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Med. Sci., Volume 6, Issue 2 (June 2018)

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Cover Story (view full-size image) Antimicrobial resistance is on the rise and is already a daily hindrance for intensivists combating [...] Read more.
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Open AccessReview Prognosis and Follow-Up of Idiopathic Pulmonary Fibrosis
Med. Sci. 2018, 6(2), 51; https://doi.org/10.3390/medsci6020051
Received: 23 May 2018 / Accepted: 11 June 2018 / Published: 14 June 2018
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Abstract
Idiopathic pulmonary fibrosis (IPF), a devastating progressive interstitial lung disease (ILD) with no known cause, is the most common and deadly of the idiopathic interstitial pneumonias. With a median survival of 3–5 years following diagnosis, IPF is characterized by a progressive decline in
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Idiopathic pulmonary fibrosis (IPF), a devastating progressive interstitial lung disease (ILD) with no known cause, is the most common and deadly of the idiopathic interstitial pneumonias. With a median survival of 3–5 years following diagnosis, IPF is characterized by a progressive decline in lung function and quality of life in most patients. Prognostic factors recognized classically that influence mortality include functional, clinical and radiological parameters. However, in recent years, there has also been progress in the knowledge of genetic factors and biomarkers that may be useful in the prognostic evaluation of these patients. On the other hand, the monitoring of the disease throughout its evolution is key to improving the prognosis of the patients, as it allows for taking therapeutic measures based on this evolution, even early remission for lung transplantation. This article reviews the main prognostic factors of the disease, as well as the most useful way to monitor the disease follow-up. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
Open AccessReview Is It Time to Change the Definition of Acute Exacerbation of Chronic Obstructive Pulmonary Disease? What Do We Need to Add?
Med. Sci. 2018, 6(2), 50; https://doi.org/10.3390/medsci6020050
Received: 7 April 2018 / Revised: 10 June 2018 / Accepted: 11 June 2018 / Published: 14 June 2018
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Abstract
Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) are associated with increased mortality, rate of hospitalization, use of healthcare resources, and have a negative impact on disease progression, quality of life and lung function of patients with chronic obstructive pulmonary disease (COPD). There
[...] Read more.
Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) are associated with increased mortality, rate of hospitalization, use of healthcare resources, and have a negative impact on disease progression, quality of life and lung function of patients with chronic obstructive pulmonary disease (COPD). There is an imperative need to homogenize the definition of AECOPD because the incidence of exacerbations has a significant influence or implication on treatment decision making, particularly in pharmacotherapy and could impact the outcome or change the statistical significance of a therapeutic intervention in clinical trials. In this review, using PubMed searches, we have analyzed the weaknesses and strengths of the different used AECOPD definitions (symptom-based, healthcare-based definition or the combinations of both), as well as the findings of the studies that have assessed the relationship of different biomarkers with the diagnosis, etiology and differential diagnosis of AECOPD and the progress towards the development of a more precise definition of COPD exacerbation. Finally, we have proposed a simple definition of AECOPD, which must be validated in future clinical trials to define its accuracy and usefulness in daily practice. Full article
(This article belongs to the Special Issue COPD Exacerbations)
Open AccessReview Shall We Focus on the Eosinophil to Guide Treatment with Systemic Corticosteroids during Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)? CON
Med. Sci. 2018, 6(2), 49; https://doi.org/10.3390/medsci6020049
Received: 18 April 2018 / Revised: 25 May 2018 / Accepted: 7 June 2018 / Published: 8 June 2018
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Abstract
The employment of systemic corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) has been shown to improve airway limitation, decrease treatment failure and risk of relapse, and may improve symptoms in addition to decreasing the length of hospital
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The employment of systemic corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) has been shown to improve airway limitation, decrease treatment failure and risk of relapse, and may improve symptoms in addition to decreasing the length of hospital stay. Nowadays, all clinical guidelines recommend systemic corticosteroids to treat moderate or severe COPD exacerbations. However, their use is associated with potential side effects, mainly hyperglycemia. In the era of precision medicine, the possibility of employing blood eosinophil count has emerged as a potential way of optimizing therapy. Issues regarding the intra-individual variability of blood eosinophil count determination, a lack of clear data regarding the real prevalence of eosinophilic acute exacerbations, the fact that previously published studies have demonstrated the benefit of systemic corticosteroids irrespective of eosinophil levels, and especially the fact that there is only one well-designed study justifying this approach have led us to think that we are not ready to use eosinophil count to guide treatment with systemic corticosteroids during acute exacerbations of COPD. Full article
(This article belongs to the Special Issue COPD Exacerbations)
Open AccessArticle Knocking out Ornithine Decarboxylase Antizyme 1 (OAZ1) Improves Recombinant Protein Expression in the HEK293 Cell Line
Med. Sci. 2018, 6(2), 48; https://doi.org/10.3390/medsci6020048
Received: 2 April 2018 / Revised: 30 May 2018 / Accepted: 1 June 2018 / Published: 8 June 2018
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Abstract
Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA) and small interfering RNA (siRNA), to identify key genes that can
[...] Read more.
Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA) and small interfering RNA (siRNA), to identify key genes that can potentially improve production or growth. The ornithine decarboxylase antizyme 1 (OAZ1) gene, a negative regulator of polyamine biosynthesis, was identified in a genome-wide siRNA screen as a potential engineering target, because its knock down by siRNA increased recombinant protein expression from human embryonic kidney 293 (HEK293) cells by two-fold. To investigate this further, the OAZ1 gene in HEK293 cells was knocked out using CRISPR genome editing. The OAZ1 knockout cell lines displayed up to four-fold higher expression of both stably and transiently expressed proteins, with comparable growth and metabolic activity to the parental cell line; and an approximately three-fold increase in intracellular polyamine content. The results indicate that genetic inactivation of OAZ1 in HEK293 cells is an effective strategy to improve recombinant protein expression in HEK293 cells. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessReview The Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease
Med. Sci. 2018, 6(2), 47; https://doi.org/10.3390/medsci6020047
Received: 30 April 2018 / Revised: 18 May 2018 / Accepted: 26 May 2018 / Published: 5 June 2018
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with prevalence increasing in parallel with the rising incidence in obesity. Believed to be a “multiple-hit” disease, several factors contribute to NAFLD initiation and progression. Of these, the gut microbiome
[...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with prevalence increasing in parallel with the rising incidence in obesity. Believed to be a “multiple-hit” disease, several factors contribute to NAFLD initiation and progression. Of these, the gut microbiome is gaining interest as a significant factor in NAFLD prevalence. In this paper, we provide an in-depth review of the progression of NAFLD, discussing the mechanistic modes of hepatocyte injury and the potential role for manipulation of the gut microbiome as a therapeutic strategy in the prevention and treatment of NAFLD. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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Open AccessReview Sleep Disturbances in Child and Adolescent Mental Health Disorders: A Review of the Variability of Objective Sleep Markers
Med. Sci. 2018, 6(2), 46; https://doi.org/10.3390/medsci6020046
Received: 25 March 2018 / Revised: 28 May 2018 / Accepted: 29 May 2018 / Published: 4 June 2018
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Abstract
Sleep disturbances are often observed in child and adolescent mental health disorders. Although previous research has identified consistent subjective reports of sleep disturbances, specific objective sleep markers have not yet been identified. We evaluated the current research on subjective and objective sleep markers
[...] Read more.
Sleep disturbances are often observed in child and adolescent mental health disorders. Although previous research has identified consistent subjective reports of sleep disturbances, specific objective sleep markers have not yet been identified. We evaluated the current research on subjective and objective sleep markers in relation to attention deficit hyperactivity disorders, autism spectrum disorders, anxiety and depressive disorders. Subjective sleep markers are more consistent than objective markers of actigraphy, polysomnography, and circadian measures. We discuss the causes of variability in objective sleep findings and suggest future directions for research. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
Open AccessReview Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease
Med. Sci. 2018, 6(2), 45; https://doi.org/10.3390/medsci6020045
Received: 26 April 2018 / Revised: 20 May 2018 / Accepted: 29 May 2018 / Published: 2 June 2018
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Abstract
The present review analyzes the results of recent clinical trials of β secretase inhibition in sporadic Alzheimer’s disease (SAD), considers the striking dichotomy between successes in tests of β-site Amyloid Precursor Protein-Cleaving Enzyme (BACE) inhibitors in healthy subjects and familial Alzheimer’s disease (FAD)
[...] Read more.
