Diseases — Open Access Journal

Bipolar disorder and borderline personality disorder are among the most frequently diagnosed psychiatric conditions. However, the nosological aspects and diagnostic boundaries of both conditions have historically been the object of considerable controversy. The present paper critically analyzes this debate, in light of available evidence. Clinical and neurobiological differences between bipolar disorder and borderline personality disorder are discussed, as well as the factors possibly involved in the overlap between both conditions and the potential implications of this. Full article

Although individually uncommon, rare diseases collectively account for a considerable proportion of disease impact worldwide. A group of rare genetic diseases called the mucopolysaccharidoses (MPSs) are characterized by accumulation of partially degraded glycosaminoglycans cellularly. MPS results in varied systemic symptoms and in some forms of the disease, neurodegeneration. Lack of treatment options for MPS with neurological involvement necessitates new avenues of therapeutic investigation. Cell and gene therapies provide putative alternatives and when coupled with genome editing technologies may provide long term or curative treatment. Clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing technology and, more recently, advances in genome editing research, have allowed for the addition of base editors to the repertoire of CRISPR-based editing tools. The latest versions of base editors are highly efficient on-targeting deoxyribonucleic acid (DNA) editors. Here, we describe a number of putative guide ribonucleic acid (RNA) designs for precision correction of known causative mutations for 10 of the MPSs. In this review, we discuss advances in base editing technologies and current techniques for delivery of cell and gene therapies to the site of global degeneration in patients with severe neurological forms of MPS, the central nervous system, including ultrasound-mediated blood-brain barrier disruption. Full article

Anxiety is a feeling of discomfort produced in face of an unknown event, as an impending cardiac surgery, that can lead to inconveniences in the intervention and subsequent recovery. Being the purpose of this research to analyze pre-surgical anxiety, a descriptive cross-sectional study among patients undergoing cardiac surgery was carried out. Data about sociodemographic variables were collected and the level of anxiety prior to surgery was assessed using the STAI-S scale. Subsequently, descriptive data analyses were performed, relationships among variables were analyzed, and a binary logistic regression model was developed in order to analyze the role of the variables involved in the development of preoperative anxiety. Sixty subjects were finally included; more than 80% had a moderate to high level of anxiety. 26.7% underwent valve surgery and 47% underwent coronary artery bypass graft (CABG) surgery, in the latter case presenting higher levels of anxiety. Statistically significant relationships were found among the level of anxiety and (a) level of studies, (b) first surgical intervention, and (c) the rating given to their previous surgical experience. We concluded that preoperative anxiety in people undergoing cardiac surgery is high and yet it is an underestimated phenomenon. The relationship between the received information and their anxiety level is inversely proportional, so that people programmed for cardiac surgery should be provided with all the information they required, through an individualized intervention. Full article

An increased interest regarding the impact of frailty on the prognosis of cardiovascular disease (CVD) has been observed in the last decade. Frailty is a syndrome characterized by a reduced biological reserve that increases the vulnerability of an individual in relation to stressors. Among the patients with CVD, a higher incidence of frailty has been reported in those with heart failure (HF). Regardless of its conceptualizations, frailty is generally associated with negative outcomes in HF and an increased risk of mortality. Psychological factors, such as depression and anxiety, increase the risk of negative outcomes on the cardiac function and mortality. Depression and anxiety are found to be common factors impacting the heart disease and quality of life (QoL) in patients with HF. Depression is considered an independent risk factor of cardiac-related incidents and death, and a strong predictor of rehospitalization. Anxiety seems to be an adequate predictor only in conjunction with depression. The relationship between psychological factors (depression and anxiety) and frailty in HF has hardly been documented. The aim of this paper is to review the reported data from relevant studies regarding the impact of depression and anxiety, and their effects on clinical outcomes and prognosis in frail patients with HF. Full article

