was interpreted by qualitative thematic analysis (QTA) to ensure the validity and reliability in detecting hesitancy across various cultural settings and permit global comparisons. Results: We found a VH of 30.3% and 11.7% of parents reported refusing to vaccinate their child. Among the VH responders, the varicella vaccine generated 35% hesitancy, measles vaccine 27.7%, Human Papillomavirus (HPV) 24.1%, and mumps vaccine 23.4%, respectively. The QTA values for percent agreement ranged from 91% to 100%. Cohen’s Kappa values ranged from 0.45 to 0.95. Contextual influences identified for VH were “media,” “leaders and lobbies,” and “perception of the pharmaceutical industry.” Individual and group influences for VH were “beliefs,” “knowledge,” and “risk/benefits (perceived).” Vaccine and vaccination specific issues for VH were “risk/benefit (rational)” and “health care practitioners (trustworthiness, competence).” Conclusions: One-third of the investigated population had expressed VH, and a further one-third of these had refused a vaccine for their child. Chicken Pox, Measles, Mumps, Rubella (MMR), and HPV vaccines generated the most hesitation. Negative information from the media was the most frequently evoked reason for VH. Full article

(This article belongs to the Special Issue Promoting Vaccine Acceptance)

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21 pages, 419 KiB

Open AccessEditor’s ChoiceReview

Role of Vitamin D Status in Diabetic Patients with Renal Disease

by Guido Gembillo, Valeria Cernaro, Antonino Salvo, Rossella Siligato, Alfredo Laudani, Michele Buemi and Domenico Santoro

Medicina 2019, 55(6), 273; https://doi.org/10.3390/medicina55060273 - 13 Jun 2019

Cited by 38 | Viewed by 4184

Abstract

Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will [...] Read more.

Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will increase by 54%, from 19,629,000 to 54,913,000 people, between 2015 and 2030. Diabetic Nephropathy (DN) affects about one-third of patients with DM and currently ranks as the first cause of end-stage kidney disease in the Western world. The complexity of interactions of Vitamin D is directly related with progressive long-term changes implicated in the worsening of renal function. These changes result in a dysregulation of the vitamin D-dependent pathways. Various studies demonstrated a pivotal role of Vitamin D supplementation in regression of albuminuria and glomerulosclerosis, contrasting the increase of glomerular basement membrane thickening and podocyte effacement, with better renal and cardiovascular outcomes. The homeostasis and regulation of the nephron’s function are absolutely dependent from the cross-talk between endothelium and podocytes. Even if growing evidence proves that vitamin D may have antiproteinuric, anti-inflammatory and renoprotective effects in patients with DN, it is still worth investigating these aspects with both more in vitro studies and randomized controlled trials in larger patient series and with adequate follow-up to confirm the effects of long-term vitamin D analogue supplementation in DN and to evaluate the effectiveness of this therapy and the appropriate dosage. Full article

(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)

13 pages, 1055 KiB

Open AccessEditor’s ChoiceReview

SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects

by Carlo Garofalo, Silvio Borrelli, Maria Elena Liberti, Michele Andreucci, Giuseppe Conte, Roberto Minutolo, Michele Provenzano and Luca De Nicola

Medicina 2019, 55(6), 268; https://doi.org/10.3390/medicina55060268 - 11 Jun 2019

Cited by 45 | Viewed by 9364

Abstract

The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that [...] Read more.

The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that is, the inhibitors of renin-angiotensin system. Nephroprotection in DKD therefore remains a major unmet need. Three recent trials testing effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) have produced great expectations on this therapy by consistently evidencing positive effects on hyperglycemia control, and more importantly, on the cardiovascular outcome of type 2 diabetes mellitus. Notably, these trials also disclosed nephroprotective effects when renal outcomes (glomerular filtration rate and albuminuria) were analyzed as secondary endpoints. On the other hand, the use of SGLT2-i can be potentially associated with some adverse effects. However, the balance between positive and negative effects is in favor of the former. The recent results of Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation Study and of other trials specifically testing these drugs in the population with chronic kidney disease, either diabetic or non-diabetic, do contribute to further improving our knowledge of these antihyperglycemic drugs. Here, we review the current state of the art of SGLT2-i by addressing all aspects of therapy, from the pathophysiological basis to clinical effectiveness. Full article

(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)

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9 pages, 1097 KiB

Open AccessEditor’s ChoiceReview

Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update

by Bruna Lo Sasso, Luisa Agnello, Giulia Bivona, Chiara Bellia and Marcello Ciaccio

