Journal of Personalized Medicine

2 pages, 178 KiB

Open AccessEditorial

Personalized Diagnosis and Therapy for Multiple Sclerosis

by Cristina Ramo-Tello

J. Pers. Med. 2022, 12(6), 1017; https://doi.org/10.3390/jpm12061017 - 20 Jun 2022

Viewed by 1476

This Special Issue, entitled “Personalized Diagnosis and Therapy for Multiple Sclerosis” encompasses eight publications that we consider relevant, because their reading will help the clinician working regularly with people who suffer from multiple sclerosis (MS) [...] Full article

(This article belongs to the Special Issue Personalized Diagnosis and Therapy for Multiple Sclerosis)

12 pages, 38781 KiB

Open AccessArticle

HR-pQCT for the Evaluation of Muscle Quality and Intramuscular Fat Infiltration in Ageing Skeletal Muscle

by Simon Kwoon-Ho Chow, Marloes van Mourik, Vivian Wing-Yin Hung, Ning Zhang, Michelle Meng-Chen Li, Ronald Man-Yeung Wong, Kwok-Sui Leung and Wing-Hoi Cheung

J. Pers. Med. 2022, 12(6), 1016; https://doi.org/10.3390/jpm12061016 - 20 Jun 2022

Cited by 2 | Viewed by 2806

Abstract

Myosteatosis is the infiltration of fat in skeletal muscle during the onset of sarcopenia. The quantification of intramuscular adipose tissue (IMAT) can be a feasible imaging modality for the clinical assessment of myosteatosis, important for the early identification of sarcopenia patients and timely [...] Read more.

Myosteatosis is the infiltration of fat in skeletal muscle during the onset of sarcopenia. The quantification of intramuscular adipose tissue (IMAT) can be a feasible imaging modality for the clinical assessment of myosteatosis, important for the early identification of sarcopenia patients and timely intervention decisions. There is currently no standardized method or consensus for such an application. The aim of this study was to develop a method for the detection and analysis of IMAT in clinical HR-pQCT images of the distal tibia to evaluate skeletal muscle during the ageing process, validated with animal and clinical experimentation. A pre-clinical model of ovariectomized (OVX) rats with known intramuscular fat infiltration was used, where gastrocnemii were scanned by micro-computed tomography (micro-CT) at an 8.4 μm isotropic voxel size, and the images were analyzed using our modified IMAT analysis protocol. IMAT, muscle density (MD), and muscle volume (MV) were compared with SHAM controls validated with Oil-red-O (ORO) staining. Furthermore, the segmentation and IMAT evaluation method was applied to 30 human subjects at ages from 18 to 81 (mean = 47.3 ± 19.2). Muscle-related parameters were analyzed with functional outcomes. In the animal model, the micro-CT adipose tissue-related parameter of IMAT% segmented at −600 HU to 100 HU was shown to strongly associate with the ORO-positively stained area (r = 0.898, p = 0.002). For the human subjects, at an adjusted threshold of −600 to −20 HU, moderate positive correlations were found between MV and MD (r = 0.642, p < 0.001), and between MV and IMAT volume (r = 0.618, p < 0.01). Moderate negative correlations were detected between MD and IMAT% (r = −0.640, p < 0.001). Strong and moderate associations were found between age and MD (r = −0.763, p < 0.01), and age and IMAT (r = 0.559, p < 0.01). There was also a strong correlation between IMAT% and chair rise time (r = 0.671, p < 0.01). The proposed HR-pQCT evaluation protocol for intramuscular adipose-tissue produced MD and IMAT results that were associated with age and physical performance measures, and were of good predictive value for the progression of myosteatosis or sarcopenia. The protocol was also validated on animal skeletal muscle samples that showed a good representation of histological lipid content with positive correlations, further supporting the clinical application for the rapid evaluation of muscle quality and objective quantification of skeletal muscle at the peripheral for sarcopenia assessment. Full article

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

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9 pages, 1064 KiB

Open AccessReview

Morphological Investigation of Mandibular Lingula: A Literature Review

by Kun-Jung Hsu, Hui-Na Lee and Chun-Ming Chen

J. Pers. Med. 2022, 12(6), 1015; https://doi.org/10.3390/jpm12061015 - 20 Jun 2022

Cited by 2 | Viewed by 2550

Abstract

Purpose: The purpose of the study was to review the literature on the shape of the mandibular lingula. Methods: English articles published from 1970 to 2021 in databases (PubMed, Web of Science, and Embase) were selected. Articles meeting the search strategy were evaluated [...] Read more.

Purpose: The purpose of the study was to review the literature on the shape of the mandibular lingula. Methods: English articles published from 1970 to 2021 in databases (PubMed, Web of Science, and Embase) were selected. Articles meeting the search strategy were evaluated based on the eligibility criteria (participants aged 18 years and over). Dry mandibles and cone beam computed tomography (CBCT) images were used as research materials. The shapes of mandibular lingula were classified as triangular, truncated, nodular, and assimilated. Results: Based on the eligibility criteria, 10 articles (six with dry mandibles and four with CBCT images) were selected for full-text reading and detailed examination. In the dry mandible group, triangular, truncated, nodular, and assimilated lingula were observed on 446, 398, 232, and 69 sides, respectively. In the CBCT group, nodular, truncated, triangular, and assimilated lingula were observed on 892, 517, 267, and 88 sides, respectively. Therefore, the most common lingula types in the dry mandible and CBCT groups were different. The assimilated type was the least common in both groups. Conclusion: In the dry mandible group, the most common lingula type was triangular, followed by truncated, nodular, and assimilated types. In the CBCT group, the most common lingula type was nodular, followed by truncated, triangular, and assimilated types. There were no significant differences in lingula types between the left and right sides of the mandible. Full article

(This article belongs to the Special Issue Prevention and Management of Oral Healthcare)

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9 pages, 260 KiB

Open AccessArticle

Surgical Treatment for Empyema Thoracis: Prognostic Role of Preoperative Transthoracic Echocardiography and Serum Calcium

by Pei-Yi Chu, Yu-Cheng Wu, Ya-Ling Lin, Hung Chang, Shih-Chun Lee, Tsai-Wang Huang and Yuan-Ming Tsai

J. Pers. Med. 2022, 12(6), 1014; https://doi.org/10.3390/jpm12061014 - 20 Jun 2022

Cited by 4 | Viewed by 1944

Abstract

Background: Empyema is a major cause of mortality and hospitalization. Symptoms include difficulty breathing and chest pain. Calcium plays an essential role in the physiology of the cardiovascular system. However, there is little evidence on the role of echocardiography and the serum calcium [...] Read more.

