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Diseases, Volume 9, Issue 4 (December 2021) – 25 articles

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Article
Cutting out Cholecystectomy on Index Hospitalization Leads to Increased Readmission Rates, Morbidity, Mortality and Cost
by , , , , , and
Diseases 2021, 9(4), 89; https://doi.org/10.3390/diseases9040089 (registering DOI) - 06 Dec 2021
Abstract
Biliary tract diseases that are not adequately treated on index hospitalization are linked to worse outcomes, including high readmission rates. Delays in care for conditions such as choledocholithiasis, gallstone pancreatitis, and cholecystitis often occur due to multiple reasons, and this delay is under-appreciated [...] Read more.
Biliary tract diseases that are not adequately treated on index hospitalization are linked to worse outcomes, including high readmission rates. Delays in care for conditions such as choledocholithiasis, gallstone pancreatitis, and cholecystitis often occur due to multiple reasons, and this delay is under-appreciated as a source of morbidity and mortality. Our study is based on the latest Nationwide Readmissions Database review and evaluated the effects of postponing definitive management to a subsequent visit. The study shows a higher 30-day readmission rate in addition to increased mortality rate, intubation rate, vasopressor use in this patient population and significantly added financial burden. Full article
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Review
Association and Risk Factors for Obstructive Sleep Apnea and Cardiovascular Diseases: A Systematic Review
Diseases 2021, 9(4), 88; https://doi.org/10.3390/diseases9040088 (registering DOI) - 02 Dec 2021
Viewed by 206
Abstract
Obstructive sleep apnea (OSA) is a serious, potentially life-threatening condition. Epidemiologic studies show that sleep apnea increases cardiovascular diseases risk factors including hypertension, obesity, and diabetes mellitus. OSA is also responsible for serious illnesses such as congestive heart failure, stroke, arrhythmias, and bronchial [...] Read more.
Obstructive sleep apnea (OSA) is a serious, potentially life-threatening condition. Epidemiologic studies show that sleep apnea increases cardiovascular diseases risk factors including hypertension, obesity, and diabetes mellitus. OSA is also responsible for serious illnesses such as congestive heart failure, stroke, arrhythmias, and bronchial asthma. The aim of this systematic review is to evaluate evidence for the association between OSA and cardiovascular disease morbidities and identify risk factors for the conditions. In a review of 34 studies conducted in 28 countries with a sample of 37,599 people, several comorbidities were identified in patients with severe OSA—these were: heart disease, stroke, kidney disease, asthma, COPD, acute heart failure, chronic heart failure, hyperlipidemia, thyroid disease, cerebral infarct or embolism, myocardial infarction, and psychological comorbidities including stress and depression. Important risk factors contributing to OSA included: age > 35 years; BMI ≥ 25 kg/m2; alcoholism; higher Epworth sleepiness scale (ESS); mean apnea duration; oxygen desaturation index (ODI); and nocturnal oxygen desaturation (NOD). Severe OSA (AHI ≥ 30) was significantly associated with excessive daytime sleepiness and oxygen desaturation index. The risk of OSA and associated disease morbidities can be reduced by controlling overweight/obesity, alcoholism, smoking, hypertension, diabetes mellitus, and hyperlipidemia. Full article
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Opinion
Ageing and Obesity Shared Patterns: From Molecular Pathogenesis to Epigenetics
Diseases 2021, 9(4), 87; https://doi.org/10.3390/diseases9040087 - 29 Nov 2021
Viewed by 170
Abstract
In modern societies, ageing and obesity represent medical challenges for healthcare professionals and caregivers. Obesity and ageing share common features including the related cellular and molecular pathways as well as the impacts they have as risk factors for a variety of diseases and [...] Read more.
In modern societies, ageing and obesity represent medical challenges for healthcare professionals and caregivers. Obesity and ageing share common features including the related cellular and molecular pathways as well as the impacts they have as risk factors for a variety of diseases and health problems. Both of these health problems also share exercise and a healthy lifestyle as the best therapeutic options. Importantly, ageing and obesity also have common epigenetic changes (histone modification, DNA methylation, noncoding RNAs, and chromatin remodeling) that are also impacted by exercise. This suggests that epigenetic pathways are among the mechanisms via which exercise induces its benefits, including ageing and obesity improvements. Exploring these interrelations and based on the fact that both ageing and obesity represent risk factors for each other, would lead to optimizing the available therapeutic approaches towards improved obesity management and healthy ageing. Full article
(This article belongs to the Special Issue Epigenetics and Disease - 2021)
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Review
Colorectal Dysplasia and Cancer Surveillance in Ulcerative Colitis
Diseases 2021, 9(4), 86; https://doi.org/10.3390/diseases9040086 - 19 Nov 2021
Viewed by 291
Abstract
Ulcerative colitis (UC) is a risk factor for the development of inflammation-associated dysplasia or colitis-associated neoplasia (CAN). This transformation results from chronic inflammation, which induces changes in epithelial proliferation, survival, and migration via the induction of chemokines and cytokines. There are notable differences [...] Read more.
