Journal of Personalized Medicine

12 pages, 1384 KiB

Open AccessReview

Implementation of MALDI Mass Spectrometry Imaging in Cancer Proteomics Research: Applications and Challenges

by Eline Berghmans, Kurt Boonen, Evelyne Maes, Inge Mertens, Patrick Pauwels and Geert Baggerman

J. Pers. Med. 2020, 10(2), 54; https://doi.org/10.3390/jpm10020054 - 22 Jun 2020

Cited by 19 | Viewed by 5645

Abstract

Studying the proteome–the entire set of proteins in cells, tissues, organs and body fluids—is of great relevance in cancer research, as differential forms of proteins are expressed in response to specific intrinsic and extrinsic signals. Discovering protein signatures/pathways responsible for cancer transformation may [...] Read more.

Studying the proteome–the entire set of proteins in cells, tissues, organs and body fluids—is of great relevance in cancer research, as differential forms of proteins are expressed in response to specific intrinsic and extrinsic signals. Discovering protein signatures/pathways responsible for cancer transformation may lead to a better understanding of tumor biology and to a more effective diagnosis, prognosis, recurrence and response to therapy. Moreover, proteins can act as a biomarker or potential drug targets. Hence, it is of major importance to implement proteomic, particularly mass spectrometric, approaches in cancer research, to provide new crucial insights into tumor biology. Recently, mass spectrometry imaging (MSI) approaches were implemented in cancer research, to provide individual molecular characteristics of each individual tumor while retaining molecular spatial distribution, essential in the context of personalized disease management and medicine. Full article

(This article belongs to the Special Issue Proteomics and Personalized Medicine)

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8 pages, 544 KiB

Open AccessArticle

rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study

by Khaled Naja, Ali Salami, Said El Shamieh and Rajaa Fakhoury

J. Pers. Med. 2020, 10(2), 53; https://doi.org/10.3390/jpm10020053 - 20 Jun 2020

Cited by 8 | Viewed by 4114

Abstract

Background and Objective: Since the treatment outcome with oral anti-diabetics differs between individuals, the objective of this study is to evaluate the significance of rs622342 in SLC22A1, CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) with regard to the efficacy of metformin/sulfonylurea combination [...] Read more.

Background and Objective: Since the treatment outcome with oral anti-diabetics differs between individuals, the objective of this study is to evaluate the significance of rs622342 in SLC22A1, CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) with regard to the efficacy of metformin/sulfonylurea combination therapy in individuals with type 2 diabetes mellitus (T2DM). Methods: Eighty-eight Lebanese individuals with T2DM received metformin/sulfonylurea combination therapy over 3 and 6 months. The clinical and biochemical characteristics were collected. Genotyping of rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 was performed using hybridization probes on real-time polymerase chain reaction (PCR) instrument. Statistical analysis was performed using SPSS 22.0. Results: The levels of fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) showed a statistically significant reduction over 3 and 6 months of follow-up (p < 0.001). An interaction between rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 (p = 0.035) was found associated with reduced levels of HbA1c levels after 3 and 6 months. A significant difference between the means of HbA1c was observed among the different groups after 3 and 6 months (p = 0.004 and p < 0.001, respectively). The most beneficial group was; AA and AC, *1*3, whereas the individuals that benefited the least were CC, *1*3 at 3 and 6 months. In contrast to HbA1c, no interaction was found between the three polymorphisms to affect FBS (p = 0.581). Conclusion: The combination of metformin/sulfonylurea therapy led to the maximum glycemic control in individuals with T2DM carrying AA or AC genotypes in SLC22A1 and *1*3 in CYP2C9. Full article

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10 pages, 1029 KiB

Open AccessArticle

Correlation between F18-FDG PET/CT Imaging and BRAF V600E Genetic Mutation for the Early Assessment of Treatment Response in Papillary Thyroid Cancers

by Andra Piciu, Maria-Iulia Larg and Doina Piciu

J. Pers. Med. 2020, 10(2), 52; https://doi.org/10.3390/jpm10020052 - 19 Jun 2020

Cited by 3 | Viewed by 3631

Abstract

In thyroid neoplastic pathology, the BRAF V600E mutation is shown to be involved in the oncogenesis of papillary thyroid cancer and its subtypes. The purpose of this study is to evaluate the correlation between the mutation of the BRAF V600E oncogene and the [...] Read more.

In thyroid neoplastic pathology, the BRAF V600E mutation is shown to be involved in the oncogenesis of papillary thyroid cancer and its subtypes. The purpose of this study is to evaluate the correlation between the mutation of the BRAF V600E oncogene and the pathological standardized uptake values (SUV) at the F18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) evaluation, for a group of 20 patients with radically treated (total thyroidectomy and radioiodine therapy) papillary thyroid cancer, with subclinical persistent disease, at 6 months after the initial treatment. We analyzed the correlations between the values of SUV and the presence of the BRAF mutation as well with other prognostic factors such as stage, age, specific tumor markers (thyroglobulin and anti-thyroglobulin), extrathyroid extension, the presence of metastatic lymph nodes or distant metastasis. The value of SUV in the case of BRAF+ (positive) patients was higher than in the negative ones, but without statistical significance, thus, the values of the SUV cannot be a predictable factor for the presence of the genetic mutation. There was a statistically significant correlation in BRAF+ subgroup between the SUV values and the positive resection limit following surgery, showing a higher SUV value in the PET/CT evaluation. No correlation was observed between the aforementioned prognostic factors involved in papillary thyroid cancer and the BRAF V600E mutation. Full article

(This article belongs to the Special Issue Present and Future of Personalised Medicine for Endocrine Cancers)

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10 pages, 261 KiB

Open AccessArticle

Risk Factors Associated with Low Back Pain among A Group of 1510 Pregnant Women

by Aleksandra Bryndal, Marian Majchrzycki, Agnieszka Grochulska, Sebastian Glowinski and Agnieszka Seremak-Mrozikiewicz

J. Pers. Med. 2020, 10(2), 51; https://doi.org/10.3390/jpm10020051 - 15 Jun 2020

Cited by 22 | Viewed by 7959

Abstract

Background: Low Back Pain (LBP) is a frequent, very common, and costly health problem. LBP, which occurs during pregnancy, may become a lifelong problem. The aim of this study was to determine the risk factors associated with LBP in pregnant women. Methods: The [...] Read more.