Background: Empyema is a major cause of mortality and hospitalization. Symptoms include difficulty breathing and chest pain. Calcium plays an essential role in the physiology of the cardiovascular system. However, there is little evidence on the role of echocardiography and the serum calcium levels of patients undergoing video-assisted thoracoscopic surgery (VATS) for empyema. This study aimed to investigate the risk factors for postoperative mortality in patients with empyema who required surgery. Methods: This single-institution retrospective study compared the outcomes of VATS for thoracic empyema (in terms of survival and mortality) in 122 patients enrolled between July 2015 and June 2019. Results: This study examined patients with thoracic empyema. The majority of the patients were males (100/122, 81.9%). The in-hospital/30-day mortality rate was 10.6% (13 patients). The calcium levels were 7.82 ± 1.17 mg/dL in the survival group and 6.88 ± 1.88 mg/dL in the mortality group (p = 0.032). In the mortality group, the utilization of echocardiography and serum calcium levels independently contributed to the risk prediction more than clinical variables. Patients in our cohort exhibited elevated pulmonary artery systolic pressure (PASP) and hypocalcemia, which were associated with increased postoperative mortality. Conclusion: Elevated PASP and calcium levels at the low end of the normal range demonstrated significant prognostic value in predicting mortality in patients with thoracic empyema who required surgical intervention. Recognizing this potential is critical in order to obtain better outcomes. Full article

(This article belongs to the Special Issue Cardiovascular Disease: Personalized Prevention, Management, and Treatment)

13 pages, 2088 KiB

Open AccessArticle

Two Genetic Mechanisms in Two Siblings with Intellectual Disability, Autism Spectrum Disorder, and Psychosis

by Yu-Shu Huang, Ting-Hsuan Fang, Belle Kung and Chia-Hsiang Chen

J. Pers. Med. 2022, 12(6), 1013; https://doi.org/10.3390/jpm12061013 - 20 Jun 2022

Cited by 10 | Viewed by 2841

Abstract

Intellectual disability (ID) and autism spectrum disorder (ASD) are complex neurodevelopmental disorders with high heritability. To search for the genetic deficits in two siblings affected with ID and ASD in a family, we first performed a genome-wide copy number variation (CNV) analysis using [...] Read more.

Intellectual disability (ID) and autism spectrum disorder (ASD) are complex neurodevelopmental disorders with high heritability. To search for the genetic deficits in two siblings affected with ID and ASD in a family, we first performed a genome-wide copy number variation (CNV) analysis using chromosomal microarray analysis (CMA). We found a 3.7 Mb microdeletion at 22q13.3 in the younger sister. This de novo microdeletion resulted in the haploinsufficiency of SHANK3 and several nearby genes involved in neurodevelopment disorders. Hence, she was diagnosed with Phelan–McDermid syndrome (PMS, OMIM#606232). We further performed whole-genome sequencing (WGS) analysis in this family. We did not detect pathogenic mutations with significant impacts on the phenotypes of the elder brother. Instead, we identified several rare, likely pathogenic variants in seven genes implicated in neurodevelopmental disorders: KLHL17, TDO2, TRRAP, EIF3F, ATP10A, DICER1, and CDH15. These variants were transmitted from his unaffected parents, indicating these variants have only moderate clinical effects. We propose that these variants worked together and led to the clinical phenotypes in the elder brother. We also suggest that the combination of multiple genes with moderate effects is part of the genetic mechanism of neurodevelopmental disorders. Full article

(This article belongs to the Special Issue Recent Advances in Precision Psychiatry)

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9 pages, 1841 KiB

Open AccessArticle

Multifactorial Analysis of Endodontic Microsurgery Using Finite Element Models

by Raphael Richert, Jean-Christophe Farges, Jean-Christophe Maurin, Jérôme Molimard, Philippe Boisse and Maxime Ducret

J. Pers. Med. 2022, 12(6), 1012; https://doi.org/10.3390/jpm12061012 - 20 Jun 2022

Cited by 4 | Viewed by 1928

Abstract

Background: The present study aimed to classify the relative contributions of four biomechanical factors—the root-end filling material, the apical preparation, the root resection length, and the bone height—on the root stresses of the resected premolar. Methods: A design of [...] Read more.

Background: The present study aimed to classify the relative contributions of four biomechanical factors—the root-end filling material, the apical preparation, the root resection length, and the bone height—on the root stresses of the resected premolar. Methods: A design of experiments approach based on a defined subset of factor combinations was conducted to calculate the influence of each factor and their interactions. Sixteen finite element models were created and analyzed using the von Mises stress criterion. The robustness of the design of experiments was evaluated with nine supplementary models. Results: The current study showed that the factors preparation and bone height had a high influence on root stresses. However, it also revealed that nearly half of the biomechanical impact was missed without considering interactions between factors, particularly between resection and preparation. Conclusions: Design of experiments appears to be a valuable strategy to classify the contributions of biomechanical factors related to endodontics. Imagining all possible interactions and their clinical impact is difficult and can require relying on one’s own experience. This study proposed a statistical method to quantify the mechanical risk when planning apicoectomy. A perspective could be to integrate the equation defined herein in future software to support decision-making. Full article

(This article belongs to the Special Issue Recent Advances and Personalized Treatment in Dental Health)

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10 pages, 242 KiB

Open AccessArticle

Ethical and Legal Aspects of Technology-Assisted Care in Neurodegenerative Disease

by Bjoern Schmitz-Luhn, Jennifer Chandler and on behalf of the iCARE-PD Consortium

J. Pers. Med. 2022, 12(6), 1011; https://doi.org/10.3390/jpm12061011 - 20 Jun 2022

Cited by 5 | Viewed by 2152

Abstract

Technological solutions are increasingly seen as a way to respond to the demands of managing complex chronic conditions, especially neurodegenerative diseases such as Parkinson’s Disease. All of these new possibilities provide a variety of chances to improve the lives of affected persons and [...] Read more.

Technological solutions are increasingly seen as a way to respond to the demands of managing complex chronic conditions, especially neurodegenerative diseases such as Parkinson’s Disease. All of these new possibilities provide a variety of chances to improve the lives of affected persons and their families, friends, and caregivers. However, there are also a number of challenges that should be considered in order to safeguard the interests of affected persons. In this article, we discuss the ethical and legal considerations associated with the use of technology-assisted care in the context of neurodegenerative conditions. Full article

(This article belongs to the Special Issue Care Personalization in Parkinson Disease)

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24 pages, 1466 KiB

Open AccessReview

Role of ABCA1 in Cardiovascular Disease

by Jing Wang, Qianqian Xiao, Luyun Wang, Yan Wang, Daowen Wang and Hu Ding

J. Pers. Med. 2022, 12(6), 1010; https://doi.org/10.3390/jpm12061010 - 20 Jun 2022

Cited by 26 | Viewed by 5520

Abstract

Cholesterol homeostasis plays a significant role in cardiovascular disease. Previous studies have indicated that ATP-binding cassette transporter A1 (ABCA1) is one of the most important proteins that maintains cholesterol homeostasis. ABCA1 mediates nascent high-density lipoprotein biogenesis. Upon binding with apolipoprotein A-I, [...] Read more.