Background: The aim of this study is to evaluate the clinical impact of intravesical Bacillus Calmette-Guérin (BCG)-induced changes in blood/urinary immune markers. Methods: Time-course changes in blood/urinary clinical parameters and mRNA expression of 13 genes in urine sediment taken eight times during the treatment course of intravesical BCG (before, every 2 weeks for 8 weeks, and after) in 24 patients with non-muscle invasive bladder cancer. The genes examined include cellular markers of four immune checkpoint proteins (PD-L1, PD-L2, PD-1, and CTLA-4), immunosuppressive cells (regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells), pan-T lymphocytes, B lymphocytes, and neutrophils. Results: Significant transient increase in gene expression was observed for PD-L1, PD-1, FOXP3, and CD204 at 6–8 doses of BCG. The patients were stratified into two groups depending on the number of genes with increased mRNA expression. Fourteen (58%) had 0–1 genes upregulated, while 10 (42%) had 2–4 genes with increased expression. No patient in the 0–1 group experienced recurrence, while 70% of patients in the 2–4 group experienced recurrence (p value = 0.037, hazard ratio = 5.93). Conclusions: Our findings suggested that increases in more than one of PD-L1, PD-1, FOXP3, and CD204, expression in the urine sediments was associated with resistance to BCG treatment. Full article

The harmonious regulation of bodily function is a necessity for healthy individuals. Looking from the viewpoint of material sciences, one can only marvel at the cellular factories, their renewal, and the overall control of messaging and control of responses. As aging progresses and/or pathologies arise, clinicians may be forced to look for replacement of organs/tissues with medical devices. Since all devices are tailored, a detailed understanding of developmental processes, including aberrant processes leading to pathologies, is crucial to provide clinicians with a suitable device. Although research in the field of epigenetics has produced effective therapeutics and diagnostic markers, our currently fragmented understanding of epigenetic processes as they relate to material development is inherently limited, with logical implications for the success of medical procedures. Here, we illustrate how material sciences for clinical applications, critically depend on all aspects of biomedical sciences, including the field of epigenetics. Full article

The development of tissues involves the direction of specific programs for gene expression among distinct cell types. These programs are often established in a heritable state by virtue of epigenetic mechanisms and corresponding pathways of cellular memory. Thus, the broad synchronization in patterns of gene expression ultimately dictates cellular consequences. Aberrations in these epigenetic mechanisms are known to be associated with a range of diseases. Herein, we highlight epigenetic factors that, when aberrantly expressed, lead to a broad range of diseases. Further, we call upon the community of biomedical researchers to share their findings related to the epigenetic factors of disease. Full article

Stenotrophomonas maltophilia has been recognized as an emerging nosocomial pathogen in invasive infections of immunocompromised, severely debilitated patients with significant underlying illnesses. The first-choice drug in these infections is sulfamethoxazole-trimethoprim (SMX/TMP), and resistance to this antimicrobial is a daunting challenge for clinicians. The aim of this study was to assess the prevalence of S. maltophilia bacteremia and SMX/TMP-resistance levels at a tertiary-care university hospital. A total of 175 episodes of S. maltophilia bacteremia were identified (2008–2012: n = 82, 2013–2017: n = 93; p = 0.061), 52% of affected patients were 60 years of age, and had recent surgery, severe injuries or underlying conditions (malignant hematologic diseases and solid tumors) in their history. Sixteen percent of isolates were resistant to SMX/TMP (2008–2012: n = 13.8%, 2013–2017: n = 17.2%; p = 0.076), and out of the resistant strains, 32.7% were also resistant to levofloxacin and colistin. Our findings on the SMX/TMP-resistance were similar to global literature data. Full article

For the purpose of human disease prevention, several methods have been developed, and are still developing, to assess the oxidative stress status (OSS) of individuals. In the present paper, we describe an approach based on electrochemical detection able to evaluate skin oxidative stress status (SOSS) as a PAOT (Pouvoir AntiOxydant Total)-Skin Score^®. Normal reference values for the PAOT-Skin Score^® were: 0–62.94 (n = 263). Intra- and inter-assay coefficients of variation were, respectively, 12.47 ± 4.29% and 7.0 ± 2.5%. Our technology showed increased skin antioxidant activity following topical application of reduced coeznyme Q₁₀ cream or vitamin C intake as orange juice or supplements. Moreover, we found significant correlations between some blood oxidative stress biomarkers and the PAOT-Skin Score^® (γ-tocopherol/α-tocopherol ratio (r = 0.43, p = 0.020); copper (r = −0.42, p = 0.022); copper/zinc ratio (r = −0.49, p = 0.006), and lipid peroxides (r = −0.43, p = 0.002)). In addition to being non–invasive, the present electrochemical methodology is also not expensive, fast, and easy to use. Full article