Background: Low Back Pain (LBP) is a frequent, very common, and costly health problem. LBP, which occurs during pregnancy, may become a lifelong problem. The aim of this study was to determine the risk factors associated with LBP in pregnant women. Methods: The study included 1510 pregnant women. A questionnaire assessing demography, lifestyle, prevalence, and characteristics was designed and used in the study. Pain intensity was assessed with the VAS (Visual Analogue Scale). The RMDQ (Roland Morris Disability Questionnaire) was used to assess the effect that low back pain had on the functional capacity of a pregnant woman. Middle (thoracic) and low back pain disability was measured with the help of the ODI (Oswestry Disability Index) questionnaire. Results: The study confirmed that lying/sleeping (49.6%) and sitting positions (38.7%) as well as walking (37.2%) are the most significant factors causing LBP. It was also found that women who had not engaged in physical activity were more likely to experience LBP. Conclusions: Predisposing factors for LBP in pregnancy are LBP in previous pregnancies, back pain during menstruation, a younger age and a lack of physical activity. Most women in pregnancy with LBP experienced minimal and mild disability. Full article

9 pages, 222 KiB

Open AccessReview

An Omics View of Emery–Dreifuss Muscular Dystrophy

by Nicolas Vignier and Antoine Muchir

J. Pers. Med. 2020, 10(2), 50; https://doi.org/10.3390/jpm10020050 - 15 Jun 2020

Cited by 3 | Viewed by 4609

Abstract

Recent progress in Omics technologies has started to empower personalized healthcare development at a thorough biomolecular level. Omics have subsidized medical breakthroughs that have started to enter clinical proceedings. The use of this scientific know-how has surfaced as a way to provide a [...] Read more.

Recent progress in Omics technologies has started to empower personalized healthcare development at a thorough biomolecular level. Omics have subsidized medical breakthroughs that have started to enter clinical proceedings. The use of this scientific know-how has surfaced as a way to provide a more far-reaching view of the biological mechanisms behind diseases. This review will focus on the discoveries made using Omics and the utility of these approaches for Emery–Dreifuss muscular dystrophy. Full article

(This article belongs to the Special Issue Understanding Neuromuscular Health and Disease: Advances in Genetics, Omics, and Molecular Function)

19 pages, 4147 KiB

Open AccessArticle

The Bluegreen Algae (AFA) Consumption over 48 h Increases the Total Number of Peripheral CD34+ Cells in Healthy Patients: Effect of Short-Term and Long-Term Nutritional Supplementation (Curcumin/AFA) on CD34+ Levels (Blood)

by José Joaquín Merino, María Eugenia Cabaña-Muñoz and María Jesús Pelaz

J. Pers. Med. 2020, 10(2), 49; https://doi.org/10.3390/jpm10020049 - 8 Jun 2020

Cited by 4 | Viewed by 7620

Abstract

Several active principles from plants could trigger the release of stem cells from the bone marrow. Stem cell mobilizers have shown side effects in patients. Thus, the purpose of this paper is to find the natural products from plants (curcuminoids, glycosinolate of sulforaphane, [...] Read more.

Several active principles from plants could trigger the release of stem cells from the bone marrow. Stem cell mobilizers have shown side effects in patients. Thus, the purpose of this paper is to find the natural products from plants (curcuminoids, glycosinolate of sulforaphane, AFA bluegreen algae), which could be potential stem mobilizes without adverse side effects. The antioxidant curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-2,5-dione], glycosinolate of sulforaphane (broccoli) or AFA (Aphanizomenon flos) extract promote beneficial effects in patients. The number of circulating stem cells were monitored by HSC marker-CD34 by flow cytometry in peripheral blood from healthy subjects. CD34 is a hematological stem cells (HSC) marker. A double-blind study was conducted in 22 healthy subjects. We have evaluated whether short-term AFA—Aphanizomenon flos aquae—algae or curcuminoids consumption (powder or liquid formulation) over 48 consecutive hours could increase the total number of peripheral CD34+ blood cells (n = 22, n = 5 subjects/group). The total number of circulating CD34+ cells were quantified after short-term and long-term nutritional supplementation; their levels were compared with their own basal levels (n = 5/group, controls: before taking any supplement) or placebo-treated patients (n = 7); their average age was 54 years old. We also evaluated whether long-term nutritional supplementation with several nutraceuticals could enhance HSC mobilization by increasing the total number of peripheral CD-34+ cell after seven or 38 consecutive days of administration (n = 5, with seven placebo-treated patients). The long-term administration take place with these doses/day [curcuminoids: 2000 mg/day, equivalent to 120 mg of curcuminoids/day), glycosinolate of sulforaphane (66 mg/day), plus AFA Algae bluegreen extract (400 mg/day)]. On the last day (10 a.m.) of treatment, blood samples were collected six hours after taking these supplements; the average age was 54 years old. Notably, the blue green AFA algae extract consumption over 48 h enhances HSC mobilization by increasing the total number of peripheral CD34+ cells. The long-term administration with curcuminoids, glycosinolate of sulforaphane, and AFA bluegreen algae extract also increased the total number of CD34-HSC cells after seven or 38 days of consecutive of administration in healthy subjects. Full article

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13 pages, 251 KiB

Open AccessArticle

Personalized Nursing: How Life Satisfaction and Occupational Burnout Influence New Competences of Polish Nurses

by Anna Bartosiewicz, Edyta Łuszczki and Katarzyna Dereń

J. Pers. Med. 2020, 10(2), 48; https://doi.org/10.3390/jpm10020048 - 8 Jun 2020

Cited by 10 | Viewed by 3976

Abstract

Nursing around the world is developing very dynamically and nurses are undertaking increasingly complex tasks. The extension of entitlements for nurses in Poland in the area of writing prescriptions and referrals for diagnostic tests seems to be a response to the development and [...] Read more.

Nursing around the world is developing very dynamically and nurses are undertaking increasingly complex tasks. The extension of entitlements for nurses in Poland in the area of writing prescriptions and referrals for diagnostic tests seems to be a response to the development and changes occurring in this profession. This will improve the standards of patient care, increase access to medical services and improve the professional status of this group. The aim of this study was to analyze the opinions of nurses regarding their preparedness for administering prescriptions and referrals for diagnostic tests depending on their sense of life satisfaction and the level of occupational burnout. The study was conducted among primary care nurses using a survey technique, using a standardized scale of life satisfaction and a scale to measure burnout. In addition, this study used a proprietary survey questionnaire containing questions regarding the self-assessment of preparedness for new competences. The results showed that nurses do not feel well prepared for new tasks. The levels of life satisfaction and burnout of the nurses surveyed significantly influenced confidence regarding their preparedness for writing prescriptions and referrals for diagnostic tests. Polish nurses have a very cautious attitude towards new competences. However, this is a breakthrough and the first step towards approving the role of an advanced practice nurse in our country. Full article

11 pages, 483 KiB

Open AccessArticle

Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study

by Giovanni Pallio, Natasha Irrera, Alessandra Bitto, Federica Mannino, Letteria Minutoli, Michelangelo Rottura, Socrate Pallio, Domenica Altavilla, Angela Alibrandi, Maria Concetta Marciano, Maria Righi, Carmen Mannucci, Vincenzo Arcoraci and Francesco Squadrito

J. Pers. Med. 2020, 10(2), 47; https://doi.org/10.3390/jpm10020047 - 1 Jun 2020

Cited by 3 | Viewed by 4119

Abstract

Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in [...] Read more.

Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A5*1 (G6986A), CYP3A4*1B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group (p = 0.001), as well as compared to the TM group (p = 0.004). Only IM pattern (p = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern (p = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system. Full article

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13 pages, 2356 KiB

Open AccessArticle

Equilibrium CT Texture Analysis for the Evaluation of Hepatic Fibrosis: Preliminary Evaluation against Histopathology and Extracellular Volume Fraction

by Jason Yeung, Balaji Ganeshan, Raymond Endozo, Andrew Hall, Simon Wan, Ashley Groves, Stuart A. Taylor and Steve Bandula

J. Pers. Med. 2020, 10(2), 46; https://doi.org/10.3390/jpm10020046 - 29 May 2020

Cited by 5 | Viewed by 4229

Abstract

Background: Evaluate equilibrium contrast-enhanced CT (EQ-CT) texture analysis (EQ-CTTA) against histologically-quantified fibrosis, serum-based enhanced liver fibrosis panel (ELF) and imaging-based extracellular volume fraction (ECV) in chronic hepatitis. Methods: This study was a re-analysis of image data from a previous prospective study. Pre- and [...] Read more.

Background: Evaluate equilibrium contrast-enhanced CT (EQ-CT) texture analysis (EQ-CTTA) against histologically-quantified fibrosis, serum-based enhanced liver fibrosis panel (ELF) and imaging-based extracellular volume fraction (ECV) in chronic hepatitis. Methods: This study was a re-analysis of image data from a previous prospective study. Pre- and equilibrium-phase post-IV contrast CT datasets were collected from patients with chronic hepatitis with contemporaneous liver biopsy and serum ELF measurement between April 2011 and July 2013. Biopsy samples were analysed to derive collagen proportionate area (CPA). EQ-CTTA was performed with a filtration histogram technique using texture analysis software, with texture quantification using statistical and histogram-based metrics (mean, skewness, standard deviation, entropy, etc.). Association between pre-contrast and EQ-CTTA against CPA, ECV and ELF was evaluated using Spearman’s rank correlation coefficient (r_s). Results: Complete datasets collected in 29 patients (16 male; 13 female), mean age (range): 49 (22–66 years). Liver ECV, CPA and ELF had a median (interquartile range) of 0.26 (0.24–0.29); 5.0 (3.0–13.7) and 9.71 (8.39–10.92). Difference in segment VII hepatic CTTA (medium texture scale) between EQ-CT and pre-contrast images was significantly and positively associated with ELF score (mean: r_s = 0.69, p < 0.001; skewness: r_s = 0.57, p = 0.007). Significant negative associations were observed between pre-contrast and EQ-CT whole hepatic CTTA (coarse texture scale) with CPA (pre-contrast, SD: r_s = −0.66, p < 0.001) and ECV (EQ-CT, entropy: r_s = −0.58, p = 0.006). Conclusions: Hepatic EQ-CTTA demonstrates significant association with validated markers of liver fibrosis, suggesting a role in non-invasive quantification of severity in diffuse fibrosis. Full article

(This article belongs to the Special Issue Biomedical Imaging and Cancers)

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14 pages, 1147 KiB

Open AccessArticle

Influence of ApoE Genotype and Clock T3111C Interaction with Cardiovascular Risk Factors on the Progression to Alzheimer’s Disease in Subjective Cognitive Decline and Mild Cognitive Impairment Patients

by Valentina Bessi, Juri Balestrini, Silvia Bagnoli, Salvatore Mazzeo, Giulia Giacomucci, Sonia Padiglioni, Irene Piaceri, Marco Carraro, Camilla Ferrari, Laura Bracco, Sandro Sorbi and Benedetta Nacmias

J. Pers. Med. 2020, 10(2), 45; https://doi.org/10.3390/jpm10020045 - 29 May 2020

Cited by 18 | Viewed by 4273

Abstract

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer’s disease. We aimed to evaluate the interaction between ApoE ε4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment [...] Read more.

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer’s disease. We aimed to evaluate the interaction between ApoE ε4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Methods: We included 68 patients who underwent clinical evaluation; neuropsychological assessment; ApoE, Clock and Per2 genotyping at baseline; and neuropsychological follow-up every 12–24 months for a mean of 13 years. We considered subjects who developed AD and non-converters. Results: Clock T3111C was detected in 47% of cases, Per2 C111G in 19% of cases. ApoE ε4 carriers presented higher risk of heart disease; Clock C-carriers were more frequently smokers than non C-carriers. During the follow-up, 17 patients progressed to AD. Age at baseline, ApoE ε 4 and dyslipidemia increased the risk of conversion to AD. ApoE ε4 carriers with history of dyslipidemia showed higher risk to convert to AD compared to ApoE ε4− groups and ApoE ε4+ without dyslipidemia patients. Clock C-carriers with history of blood hypertension had a higher risk of conversion to AD. Conclusions: ApoE and Clock T3111C seem to interact with cardiovascular risk factors in SCD and MCI patients influencing the progression to AD. Full article

(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)

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8 pages, 263 KiB

Open AccessArticle

Bruxism Throughout the Lifespan and Variants in MMP2, MMP9 and COMT

by Alexandre R. Vieira, Rafaela Scariot, Jennifer T. Gerber, Juliana Arid, Erika C. Küchler, Aline M. Sebastiani, Marcelo Palinkas, Kranya V. Díaz-Serrano, Carolina P. Torres, Simone C. H. Regalo, Paulo Nelson-Filho, Diego G. Bussaneli, Kathleen Deeley and Adriana Modesto

J. Pers. Med. 2020, 10(2), 44; https://doi.org/10.3390/jpm10020044 - 27 May 2020

Cited by 10 | Viewed by 4265

Abstract

Bruxism is a masticatory muscle activity characterized by grinding of the teeth and clenching of the jaw that causes tooth wear and breakage, temporomandibular joint disorders, muscle pain, and headache. Bruxism occurs in both adults and children. Clinical characteristics and habits were evaluated [...] Read more.

Bruxism is a masticatory muscle activity characterized by grinding of the teeth and clenching of the jaw that causes tooth wear and breakage, temporomandibular joint disorders, muscle pain, and headache. Bruxism occurs in both adults and children. Clinical characteristics and habits were evaluated in an adult sample. Moreover, we used DNA samples from 349 adults and 151 children to determine the presence of association with specific genes. Genomic DNA was obtained from saliva. The markers rs2241145 and rs243832 (metalloproteinase 2 (MMP2)), rs13925 and rs2236416 (metalloproteinase 9 (MMP9)), and rs6269 (cathecol-o-methyltransferase (COMT)) were genotyped. Data were submitted to statistical analysis with a significance level of 0.05. In adults, in univariate logistic regression, presence of caries, attrition, and use of alcohol were increased in bruxism individuals (p < 0.05). In addition, in adults, there was an association between bruxism and MMP9 (rs13925, p = 0.0001) and bruxism and COMT (rs6269, p = 0.003). In children, a borderline association was observed for MMP9 (rs2236416, p = 0.08). When we performed multivariate logistic regression analyses in adults, the same clinical characteristics remained associated with bruxism, and orthodontic treatment was also associated, besides rs13925, in the AG genotype (p = 0.015, OR_a: 3.40 (1.27–9.07)). For the first time, we provide statistical evidence that these genes are associate with bruxism. Full article

(This article belongs to the Special Issue Molecular Diagnosis and New Therapeutic Approach of Oral Diseases)

29 pages, 957 KiB

Open AccessFeature PaperArticle

Targeted Nutritional Intervention for Patients with Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1

by Rebecca Power, John M. Nolan, Alfonso Prado-Cabrero, Robert Coen, Warren Roche, Tommy Power, Alan N. Howard and Ríona Mulcahy

J. Pers. Med. 2020, 10(2), 43; https://doi.org/10.3390/jpm10020043 - 25 May 2020

Cited by 19 | Viewed by 7520

Abstract

Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy [...] Read more.

Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy individuals. Therefore, it is likely that these individuals will benefit from targeted nutritional intervention, given that poor nutrition is one of the many modifiable risk factors for MCI. Evidence to date suggests that these nutritional compounds can work independently to optimize the neurocognitive environment, primarily due to their antioxidant and anti-inflammatory properties. To date, however, no interventional studies have examined the potential synergistic effects of a combination of ω-3FAs, carotenoids and vitamin E on the cognitive function of patients with MCI. Individuals with clinically confirmed MCI consumed an ω-3FA plus carotenoid plus vitamin E formulation or placebo for 12 months. Cognitive performance was determined from tasks that assessed global cognition and episodic memory. Ω-3FAs, carotenoids, and vitamin E were measured in blood. Carotenoid concentrations were also measured in tissue (skin and retina). Individuals consuming the active intervention (n = 6; median [IQR] age 73.5 [69.5–80.5] years; 50% female) exhibited statistically significant improvements (p < 0.05, for all) in tissue carotenoid concentrations, and carotenoid and ω-3FA concentrations in blood. Trends in improvements in episodic memory and global cognition were also observed in this group. In contrast, the placebo group (n = 7; median [IQR] 72 (69.5–75.5) years; 89% female) remained unchanged or worsened for all measurements (p > 0.05). Despite a small sample size, this exploratory study is the first of its kind to identify trends in improved cognitive performance in individuals with MCI following supplementation with ω-3FAs, carotenoids, and vitamin E. Full article

(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)

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20 pages, 656 KiB

Open AccessReview

Obesity and Diabetes Mediated Chronic Inflammation: A Potential Biomarker in Alzheimer’s Disease

by Md Shahjalal Hossain Khan and Vijay Hegde

J. Pers. Med. 2020, 10(2), 42; https://doi.org/10.3390/jpm10020042 - 22 May 2020

Cited by 35 | Viewed by 7747

Abstract

Alzheimer’s disease (AD) is the sixth leading cause of death and is correlated with obesity, which is the second leading cause of preventable diseases in the United States. Obesity, diabetes, and AD share several common features, and inflammation emerges as the central link. [...] Read more.

Alzheimer’s disease (AD) is the sixth leading cause of death and is correlated with obesity, which is the second leading cause of preventable diseases in the United States. Obesity, diabetes, and AD share several common features, and inflammation emerges as the central link. High-calorie intake, elevated free fatty acids, and impaired endocrine function leads to insulin resistance and systemic inflammation. Systemic inflammation triggers neuro-inflammation, which eventually hinders the metabolic and regulatory function of the brain mitochondria leading to neuronal damage and subsequent AD-related cognitive decline. As an early event in the pathogenesis of AD, chronic inflammation could be considered as a potential biomarker in the treatment strategies for AD. Full article

(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)

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20 pages, 296 KiB

Open AccessReview

Wise Management of Ovarian Cancer: On the Cutting Edge

by Stergios Boussios, Christos Mikropoulos, Eleftherios Samartzis, Peeter Karihtala, Michele Moschetta, Matin Sheriff, Afroditi Karathanasi, Agne Sadauskaite, Elie Rassy and Nicholas Pavlidis

J. Pers. Med. 2020, 10(2), 41; https://doi.org/10.3390/jpm10020041 - 21 May 2020

Cited by 54 | Viewed by 8206

Abstract

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. [...] Read more.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

12 pages, 1357 KiB

Open AccessArticle

The CFTR Mutation c.3453G > C (D1152H) Confers an Anion Selectivity Defect in Primary Airway Tissue that Can be Rescued by Ivacaftor

by Onofrio Laselva, Theo J. Moraes, Gengming He, Claire Bartlett, Ida Szàrics, Hong Ouyang, Tarini N. A. Gunawardena, Lisa Strug, Christine E. Bear and Tanja Gonska

J. Pers. Med. 2020, 10(2), 40; https://doi.org/10.3390/jpm10020040 - 13 May 2020

Cited by 24 | Viewed by 5411

Abstract

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene variant, c.3453G > C (D1152H), is associated with mild Cystic Fibrosis (CF) disease, though there is considerable clinical variability ranging from no detectable symptoms to lung disease with early acquisition of Pseudomonas aeruginosa. The [...] Read more.

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene variant, c.3453G > C (D1152H), is associated with mild Cystic Fibrosis (CF) disease, though there is considerable clinical variability ranging from no detectable symptoms to lung disease with early acquisition of Pseudomonas aeruginosa. The approval extension of ivacaftor, the first CFTR modulator drug approved, to include D1152H was based on a positive drug response of defective CFTR-D1152H chloride channel function when expressed in FRT cells. Functional analyses of primary human nasal epithelial cells (HNE) from an individual homozygous for D1152H now revealed that while CFTR-D1152H demonstrated normal, wild-type level chloride conductance, its bicarbonate-selective conductance was impaired. Treatment with ivacaftor increased this bicarbonate-selective conductance. Extensive genetic, protein and functional analysis of the nasal cells of this D1152H/D1152H patient revealed a 90% reduction of CFTR transcripts due to the homozygous presence of the 5T polymorphism in the poly-T tract forming a complex allele with D1152H. Thus, we confirm previous observation in patient-derived tissue that 10% normal CFTR transcripts confer normal, wild-type level chloride channel activity. Together, this study highlights the benefit of patient-derived tissues to study the functional expression and pharmacological modulation of CF-causing mutations, in order to understand pathogenesis and therapeutic responses. Full article

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7 pages, 1193 KiB

Open AccessArticle

Increased Demodex Density in Patients Hospitalized for Worsening Heart Failure

by Serkan Yüksel and Esra Pancar Yüksel

J. Pers. Med. 2020, 10(2), 39; https://doi.org/10.3390/jpm10020039 - 13 May 2020

Cited by 3 | Viewed by 3880

Abstract

Infection is an important factor leading to the exacerbation of heart failure (HF), resulting in hospitalization. Demodex species are obligatory parasites in human skin, and increased density was reported in immunocompromised patients. In this study, we aimed to investigate the Demodex density in [...] Read more.