Cholesterol homeostasis plays a significant role in cardiovascular disease. Previous studies have indicated that ATP-binding cassette transporter A1 (ABCA1) is one of the most important proteins that maintains cholesterol homeostasis. ABCA1 mediates nascent high-density lipoprotein biogenesis. Upon binding with apolipoprotein A-I, ABCA1 facilitates the efflux of excess intracellular cholesterol and phospholipids and controls the rate-limiting step of reverse cholesterol transport. In addition, ABCA1 interacts with the apolipoprotein receptor and suppresses inflammation through a series of signaling pathways. Thus, ABCA1 may prevent cardiovascular disease by inhibiting inflammation and maintaining lipid homeostasis. Several studies have indicated that post-transcriptional modifications play a critical role in the regulation of ABCA1 transportation and plasma membrane localization, which affects its biological function. Meanwhile, carriers of the loss-of-function ABCA1 gene are often accompanied by decreased expression of ABCA1 and an increased risk of cardiovascular diseases. We summarized the ABCA1 transcription regulation mechanism, mutations, post-translational modifications, and their roles in the development of dyslipidemia, atherosclerosis, ischemia/reperfusion, myocardial infarction, and coronary heart disease. Full article

(This article belongs to the Special Issue Cardiovascular Diseases—From Risk Factors to Diagnosis and Personalized Management)

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13 pages, 832 KiB

Open AccessCommentary

Researching Mitigation of Alcohol Binge Drinking in Polydrug Abuse: KCNK13 and RASGRF2 Gene(s) Risk Polymorphisms Coupled with Genetic Addiction Risk Severity (GARS) Guiding Precision Pro-Dopamine Regulation

by Kenneth Blum, Mark S. Brodie, Subhash C. Pandey, Jean Lud Cadet, Ashim Gupta, Igor Elman, Panayotis K. Thanos, Marjorie C. Gondre-Lewis, David Baron, Shan Kazmi, Abdalla Bowirrat, Marcelo Febo, Rajendra D. Badgaiyan, Eric R. Braverman, Catherine A. Dennen and Mark S. Gold

J. Pers. Med. 2022, 12(6), 1009; https://doi.org/10.3390/jpm12061009 - 20 Jun 2022

Cited by 9 | Viewed by 2805

Abstract

Excessive alcohol intake, e.g., binge drinking, is a serious and mounting public health problem in the United States and throughout the world. Hence the need for novel insights into the underlying neurobiology that may help improve prevention and therapeutic strategies. Therefore, our group [...] Read more.

Excessive alcohol intake, e.g., binge drinking, is a serious and mounting public health problem in the United States and throughout the world. Hence the need for novel insights into the underlying neurobiology that may help improve prevention and therapeutic strategies. Therefore, our group employed a darkness-induced alcohol intake protocol to define the reward deficiency domains of alcohol and other substance use disorders in terms of reward pathways’ reduced dopamine signaling and its restoration via specifically-designed therapeutic compounds. It has been determined that KCNK13 and RASGRF2 genes, respectively, code for potassium two pore domain channel subfamily K member 13 and Ras-specific guanine nucleotide-releasing factor 2, and both genes have important dopamine-related functions pertaining to alcohol binge drinking. We present a hypothesis that identification of KCNK13 and RASGRF2 genes’ risk polymorphism, coupled with genetic addiction risk score (GARS)-guided precision pro-dopamine regulation, will mitigate binge alcohol drinking. Accordingly, we review published reports on the benefits of this unique approach and provide data on favorable outcomes for both binge-drinking animals and drunk drivers, including reductions in alcohol intake and prevention of relapse to drinking behavior. Since driving under the influence of alcohol often leads to incarceration rather than rehabilitation, there is converging evidence to support the utilization of GARS with or without KCNK13 and RASGRF2 risk polymorphism in the legal arena, whereby the argument that “determinism” overrides the “free will” account may be a plausible defense strategy. Obviously, this type of research is tantamount to helping resolve a major problem related to polydrug abuse. Full article

(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)

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11 pages, 899 KiB

Open AccessSystematic Review

The Role of Hemodynamics through the Circle of Willis in the Development of Intracranial Aneurysm: A Systematic Review of Numerical Models

by Yuanyuan Shen, Rob Molenberg, Reinoud P. H. Bokkers, Yanji Wei, Maarten Uyttenboogaart and J. Marc C. van Dijk

J. Pers. Med. 2022, 12(6), 1008; https://doi.org/10.3390/jpm12061008 - 20 Jun 2022

Cited by 8 | Viewed by 4749

Abstract

Background: The role of regional hemodynamics in the intracranial aneurysmal formation, growth, and rupture has been widely discussed based on numerical models over the past decades. Variation of the circle of Willis (CoW), which results in hemodynamic changes, is associated with the aneurysmal [...] Read more.

Background: The role of regional hemodynamics in the intracranial aneurysmal formation, growth, and rupture has been widely discussed based on numerical models over the past decades. Variation of the circle of Willis (CoW), which results in hemodynamic changes, is associated with the aneurysmal formation and rupture. However, such correlation has not been further clarified yet. The aim of this systematic review is to investigate whether simulated hemodynamic indices of the CoW are relevant to the formation, growth, or rupture of intracranial aneurysm. Methods: We conducted a review of MEDLINE, Web of Science, and EMBASE for studies on the correlation between hemodynamics indices of the CoW derived from numerical models and intracranial aneurysm up to December 2020 in compliance with PRISMA guidelines. Results: Three case reports out of 1046 publications met our inclusion and exclusion criteria, reporting 13 aneurysms in six patients. Eleven aneurysms were unruptured, and the state of the other two aneurysms was unknown. Wall shear stress, oscillatory shear index, von-Mises tension, flow velocity, and flow rate were reported as hemodynamic indices. Due to limited cases and significant heterogeneity between study settings, meta-analysis could not be performed. Conclusion: Numerical models can provide comprehensive information on the cerebral blood flow as well as local flow characteristics in the intracranial aneurysm. Based on only three case reports, no firm conclusion can be drawn regarding the correlation between hemodynamic parameters in the CoW derived from numerical models and aneurysmal formation or rupture. Due to the inherent nature of numerical models, more sensitive analysis and rigorous validations are required to determine its measurement error and thus extend their application into clinical practice for personalized management. Prospero registration number: CRD42021125169. Full article

(This article belongs to the Special Issue Cardiovascular Diseases—From Risk Factors to Diagnosis and Personalized Management)

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31 pages, 3515 KiB

Open AccessArticle

Regulation of Key Immune-Related Genes in the Heart Following Burn Injury

by Jake J. Wen, Keyan Mobli, Geetha L. Radhakrishnan and Ravi S. Radhakrishnan

J. Pers. Med. 2022, 12(6), 1007; https://doi.org/10.3390/jpm12061007 - 20 Jun 2022

Cited by 3 | Viewed by 2606

Abstract

Immune cascade is one of major factors leading to cardiac dysfunction after burn injury. TLRs are a class of pattern-recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen. The Rat Toll-Like [...] Read more.

Immune cascade is one of major factors leading to cardiac dysfunction after burn injury. TLRs are a class of pattern-recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen. The Rat Toll-Like Receptor (TLR) Signaling Pathway RT² Profiler PCR Array profiles the expression of 84 genes central to TLR-mediated signal transduction and innate immunity, and is a validated tool for identifying differentially expressed genes (DEGs). We employed the PCR array to identify burn-induced cardiac TLR-signaling-related DEGs. A total of 38 up-regulated DEGs and 19 down-regulated DEGs were identified. Network analysis determined that all DEGS had 10 clusters, while up-regulated DEGs had 6 clusters and down-regulated DEGs had 5 clusters. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were involved in TLR signaling, the RIG-I-Like receptor signaling pathway, the IL-17 signaling pathway, and the NFkB signaling pathway. Function analysis indicated that DEGs were associated with Toll-like receptor 2 binding, Lipopeptide binding, Toll-like receptor binding, and NAD(P)+ nucleosidase activity. The validation of 18 up-regulated DEGs (≥10-fold change) and 6 down-regulated DEGs (≤5-fold change) demonstrated that the PCR array is a trusted method for identifying DEGs. The analysis of validated DEG-derived protein–protein interaction networks will guide our future investigations. In summary, this study not only identified the TLR-signaling-pathway-related DEGs after burn injury, but also confirmed that the burn-induced cardiac cytokine cascade plays an important role in burn-induced heart dysfunction. The results will provide the novel therapeutic targets to protect the heart after burn injury. Full article

(This article belongs to the Section Mechanisms of Diseases)

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15 pages, 887 KiB

Open AccessProtocol

A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder

by Duncan C. Honeycutt, Melissa P. DelBello, Jeffrey R. Strawn, Laura B. Ramsey, Luis R. Patino, Kyle Hinman, Jeffrey Welge, David J. Miklowitz, Booil Jo, Thomas J. Blom, Kaitlyn M. Bruns, Sarah K. Hamill Skoch, Nicole Starace, Maxwell J. Tallman and Manpreet K. Singh

J. Pers. Med. 2022, 12(6), 1006; https://doi.org/10.3390/jpm12061006 - 20 Jun 2022

Cited by 2 | Viewed by 3308

Abstract

Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth [...] Read more.

Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12–17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures. Full article

(This article belongs to the Section Pharmacogenetics)

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17 pages, 1787 KiB

Open AccessArticle

Intestinal Permeability and Dysbiosis in Female Patients with Recurrent Cystitis: A Pilot Study

by Cristina Graziani, Lucrezia Laterza, Claudia Talocco, Marco Pizzoferrato, Nicoletta Di Simone, Silvia D’Ippolito, Caterina Ricci, Jacopo Gervasoni, Silvia Persichilli, Federica Del Chierico, Valeria Marzano, Stefano Levi Mortera, Aniello Primiano, Andrea Poscia, Francesca Romana Ponziani, Lorenza Putignani, Andrea Urbani, Valentina Petito, Federica Di Vincenzo, Letizia Masi, Loris Riccardo Lopetuso, Giovanni Cammarota, Daniela Romualdi, Antonio Lanzone, Antonio Gasbarrini and Franco Scaldaferri Show full author list Hide full author list

J. Pers. Med. 2022, 12(6), 1005; https://doi.org/10.3390/jpm12061005 - 20 Jun 2022

Cited by 5 | Viewed by 3378

Abstract

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most [...] Read more.

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections. Full article

(This article belongs to the Special Issue Targeting the Microbiome for Disease Diagnosis and Therapy: New Frontiers for Personalized Medicine)

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13 pages, 1660 KiB

Open AccessArticle

Psilocybin—Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience

by Vojtěch Viktorin, Inga Griškova-Bulanova, Aleksandras Voicikas, Dominika Dojčánová, Peter Zach, Anna Bravermanová, Veronika Andrashko, Filip Tylš, Jakub Korčák, Michaela Viktorinová, Vlastimil Koudelka, Kateřina Hájková, Martin Kuchař, Jiří Horáček, Martin Brunovský and Tomáš Páleníček

J. Pers. Med. 2022, 12(6), 1004; https://doi.org/10.3390/jpm12061004 - 19 Jun 2022

Cited by 5 | Viewed by 3771

Abstract

Psilocybin is a classical serotoninergic psychedelic that induces cognitive disruptions similar to psychosis. Gamma activity is affected in psychosis and is tightly related to cognitive processing. The 40 Hz auditory steady-state responses (ASSR) are frequently used as indicators to test the ability to [...] Read more.

Psilocybin is a classical serotoninergic psychedelic that induces cognitive disruptions similar to psychosis. Gamma activity is affected in psychosis and is tightly related to cognitive processing. The 40 Hz auditory steady-state responses (ASSR) are frequently used as indicators to test the ability to generate gamma activity. Based on previous literature, we studied the impact of psilocybin on 40 Hz ASSR in healthy volunteers. The study was double blind and placebo controlled with a crossover design. A sample of 20 healthy subjects (10M/10F) received psilocybin orally 0.26 mg/kg or placebo. Participants were measured four times in total, one time before ingestion of psilocybin/placebo and one time after ingestion, during the peak of intoxication. A series of 500 ms click trains were used for stimulation. Psilocybin induced a psychedelic effect and decreased 40 Hz ASSR phase-locking index compared to placebo. The extent of the attenuation was related to Cognition and Affect on the Hallucinogen Rating Scale. The current study shows that psilocybin lowers the synchronization level and the amplitude of 40 Hz auditory steady-state responses, which yields further support for the role of gamma oscillations in cognitive processing and its disturbance. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

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9 pages, 955 KiB

Open AccessArticle

IL-10 Induced by mTNF Crosslinking-Mediated Reverse Signaling in a Whole Blood Assay Is Predictive of Response to TNFi Therapy in Rheumatoid Arthritis

by Marco Krasselt, Natalya Gruz, Matthias Pierer, Christoph Baerwald and Ulf Wagner

J. Pers. Med. 2022, 12(6), 1003; https://doi.org/10.3390/jpm12061003 - 19 Jun 2022

Cited by 2 | Viewed by 1719

Abstract

(1) Background: To date, the response of patients with rheumatoid arthritis (RA) to the various biologic DMARD available cannot be predicted due to a lack of reliable biomarkers. Based on our preliminary work on tmTNF reverse signaling, we developed a whole-blood assay measuring [...] Read more.

(1) Background: To date, the response of patients with rheumatoid arthritis (RA) to the various biologic DMARD available cannot be predicted due to a lack of reliable biomarkers. Based on our preliminary work on tmTNF reverse signaling, we developed a whole-blood assay measuring tmTNF crosslinking-induced IL-10 production to predict the response to TNF inhibitor (TNFi) therapy. (2) Methods: This prospective study included patients with active RA. Depending on the clinical judgment of the attending rheumatologist, either therapy with a TNF or JAK inhibitor was initiated. Clinical parameters and blood samples were obtained at baseline and after 8 weeks of therapy. The blood samples were collected using a newly developed whole-blood assay based on the principle of tmTNF reverse signalling. Subsequently, IL-10 was measured via enzyme-linked immunosorbent assay (ELISA) technique. (3) Results: 63 patients with RA were enrolled. In fifteen patients, TNFi therapy was initiated, while eight patients started a JAKi treatment. The cross-sectional analysis of all patients showed a positive correlation between tmTNF crosslinking-induced IL-10 and parameters of disease activity (CRP [r = 0.4091, p = 0.0009], DAS28 [r = 0.3303, p = 0.0082]) at baseline. In the TNFi treatment study, IL-10 was found to be significantly higher in EULAR responders than in non-responders (p = 0.0033). After initiation of JAKi treatment, in contrast, IL-10 induction was not linked to response. Longitudinal analysis of the TNFi-treated patients revealed IL-10 to decrease in responders (p = 0.04), but not in non-responders after 8 weeks of therapy. Of importance, the IL-10 production at baseline correlated inversely with TNFi response determined by ΔDAS28 in patients with TNFi treatment (r = −0.5299, p = 0.0422) while no such link was observed under JAKi therapy (p = 0.22). Receiver operation characteristics (ROC) analysis demonstrated a high performance of tmTNF/crosslinking-induced IL-10 in predicting a TNFi therapy response according to the EULAR criteria (AUC = 0.9286, 95% Confidence interval 0.7825–1.000, p = 0.0055). (4) Conclusions: In this pilot investigation, we demonstrated the feasibility of a whole-blood assay measuring tmTNF-induced IL-10 to predict clinical response to TNF inhibitor treatment. This approach might support rheumatologists in their decision for an individually tailored RA therapy. Full article

(This article belongs to the Section Personalized Therapy and Drug Delivery)

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12 pages, 1783 KiB

Open AccessArticle

Translated Mutant DSPP mRNA Expression Level Impacts the Severity of Dentin Defects

by Youn Jung Kim, Yejin Lee, Hong Zhang, Figen Seymen, Mine Koruyucu, Sule Bayrak, Nuray Tuloglu, James P. Simmer, Jan C.-C. Hu and Jung-Wook Kim

J. Pers. Med. 2022, 12(6), 1002; https://doi.org/10.3390/jpm12061002 - 19 Jun 2022

Cited by 8 | Viewed by 2188

Abstract

Hereditary dentin defects are conventionally classified into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia (DD). Mutations in the dentin sialophosphoprotein (DSPP) gene have been identified to cause DGI type II and III and DD type II; [...] Read more.