Medicina 2019, 55(6), 245; https://doi.org/10.3390/medicina55060245 - 04 Jun 2019

Cited by 38 | Viewed by 5456

Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of [...] Read more.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of the pathophysiology of the disease. The diagnostic criteria have been modified several times over the years. Basically, they include clinical symptoms, presence of typical lesions detected by magnetic resonance imaging (MRI), and laboratory findings. The analysis of cerebrospinal fluid (CSF) allows an evaluation of inflammatory processes circumscribed to the CNS and reflects changes in the immunological pattern due to the progression of the pathology, being fundamental in the diagnosis and monitoring of MS. The detection of the oligoclonal bands (OCBs) in both CSF and serum is recognized as the “gold standard” for laboratory diagnosis of MS, though presents analytical limitations. Indeed, current protocols for OCBs assay are time-consuming and require an operator-dependent interpretation. In recent years, the quantification of free light chain (FLC) in CSF has emerged to assist clinicians in the diagnosis of MS. This article reviews the current knowledge on CSF biomarkers used in the diagnosis of MS, in particular on the validated assays and on the alternative biomarkers of intrathecal synthesis. Full article

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14 pages, 503 KiB

Open AccessEditor’s ChoiceReview

GLP-1 Receptor Agonists and Kidney Protection

by Eulalia Valentina Greco, Giuseppina Russo, Annalisa Giandalia, Francesca Viazzi, Roberto Pontremoli and Salvatore De Cosmo

Medicina 2019, 55(6), 233; https://doi.org/10.3390/medicina55060233 - 31 May 2019

Cited by 81 | Viewed by 8291

Abstract

Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). Diabetic nephropathy (DN) is determined by specific pathological structural and functional alterations of the kidneys in patients with diabetes, and its clinical manifestations are albuminuria and decline of glomerular [...] Read more.

Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). Diabetic nephropathy (DN) is determined by specific pathological structural and functional alterations of the kidneys in patients with diabetes, and its clinical manifestations are albuminuria and decline of glomerular filtration rate (GFR). Apart from renin–angiotensin–aldosterone system (RAAS) inhibitors, no other drugs are currently available as therapy for diabetic kidney disease (DKD). Glucagon-like peptide-1 receptor (GLP-1R) agonists are a new class of anti-hyperglycemic drugs which have been demonstrated to prevent the onset of macroalbuminuria and reduce the decline of GFR in diabetic patients. These drugs may exert their beneficial actions on the kidneys through blood glucose- and blood pressure (BP)-lowering effects, reduction of insulin levels and weight loss. Clinical benefits of GLP-1R agonists were acknowledged due to data from large randomized phase III clinical trials conducted to assess their cardiovascular(CV) safety. These drugs improved renal biomarkers in placebo-controlled clinical studies, with effects supposed to be independent of the actions on glycemic control. In this review, we will focus on the actions of GLP-1R agonists on glucose metabolism and kidney physiology, and evaluate direct and indirect mechanisms through which these drugs may confer renal protection. Full article

(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)

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19 pages, 1221 KiB

Open AccessEditor’s ChoiceReview

Non-Celiac Gluten Sensitivity: A Review

by Anna Roszkowska, Marta Pawlicka, Anna Mroczek, Kamil Bałabuszek and Barbara Nieradko-Iwanicka

Medicina 2019, 55(6), 222; https://doi.org/10.3390/medicina55060222 - 28 May 2019

Cited by 59 | Viewed by 15406

Abstract

Background and objectives: Grain food consumption is a trigger of gluten related disorders: celiac disease, non-celiac gluten sensitivity (NCGS) and wheat allergy. They demonstrate with non-specific symptoms: bloating, abdominal discomfort, diarrhea and flatulence. Aim: The aim of the review is to summarize data [...] Read more.