The present review analyzes the results of recent clinical trials of β secretase inhibition in sporadic Alzheimer’s disease (SAD), considers the striking dichotomy between successes in tests of β-site Amyloid Precursor Protein-Cleaving Enzyme (BACE) inhibitors in healthy subjects and familial Alzheimer’s disease (FAD) models versus persistent failures of clinical trials and interprets it as a confirmation of key predictions for a mechanism of amyloid precursor protein (APP)-independent, β secretase inhibition-resistant production of β amyloid in SAD, previously proposed by us. In light of this concept, FAD and SAD should be regarded as distinctly different diseases as far as β-amyloid generation mechanisms are concerned, and whereas β secretase inhibition would be neither applicable nor effective in the treatment of SAD, the β-site APP-Cleaving Enzyme (BACE) inhibitor(s) deemed failed in SAD trials could be perfectly suitable for the treatment of FAD. Moreover, targeting the aspects of Alzheimer’s disease (AD) other than cleavages of the APP by β and α secretases should have analogous impacts in both FAD and SAD. Full article
(This article belongs to the collection Advances in the Pathogenesis of Neurodegenerative Diseases)
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Open AccessFeature PaperReview Consolidation and Exacerbation of COPD
Med. Sci. 2018, 6(2), 44; https://doi.org/10.3390/medsci6020044
Received: 7 March 2018 / Revised: 30 May 2018 / Accepted: 31 May 2018 / Published: 1 June 2018
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Abstract
Twenty percent of chronic obstructive pulmonary disease (COPD) patients admitted to hospital because of an ‘exacerbation’ will have consolidation visible on a chest X-ray. The presence of consolidation is associated with higher mortality. Imperfect definitions of COPD exacerbation and pneumonia, and incomplete and
[...] Read more.
Twenty percent of chronic obstructive pulmonary disease (COPD) patients admitted to hospital because of an ‘exacerbation’ will have consolidation visible on a chest X-ray. The presence of consolidation is associated with higher mortality. Imperfect definitions of COPD exacerbation and pneumonia, and incomplete and imperfect diagnostic tests, have resulted in a debate about whether these episodes are best thought of as ‘exacerbation with consolidation’ or ‘pneumonia in a person with COPD’. With the current views that exacerbations are not all identical, and that they can be ‘phenotyped’ to identify episodes with different prognosis and treatment response, perhaps these episodes are best-considered a phenotype of exacerbation. Whatever the terminology, the important clinical message is to recognise that those with consolidation have higher mortality, and likely different responses to treatment. Full article
(This article belongs to the Special Issue COPD Exacerbations)
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Open AccessReview The Role of Systems Biologic Approach in Cell Signaling and Drug Development Responses—A Mini Review
Med. Sci. 2018, 6(2), 43; https://doi.org/10.3390/medsci6020043
Received: 17 April 2018 / Revised: 21 May 2018 / Accepted: 25 May 2018 / Published: 30 May 2018
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Abstract
The immune system is an integral aspect of the human defense system and is primarily responsible for and involved in the communication between the immune cells. It also plays an important role in the protection of the organism from foreign invaders. Recent studies
[...] Read more.
The immune system is an integral aspect of the human defense system and is primarily responsible for and involved in the communication between the immune cells. It also plays an important role in the protection of the organism from foreign invaders. Recent studies in the literature have described its role in the process of hematopoiesis, lymphocyte recruitment, T cell subset differentiation and inflammation. However, the specific molecular mechanisms underlying these observations remain elusive, impeding the elaborate manipulation of cytokine sequential delivery in tissue repair. Previously, the discovery of new drugs and systems biology went hand in hand; although Systems biology as a term has only originated in the last century. Various new chemicals were tested on the human body, and studied through observation. Animal models replaced humans for initial trials, but the interactions, response, dose and effect between animals and humans could not be directly correlated. Therefore, there is a need to form disease models outside of human subjects to check the effectiveness and response of the newer natural or synthetic chemicals. These emulate human disease conditions wherein the behavior of the chemicals would be similar in the disease model and humans. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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Open AccessConference Report ENABLE 2017, the First EUROPEAN PhD and Post-Doc Symposium. Session 4: From Discovery to Cure: The Future of Therapeutics
Med. Sci. 2018, 6(2), 42; https://doi.org/10.3390/medsci6020042
Received: 26 March 2018 / Accepted: 16 April 2018 / Published: 28 May 2018
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Abstract
The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European Research Institutes (Institute for Research in Biomedicine—IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences—RIMLS, the Netherlands; Novo Nordisk Foundation Center
[...] Read more.
The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European Research Institutes (Institute for Research in Biomedicine—IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences—RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research—NNF CPR, Denmark; European School of Molecular Medicine—SEMM, Italy) and an innovative science communication agency (Scienseed). With the aim of promoting biomedical science of excellence in Europe, ENABLE organizes an annual three-day international event. This gathering includes a top-level scientific symposium bringing together leading scientists, PhD students, and post-doctoral fellows; career development activities supporting the progression of young researchers and fostering discussion about opportunities beyond the bench; and outreach activities stimulating the interaction between science and society. The first European PhD and Postdoc Symposium, entitled “Breaking Down Complexity: Innovative Models and Techniques in Biomedicine”, was hosted by the vibrant city of Barcelona. The scientific program of the conference was focused on the most recent advances and applications of modern techniques and models in biomedical research and covered a wide range of topics, from synthetic biology to translational medicine. Overall, the event was a great success, with more than 200 attendees from all over Europe actively participating in the symposium by presenting their research and exchanging ideas with their peers and world-renowned scientists. Full article
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Open AccessFeature PaperReview Myc, Oncogenic Protein Translation, and the Role of Polyamines
Med. Sci. 2018, 6(2), 41; https://doi.org/10.3390/medsci6020041
Received: 9 April 2018 / Revised: 19 May 2018 / Accepted: 22 May 2018 / Published: 25 May 2018
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Abstract
Deregulated protein synthesis is a common feature of cancer cells, with many oncogenic signaling pathways directly augmenting protein translation to support the biomass needs of proliferating tissues. MYC’s ability to drive oncogenesis is a consequence of its essential role as a governor linking
[...] Read more.