Hereditary dentin defects are conventionally classified into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia (DD). Mutations in the dentin sialophosphoprotein (DSPP) gene have been identified to cause DGI type II and III and DD type II; therefore, these are not three different conditions, but rather allelic disorders. In this study, we recruited three families with varying clinical phenotypes from DGI-III to DD-II and performed mutational analysis by candidate gene analysis or whole-exome sequencing. Three novel mutations including a silent mutation (NM_014208.3: c.52-2del, c.135+1G>C, and c.135G>A; p.(Gln45=)) were identified, all of which affected pre-mRNA splicing. Comparison of the splicing assay results revealed that the expression level of the DSPP exon 3 deletion transcript correlated with the severity of the dentin defects. This study did not only expand the mutational spectrum of DSPP gene, but also advanced our understanding of the molecular pathogenesis impacting the severity of hereditary dentin defects. Full article

(This article belongs to the Special Issue Precision Medicine in Oral Science and Dentistry)

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30 pages, 2449 KiB

Open AccessArticle

Co-Designing an Integrated Care Network with People Living with Parkinson’s Disease: A Heterogeneous Social Network of People, Resources and Technologies

by Amélie Gauthier-Beaupré, Emely Poitras, Sylvie Grosjean, Tiago A. Mestre and on behalf of the iCARE-PD Consortium

J. Pers. Med. 2022, 12(6), 1001; https://doi.org/10.3390/jpm12061001 - 19 Jun 2022

Cited by 2 | Viewed by 3229

Abstract

As part of the iCARE-PD project, a multinational and multidisciplinary research endeavour to address complex care in Parkinson’s disease, a Canadian case study focused on gaining a better understanding of people living with Parkinson’s disease (PwP) experiences with health and medical services, particularly [...] Read more.

As part of the iCARE-PD project, a multinational and multidisciplinary research endeavour to address complex care in Parkinson’s disease, a Canadian case study focused on gaining a better understanding of people living with Parkinson’s disease (PwP) experiences with health and medical services, particularly their vision for a sustainable, tailored and integrated care delivery network. The multifaceted nature of the condition means that PwP must continuously adapt and adjust to every aspect of their lives, and progressively rely on support from care partners (CP) and various health care professionals (HCP). To envision the integrated care delivery network from the perspective of PwP, the study consisted of designing scenarios for an integrated care delivery network with patients, their CP and their HCP, as well as identifying key requirements for designing an integrated care delivery network. The results demonstrate that numerous networks interact, representing specific inscriptions, actors and mediators who meet at specific crossing points. This resulted in the creation of a roadmap and toolkit that takes into consideration the unique challenges faced by PwP, and the necessity for an integrated care delivery network that can be personalized and malleable so as to adapt to evolving and changing needs over time. Full article

(This article belongs to the Special Issue Care Personalization in Parkinson Disease)

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11 pages, 600 KiB

Open AccessArticle

Venous Segmental Flow Changes after Superficial Venous Intervention Demonstrating by Quantitative Phase-Contrast Magnetic Resonance Analysis: Preliminary Data from a Longitudinal Cohort Study

by Chien-Wei Chen, Yuan-Hsi Tseng, Chih-Chen Kao, Yeh Giin Ngo, Chung-Yuan Lee, Teng-Yao Yang, Yu-Hui Lin and Yao-Kuang Huang

J. Pers. Med. 2022, 12(6), 1000; https://doi.org/10.3390/jpm12061000 - 19 Jun 2022

Viewed by 1847

Abstract

The effects of superficial venous intervention on hemodynamics can be quantified using two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI). Twelve patients received pre- and postintervention 2D PC-MRI analysis using quantitative hemodynamic parameters. Fifteen healthy volunteers served as controls. The 2D PC-MRI results of [...] Read more.

The effects of superficial venous intervention on hemodynamics can be quantified using two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI). Twelve patients received pre- and postintervention 2D PC-MRI analysis using quantitative hemodynamic parameters. Fifteen healthy volunteers served as controls. The 2D PC-MRI results of the target limbs (limbs scheduled for intervention for venous reflux) differed from those of the controls in terms of stroke volume (SV), forward flow volume (FFV), absolute stroke volume (ASV), and mean flux (MF) in all venous segments. The velocity time integral (VTI) and mean velocity (MV) of the popliteal vein (PV) segments were similar between the target limbs and controls preoperatively. After intervention, the target limbs exhibited an increase in VTI and MV in the femoral vein (FV) and PV segments. We compared the target and nontreated limbs of the individual patients preoperatively and postoperatively to minimalize individual bias. All QFlow parameter ratios in the FV segment increased after venous intervention (VTI, p = 0.025; MV, p = 0.024). In the PV segment, FFV and ASV increased significantly (p = 0.035 and 0.024, respectively). After interventions, the volume (FFV and ASV) of the PV segment and the efficiency (VTI and MV) of the FV segment significantly increased. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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12 pages, 284 KiB

Open AccessEditor’s ChoiceReview

Biologic Therapies in Pediatric Asthma

by Evanthia P. Perikleous, Paschalis Steiropoulos, Evangelia Nena and Emmanouil Paraskakis

J. Pers. Med. 2022, 12(6), 999; https://doi.org/10.3390/jpm12060999 - 18 Jun 2022

Cited by 14 | Viewed by 3192

Abstract

Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced [...] Read more.

Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced and very promising treatment alternative, eventually directing toward a successful precision medicine approach. The application of currently approved add-on treatments for severe asthma in children, namely omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab have been shown to be effective in terms of asthma control and exacerbation rate. However, to date, information is still lacking regarding its long-term use. As a result, data are frequently extrapolated from adult studies. Thus, the selection of the appropriate biologic agent, the potential predictors of good asthma response, and the long-term outcome in the pediatric population are still to be further investigated. The aim of the present study was to provide an overview of the current status of the latest evidence about all licensed monoclonal antibodies (mAbs) that have emerged and been applied to the field of asthma management. The innovative future targets are also briefly discussed. Full article

(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)

12 pages, 3640 KiB

Open AccessArticle

Three-Dimensional Postoperative Results Prediction for Orthognathic Surgery through Deep Learning-Based Alignment Network

by Seung Hyun Jeong, Min Woo Woo, Dong Sun Shin, Han Gyeol Yeom, Hun Jun Lim, Bong Chul Kim and Jong Pil Yun

J. Pers. Med. 2022, 12(6), 998; https://doi.org/10.3390/jpm12060998 - 18 Jun 2022

Cited by 5 | Viewed by 2635

Abstract

To date, for the diagnosis of dentofacial dysmorphosis, we have relied almost entirely on reference points, planes, and angles. This is time consuming, and it is also greatly influenced by the skill level of the practitioner. To solve this problem, we wanted to [...] Read more.