Background and objectives: Grain food consumption is a trigger of gluten related disorders: celiac disease, non-celiac gluten sensitivity (NCGS) and wheat allergy. They demonstrate with non-specific symptoms: bloating, abdominal discomfort, diarrhea and flatulence. Aim: The aim of the review is to summarize data about pathogenesis, symptoms and criteria of NCGS, which can be helpful for physicians. Materials and Methods: The PubMed and Google Scholar databases were searched in January 2019 with phrases: ’non-celiac gluten sensitivity’, non-celiac gluten sensitivity’, non-celiac wheat gluten sensitivity’, non-celiac wheat gluten sensitivity’, and gluten sensitivity’. More than 1000 results were found. A total of 67 clinical trials published between 1989 and 2019 was scanned. After skimming abstracts, 66 articles were chosen for this review; including 26 clinical trials. Results: In 2015, Salerno Experts’ Criteria of NCGS were published. The Salerno first step is assessing the clinical response to gluten free diet (GFD) and second is measuring the effect of reintroducing gluten after a period of treatment with GFD. Several clinical trials were based on the criteria. Conclusions: Symptoms of NCGS are similar to other gluten-related diseases, irritable bowel syndrome and Crohn’s disease. With Salerno Experts’ Criteria of NCGS, it is possible to diagnose patients properly and give them advice about nutritional treatment. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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6 pages, 267 KiB

Open AccessEditor’s ChoiceReview

Suicidality in Borderline Personality Disorder

by Joel Paris

Medicina 2019, 55(6), 223; https://doi.org/10.3390/medicina55060223 - 28 May 2019

Cited by 104 | Viewed by 25961

Abstract

Borderline personality disorder (BPD) is associated with suicidal behaviors and self-harm. Up to 10% of BPD patients will die by suicide. However, no research data support the effectiveness of suicide prevention in this disorder, and hospitalization has not been shown to be useful. [...] Read more.

Borderline personality disorder (BPD) is associated with suicidal behaviors and self-harm. Up to 10% of BPD patients will die by suicide. However, no research data support the effectiveness of suicide prevention in this disorder, and hospitalization has not been shown to be useful. The most evidence-based treatment methods for BPD are specifically designed psychotherapies. Full article

(This article belongs to the Special Issue Preventing Suicide in Patients with Mental Disorders)

13 pages, 852 KiB

Open AccessEditor’s ChoiceArticle

Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation

by Jeand Baloch, Muhammad Farhan Sohail, Hafiz Shaib Sarwar, Maria Hassan Kiani, Gul Majid Khan, Sarwat Jahan, Muhammad Rafay, Muhammad Tausif Chaudhry, Masoom Yasinzai and Gul Shahnaz

Medicina 2019, 55(5), 210; https://doi.org/10.3390/medicina55050210 - 24 May 2019

Cited by 74 | Viewed by 5706

Abstract

Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the [...] Read more.

Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT₁₄) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT₁₄) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT₁₄) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine. Full article

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14 pages, 586 KiB

Open AccessEditor’s ChoiceReview

Dietary and Pharmacological Treatment of Nonalcoholic Fatty Liver Disease

by Anna Jeznach-Steinhagen, Joanna Ostrowska, Aneta Czerwonogrodzka-Senczyna, Iwona Boniecka, Urszula Shahnazaryan and Alina Kuryłowicz

Medicina 2019, 55(5), 166; https://doi.org/10.3390/medicina55050166 - 20 May 2019

Cited by 35 | Viewed by 6312

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the developed world. Simple hepatic steatosis is mild, but the coexistence of steatohepatitis (NASH) and fibrosis increases the risk of hepatocellular carcinoma. Proper dietary and pharmacological treatment is essential for [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the developed world. Simple hepatic steatosis is mild, but the coexistence of steatohepatitis (NASH) and fibrosis increases the risk of hepatocellular carcinoma. Proper dietary and pharmacological treatment is essential for preventing NAFLD progression. The first-line treatment should include dietary intervention and increased physical activity. The diet should be based on the food pyramid, with a choice of products with low glycemic index, complex carbohydrates in the form of low-processed cereal products, vegetables, and protein-rich products. Usage of insulin-sensitizing substances, pro- and prebiotics, and vitamins should also be considered. Such a therapeutic process is intended to support both liver disease and obesity-related pathologies, including insulin resistance, diabetes, dyslipidemia, and blood hypertension. In the pharmacological treatment of NAFLD, apart from pioglitazone, there are new classes of antidiabetic drugs that are of value, such as glucagon-like peptide 1 analogs and sodium/glucose cotransporter 2 antagonists, while several other compounds that target different pathogenic pathways are currently being tested in clinical trials. Liver biopsies should only be considered when there is a lack of decline in liver enzymes after 6 months of the abovementioned treatment. Dietary intervention is recommended in all patients with NAFLD, while pharmacological treatment is recommended especially for those with NASH and showing significant fibrosis in a biopsy. Full article

(This article belongs to the Special Issue Non Alcoholic Fatty Liver Disease)

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12 pages, 346 KiB

Open AccessEditor’s ChoiceArticle

Impact of Maternal Diet on Human Milk Composition Among Lactating Women in Latvia

by Līva Aumeistere, Inga Ciproviča, Dace Zavadska, Juris Andersons, Viktors Volkovs and Kristīne Ceļmalniece

Medicina 2019, 55(5), 173; https://doi.org/10.3390/medicina55050173 - 20 May 2019

Cited by 45 | Viewed by 4407

Abstract

Background and objectives: Many studies indicate that the maternal diet is an important factor affecting human milk composition. Human milk composition among lactating women in Latvia, as well as the maternal diet during lactation, has not been sufficiently studied. The aim of [...] Read more.