Infection is an important factor leading to the exacerbation of heart failure (HF), resulting in hospitalization. Demodex species are obligatory parasites in human skin, and increased density was reported in immunocompromised patients. In this study, we aimed to investigate the Demodex density in hospitalized HF patients compared to that of healthy controls. Methods: This study included 36 HF patients and 36 age and sex-matched healthy controls. Five standardized biopsies were taken from the face of participants and assessed for Demodex by a light microscope. Results: At least one Demodex mite was detected in 20 HF patients and nine of the control group. The number of Demodex mites was significantly higher in the HF group (median 1; min. 0 and max. 10) compared to the control group (median 0; minimum. 0 and maximum. 3). Demodicidosis was positive in 14 of the HF patients. Demodicidosis was not detected in the control group. Conclusions: This study showed that Demodex positivity is more common in HF patients hospitalized for HF exacerbation. Demodicidosis should be considered in hospitalized HF patients. Full article

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14 pages, 381 KiB

Open AccessFeature PaperArticle

Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network

by John A. Lynch, Richard R. Sharp, Sharon A. Aufox, Sarah T. Bland, Carrie Blout, Deborah J. Bowen, Adam H. Buchanan, Colin Halverson, Margaret Harr, Scott J. Hebbring, Nora Henrikson, Christin Hoell, Ingrid A. Holm, Gail Jarvik, Iftikhar J. Kullo, David C. Kochan, Eric B. Larson, Amanda Lazzeri, Kathleen A. Leppig, Jill Madden, Maddalena Marasa, Melanie F. Myers, Josh Peterson, Cynthia A. Prows, Alanna Kulchak Rahm, James Ralston, Hila Milo Rasouly, Aaron Scrol, Maureen E. Smith, Amy Sturm, Kelsey Stuttgen, Georgia Wiesner, Marc S. Williams, Julia Wynn and Janet L. Williams Show full author list Hide full author list

J. Pers. Med. 2020, 10(2), 38; https://doi.org/10.3390/jpm10020038 - 13 May 2020

Cited by 14 | Viewed by 6364

Abstract

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine [...] Read more.

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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22 pages, 323 KiB

Open AccessReview

Future Trends in Nebulized Therapies for Pulmonary Disease

by Sean D. McCarthy, Héctor E. González and Brendan D. Higgins

J. Pers. Med. 2020, 10(2), 37; https://doi.org/10.3390/jpm10020037 - 10 May 2020

Cited by 41 | Viewed by 8901

Abstract

Aerosol therapy is a key modality for drug delivery to the lungs of respiratory disease patients. Aerosol therapy improves therapeutic effects by directly targeting diseased lung regions for rapid onset of action, requiring smaller doses than oral or intravenous delivery and minimizing systemic [...] Read more.

Aerosol therapy is a key modality for drug delivery to the lungs of respiratory disease patients. Aerosol therapy improves therapeutic effects by directly targeting diseased lung regions for rapid onset of action, requiring smaller doses than oral or intravenous delivery and minimizing systemic side effects. In order to optimize treatment of critically ill patients, the efficacy of aerosol therapy depends on lung morphology, breathing patterns, aerosol droplet characteristics, disease, mechanical ventilation, pharmacokinetics, and the pharmacodynamics of cell-drug interactions. While aerosol characteristics are influenced by drug formulations and device mechanisms, most other factors are reliant on individual patient variables. This has led to increased efforts towards more personalized therapeutic approaches to optimize pulmonary drug delivery and improve selection of effective drug types for individual patients. Vibrating mesh nebulizers (VMN) are the dominant device in clinical trials involving mechanical ventilation and emerging drugs. In this review, we consider the use of VMN during mechanical ventilation in intensive care units. We aim to link VMN fundamentals to applications in mechanically ventilated patients and look to the future use of VMN in emerging personalized therapeutic drugs. Full article

(This article belongs to the Special Issue The Interface between Human Physiology and Medical Device Development)

11 pages, 2961 KiB

Open AccessArticle

Comparison of the Hemodynamic Performance of Two Neuromuscular Electrical Stimulation Devices Applied to the Lower Limb

by Sahar Avazzadeh, Andrea O’Farrell, Kate Flaherty, Sandra O’Connell, Gearóid ÓLaighin and Leo R. Quinlan

J. Pers. Med. 2020, 10(2), 36; https://doi.org/10.3390/jpm10020036 - 7 May 2020

Cited by 4 | Viewed by 4460

Abstract

Currently, 1% of the population of the Western world suffers from venous leg ulcers as a result of chronic venous insufficiency. Current treatment involves the use of moist wound healing, compression bandages, and intermittent pneumatic compression. Neuromuscular electrical stimulation is a novel potential [...] Read more.

Currently, 1% of the population of the Western world suffers from venous leg ulcers as a result of chronic venous insufficiency. Current treatment involves the use of moist wound healing, compression bandages, and intermittent pneumatic compression. Neuromuscular electrical stimulation is a novel potential new therapeutic method for the promotion of increased lower limb hemodynamics. The aim of this study was to measure the hemodynamic changes in the lower limb with the use of two neuromuscular electrical stimulation devices. Twelve healthy volunteers received two neuromuscular stimulation device interventions. The Geko^TM and National University of Ireland (NUI) Galway neuromuscular electrical stimulation devices were randomized between dominant and non-dominant legs. Hemodynamic measurements of peak venous velocity (cm/s), the time average mean velocity (TAMEAN) (cm/s), and ejected volume (mL) of blood were recorded. Peak venous velocity was significantly increased by the Geko^TM and the NUI Galway device compared to baseline blood flow (p < 0.0001), while only the voluntary contraction produced significant increases in TAMEAN and ejected volume (both p < 0.05). Neuromuscular muscular electrical stimulation can produce adequate increases in lower limb hemodynamics sufficient to prevent venous stasis. Greater use of neuromuscular stimulation devices could be considered in the treatment of conditions related to chronic venous insufficiency but requires further research. Full article

(This article belongs to the Special Issue The Interface between Human Physiology and Medical Device Development)

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4 pages, 198 KiB

Open AccessEditorial

Personalized Dentistry: Approaching a New Way for Diagnosis and Treatment of Oral Diseases

by Romeo Patini

J. Pers. Med. 2020, 10(2), 35; https://doi.org/10.3390/jpm10020035 - 1 May 2020

Cited by 4 | Viewed by 4519

Abstract

For years, it has been thought that the field of dentistry was referring exclusively to some diseases that strictly affect the oral cavity. Dental caries, periodontal disease, and pathologies associated with their worsening were considered almost the only interest in scientific research in [...] Read more.