To date, for the diagnosis of dentofacial dysmorphosis, we have relied almost entirely on reference points, planes, and angles. This is time consuming, and it is also greatly influenced by the skill level of the practitioner. To solve this problem, we wanted to know if deep neural networks could predict postoperative results of orthognathic surgery without relying on reference points, planes, and angles. We use three-dimensional point cloud data of the skull of 269 patients. The proposed method has two main stages for prediction. In step 1, the skull is divided into six parts through the segmentation network. In step 2, three-dimensional transformation parameters are predicted through the alignment network. The ground truth values of transformation parameters are calculated through the iterative closest points (ICP), which align the preoperative part of skull to the corresponding postoperative part of skull. We compare pointnet, pointnet++ and pointconv for the feature extractor of the alignment network. Moreover, we design a new loss function, which considers the distance error of transformed points for a better accuracy. The accuracy, mean intersection over union (mIoU), and dice coefficient (DC) of the first segmentation network, which divides the upper and lower part of skull, are 0.9998, 0.9994, and 0.9998, respectively. For the second segmentation network, which divides the lower part of skull into 5 parts, they were 0.9949, 0.9900, 0.9949, respectively. The mean absolute error of transverse, anterior–posterior, and vertical distance of part 2 (maxilla) are 0.765 mm, 1.455 mm, and 1.392 mm, respectively. For part 3 (mandible), they were 1.069 mm, 1.831 mm, and 1.375 mm, respectively, and for part 4 (chin), they were 1.913 mm, 2.340 mm, and 1.257 mm, respectively. From this study, postoperative results can now be easily predicted by simply entering the point cloud data of computed tomography. Full article

(This article belongs to the Special Issue Recent Advances and Personalized Treatment in Dental Health)

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7 pages, 1292 KiB

Open AccessCase Report

Rapid Personalised Virtual Planning and On-Demand Surgery for Acute Spinal Trauma Using 3D-Printing, Biomodelling and Patient-Specific Implant Manufacture

by Ralph Jasper Mobbs, William C. H. Parr, Christopher Huang and Tajrian Amin

J. Pers. Med. 2022, 12(6), 997; https://doi.org/10.3390/jpm12060997 - 18 Jun 2022

Cited by 4 | Viewed by 2157

Abstract

Three-dimensional printing is a rapidly growing field, with extensive application to orthopaedics and spinal surgery. Three-dimensional-printed (3DP) patient-specific implants (PSIs) offer multiple potential benefits over generic alternatives, with their use increasingly being described in the spinal literature. This report details a unique, emergency [...] Read more.

Three-dimensional printing is a rapidly growing field, with extensive application to orthopaedics and spinal surgery. Three-dimensional-printed (3DP) patient-specific implants (PSIs) offer multiple potential benefits over generic alternatives, with their use increasingly being described in the spinal literature. This report details a unique, emergency case of a traumatic spinal injury in a 31-year-old male, acquired rurally and treated with a 3DP PSI in a tertiary unit. With increasing design automation and process improvements, rapid, on-demand virtual surgical planning (VSP) and 3DP PSIs may present the future of orthopaedics and trauma care, enabling faster, safer, and more cost-effective patient-specific procedures. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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15 pages, 1693 KiB

Open AccessArticle

Physiologic Range of Myocardial Mechano-Energetic Efficiency among Healthy Subjects: Impact of Gender and Age

by Francesco Ferrara, Valentina Capone, Filippo Cademartiri, Olga Vriz, Rosangela Cocchia, Brigida Ranieri, Monica Franzese, Rossana Castaldo, Antonello D’Andrea, Rodolfo Citro, Salvatore Chianese, Roberto Annunziata, Flavio Marullo, Mario Siniscalchi, Marianna Conte, Chiara Sepe, Renato Maramaldi, Salvatore Rega, Giuseppe Russo, Massimo Majolo, Eliana Raiola, Andrea Salzano, Ciro Mauro, Bruno Trimarco, Raffaele Izzo and Eduardo Bossone Show full author list Hide full author list

J. Pers. Med. 2022, 12(6), 996; https://doi.org/10.3390/jpm12060996 - 18 Jun 2022

Cited by 7 | Viewed by 2036

Abstract

Background: Myocardial mechano-energetic efficiency (MEE) is the capability of the left ventricle (LV) to convert the chemical energy obtained from the cardiac oxidative metabolism into mechanical work. The aim of present study was to establish normal non-invasive MEE and MEEi reference values. Methods: [...] Read more.

Background: Myocardial mechano-energetic efficiency (MEE) is the capability of the left ventricle (LV) to convert the chemical energy obtained from the cardiac oxidative metabolism into mechanical work. The aim of present study was to establish normal non-invasive MEE and MEEi reference values. Methods: In total, 1168 healthy subjects underwent physical examinations, clinical assessment, and standardized transthoracic echocardiographic (TTE) examination. MEE was obtained by TTE as the ratio between stroke volume (SV) and heart rate (HR): MEE = SV/HR [HR expressed in seconds (HR/60)]. Because MEE is highly related to left ventricular mass (LVM), MEE was then divided by LVM with the purpose of obtaining an estimate of energetic expenditure per unit of myocardial mass (i.e., indexed MEE, MEEi, mL/s/g). Results: The mean values of MEE and MEEi in the overall population were 61.09 ± 18.19 mL/s; 0.45 ± 0.14, respectively. In a multivariable analysis, gender, body surface area (BSA), diastolic blood pressure, left atrial volume indexed to BSA, E/e’ and tricuspid annular plane systolic excursion (TAPSE) were the independent variables associated with MEE, while age, gender, BSA and TAPSE were the independent variables associated with MEEi. Conclusions: The knowledge of age- and gender-based MEE and MEEi normal values may improve the global assessment of LV cardiac mechanics and serve as a reference to identify phenotypes at high risk of cardiovascular events. Full article

(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)

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20 pages, 1613 KiB

Open AccessReview

Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths

by Miguel A. Ortega, Cielo García-Montero, Oscar Fraile-Martinez, Paolo Colet, Ardak Baizhaxynova, Kymbat Mukhtarova, Melchor Alvarez-Mon, Kaznagul Kanatova, Angel Asúnsolo and Antonio Sarría-Santamera

J. Pers. Med. 2022, 12(6), 995; https://doi.org/10.3390/jpm12060995 - 18 Jun 2022

Cited by 9 | Viewed by 3173

Abstract

Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to [...] Read more.

Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic. Full article

(This article belongs to the Special Issue Personalized Medicine and Management of COVID-19)

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13 pages, 2145 KiB

Open AccessArticle

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination

by Roberto Cangemi, Manuela Di Franco, Antonio Angeloni, Alessandra Zicari, Vincenzo Cardinale, Marcella Visentini, Guido Antonelli, Anna Napoli, Emanuela Anastasi, Giulio Francesco Romiti, Fabrizio d’Alba, Domenico Alvaro, Antonella Polimeni, Stefania Basili and SAPIENZAVAX Collaborators

J. Pers. Med. 2022, 12(6), 994; https://doi.org/10.3390/jpm12060994 - 18 Jun 2022

Cited by 6 | Viewed by 4018

Abstract

Vaccine-induced immunity is a key strategy in the long-term control of the COVID-19 pandemic. The aim of our study was to explore the relationship between mRNA vaccine-induced antibodies and gender-sensitive variables among healthcare workers. Two thousand-sixty-five volunteers who received the BNT162b2 vaccine were [...] Read more.