Deregulated protein synthesis is a common feature of cancer cells, with many oncogenic signaling pathways directly augmenting protein translation to support the biomass needs of proliferating tissues. MYC’s ability to drive oncogenesis is a consequence of its essential role as a governor linking cell cycle entry with the requisite increase in protein synthetic capacity, among other biomass needs. To date, direct pharmacologic inhibition of MYC has proven difficult, but targeting oncogenic signaling modules downstream of MYC, such as the protein synthetic machinery, may provide a viable therapeutic strategy. Polyamines are essential cations found in nearly all living organisms that have both direct and indirect roles in the control of protein synthesis. Polyamine metabolism is coordinately regulated by MYC to increase polyamines in proliferative tissues, and this is further augmented in the many cancer cells harboring hyperactivated MYC. In this review, we discuss MYC-driven regulation of polyamines and protein synthetic capacity as a key function of its oncogenic output, and how this dependency may be perturbed through direct pharmacologic targeting of components of the protein synthetic machinery, such as the polyamines themselves, the eukaryotic translation initiation factor 4F (eIF4F) complex, and the eukaryotic translation initiation factor 5A (eIF5A). Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessFeature PaperArticle Feasibility of Antimicrobial Stewardship (AMS) in Critical Care Settings: A Multidisciplinary Approach Strategy
Med. Sci. 2018, 6(2), 40; https://doi.org/10.3390/medsci6020040
Received: 11 March 2018 / Revised: 16 May 2018 / Accepted: 16 May 2018 / Published: 25 May 2018
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Abstract
Antimicrobial resistance is escalating and triggers clinical decision-making challenges when treating infections in patients admitted to intensive care units (ICU). Antimicrobial stewardship (AMS) may help combat this problem, but it can be difficult to implement in critical care settings. The implementation of multidisciplinary
[...] Read more.
Antimicrobial resistance is escalating and triggers clinical decision-making challenges when treating infections in patients admitted to intensive care units (ICU). Antimicrobial stewardship (AMS) may help combat this problem, but it can be difficult to implement in critical care settings. The implementation of multidisciplinary AMS in ICUs could be more challenging than what is currently suggested in the literature. Our main goal was to analyze the reduction in duration of treatment (DOT) for the most commonly used antibacterial and antifungal agents during the first six months of 2014, and during the same period two years later (2016). A total of 426 and 424 patient encounters, respectively, were documented and collected from the intensive care unit’s electronic patient record system. Daily multidisciplinary ward rounds were conducted for approximately 30–40 min, with the goal of optimizing antimicrobial therapy in order to analyze the feasibility of implementing AMS. The only antimicrobial agent which showed a significant reduction in the number of prescriptions and in the duration of treatment during the second audit was vancomycin, while linezolid showed an increase in the number of prescriptions with no significant prolongation of the duration of treatment. A trend of reduction was also seen in the DOT for co-amoxiclavulanate and in the number of prescriptions of anidulafungin without any corresponding increases being observed for other broad-spectrum anti-infective agents (p-values of 0.07 and 0.05, respectively). Full article
Open AccessReview Tools for Detection of Schistosomiasis in Resource Limited Settings
Med. Sci. 2018, 6(2), 39; https://doi.org/10.3390/medsci6020039
Received: 4 May 2018 / Revised: 15 May 2018 / Accepted: 16 May 2018 / Published: 23 May 2018
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Abstract
Schistosomiasis is a debilitating disease affecting over 200 million people, with the highest burden of morbidity and mortality in African countries. Despite its huge impact on the health and socio-economic burden of the society, it remains a neglected tropical disease, with limited attention
[...] Read more.