For years, it has been thought that the field of dentistry was referring exclusively to some diseases that strictly affect the oral cavity. Dental caries, periodontal disease, and pathologies associated with their worsening were considered almost the only interest in scientific research in dentistry. Recent studies have begun to shed light on the effect of the oral microbiota on general health and on the crucial role of dentistry in its maintenance. In this way, we came to understand that the bacterial populations that make up the oral microbiota can vary profoundly between individuals and that contribute in a fundamental way to outlining the so-called “oral signature”. This characteristic is called into question to evaluate the susceptibility, or lack thereof, of the subject to the contraction of a wide range of pathologies, apparently not connected with oral health. From this evidence, it will also be possible to study therapeutic approaches aimed at the eradication of species considered at risk or colonization with species considered protective; thus, giving life to so-called “personalized dentistry”. Therefore, this Special Issue is aimed at spreading the scientific knowledge over the current limits in terms of new molecular and culturomic approaches towards the diagnosis of oral microbiota and the treatment techniques of eventually associated systemic diseases. In vivo studies and systematic literature reviews with quantitative analysis of results, when possible, will be given a high priority. Full article

(This article belongs to the Special Issue Molecular Diagnosis and New Therapeutic Approach of Oral Diseases)

27 pages, 1261 KiB

Open AccessReview

Neurophysiological Hallmarks of Neurodegenerative Cognitive Decline: The Study of Brain Connectivity as A Biomarker of Early Dementia

by Paolo Maria Rossini, Francesca Miraglia, Francesca Alù, Maria Cotelli, Florinda Ferreri, Riccardo Di Iorio, Francesco Iodice and Fabrizio Vecchio

J. Pers. Med. 2020, 10(2), 34; https://doi.org/10.3390/jpm10020034 - 30 Apr 2020

Cited by 29 | Viewed by 7207

Abstract

Neurodegenerative processes of various types of dementia start years before symptoms, but the presence of a “neural reserve”, which continuously feeds and supports neuroplastic mechanisms, helps the aging brain to preserve most of its functions within the “normality” frame. Mild cognitive impairment (MCI) [...] Read more.

Neurodegenerative processes of various types of dementia start years before symptoms, but the presence of a “neural reserve”, which continuously feeds and supports neuroplastic mechanisms, helps the aging brain to preserve most of its functions within the “normality” frame. Mild cognitive impairment (MCI) is an intermediate stage between dementia and normal brain aging. About 50% of MCI subjects are already in a stage that is prodromal-to-dementia and during the following 3 to 5 years will develop clinically evident symptoms, while the other 50% remains at MCI or returns to normal. If the risk factors favoring degenerative mechanisms are modified during early stages (i.e., in the prodromal), the degenerative process and the loss of abilities in daily living activities will be delayed. It is therefore extremely important to have biomarkers able to identify—in association with neuropsychological tests—prodromal-to-dementia MCI subjects as early as possible. MCI is a large (i.e., several million in EU) and substantially healthy population; therefore, biomarkers should be financially affordable, largely available and non-invasive, but still accurate in their diagnostic prediction. Neurodegeneration initially affects synaptic transmission and brain connectivity; methods exploring them would represent a 1st line screening. Neurophysiological techniques able to evaluate mechanisms of synaptic function and brain connectivity are attracting general interest and are described here. Results are quite encouraging and suggest that by the application of artificial intelligence (i.e., learning-machine), neurophysiological techniques represent valid biomarkers for screening campaigns of the MCI population. Full article

(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)

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9 pages, 1318 KiB

Open AccessArticle

SPIDER as A Rehabilitation Tool for Patients with Neurological Disabilities: The Preliminary Research

by Sebastian Glowinski and Andrzej Blazejewski

J. Pers. Med. 2020, 10(2), 33; https://doi.org/10.3390/jpm10020033 - 30 Apr 2020

Cited by 12 | Viewed by 5531

Abstract

(1) Background and purpose: SPIDER (Strengthening Program for Intensive Developmental Exercises and activities for Reaching health capability) is dedicated for patients suffering from Cerebral Palsy, Sclerosis Multiplex, Spinal Bifida, Spinal Muscular Atrophy and strokes. Authors proposed a computer model for the evaluation patient’s [...] Read more.

(1) Background and purpose: SPIDER (Strengthening Program for Intensive Developmental Exercises and activities for Reaching health capability) is dedicated for patients suffering from Cerebral Palsy, Sclerosis Multiplex, Spinal Bifida, Spinal Muscular Atrophy and strokes. Authors proposed a computer model for the evaluation patient’s condition and the rehabilitation progress. (2) Methods: The 2-year-old and 76-year-old patients with neurological problems, who underwent individual therapy included balancing and coordination practising with SPIDER device. The model comparing the forces, which act during the therapy process, such as the expander and gravity forces, was worked out using Matlab software. (3) Results: The model allowed controlling the changes into the patients centre of gravity forces continuous adjustment and postural stability during any patient’s movement. After rehabilitation sessions, lasted for 28 days during which patients received the progress information and the therapist got the numeric data, regarding the period of the therapy. (4) Conclusions: The first patient was able to move, dramatically improved the ability to balance and coordination. The second one presented change in gait, improvement in mobility, motor function and decreased fall risk. The proposed computer model gives information about the forces acting to the patient body. The physiotherapist can evaluate the progress of patient verticalization and receive information, in the form of numbers and charts. Full article

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16 pages, 1137 KiB

Open AccessArticle

Deficits in Mitochondrial Spare Respiratory Capacity Contribute to the Neuropsychological Changes of Alzheimer’s Disease

by Simon M. Bell, Matteo De Marco, Katy Barnes, Pamela J. Shaw, Laura Ferraiuolo, Daniel J. Blackburn, Heather Mortiboys and Annalena Venneri

J. Pers. Med. 2020, 10(2), 32; https://doi.org/10.3390/jpm10020032 - 29 Apr 2020

Cited by 23 | Viewed by 6720

Abstract

Alzheimer’s disease (AD) is diagnosed using neuropsychological testing, supported by amyloid and tau biomarkers and neuroimaging abnormalities. The cause of neuropsychological changes is not clear since they do not correlate with biomarkers. This study investigated if changes in cellular metabolism in AD correlate [...] Read more.

Alzheimer’s disease (AD) is diagnosed using neuropsychological testing, supported by amyloid and tau biomarkers and neuroimaging abnormalities. The cause of neuropsychological changes is not clear since they do not correlate with biomarkers. This study investigated if changes in cellular metabolism in AD correlate with neuropsychological changes. Fibroblasts were taken from 10 AD patients and 10 controls. Metabolic assessment included measuring total cellular ATP, extracellular lactate, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolytic function. All participants were assessed with neuropsychological testing and brain structural MRI. AD patients had significantly lower scores in delayed and immediate recall, semantic memory, phonemic fluency and Mini Mental State Examination (MMSE). AD patients also had significantly smaller left hippocampal, left parietal, right parietal and anterior medial prefrontal cortical grey matter volumes. Fibroblast MMP, mitochondrial spare respiratory capacity (MSRC), glycolytic reserve, and extracellular lactate were found to be lower in AD patients. MSRC/MMP correlated significantly with semantic memory, immediate and delayed episodic recall. Correlations between MSRC and delayed episodic recall remained significant after controlling for age, education and brain reserve. Grey matter volumes did not correlate with MRSC/MMP. AD fibroblast metabolic assessment may represent an emergent disease biomarker of AD. Full article

(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)

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12 pages, 1469 KiB

Open AccessArticle

Application of Machine Learning Technique to Distinguish Parkinson’s Disease Dementia and Alzheimer’s Dementia: Predictive Power of Parkinson’s Disease-Related Non-Motor Symptoms and Neuropsychological Profile

by Haewon Byeon

J. Pers. Med. 2020, 10(2), 31; https://doi.org/10.3390/jpm10020031 - 28 Apr 2020

Cited by 12 | Viewed by 4825

Abstract

In order to develop a predictive model that can distinguish Parkinson’s disease dementia (PDD) from other dementia types, such as Alzheimer’s dementia (AD), it is necessary to evaluate and identify the predictive accuracy of the cognitive profile while considering the non-motor symptoms, such [...] Read more.