Vaccine-induced immunity is a key strategy in the long-term control of the COVID-19 pandemic. The aim of our study was to explore the relationship between mRNA vaccine-induced antibodies and gender-sensitive variables among healthcare workers. Two thousand-sixty-five volunteers who received the BNT162b2 vaccine were enrolled in the study and followed up. Demographic, clinical, and social variables (educational level, marital status, occupation, childcare) were evaluated through a self-administered questionnaire. Anti-Spike (S) IgG were measured at 1 month (T1) and at 5 months (T2) after the second vaccine dose. At T1, median anti-S IgG values were 693 [394–>800] AU/mL (1 AU = 2.6 BAU). Values > 800 AU/mL (2080 BAU/mL) were directly associated with a previous COVID-19 (p < 0.001) infection and inversely with age (p < 0.001), smoking habit (p < 0.001), and autoimmune diseases (p < 0.001). At T2, a significant decreasing in anti-S IgG values was observed (187 [81–262] AU/mL), with a median decrease of 72 [60–82]%. On multivariate data analysis, a reduction of more than 82% was directly associated with male sex (p < 0.021), age (p < 0.001), smoking (p = 0.038), hypertension (p = 0.042), and, inversely, with previous COVID-19 infection (p < 0.001) and being “cohabiting” (p = 0.005). Our findings suggest that demographic, clinical, and social variables play a role in anti-S IgG values decreasing in long-term follow up and should be considered to find personalized vaccine schedules. Full article

(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)

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12 pages, 2323 KiB

Open AccessArticle

Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype

by Silvia Grassilli, Federica Brugnoli, Stefano Cairo, Nicoletta Bianchi, Jean-Gabriel Judde and Valeria Bertagnolo

J. Pers. Med. 2022, 12(6), 993; https://doi.org/10.3390/jpm12060993 - 17 Jun 2022

Cited by 4 | Viewed by 2394

Abstract

Triple negative breast cancer (TNBC) represents the most aggressive breast tumor, showing a high intrinsic variability in terms of both histopathological features and response to therapies. Blocking the Akt signaling pathway is a well-studied approach in the treatment of aggressive breast tumors. The [...] Read more.

Triple negative breast cancer (TNBC) represents the most aggressive breast tumor, showing a high intrinsic variability in terms of both histopathological features and response to therapies. Blocking the Akt signaling pathway is a well-studied approach in the treatment of aggressive breast tumors. The high homology among the Akt isoforms and their distinct, and possibly opposite, oncogenic functions made it difficult to develop effective drugs. Here we investigated the role of Vav1 as a potential down-regulator of individual Akt isozymes. We revealed that the over-expression of Vav1 in triple negative MDA-MB-231 cells reduced only the Akt2 isoform, acting at the post-transcriptional level through the up-modulation of miR-29b. The Vav1/miR-29b dependent decrease in Akt2 was correlated with a reduced lung colonization of circulating MDA-MB-231 cells. In cell lines established from PDX, the Vav1 induced down-modulation of Akt2 is strongly dependent on miR-29b and occurs only in some TNBC tumors. These findings may contribute to better classify breast tumors having the triple negative phenotype, and suggest that the activation of the Vav1/miR-29b axis, precisely regulating the amount of an Akt isozyme crucial for tumor dissemination, could have great potential for driving more accurate therapies to TNBCs, often not eligible or resistant to treatments. Full article

(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)

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12 pages, 2228 KiB

Open AccessReview

Blood Cell Count Inflammatory Markers as Prognostic Indicators of Periodontitis: A Systematic Review and Meta-Analysis

by Oana Almășan, Daniel-Corneliu Leucuța and Mihaela Hedeșiu

J. Pers. Med. 2022, 12(6), 992; https://doi.org/10.3390/jpm12060992 - 17 Jun 2022

Cited by 10 | Viewed by 2608

Abstract

(1) Background: Our study aimed to assess the association between the neutrophil to lymphocyte ratio (NLR), platelet to leukocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), red cell distribution width (RDW), and systemic immune inflammation index (SII) and periodontitis. (2) Methods: We searched [...] Read more.

(1) Background: Our study aimed to assess the association between the neutrophil to lymphocyte ratio (NLR), platelet to leukocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), red cell distribution width (RDW), and systemic immune inflammation index (SII) and periodontitis. (2) Methods: We searched PubMed, Embase, Scopus, Web of Science, and LILACS databases, identifying observational studies. The Newcastle Ottawa scale was used to evaluate the quality of the included studies. The principal summary outcome measure in our random effects meta-analysis was the mean difference (MD). (3) Results: After screening 682 search results, a total of 10 studies including 3164 subjects were selected for quantitative assessment. We found a higher mean NLR, PLR, and LMR in the periodontitis group compared to the control group (0.41 (95% CI 0.12–0.7), p = 0.006; 7.43 (95% CI 0.31–14.54), p = 0.04; 2.05 (95% CI 0.27–3.83), p = 0.024). No differences were observed for RDW. (4) Conclusions: We found an association between NLR, LMR, and PLR and periodontitis, which might be thought of as emerging blood cell count inflammatory biomarkers that could shed light on the link between periodontitis and systemic disbalances, as well as for periodontitis prognosis and grading. Full article

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15 pages, 3253 KiB

Open AccessArticle

TRIM24 Expression as an Independent Biomarker for Prognosis and Tumor Recurrence in HNSCC

by Luise Klapper, Christian Idel, Patrick Kuppler, Tobias Jagomast, Amelie von Bernuth, Karl-Ludwig Bruchhage, Dirk Rades, Anne Offermann, Jutta Kirfel, Sven Perner and Julika Ribbat-Idel

J. Pers. Med. 2022, 12(6), 991; https://doi.org/10.3390/jpm12060991 - 17 Jun 2022

Cited by 7 | Viewed by 2087

Abstract

Background: Head and neck squamous cell carcinomas (HNSCCs) are among the most common cancers in humans worldwide and have a rather poor prognosis. TRIM24 has various intracellular functions and was identified in other cancer entities as a poor prognostic factor for patients. Methods: [...] Read more.