Hereditary gingival fibromatosis is a disorder for which the etiology remains unknown. We aimed to evaluate the fibroblasts and histological alterations to give new clues. A father and a daughter of a family showing gingival hereditary fibromatosis were treated, and gingival biopsies were obtained. A histological study revealed dense fibrous tissue, basal lamina disruption, and epithelial cell migration into the connective tissue. Fibroblasts were cultured from the father and daughter and compared with those from a healthy control patient. The results of the biochemical analysis showed increased collagen synthesis, reduced antioxidant CoQ₁₀ content, and high levels of lipid peroxidation. Additionally, fibroblasts culture incubation with the oxidant H₂O₂ increased collagen levels that have been reduced by the addition of the antioxidant CoQ₁₀. We conclude that some fibroblasts metabolic alterations play a significant role in initiating and maintaining persistent fibrotic tissue. Oxidative stress influences the fibroblasts collagen production and could play a particular role in the pathogenesis of hereditary gingival fibromatosis. Full article

Rhabdomyolysis is caused by extensive damage to skeletal muscles resulting in elevated creatine phosphokinase (CPK), Lactate dehydrogenase (LDH), and aspartate aminotransferase (AST), leading to life-threatening consequences like acute renal failure, cardiac arrhythmias, and hyperthermia. A variety of causes for muscle damage are known, and one of the most common is drug-induced. Statins and many other agents are known to induce muscle damage, but here we report Entresto™ (Sacubitril/Valsartan) induced rhabdomyolysis which has not been previously reported as solely responsible in the literature. Full article

Herpes simplex virus (HSV) is the leading cause of proctitis in HIV-infected individuals. However, no cases of rectal masses secondary to HSV infection have been reported to date. Herein, we present the case of a 45-year-old man with HIV infection who developed rectal pain and bleeding, along with dysuria and voiding difficulty. Colonoscopy revealed proctitis and a rectal mass with features concerning for rectal cancer. Histologic sections of the rectal mass biopsy demonstrated colorectal mucosa with viral cytopathic changes, ulceration, granulation tissue, marked inflammatory infiltrate, and fibrinopurulent exudate. Immunohistochemistry for herpes simplex virus-1 was positive in epithelial cells demonstrating a viral cytopathic effect. The patient was treated with valacyclovir for 3 weeks, which led to complete resolution of his symptoms. Follow-up sigmoidoscopy at 6 months did not show any masses. Our case illustrates the importance of considering HSV in the differential diagnosis of rectal masses. We advocate the routine use of viral immunohistochemistry for the evaluation of rectal tumors, especially in patients with clinical manifestations and endoscopic findings consistent with proctitis. Full article

Pertussis (“whooping cough”) is a re-emerging disease with increasing incidence among fully vaccinated individuals. We explored the genetic diversity of five Bordetella pertussis proteins used to generate the subunit vaccine across ancestral and newly emergent strains using immunoinformatics and evolutionary selection measurements. The five subunits of pertussis toxin (Ptx1–Ptx5) were highly conserved with regard to sequence, predicted structure, predicted antigenicity, and were under purifying selection. In contrast, the adhesin proteins pertactin (Prn) and filamentous hemagglutinin (FHA) were under statistically significant (p < 0.01) diversifying selection. Most heavily diversified sites of each protein fell within antigenic epitopes, and the functional adhesin motifs were conserved. Protein secondary structure was conserved despite sequence diversity for FHA but was changeable in Prn. These findings suggest that subunit vaccine-derived immunity does not impact Ptx1–Ptx5 but may apply evolutionary pressure to Prn and FHA to undergo diversifying selection. These findings offer further insight into the emergence of vaccine-resistant strains of B. pertussis. Full article

Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c.1222 T>G, p. (Cys408Gly)). Immune deficiency in these patients ranged from late-onset combined immunodeficiency (CID) with severe respiratory tract infections and recurrent shingles to asymptomatic selective antibody deficiency. Evident clinical heterogeneity manifested despite a common genetic background, suggesting the pathogenic relevance of epigenetic modification. Immunological follow-up reveals a previously unidentified gradual depletion of B and CD4⁺ T cells in all three presented patients with transition of a common variable immunodeficiency (CVID)-like disease to late-onset-CID in one of them. Considering all previously published cases with ICF2, we identify inadequate antibody responses to vaccines and reduction in CD27⁺ memory B cells as prevalent immunological traits. High mortality among ICF2 patients (20%) together with the progressive course of immunodeficiency suggest that hematopoietic stem cell transplantation (HSCT) should be considered as a treatment option in due time. Full article

The Disgust Scale has been designed to measure disgust propensity—the individual ease in experiencing disgust. The present study aimed to explore the validity, reliability, the factor structure, and the measurement invariance of the Greek version of the Disgust Scale-Revised (DS-R). A sample of 754 healthy participants completed the Greek version of the DS-R. A subset (n = 363) also completed the revised Symptom checked list and the Eysenck Personality Questionnaire, in order to examine the concurrent validity. Exploratory and Confirmatory factor analyses in different subsets were used to examine the factor structure. Multiple indicators–multiple causes model (MIMIC) models were used to assess the measurement invariance across gender and age. Demographic influences were assessed using t-tests, ANOVA, and Pearson’s correlations. Exploratory factor analysis concluded to two and three factor models, with a factor structure similar to the ones proposed in the literature. Confirmatory factor analysis and bi-factor analysis provided evidence in favor of the three-factor solution. Measurement invariance test revealed differences in six items across gender, and three items across age. The psychometric properties of the factors were satisfactory. Demographic influences on the responses were present, especially with respect to gender. The Greek version of the DS-R demonstrated satisfactory psychometric properties, making it suitable for use for the Greek population. Full article

Handgrip strength (HS) and knee extensor muscle strength (KEMS) showed a negative correlation with the Disabilities of the Arm, Shoulder, and Hand (DASH) score at one month following cardiac surgery. We performed a longitudinal study to examine changes in HS/KEMS and DASH score during phase II cardiac rehabilitation (CR) in patients after cardiac surgery. We measured and assessed HS, KEMS, and DASH score in 41 consecutive patients at one and three months following cardiac surgery and examined the relation between these factors at three months following cardiac surgery. Wilcoxon signed-rank test and Spearman correlation coefficients were used to analyze the results. Finally, 26 patients (63.2 years, 73.1% male) were analyzed. There were significant differences from one month to three months following cardiac surgery in HS (26.78 ± 8.26 to 31.35 ± 9.41 kgf, p < 0.001), KEMS (1.53 ± 0.42 to 1.72 ± 0.46 Nm/kg, p = 0.001), and DASH score (14.76 ± 12.58 to 7.62 ± 9.29, p < 0.001). DASH score correlated negatively with HS (r = −0.41, p = 0.01) but not with KEMS (r = −0.32, p = 0.09) after three months of phase II CR. Although HS, KEMS, and DASH scores changed significantly from one to three months following cardiac surgery during phase II CR, only HS correlated negatively with DASH score at three months following cardiac surgery. Full article

Ancient Egyptians smeared a mixture of dark soil on their eyelids and believed it protected eyes from unknown forces (illness). Recent studies have proven that the dark soil across the Nile River is rich in natural compounds including lead sulfide, which in low levels, promotes the production of nitric oxide (240-fold) by keratinocytes, with strong immune stimulatory and antimicrobial properties. Current investigations reveal anti-inflammatory and anti-infectious activities—including cytokines and chemokines—in saliva, as well as its friendly microbiota, which lines the surface of the oral cavity, its protection against inflammatory and infectious organisms in the stoma and other organs, such as the cardiovascular and central nervous systems. In fact, saliva may soon become a safe and practical surrogate biomarker for genomic/proteomic evaluations and to replace painful blood drawing and its side effects. Another example is leprosy, or Hansen’s disease, a chronic inflammatory syndrome and neglected tropical disease, which affects the skin, and peripheral and trigeminal neurons causing a lack of sensation to heat and cold and loss of extremities. Leprosy has horrified humans for over 2000 years, as lepers were considered unclean sinners and were subsequently drawn out of towns. This communication scrutinizes the past and the present state of saliva and leprosy to encounter possible mystery and/or wisdom in ancient healing as the mixture of “sputum and dirt” as reported in the biblical time. Full article