In order to develop a predictive model that can distinguish Parkinson’s disease dementia (PDD) from other dementia types, such as Alzheimer’s dementia (AD), it is necessary to evaluate and identify the predictive accuracy of the cognitive profile while considering the non-motor symptoms, such as depression and rapid eye movement (REM) sleep behavior disorders. This study compared Parkinson’s disease (PD)’s non-motor symptoms and the diagnostic predictive power of cognitive profiles that distinguish AD and PD using machine learning. This study analyzed 118 patients with AD and 110 patients with PDD, and all subjects were 60 years or older. In order to develop the PDD prediction model, the dataset was divided into training data (70%) and test data (30%). The prediction accuracy of the model was calculated by the recognition rate. The results of this study show that Parkinson-related non-motor symptoms, such as REM sleep behavior disorders, and cognitive screening tests, such as Korean version of Montreal Cognitive Assessment, were highly accurate factors for predicting PDD. It is required to develop customized screening tests that can detect PDD in the early stage based on these results. Furthermore, it is believed that including biomarkers such as brain images or cerebrospinal fluid as input variables will be more useful for developing PDD prediction models in the future. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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12 pages, 212 KiB

Open AccessArticle

Returning Results in the Genomic Era: Initial Experiences of the eMERGE Network

by Georgia L. Wiesner, Alanna Kulchak Rahm, Paul Appelbaum, Sharon Aufox, Sarah T. Bland, Carrie L. Blout, Kurt D. Christensen, Wendy K. Chung, Ellen Wright Clayton, Robert C. Green, Margaret H. Harr, Nora Henrikson, Christin Hoell, Ingrid A. Holm, Gail P. Jarvik, Iftikhar J. Kullo, Philip E. Lammers, Eric B. Larson, Noralane M. Lindor, Maddalena Marasa, Melanie F. Myers, Josh F. Peterson, Cynthia A. Prows, James D. Ralston, Hila Milo Rasouly, Richard R. Sharp, Maureen E. Smith, Sara L. Van Driest, Janet L. Williams, Marc S. Williams, Julia Wynn and Kathleen A. Leppig Show full author list Hide full author list

J. Pers. Med. 2020, 10(2), 30; https://doi.org/10.3390/jpm10020030 - 27 Apr 2020

Cited by 39 | Viewed by 7157

Abstract

A goal of the 3rd phase of the Electronic Medical Records and Genomics (eMERGE3) Network was to examine the return of results (RoR) of actionable variants in more than 100 genes to consenting participants and their healthcare providers. Each of the 10 eMERGE [...] Read more.

A goal of the 3rd phase of the Electronic Medical Records and Genomics (eMERGE3) Network was to examine the return of results (RoR) of actionable variants in more than 100 genes to consenting participants and their healthcare providers. Each of the 10 eMERGE sites developed plans for three essential elements of the RoR process: Disclosure to the participant, notification of the health care provider, and integration of results into the electronic health record (EHR). Procedures and protocols around these three elements were adapted as appropriate to individual site requirements and limitations. Detailed information about the RoR procedures at each site was obtained through structured telephone interviews and follow-up surveys with the clinical investigator leading or participating in the RoR process at each eMERGE3 institution. Because RoR processes at each of the 10 sites allowed for taking into account differences in population, disease focus and institutional requirements, significant heterogeneity of process was identified, including variability in the order in which patients and clinicians were notified and results were placed in the EHR. This heterogeneity in the process flow for eMERGE3 RoR reflects the “real world” of genomic medicine in which RoR procedures must be shaped by the needs of the patients and institutional environments. Full article

15 pages, 1092 KiB

Open AccessFeature PaperArticle

Pharmacogenomic (PGx) Counseling: Exploring Participant Questions about PGx Test Results

by Tara Schmidlen, Amy C. Sturm and Laura B. Scheinfeldt

J. Pers. Med. 2020, 10(2), 29; https://doi.org/10.3390/jpm10020029 - 23 Apr 2020

Cited by 6 | Viewed by 5379

Abstract

As pharmacogenomic (PGx) use in healthcare increases, a better understanding of patient needs will be necessary to guide PGx result delivery. The Coriell Personalized Medicine Collaborative (CPMC) is a prospective study investigating the utility of personalized medicine. Participants received online genetic risk reports [...] Read more.

As pharmacogenomic (PGx) use in healthcare increases, a better understanding of patient needs will be necessary to guide PGx result delivery. The Coriell Personalized Medicine Collaborative (CPMC) is a prospective study investigating the utility of personalized medicine. Participants received online genetic risk reports for 27 potentially actionable complex diseases and 7 drug–gene pairs and could request free, telephone-based genetic counseling (GC). To explore the needs of individuals receiving PGx results, we conducted a retrospective qualitative review of inquiries from CPMC participants who requested counseling from March 2009 to February 2017. Eighty out of 690 (12%) total GC inquiries were focused on the discussion of PGx results, and six salient themes emerged: “general help”, “issues with drugs”, “relevant disease experience”, “what do I do now?”, “sharing results”, and “other drugs”. The number of reported medications with a corresponding PGx result and participant engagement were significantly associated with PGx GC requests (p < 0.01 and p < 0.02, respectively). Our work illustrates a range of questions raised by study participants receiving PGx test results, most of which were addressed by a genetic counselor with few requiring referrals to prescribing providers or pharmacists. These results further support a role for genetic counselors in the team-based approach to optimal PGx result delivery. Full article

(This article belongs to the Special Issue Pharmacogenomics: From Basic Research to Clinical Implementation)

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14 pages, 3708 KiB

Open AccessArticle

Statistical Shape Analysis of Ascending Thoracic Aortic Aneurysm: Correlation between Shape and Biomechanical Descriptors

by Federica Cosentino, Giuseppe M Raffa, Giovanni Gentile, Valentina Agnese, Diego Bellavia, Michele Pilato and Salvatore Pasta

J. Pers. Med. 2020, 10(2), 28; https://doi.org/10.3390/jpm10020028 - 22 Apr 2020

Cited by 28 | Viewed by 6450

Abstract

An ascending thoracic aortic aneurysm (ATAA) is a heterogeneous disease showing different patterns of aortic dilatation and valve morphologies, each with distinct clinical course. This study aimed to explore the aortic morphology and the associations between shape and function in a population of [...] Read more.