Background and objectives: Many studies indicate that the maternal diet is an important factor affecting human milk composition. Human milk composition among lactating women in Latvia, as well as the maternal diet during lactation, has not been sufficiently studied. The aim of this research was to assess dietary habits and macronutrient intake among lactating women in Latvia and to examine the effect of diet on human milk composition. Materials and Methods: Research was conducted between November 2016 and December 2017. Mature human milk samples (n = 61) along with a 72h food diary, a food frequency questionnaire (FFQ), and a questionnaire about maternal and infant characteristics were obtained from voluntary women who were recruited via an invitation published in a social media member group for nursing mothers. Fat content in human milk was determined by LVS ISO 2446:2008, protein content was determined by LVS EN ISO 8968-1:2014, lactose was determined by ISO 22662:2007, and the fatty acid profile was analyzed using gas chromatography. Dietary data were evaluated using the Finnish food composition database Fineli, release 19 (3 March 2018). Results: Median values for fat, protein, and lactose in mature human milk were 4.40%, 1.08%, and 6.52%, respectively. Predominant fatty acids in human milk were oleic acid (C18:1 n9c), palmitic acid (C16:0), and linoleic acid (C18:2 n6c) at 34.60%, 24.00%, and 11.00% of total fatty acids, respectively. The trans elaidic acid (C18:1 n9t) level was <0.10% in all human milk samples. Significant, positive associations (p < 0.05) were found between maternal dietary intake of linoleic, α-linolenic, docosahexaenoic, total cis-monounsaturated, total cis-polyunsaturated, and total n-6 and n-3 polyunsaturated fatty acids, the ratio of n-6/n-3, and the level of these fatty acids in human milk. Total energy and carbohydrate intake among participants were lower, but total fat, saturated fat, and sugar intake were higher than recommended. Protein, linoleic acid, and α-linolenic acid intake were adequate, but docosahexaenoic acid intake was noticeably lower than recommended. Women should be supported with information regarding their nutritional needs during lactation and the possible impact of diet on human milk composition. Conclusion: Macronutrient (fat, protein, and lactose) content in human milk is not affected by maternal diet. Conversely, the human milk fatty acid profile is affected by the immediate diet consumed by the mother. Habitual dietary habits can also impact the fatty acid profile of human milk. Full article

8 pages, 979 KiB

Open AccessEditor’s ChoiceArticle

Optimal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Cut-Offs: A Cross-Sectional Study in the Czech Population

by Dagmar Horáková, Ladislav Štěpánek, Vladimír Janout, Jana Janoutová, Dalibor Pastucha, Helena Kollárová, Alena Petráková, Lubomír Štěpánek, Roman Husár and Karel Martiník

Medicina 2019, 55(5), 158; https://doi.org/10.3390/medicina55050158 - 17 May 2019

Cited by 45 | Viewed by 5323

Abstract

Background and Objectives: The key pathogenetic mechanism of glucose metabolism disorders, insulin resistance (IR), can be assessed using the Homeostasis Model Assessment of IR (HOMA-IR). However, its application in clinical practice is limited due to the absence of cut-offs. In this study, we [...] Read more.