Background: Head and neck squamous cell carcinomas (HNSCCs) are among the most common cancers in humans worldwide and have a rather poor prognosis. TRIM24 has various intracellular functions and was identified in other cancer entities as a poor prognostic factor for patients. Methods: The expression of TRIM24 was evaluated by using immunohistochemistry. We used a large and representative cohort of 341 HNSCC patients. Data derived from immunohistochemistry evaluation was correlated with clinicopathological data from HNSCC patients. Results: The TRIM24 expression in HNSCC primary tumors is negatively correlated with the p16 status of the tumor tissues. Primary tumors of patients who developed a local recurrence were significantly more often positive for TRIM24. Kaplan–Meier analyses and Cox regression showed that patients with TRIM24 expressing tumors have significantly worse overall survival and progression-free survival and that TRIM24 expression is independent of other established risk factors. Conclusions: TRIM24 might be a new prognostic biomarker for the survival prognosis and early detection of local recurrences in HNSCC patients. It could be used for risk stratification of HNSCC patients and to identify those patients who are more prone to develop a local recurrence and therefore could profit from more frequent follow-up examinations. Full article

(This article belongs to the Section Mechanisms of Diseases)

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16 pages, 2302 KiB

Open AccessArticle

Prediction of All-Cause Mortality Following Percutaneous Coronary Intervention in Bifurcation Lesions Using Machine Learning Algorithms

by Jacopo Burrello, Guglielmo Gallone, Alessio Burrello, Daniele Jahier Pagliari, Eline H. Ploumen, Mario Iannaccone, Leonardo De Luca, Paolo Zocca, Giuseppe Patti, Enrico Cerrato, Wojciech Wojakowski, Giuseppe Venuti, Ovidio De Filippo, Alessio Mattesini, Nicola Ryan, Gérard Helft, Saverio Muscoli, Jing Kan, Imad Sheiban, Radoslaw Parma, Daniela Trabattoni, Massimo Giammaria, Alessandra Truffa, Francesco Piroli, Yoichi Imori, Bernardo Cortese, Pierluigi Omedè, Federico Conrotto, Shao-Liang Chen, Javier Escaned, Rosaly A. Buiten, Clemens Von Birgelen, Paolo Mulatero, Gaetano Maria De Ferrari, Silvia Monticone and Fabrizio D’Ascenzo Show full author list Hide full author list

J. Pers. Med. 2022, 12(6), 990; https://doi.org/10.3390/jpm12060990 - 17 Jun 2022

Cited by 3 | Viewed by 2227

Abstract

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, [...] Read more.

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74–0.83) in the overall population, 0.74 (0.62–0.85) at internal validation and 0.71 (0.62–0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance. Full article

(This article belongs to the Special Issue Cardiovascular Disease Risk Stratification in the Era of Machine Learning and Personalized Medicine)

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13 pages, 1847 KiB

Open AccessArticle

Evaluation of a Diagnostic and Management Algorithm for Adult Caustic Ingestion: New Concept of Severity Stratification and Patient Categorization

by Yu-Jhou Chen, Chen-June Seak, Hao-Tsai Cheng, Chien-Cheng Chen, Tsung-Hsing Chen, Chang-Mu Sung, Chip-Jin Ng, Shih-Ching Kang, Ming-Yao Su and Sen-Yung Hsieh

J. Pers. Med. 2022, 12(6), 989; https://doi.org/10.3390/jpm12060989 - 17 Jun 2022

Cited by 9 | Viewed by 7976

Abstract

Background: Caustic ingestion has gained increasing attention worldwide. However, the insight into whether to use esophagogastroduodenoscopy (EGD) or computed tomography (CT) for first-line investigation remains controversial. This study aimed to evaluate a diagnostic and management algorithm that combines EGD and CT for rapid [...] Read more.

Background: Caustic ingestion has gained increasing attention worldwide. However, the insight into whether to use esophagogastroduodenoscopy (EGD) or computed tomography (CT) for first-line investigation remains controversial. This study aimed to evaluate a diagnostic and management algorithm that combines EGD and CT for rapid triage. Methods: We established an algorithm for our hospital in 2013, aiming to maximize the benefits and minimize the limitations of EGD and CT. Then, we retrospectively analyzed the 163 enrolled patients treated between 2014 and 2019 and categorized them into 4 groups: A = 3 (1.8%): with perforation signs and directly confirmed by CT, B = 10 (6.1%): clinically suspected perforation but not initially proven by CT, C = 91 (55.8%): initial perforation less favored but with EGD grade ≥ 2b or GI/systemic complications, and D = 59 (36.2%): clinically stable with EGD grade ≤ 2a, according to initial signs/symptoms and EGD/CT grading. The morbidity and mortality of each group were analyzed. The predictive values of EGD and CT were examined by logistic regression analyses and receiver operating characteristic (ROC) curves. Results: The outcomes of such algorithm were reported. CT was imperative for patients with toxic signs and suspected perforation. For non-emergent operations, additional EGD was safe and helpful in identifying surgical necessity. For patients with an initially low perforation risk, EGD alone sufficiently determined admission necessity. Among inpatients, EGD provided excellent discrimination for predicting the risk for signs/symptoms’ deterioration. Routine additional CT was only beneficial for those with deteriorating signs/symptoms. Conclusions: According to the analyses, initial signs/symptoms help to choose EGD or CT as the first-line investigative tool in caustic patients. CT is necessary for seriously injured patients, but it cannot replace EGD for moderate/mild injuries. The severity stratification and patient categorization help to simplify complex scenarios, accelerate decision-making, and prevent unnecessary intervention/therapy. External validation in a larger sample size is further indicated for this algorithm. Full article

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Open AccessArticle

CardioNet: Automatic Semantic Segmentation to Calculate the Cardiothoracic Ratio for Cardiomegaly and Other Chest Diseases

by Abbas Jafar, Muhammad Talha Hameed, Nadeem Akram, Umer Waqas, Hyung Seok Kim and Rizwan Ali Naqvi

J. Pers. Med. 2022, 12(6), 988; https://doi.org/10.3390/jpm12060988 - 17 Jun 2022

Cited by 19 | Viewed by 3009

Abstract

Semantic segmentation for diagnosing chest-related diseases like cardiomegaly, emphysema, pleural effusions, and pneumothorax is a critical yet understudied tool for identifying the chest anatomy. A dangerous disease among these is cardiomegaly, in which sudden death is a high risk. An expert medical practitioner [...] Read more.

Semantic segmentation for diagnosing chest-related diseases like cardiomegaly, emphysema, pleural effusions, and pneumothorax is a critical yet understudied tool for identifying the chest anatomy. A dangerous disease among these is cardiomegaly, in which sudden death is a high risk. An expert medical practitioner can diagnose cardiomegaly early using a chest radiograph (CXR). Cardiomegaly is a heart enlargement disease that can be analyzed by calculating the transverse cardiac diameter (TCD) and the cardiothoracic ratio (CTR). However, the manual estimation of CTR and other chest-related diseases requires much time from medical experts. Based on their anatomical semantics, artificial intelligence estimates cardiomegaly and related diseases by segmenting CXRs. Unfortunately, due to poor-quality images and variations in intensity, the automatic segmentation of the lungs and heart with CXRs is challenging. Deep learning-based methods are being used to identify the chest anatomy segmentation, but most of them only consider the lung segmentation, requiring a great deal of training. This work is based on a multiclass concatenation-based automatic semantic segmentation network, CardioNet, that was explicitly designed to perform fine segmentation using fewer parameters than a conventional deep learning scheme. Furthermore, the semantic segmentation of other chest-related diseases is diagnosed using CardioNet. CardioNet is evaluated using the JSRT dataset (Japanese Society of Radiological Technology). The JSRT dataset is publicly available and contains multiclass segmentation of the heart, lungs, and clavicle bones. In addition, our study examined lung segmentation using another publicly available dataset, Montgomery County (MC). The experimental results of the proposed CardioNet model achieved acceptable accuracy and competitive results across all datasets. Full article

(This article belongs to the Special Issue The Challenges and Prospects in Cardiology)

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J. Pers. Med., Volume 12, Issue 6 (June 2022) – 167 articles

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