Schistosomiasis is a debilitating disease affecting over 200 million people, with the highest burden of morbidity and mortality in African countries. Despite its huge impact on the health and socio-economic burden of the society, it remains a neglected tropical disease, with limited attention from governments and stakeholders in healthcare. One of the critical areas that is hugely under-developed is the development of accurate diagnostics for both intestinal and urogenital schistosomiasis. Diagnosis of schistosomiasis is important for the detection and treatment of disease in endemic and non-endemic settings. A conclusive detection method is also an indispensable part of treatment, both in the clinic and during mass drug administration (MDA), for the monitoring efficacy of treatment. Here, we review the available diagnostic methods and discuss the challenges encountered in diagnosis in resource limited settings. We also present the available diagnostics and cost implications for deployment in resource limited settings. Lastly, we emphasize the need for more funding directed towards the development of affordable diagnostic tools that is affordable for endemic countries as we work towards the elimination of the disease. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
Open AccessArticle Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients
Med. Sci. 2018, 6(2), 38; https://doi.org/10.3390/medsci6020038
Received: 8 April 2018 / Revised: 5 May 2018 / Accepted: 15 May 2018 / Published: 22 May 2018
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Abstract
The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with
[...] Read more.
The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD. Full article
(This article belongs to the Section Cardiovascular Disease)
Open AccessArticle Pituitary, Gonadal, Thyroid Hormones and Endocrine Disruptors in Pre and Postmenopausal Nigerian Women with ER-, PR- and HER-2-Positive and Negative Breast Cancers
Med. Sci. 2018, 6(2), 37; https://doi.org/10.3390/medsci6020037
Received: 17 April 2018 / Revised: 3 May 2018 / Accepted: 15 May 2018 / Published: 18 May 2018
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Abstract
Breast cancer is broadly sub-divided into hormone responsive and non-hormone responsive subtypes. Estradiol has been associated with hormone responsive breast cancers. There is, however, a paucity of information on the role of sex hormones, gonadotropins, and thyroid hormone in non-hormone responsive breast cancer.
[...] Read more.
Breast cancer is broadly sub-divided into hormone responsive and non-hormone responsive subtypes. Estradiol has been associated with hormone responsive breast cancers. There is, however, a paucity of information on the role of sex hormones, gonadotropins, and thyroid hormone in non-hormone responsive breast cancer. This study aimed to determine differences in the serum levels of sex hormones, gonadotropins, thyroid hormones, and endocrine disruptors (lead, cadmium, and arsenic) in Nigerian women with hormone responsive and non-hormone responsive breast cancers. Seventy-nine non-pregnant women aged 28–80 years with histologically confirmed breast cancer were recruited, pre-therapy, into this cross-sectional study. They comprised 52 premenopausal women and 27 postmenopausal women recruited from the Surgical Oncology Clinic of the Department of Surgery, University College Hospital, Ibadan. Comparison of biochemical parameters were based on the positivity (+) and negativity (−) of estrogen receptor (ER), progesterone receptor (PR) and human epithelial receptor-2 (HER-2). Estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were determined using enzyme immunoassay (EIA). Serum lead, cadmium and arsenic were determined using atomic absorption spectrophotometry (AAS). Expression of ER, PR and HER2 were determined using immunohistochemistry. Data was analyzed using Mann-Whitney U-test and multiple regression, with p < 0.05 considered as being statistically significant. Estradiol and progesterone were significantly higher in breast cancer participants with ER and PR compared with those with ER+ and PR+ breast cancer (p < 0.05). Follicle stimulating hormone and LH levels were significantly higher in participants with ER+ and PR+ breast cancer compared with participants with ER and PR breast cancer (p < 0.05). Arsenic was inversely related with TSH in premenopausal participants with ER and PR (β = −0.305; β = −0.304, respectively). Sex hormones and gonadotropins appear to be involved in the pathogenesis of triple negative and luminal breast cancer, respectively. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
Open AccessArticle Inhibition of Insulin Degrading Enzyme and Insulin Degradation by UV-Killed Lactobacillus acidophilus
Med. Sci. 2018, 6(2), 36; https://doi.org/10.3390/medsci6020036
Received: 9 March 2018 / Revised: 21 April 2018 / Accepted: 8 May 2018 / Published: 11 May 2018
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Abstract
Probiotics have beneficial effects on management of type 2 diabetes (T2D). The major hallmarks of T2D are insulin deficiency and insulin resistance which emphasize insulin therapy in onset of disease. Lactobacilli such as Lactobacillus acidophilus (L. acidophilus) have well known properties
[...] Read more.