An ascending thoracic aortic aneurysm (ATAA) is a heterogeneous disease showing different patterns of aortic dilatation and valve morphologies, each with distinct clinical course. This study aimed to explore the aortic morphology and the associations between shape and function in a population of ATAA, while further assessing novel risk models of aortic surgery not based on aortic size. Shape variability of n = 106 patients with ATAA and different valve morphologies (i.e., bicuspid versus tricuspid aortic valve) was estimated by statistical shape analysis (SSA) to compute a mean aortic shape and its deformation. Once the computational atlas was built, principal component analysis (PCA) allowed to reduce the complex ATAA anatomy to a few shape modes, which were correlated to shear stress and aortic strain, as determined by computational analysis. Findings demonstrated that shape modes are associated to specific morphological features of aneurysmal aorta as the vessel tortuosity and local bulging of the ATAA. A predictive model, built with principal shape modes of the ATAA wall, achieved better performance in stratifying surgically operated ATAAs versus monitored ATAAs, with respect to a baseline model using the maximum aortic diameter. Using current imaging resources, this study demonstrated the potential of SSA to investigate the association between shape and function in ATAAs, with the goal of developing a personalized approach for the treatment of the severity of aneurysmal aorta. Full article

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9 pages, 1002 KiB

Open AccessArticle

Opioid Induced Hyperalgesia, a Research Phenomenon or a Clinical Reality? Results of a Canadian Survey

by Grisell Vargas-Schaffer, Suzie Paquet, Andrée Neron and Jennifer Cogan

J. Pers. Med. 2020, 10(2), 27; https://doi.org/10.3390/jpm10020027 - 21 Apr 2020

Cited by 18 | Viewed by 8609

Abstract

Background: Very little is known regarding the prevalence of opioid induced hyperalgesia (OIH) in day to day medical practice. The aim of this study was to evaluate the physician’s perception of the prevalence of OIH within their practice, and to assess the level [...] Read more.

Background: Very little is known regarding the prevalence of opioid induced hyperalgesia (OIH) in day to day medical practice. The aim of this study was to evaluate the physician’s perception of the prevalence of OIH within their practice, and to assess the level of physician’s knowledge with respect to the identification and treatment of this problem. Methods: An electronic questionnaire was distributed to physicians who work in anesthesiology, chronic pain, and/or palliative care in Canada. Results: Of the 462 responses received, most were from male (69%) anesthesiologists (89.6%), in the age range of 36 to 64 years old (79.8%). In this study, the suspected prevalence of OIH using the average number of patients treated per year with opioids was 0.002% per patient per physician practice year for acute pain, and 0.01% per patient per physician practice year for chronic pain. Most physicians (70.2%) did not use clinical tests to help make a diagnosis of OIH. The treatment modalities most frequently used were the addition of an NMDA antagonist, combined with lowering the opioid doses and using opioid rotation. Conclusions: The perceived prevalence of OIH in clinical practice is a relatively rare phenomenon. Furthermore, more than half of physicians did not use a clinical test to confirm the diagnosis of OIH. The two main treatment modalities used were NMDA antagonists and opioid rotation. The criteria for the diagnosis of OIH still need to be accurately defined. Full article

(This article belongs to the Special Issue Chronic Pain)

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14 pages, 1915 KiB

Open AccessReview

New Insights into the Molecular Bases of Familial Alzheimer’s Disease

by Valeria D’Argenio and Daniela Sarnataro

J. Pers. Med. 2020, 10(2), 26; https://doi.org/10.3390/jpm10020026 - 19 Apr 2020

Cited by 21 | Viewed by 8331

Abstract

Like several neurodegenerative disorders, such as Prion and Parkinson diseases, Alzheimer’s disease (AD) is characterized by spreading mechanism of aggregated proteins in the brain in a typical “prion-like” manner. Recent genetic studies have identified in four genes associated with inherited AD (amyloid precursor [...] Read more.

Like several neurodegenerative disorders, such as Prion and Parkinson diseases, Alzheimer’s disease (AD) is characterized by spreading mechanism of aggregated proteins in the brain in a typical “prion-like” manner. Recent genetic studies have identified in four genes associated with inherited AD (amyloid precursor protein-APP, Presenilin-1, Presenilin-2 and Apolipoprotein E), rare mutations which cause dysregulation of APP processing and alterations of folding of the derived amyloid beta peptide (Aβ). Accumulation and aggregation of Aβ in the brain can trigger a series of intracellular events, including hyperphosphorylation of tau protein, leading to the pathological features of AD. However, mutations in these four genes account for a small of the total genetic risk for familial AD (FAD). Genome-wide association studies have recently led to the identification of additional AD candidate genes. Here, we review an update of well-established, highly penetrant FAD-causing genes with correlation to the protein misfolding pathway, and novel emerging candidate FAD genes, as well as inherited risk factors. Knowledge of these genes and of their correlated biochemical cascade will provide several potential targets for treatment of AD and aging-related disorders. Full article

(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)

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9 pages, 733 KiB

Open AccessArticle

The Brain Metabolic Correlates of the Main Indices of Neuropsychological Assessment in Alzheimer’s Disease

by Agostino Chiaravalloti, Maria Ricci, Daniele Di Biagio, Luca Filippi, Alessandro Martorana and Orazio Schillaci

J. Pers. Med. 2020, 10(2), 25; https://doi.org/10.3390/jpm10020025 - 18 Apr 2020

Cited by 6 | Viewed by 4535

Abstract

Background: The study aimed to investigate the relationships between F-18 fluorodeoxyglucose (18F)FDG uptake and neuropsychological assessment in Alzheimer’s disease (AD). Methods: We evaluated 116 subjects with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a brain PET/CT with (18F)FDG, cerebrospinal fluid [...] Read more.

Background: The study aimed to investigate the relationships between F-18 fluorodeoxyglucose (18F)FDG uptake and neuropsychological assessment in Alzheimer’s disease (AD). Methods: We evaluated 116 subjects with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a brain PET/CT with (18F)FDG, cerebrospinal fluid (CSF) assay, mini-mental state examination (MMSE) and further neuropsychological tests: Rey auditory verbal learning test, immediate recall (RAVLT immediate); Rey auditory verbal learning test, delayed recall (RAVLT, delayed); Rey complex figure test, copy (RCFT, copy); Rey complex figure test, delayed recall (RCFT, delayed); Raven’s colored progressive matrices (RCPM); phonological word fluency test (PWF) and Stroop test. We performed the statistical analysis by using statistical parametric mapping (SPM12; Wellcome Department of Cognitive Neurology, London, UK). Results: A significant relationship has been reported between (18F)FDG uptake and RAVLT immediate test in Brodmann area (BA)37 and BA22 and with RCFT, copy in BA40, and BA7. We did not find any significant relationships with other tests. Conclusion: In the AD population, brain (18F)FDG uptake is moderately related to the neuropsychological assessment, suggesting a limited impact on statistical data analysis of glucose brain metabolism. Full article

(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)

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