Background and Objectives: The key pathogenetic mechanism of glucose metabolism disorders, insulin resistance (IR), can be assessed using the Homeostasis Model Assessment of IR (HOMA-IR). However, its application in clinical practice is limited due to the absence of cut-offs. In this study, we aimed to define the cut-offs for the Czech population. Methods: After undergoing anthropometric and biochemical studies, the sample of 3539 individuals was divided into either nondiabetics, including both subjects with normal glucose tolerance (NGT, n = 1947) and prediabetics (n = 1459), or diabetics (n = 133). The optimal HOMA-IR cut-offs between subgroups were determined to maximize the sum of the sensitivity and specificity for diagnosing type 2 diabetes mellitus (T2DM) or prediabetes. The predictive accuracy was illustrated using receiver operating characteristic (ROC) curves. Logistic regression was performed to assess the association between a target variable (presence/absence of T2DM) depending on the HOMA-IR score as well as on the age and sex. Results: The HOMA-IR cut-off between nondiabetics and diabetics for both sexes together was 3.63, with a sensitivity of 0.56 and a specificity of 0.86. The area under the ROC curve was 0.73 for T2DM diagnosing in both sexes. The HOMA-IR cut-off between the NGT subjects and prediabetics was 1.82, with a sensitivity of 0.60 and a specificity of 0.66. Logistic regression showed that increased HOMA-IR is a risk factor for the presence of T2DM (odds ratio (OR) 1.2, 95% confidence interval (CI) 1.14–1.28, p < 0.0001). The predictive ability of HOMA-IR in diagnosing T2DM is statistically significantly lower in females (OR 0.66, 95% CI 0.44–0.98). The results are valid for middle-aged European adults. Conclusions: The results suggest the existence of HOMA-IR cut-offs signaling established IR. Introduction of the instrument into common clinical practice, together with the known cut-offs, may contribute to preventing T2DM. Full article

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15 pages, 2528 KiB

Open AccessEditor’s ChoiceArticle

Effects of Quercetin-Loaded Nanoparticles on MCF-7 Human Breast Cancer Cells

by Firoozeh Niazvand, Mahmoud Orazizadeh, Layasadat Khorsandi, Mohammadreza Abbaspour, Esrafil Mansouri and Ali Khodadadi

Medicina 2019, 55(4), 114; https://doi.org/10.3390/medicina55040114 - 22 Apr 2019

Cited by 81 | Viewed by 5779

Abstract

Background and objectives: Previous studies have shown anti-tumor activity of quercetin (QT). However, the low bioavailability of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the growth of [...] Read more.

Background and objectives: Previous studies have shown anti-tumor activity of quercetin (QT). However, the low bioavailability of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the growth of MCF-7 human breast cancer cells. Materials and Methods: MCF-7 and MCF-10A (non-tumorigenic cell line) cell lines treated with 25 µmol/mL of QT or QT-SLNs for 48 h. Cell viability, colony formation, oxidative stress, and apoptosis were evaluated to determine the toxic effects of the QT-SLNs. Results: The QT-SLNs with appropriate characteristics (particle size of 85.5 nm, a zeta potential of −22.5 and encapsulation efficiency of 97.6%) were prepared. The QT-SLNs showed sustained QT release until 48 h. Cytotoxicity assessments indicated that QT-SLNs inhibited MCF-7 cells growth with a low IC₅₀ (50% inhibitory concentration) value, compared to the free QT. QT-SLNs induced a significant decrease in the viability and proliferation of MCF-7 cells, compared to the free QT. QT-SLN significantly increased reactive oxygen species (ROS) level and MDA contents and significantly decreased antioxidant enzyme activity in the MCF-7 cells. Following QT-SLNs treatment, the expression of the Bcl-2 protein significantly decreased, whereas Bx expression showed a significant increase in comparison with free QT-treated cells. Furthermore, The QT-SLNs significantly increased apoptotic and necrotic indexes in MCF-7 cells. Viability, proliferation, oxidative stress and apoptosis of MCF-10A cells were not affected by QT or QT-SLNs. Conclusions: According to the results of this study, SLN significantly enhanced the toxic effect of QT against human breast cancer cells. Full article

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14 pages, 3076 KiB

Open AccessEditor’s ChoiceArticle

Nonenzymatic Serum Antioxidant Capacity in IBD and Its Association with the Severity of Bowel Inflammation and Corticosteroids Treatment

by Katarzyna Neubauer, Radoslaw Kempinski, Malgorzata Matusiewicz, Iwona Bednarz-Misa and Malgorzata Krzystek-Korpacka

Medicina 2019, 55(4), 88; https://doi.org/10.3390/medicina55040088 - 02 Apr 2019

Cited by 18 | Viewed by 2790

Abstract

Background and objectives: Oxidative stress signalling plays a monumental role in inflammatory bowel disease (IBD). Reduction of oxidative stress might control inflammation, block tissue damage, and reverse natural history of IBD. We assessed the serum concentrations of free thiols (FT) and uric [...] Read more.