Probiotics have beneficial effects on management of type 2 diabetes (T2D). The major hallmarks of T2D are insulin deficiency and insulin resistance which emphasize insulin therapy in onset of disease. Lactobacilli such as Lactobacillus acidophilus (L. acidophilus) have well known properties on prevention of T2D and insulin resistance but not on insulin degradation. Insulin-degrading enzyme (IDE) degrades insulin in the human body. We studied the effects of cell-free supernatant (CFS) and ultraviolet (UV)-killed L. acidophilus (ATCC 314) on IDE activity and insulin degradation in vitro. Cell growth inhibition by CFS and UV-killed L. acidophilus (ATCC 314) was studied and Western blotting and a fluoregenic assay was performed to determine IDE expression and its activity, respectively. Insulin degradation was evaluated by sandwich enzyme-linked immunosorbent assay(ELISA). IDE expression and activity was reduced by CFS and UV-killed L. acidophilus (ATCC 314). Although, decreased enzyme expression and activity was not significant for CFS in contrast to MRL (MRS with same pH as CFS). Also, reduction in IDE activity was not statistically considerable when compared to IDE expression. Insulin degradation was increased by CFS but decreased by UV-killed L. acidophilus (ATCC 314). Full article
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Open AccessReview Characteristics and Management of Community-Acquired Pneumonia in the Era of Global Aging
Med. Sci. 2018, 6(2), 35; https://doi.org/10.3390/medsci6020035
Received: 20 March 2018 / Revised: 25 April 2018 / Accepted: 26 April 2018 / Published: 30 April 2018
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Abstract
Community-acquired pneumonia (CAP) can occur at any time of life, but its incidence and risk of death are linked to increasing age. CAP in the elderly is a major health problem associated with high rates of readmission, morbidity, and mortality. Since the clinical
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Community-acquired pneumonia (CAP) can occur at any time of life, but its incidence and risk of death are linked to increasing age. CAP in the elderly is a major health problem associated with high rates of readmission, morbidity, and mortality. Since the clinical presentation of pneumonia in the elderly may be atypical, clinicians should suspect pneumonia in older patients presenting symptoms such as falls and altered mental status, fatigue, lethargy, delirium, anorexia, in order to avoid the complications associated with delayed diagnosis and therapy. Streptococcus pneumoniae remains the most frequently reported pathogen in this population. However, particular attention should be paid to patients with risk factors for multidrug resistant pathogens, because a large proportion of elderly persons present multimorbidity. Vaccination is one of the most important preventive approaches for CAP in the elderly. In addition, lifestyle-tailored interventions for different modifiable risk factors will help to reduce the risk of pneumonia in elderly persons. Surveillance of etiological pathogens may improve vaccination policies in this population. Full article
(This article belongs to the Section Pneumology and Respiratory Diseases)
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Open AccessReview The Role of Adipokines in Intervertebral Disc Degeneration
Med. Sci. 2018, 6(2), 34; https://doi.org/10.3390/medsci6020034
Received: 9 February 2018 / Revised: 17 April 2018 / Accepted: 19 April 2018 / Published: 24 April 2018
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Abstract
Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor
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Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor of IDD, is now increasingly being recognized as a systemic inflammatory state with adipokines being postulated as likely inflammatory mediators. The aim of this review was to summarize the current literature regarding the inflammatory role of adipokines in the pathophysiology of IDD. A systematic literature search was performed using the OVID Medline, EMBASE and PubMed databases to identify all studies assessing IDD and adipokines. Fifteen studies were included in the present review. Leptin was the most commonly assessed adipokine. Ten of 15 studies were conducted in humans; three in rats and two in both humans and rats. Studies focused on a variety of topics ranging from receptor identification, pathway analysis, genetic associations, and proteonomics. Currently, data from both human and animal experiments demonstrate significant effects of leptin and adiponectin on the internal milieu of intervertebral discs. However, future studies are needed to determine the molecular pathway relationships between adipokines in the pathophysiology of IDD as avenues for future therapeutic targets. Full article
(This article belongs to the Section Endocrinology and Metabolic Diseases)
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Open AccessReview Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives
Med. Sci. 2018, 6(2), 33; https://doi.org/10.3390/medsci6020033
Received: 15 February 2018 / Revised: 4 April 2018 / Accepted: 11 April 2018 / Published: 18 April 2018
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Abstract
Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications, such as the
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Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications, such as the removal of introns and signal peptides, and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing inactive proMPO by the insertion of a heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into the extracellular fluid after oxidative stress and different inflammatory responses. Myeloperoxidase is the only type of peroxidase that uses H2O2 to oxidize several halides and pseudohalides to form different hypohalous acids. So, the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation and can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and the pathogenesis of several other major chronic diseases such as rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes, and cancer have been reported to be linked with MPO-derived oxidants. Thus, the enhanced level of MPO activity is one of the best diagnostic tools of inflammatory and oxidative stress biomarkers among these commonly-occurring diseases. Full article
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Open AccessReview The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases
Med. Sci. 2018, 6(2), 32; https://doi.org/10.3390/medsci6020032
Received: 12 March 2018 / Revised: 9 April 2018 / Accepted: 10 April 2018 / Published: 17 April 2018
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Abstract
The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production.