Background and objectives: Oxidative stress signalling plays a monumental role in inflammatory bowel disease (IBD). Reduction of oxidative stress might control inflammation, block tissue damage, and reverse natural history of IBD. We assessed the serum concentrations of free thiols (FT) and uric acid (SUA), together constituting a large part of nonenzymatic serum antioxidant capacity, as well as total antioxidant status (TAS) with reference to IBD phenotype, activity, co-occurrence of anemia, and treatment with azathioprine (AZA) and corticosteroids (CS). Additionally, we appraised the potential of uric acid, thiol stress, and TAS as mucosal healing (MH) markers in ulcerative colitis. Materials and methods: SUA, FT, and TAS were measured colorimetrically using, respectively, uricase, Ellman’s and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods. Results: The study group consisted of 175 individuals: 57 controls, 71 ulcerative colitis (UC), and 47 Crohn’s disease (CD) patients. When compared to controls, SUA levels were significantly lower in patients with CD, and FT and TAS levels were significantly lower in patients with CD and UC. In UC patients, SUA, FT, and TAS inversely correlated with the severity of bowel inflammation. As MH markers, SUA displayed better overall accuracy and higher specificity than FT. In active CD, FT, and SUA were significantly lower in patients with anemia. FT was significantly lower in patients treated with corticosteroids. Conclusions: IBD patients, regardless the disease phenotype, have systemic thiol stress, depleted total antioxidant capacity, and reduced concentrations of uric acid, reflecting, to various degrees, clinical and local disease activity as well as presence of anaemia, the most common extraintestinal manifestation of IBD. Evaluation of systemic total antioxidant status may be useful in noninvasive assessment of mucosal healing. Our findings on thiol stress provide an additional aspect on adverse effects of corticosteroids therapy. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease: Causes, Symptoms, Diet and Treatment)

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10 pages, 516 KiB

Open AccessEditor’s ChoiceReview

Impact of Different Types of Diet on Gut Microbiota Profiles and Cancer Prevention and Treatment

by Rainer J. Klement and Valerio Pazienza

Medicina 2019, 55(4), 84; https://doi.org/10.3390/medicina55040084 - 29 Mar 2019

Cited by 89 | Viewed by 15834

Abstract

Diet is frequently considered as a food regimen focused on weight loss, while it is actually the sum of food consumed by the organism. Western diets, modern lifestyle, sedentary behaviors, smoking habits, and drug consumption have led to a significant reduction of gut [...] Read more.

Diet is frequently considered as a food regimen focused on weight loss, while it is actually the sum of food consumed by the organism. Western diets, modern lifestyle, sedentary behaviors, smoking habits, and drug consumption have led to a significant reduction of gut microbial diversity, which is linked to many non-communicable diseases (NCDs). The latter kill 40 million people each year, equivalent to more than 70% of all deaths globally. Among NCDs, tumors play a major role, being responsible for 29% of deaths from NCDs. A link between diet, microbiota, and cancer prevention and treatment has recently been unveiled, underlining the importance of a new food culture based on limiting dietary surplus and on preferring healthier foods. Here, we review the effects of some of the most popular “cancer-specific” diets on microbiota composition and their potential impact on cancer prevention and treatment. Full article

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9 pages, 11202 KiB

Open AccessEditor’s ChoiceArticle

Gastroprotective Effect of Zingerone on Ethanol-Induced Gastric Ulcers in Rats

by Neda Sistani Karampour, Ardeshir Arzi, Anahita Rezaie, Marzieh Pashmforoosh and Fatemeh Kordi

Medicina 2019, 55(3), 64; https://doi.org/10.3390/medicina55030064 - 11 Mar 2019

Cited by 72 | Viewed by 5312

Abstract

Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect [...] Read more.

Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect of zingerone on ethanol-induced gastric ulcers in rats. Materials and Methods: Gastric ulcers were induced by ethanol (96%, 5 mL/kg, po) in male wistar rats and zingerone (50, 100, and 200 mg/kg) was administrated orally. Normal saline and ranitidine were used as negative and positive control, respectively. In this study, the number and length of ulcers, and malondialdehyde (MDA) and nitric oxide (NO) levels in stomach tissues were determined. Results: The findings showed that the mean number and length of gastric ulcers were significantly lower in zingerone-received groups than ethanol group (P < 0.05). The level of malondialdehyde was decreased in the stomach of zingerone groups (P < 0.05) compared to the ethanol group. In addition, zingerone treatment prevented the decrease of nitric oxide level by ethanol in the stomach tissue. Conclusions: The present study showed that zingerone has a protective effect on the ethanol-induced gastric ulcer, which may be due to its free radical scavenging activity. Full article

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13 pages, 819 KiB

Open AccessEditor’s ChoiceArticle

Ventilator-Associated Pneumonia due to Drug-Resistant Acinetobacter baumannii: Risk Factors and Mortality Relation with Resistance Profiles, and Independent Predictors of In-Hospital Mortality

by Aušra Čiginskienė, Asta Dambrauskienė, Jordi Rello and Dalia Adukauskienė

Medicina 2019, 55(2), 49; https://doi.org/10.3390/medicina55020049 - 13 Feb 2019

Cited by 54 | Viewed by 4900

Abstract

Background and objectives: High mortality and healthcare costs area associated with ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (A. baumannii). The data concerning the link between multidrug-resistance of A. baumannii strains and outcomes remains controversial. Therefore, we aimed to identify the [...] Read more.

Background and objectives: High mortality and healthcare costs area associated with ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (A. baumannii). The data concerning the link between multidrug-resistance of A. baumannii strains and outcomes remains controversial. Therefore, we aimed to identify the relation of risk factors for ventilator-associated pneumonia (VAP) and mortality with the drug resistance profiles of Acinetobacter baumannii (A. baumannii) and independent predictors of in-hospital mortality. Methods: A retrospective ongoing cohort study of 60 patients that were treated for VAP due to drug-resistant A. baumannii in medical-surgical intensive care units (ICU) over a two-year period was conducted. Results: The proportions of multidrug-resistant (MDR), extensively drug-resistant (XDR), and potentially pandrug-resistant (pPDR) A. baumannii were 13.3%, 68.3%, and 18.3%, respectively. The SAPS II scores on ICU admission were 42.6, 48.7, and 49 (p = 0.048); hospital length of stay (LOS) prior to ICU was 0, one, and two days (p = 0.036), prior to mechanical ventilation (MV)—0, 0, and three days (p = 0.013), and carbapenem use prior to VAP—50%, 29.3%, and 18.2% (p = 0.036), respectively. The overall in-hospital mortality rate was 63.3%. In MDR, XDR, and pPDR A. baumannii VAP groups, it was 62.5%, 61.3%, and 72.7% (p = 0.772), respectively. Binary logistic regression analysis showed that female gender (95% OR 5.26; CI: 1.21–22.83), SOFA score on ICU admission (95% OR 1.28; CI: 1.06–1.53), and RBC transfusion (95% OR 5.98; CI: 1.41–25.27) were all independent predictors of in-hospital mortality. Conclusions: The VAP risk factors: higher SAPS II score, increased hospital LOS prior to ICU, and MV were related to the higher resistance profile of A. baumannii. Carbapenem use was found to be associated with the risk of MDR A. baumannii VAP. Mortality due to drug-resistant A. baumannii VAP was high, but it was not associated with the A. baumannii resistance profile. Female gender, SOFA score, and RBC transfusion were found to be independent predictors of in-hospital mortality. Full article

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16 pages, 1560 KiB

Open AccessEditor’s ChoiceReview

Targeted Therapies in Cholangiocarcinoma: Emerging Evidence from Clinical Trials

by Maria Maddalena Simile, Paola Bagella, Gianpaolo Vidili, Angela Spanu, Roberto Manetti, Maria Antonietta Seddaiu, Sergio Babudieri, Giordano Madeddu, Pier Andrea Serra, Matteo Altana and Panagiotis Paliogiannis

Medicina 2019, 55(2), 42; https://doi.org/10.3390/medicina55020042 - 08 Feb 2019

Cited by 60 | Viewed by 6203

Abstract

Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs [...] Read more.

Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs and symptoms in the early stages. This fact, along with the poor results of the local and systemic therapies currently employed, is responsible for the poor outcome of CCA patients and strongly supports the need for novel therapeutic agents and strategies. In recent years, the introduction of next-generation sequencing technologies has opened new horizons for a better understanding of the genetic pathophysiology of CCA and, consequently, for the identification and evaluation of new treatments tailored to the molecular features or alterations progressively elucidated. In this review article, we describe the potential targets under investigation and the current molecular therapies employed in biliary tract cancers. In addition, we summarize the main drugs against CCA under evaluation in ongoing trials and describe the preliminary data coming from these pioneering studies. Full article

(This article belongs to the Special Issue Liver Cancer: Molecular Mechanisms and Targeted Therapies)

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14 pages, 657 KiB

Open AccessEditor’s ChoiceReview

Prevention and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis

by Goda Daugėlaitė, Kristė Užkuraitytė, Eglė Jagelavičienė and Aleksas Filipauskas

Medicina 2019, 55(2), 25; https://doi.org/10.3390/medicina55020025 - 22 Jan 2019

Cited by 82 | Viewed by 15452

Abstract

Background and objectives: Oral mucositis is one of the main adverse events of cancer treatment with chemotherapy or radiation therapy. It presents as erythema, atrophy or/and ulceration of oral mucosa. It occurs in almost all patients, who receive radiation therapy of the [...] Read more.