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The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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Open AccessReview Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells
Med. Sci. 2018, 6(2), 31; https://doi.org/10.3390/medsci6020031
Received: 12 February 2018 / Revised: 24 March 2018 / Accepted: 3 April 2018 / Published: 13 April 2018
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Abstract
Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20–30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise
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Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20–30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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Open AccessArticle Cimetidine: A Safe Treatment Option for Cutaneous Warts in Pediatric Heart Transplant Recipients
Med. Sci. 2018, 6(2), 30; https://doi.org/10.3390/medsci6020030
Received: 21 February 2018 / Revised: 26 March 2018 / Accepted: 3 April 2018 / Published: 8 April 2018
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Abstract
Background and Objectives: Immunosuppressed individuals are at particularly increased risk for human papilloma virus-related infections. The primary objective of our study is to determine if there are any adverse effects associated with high-dose cimetidine treatment. A secondary objective is to report our
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Background and Objectives: Immunosuppressed individuals are at particularly increased risk for human papilloma virus-related infections. The primary objective of our study is to determine if there are any adverse effects associated with high-dose cimetidine treatment. A secondary objective is to report our experience with cimetidine in the treatment of cutaneous warts in pediatric heart transplant recipients. Methods and Results: This was a retrospective observational study. A total of 8 pediatric heart transplant recipients diagnosed with multiple recalcitrant warts were the subject of the study. All patients were treated with cimetidine (30–40 mg/kg/day) in two divided doses for 3 to 6 month durations. All patients had complete resolution of their lesions except 1 patient who had no clinical improvement. Of these 8 patients, one had recurrence of warts at one year follow-up, which resolved with restarting cimetidine therapy. One patient who had only 3 months of cimetidine therapy had immediate relapse after cimetidine was stopped. None of them had significant change in their tacrolimus trough, serum creatinine, and alanine transaminase levels. No adverse events were reported except one patient experienced mild gynecomastia. Conclusion: Cimetidine can be a safe and alternative treatment option for multiple warts in pediatric heart transplant recipients. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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Open AccessReview Clostridium Bacteria and Autism Spectrum Conditions: A Systematic Review and Hypothetical Contribution of Environmental Glyphosate Levels
Med. Sci. 2018, 6(2), 29; https://doi.org/10.3390/medsci6020029
Received: 17 March 2018 / Revised: 27 March 2018 / Accepted: 27 March 2018 / Published: 4 April 2018
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Abstract
Nowadays, there seems to be a consensus about the multifactorial nature of autism spectrum disorders (ASD). The literature provides hypotheses dealing with numerous environmental factors and genes accounting for the apparently higher prevalence of this condition. Researchers have shown evidence regarding the impact
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Nowadays, there seems to be a consensus about the multifactorial nature of autism spectrum disorders (ASD). The literature provides hypotheses dealing with numerous environmental factors and genes accounting for the apparently higher prevalence of this condition. Researchers have shown evidence regarding the impact of gut bacteria on neurological outcomes, altering behavior and potentially affecting the onset and/or severity of psychiatric disorders. Pesticides and agrotoxics are also included among this long list of ASD-related environmental stressors. Of note, ingestion of glyphosate (GLY), a broad-spectrum systemic herbicide, can reduce beneficial bacteria in the gastrointestinal tract microbiota without exerting any effects on the Clostridium population, which is highly resistant to this herbicide. In the present study, (i) we performed a systematic review to evaluate the relationship between Clostridium bacteria and the probability of developing and/or aggravating autism among children. For that purpose, electronic searches were performed on Medline/PubMed and Scielo databases for identification of relevant studies published in English up to December 2017. Two independent researches selected the studies and analyzed the data. The results of the present systematic review demonstrate an interrelation between Clostridium bacteria colonization of the intestinal tract and autism. Finally, (ii) we also hypothesize about how environmental GLY levels may deleteriously influence the gut–brain axis by boosting the growth of Clostridium bacteria in autistic toddlers. Full article
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Open AccessArticle Relationship between Response to PDE5 Inhibitors and Penile Duplex Doppler Ultrasound in Erectile Dysfunction
Med. Sci. 2018, 6(2), 28; https://doi.org/10.3390/medsci6020028
Received: 22 January 2018 / Revised: 18 March 2018 / Accepted: 22 March 2018 / Published: 26 March 2018
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Abstract
The relationship between the results of penile duplex Doppler ultrasound (PDDU) and response to vardenafil was investigated in patients diagnosed with erectile dysfunction (ED). Data from 148 patients with ED were analyzed retrospectively. Patients who did not respond to therapy were classified in