Background and objectives: Oral mucositis is one of the main adverse events of cancer treatment with chemotherapy or radiation therapy. It presents as erythema, atrophy or/and ulceration of oral mucosa. It occurs in almost all patients, who receive radiation therapy of the head and neck area and from 20% to 80% of patients who receive chemotherapy. There are few clinical trials in the literature proving any kind of treatment or prevention methods to be effective. Therefore, the aim of this study is to perform systematic review of literature and examine the most effective treatment and prevention methods for chemotherapy or/and radiotherapy induced oral mucositis. Materials and methods: Clinical human trials, published from 1 January 2007 to 31 December 2017 in English, were included in this systematic review of literature. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) protocol was followed while planning, providing objectives, selecting studies and analyzing data for this systematic review. “MEDLINE” and “PubMed Central” databases were used to search eligible clinical trials. Clinical trials researching medication, oral hygiene, cryotherapy or laser therapy efficiency in treatment or/and prevention of oral mucositis were included in this systematic review. Results: Results of the studies used in this systematic review of literature showed that laser therapy, cryotherapy, professional oral hygiene, antimicrobial agents, Royal jelly, L. brevis lozenges, Zync supplementation and Benzydamine are the best treatment or/and prevention methods for oral mucositis. Conclusions: Palifermin, Chlorhexidine, Smecta, Actovegin, Kangfuxin, L. brevis lozenges, Royal jelly, Zync supplement, Benzydamine, cryotherapy, laser therapy and professional oral hygiene may be used in oral mucositis treatment and prevention. Full article

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18 pages, 3333 KiB

Open AccessEditor’s ChoiceArticle

Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis

by Md. Rezanur Rahman, Tania Islam, Esra Gov, Beste Turanli, Gizem Gulfidan, Md. Shahjaman, Nilufa Akhter Banu, Md. Nurul Haque Mollah, Kazim Yalcin Arga and Mohammad Ali Moni

Medicina 2019, 55(1), 20; https://doi.org/10.3390/medicina55010020 - 17 Jan 2019

Cited by 56 | Viewed by 7210

Abstract

Background and objectives: Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world, but early diagnosis ameliorates the survival of CRC. This report aimed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed [...] Read more.

Background and objectives: Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world, but early diagnosis ameliorates the survival of CRC. This report aimed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed two microarray datasets (GSE35279 and GSE21815) from the Gene Expression Omnibus (GEO) to identify mutual differentially expressed genes (DEGs). We integrated DEGs with protein–protein interaction and transcriptional/post-transcriptional regulatory networks to identify reporter signaling and regulatory molecules; utilized functional overrepresentation and pathway enrichment analyses to elucidate their roles in biological processes and molecular pathways; performed survival analyses to evaluate their prognostic performance; and applied drug repositioning analyses through Connectivity Map (CMap) and geneXpharma tools to hypothesize possible drug candidates targeting reporter molecules. Results: A total of 727 upregulated and 99 downregulated DEGs were detected. The PI3K/Akt signaling, Wnt signaling, extracellular matrix (ECM) interaction, and cell cycle were identified as significantly enriched pathways. Ten hub proteins (ADNP, CCND1, CD44, CDK4, CEBPB, CENPA, CENPH, CENPN, MYC, and RFC2), 10 transcription factors (ETS1, ESR1, GATA1, GATA2, GATA3, AR, YBX1, FOXP3, E2F4, and PRDM14) and two microRNAs (miRNAs) (miR-193b-3p and miR-615-3p) were detected as reporter molecules. The survival analyses through Kaplan–Meier curves indicated remarkable performance of reporter molecules in the estimation of survival probability in CRC patients. In addition, several drug candidates including anti-neoplastic and immunomodulating agents were repositioned. Conclusions: This study presents biomarker signatures at protein and RNA levels with prognostic capability in CRC. We think that the molecular signatures and candidate drugs presented in this study might be useful in future studies indenting the development of accurate diagnostic and/or prognostic biomarker screens and efficient therapeutic strategies in CRC. Full article

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