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The relationship between the results of penile duplex Doppler ultrasound (PDDU) and response to vardenafil was investigated in patients diagnosed with erectile dysfunction (ED). Data from 148 patients with ED were analyzed retrospectively. Patients who did not respond to therapy were classified in to Group I (n = 32), those who responded partially were classified into Group II (n = 40), and complete responders were classified into Group III (n = 76). Age, comorbidities, and vascular and penile pathologies were compared among the three groups. While diabetes mellitus (DM) and dyslipidemia positivity adversely affected the response to treatment, the presence of hypertension (HT), Peyronie’s disease and priapism increased the therapeutic response to the treatment (p < 0.05). Arterial insufficiency was present in 20 (30.3%), 25 (37.9%) and 21 (31.8%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Venous insufficiency was observed in three (14.3%) patients in Group I and in eight (85.7%) patients in Group III (p = 0.001). Arterial/venous insufficiency was seen in 9 (30%), 14 (46.7%) and 7 (23.3%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). The response rate to treatment was highest in normal patients according to PDDU, followed by patients with venous insufficiency. In addition, it was found that DM decreased the response to treatment, whereas the response increased in cases with HT, priapism and Peyronie’s disease. Full article
Open AccessReview Live Bacterial Vectors—A Promising DNA Vaccine Delivery System
Med. Sci. 2018, 6(2), 27; https://doi.org/10.3390/medsci6020027
Received: 24 January 2018 / Revised: 19 March 2018 / Accepted: 19 March 2018 / Published: 23 March 2018
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Abstract
Vaccination is one of the most successful immunology applications that has considerably improved human health. The DNA vaccine is a new vaccine being developed since the early 1990s. Although the DNA vaccine is promising, no human DNA vaccine has been approved to date.
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Vaccination is one of the most successful immunology applications that has considerably improved human health. The DNA vaccine is a new vaccine being developed since the early 1990s. Although the DNA vaccine is promising, no human DNA vaccine has been approved to date. The main problem facing DNA vaccine efficacy is the lack of a DNA vaccine delivery system. Several studies explored this limitation. One of the best DNA vaccine delivery systems uses a live bacterial vector as the carrier. The live bacterial vector induces a robust immune response due to its natural characteristics that are recognized by the immune system. Moreover, the route of administration used by the live bacterial vector is through the mucosal route that beneficially induces both mucosal and systemic immune responses. The mucosal route is not invasive, making the vaccine easy to administer, increasing the patient’s acceptance. Lactic acid bacterium is one of the most promising bacteria used as a live bacterial vector. However, some other attenuated pathogenic bacteria, such as Salmonella spp. and Shigella spp., have been used as DNA vaccine carriers. Numerous studies showed that live bacterial vectors are a promising candidate to deliver DNA vaccines. Full article
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Open AccessArticle Socio-Economic Predictors and Distribution of Tuberculosis Incidence in Beijing, China: A Study Using a Combination of Spatial Statistics and GIS Technology
Med. Sci. 2018, 6(2), 26; https://doi.org/10.3390/medsci6020026
Received: 17 January 2018 / Revised: 10 March 2018 / Accepted: 12 March 2018 / Published: 21 March 2018
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Abstract
Evidence shows that multiple factors, such as socio-economic status and access to health care facilities, affect tuberculosis (TB) incidence. However, there is limited literature available with respect to the correlation between socio-economic/health facility factors and tuberculosis incidence. This study aimed to explore the
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Evidence shows that multiple factors, such as socio-economic status and access to health care facilities, affect tuberculosis (TB) incidence. However, there is limited literature available with respect to the correlation between socio-economic/health facility factors and tuberculosis incidence. This study aimed to explore the relationship between TB incidence and socio-economic/health service predictors in the study settings. A retrospective spatial regression analysis was carried out based on new sputum smear-positive pulmonary TB cases in Beijing districts. Global Moran’s I analysis was adopted to detect the spatial dependency followed by spatial regression models (spatial lag model, and spatial error model) along with the ordinary least square model were applied to examine the correlation between TB incidence and predictors. A high incidence of TB was seen in densely populated districts in Beijing, e.g., Haidian, Mentougou, and Xicheng. After comparing the R2, log-likelihood, and Akaike information criterion (AIC) values among three models, the spatial error model (R2 = 0.413; Log Likelihood = −591; AIC = 1199.76) identified the best model fit for the spatial regression model. The study showed that the number of beds in health institutes (p < 0.001) and per capita gross domestic product (GDP) (p = 0.025) had a positive effect on TB incidence, whereas population density (p < 0.001) and migrated population (p < 0.001) had an adverse impact on TB incidence in the study settings. High TB incidence districts were detected in urban and densely populated districts in Beijing. Our findings suggested that socio-economic predictors influence TB incidence. These findings may help to guide TB control programs and promote targeted intervention. Full article
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