Ulcerative colitis (UC) is a risk factor for the development of inflammation-associated dysplasia or colitis-associated neoplasia (CAN). This transformation results from chronic inflammation, which induces changes in epithelial proliferation, survival, and migration via the induction of chemokines and cytokines. There are notable differences in genetic mutation profiles between CAN in UC patients and sporadic colorectal cancer in the general population. Colonoscopy is the cornerstone for surveillance and management of dysplasia in these patients. There are several modalities to augment the quality of endoscopy for the better detection of dysplastic or neoplastic lesions, including the use of high-definition white-light exam and image-enhanced colonoscopy, which are described in this review. Clinical practice guidelines regarding surveillance strategies in UC have been put forth by various GI societies, and overall, there is agreement between them except for some differences, which we highlight in this article. These guidelines recommend that endoscopically detected dysplasia, if feasible, should be resected endoscopically. Advanced newer techniques, such as endoscopic mucosal resection and endoscopic submucosal dissection, have been utilized in the treatment of CAN. Surgery has traditionally been the mainstay of treating such advanced lesions, and in cases where endoscopic resection is not feasible, a proctocolectomy, followed by ileal pouch-anal anastomosis, is generally recommended. In this review we summarize the approach to surveillance for cancer and dysplasia in UC. We also highlight management strategies if dysplasia is detected. Full article
(This article belongs to the Special Issue Gastrointestinal Tract Inflammation and Cancers)
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Review
Implications of Glycosaminoglycans on Viral Zoonotic Diseases
Diseases 2021, 9(4), 85; https://doi.org/10.3390/diseases9040085 - 17 Nov 2021
Viewed by 281
Abstract
Zoonotic diseases are infectious diseases that pass from animals to humans. These include diseases caused by viruses, bacteria, fungi, and parasites and can be transmitted through close contact or through an intermediate insect vector. Many of the world’s most problematic zoonotic diseases are [...] Read more.
Zoonotic diseases are infectious diseases that pass from animals to humans. These include diseases caused by viruses, bacteria, fungi, and parasites and can be transmitted through close contact or through an intermediate insect vector. Many of the world’s most problematic zoonotic diseases are viral diseases originating from animal spillovers. The Spanish influenza pandemic, Ebola outbreaks in Africa, and the current SARS-CoV-2 pandemic are thought to have started with humans interacting closely with infected animals. As the human population grows and encroaches on more and more natural habitats, these incidents will only increase in frequency. Because of this trend, new treatments and prevention strategies are being explored. Glycosaminoglycans (GAGs) are complex linear polysaccharides that are ubiquitously present on the surfaces of most human and animal cells. In many infectious diseases, the interactions between GAGs and zoonotic pathogens correspond to the first contact that results in the infection of host cells. In recent years, researchers have made progress in understanding the extraordinary roles of GAGs in the pathogenesis of zoonotic diseases, suggesting potential therapeutic avenues for using GAGs in the treatment of these diseases. This review examines the role of GAGs in the progression, prevention, and treatment of different zoonotic diseases caused by viruses. Full article
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Article
Saving Resources: SARS-CoV-2 Diagnostics by Real-Time RT-PCR Using Reduced Reaction Volumes
Diseases 2021, 9(4), 84; https://doi.org/10.3390/diseases9040084 - 15 Nov 2021
Viewed by 280
Abstract
Since the beginning of 2020, the betacoronavirus SARS-CoV-2 is causing a global pandemic of an acute respiratory disease termed COVID-19. The diagnostics of the novel disease is primarily based on direct virus detection by RT-PCR; however, the availability of test kits may become [...] Read more.
Since the beginning of 2020, the betacoronavirus SARS-CoV-2 is causing a global pandemic of an acute respiratory disease termed COVID-19. The diagnostics of the novel disease is primarily based on direct virus detection by RT-PCR; however, the availability of test kits may become a major bottleneck, when millions of tests are performed per week. To increase the flexibility of SARS-CoV-2 diagnostics, three real-time RT-PCR assays listed on the homepage of the World Health Organization were selected and investigated regarding their compatibility with three different RT-PCR kits. Furthermore, the reaction volume of the PCR chemistry was reduced up to half of the original protocol to make the individual reactions more cost- and resource-effective. When testing dilution series of culture-grown virus, nearly identical quantification cycle values (Cq) were obtained for all RT-PCR assay/chemistry combinations. Regarding the SARS-CoV-2 detection in clinical samples, agreeing results were obtained for all combinations for virus negative specimens and swabs containing high to medium viral genome loads. In cases of very low SARS-CoV-2 genome loads (Cq > 36), inconsistent results were observed, with some test runs scoring negative and some positive. However, no preference of a specific target within the viral genome (E, RdRp, or N) or of a certain chemistry was seen. In summary, a reduction of the reaction volume and the type of PCR chemistry did not influence the PCR sensitivity. Full article
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Article
Trends of Foodborne Diseases in Mississippi: Association with Racial and Economic Disparities
Diseases 2021, 9(4), 83; https://doi.org/10.3390/diseases9040083 - 13 Nov 2021
Viewed by 317
Abstract
Background: Foodborne diseases are a major source of concern in USA. These diseases are a burden on public health and significantly contribute to the cost of health care. There is an urgent need to understand the contributing factors for such outbreaks, especially in [...] Read more.
Background: Foodborne diseases are a major source of concern in USA. These diseases are a burden on public health and significantly contribute to the cost of health care. There is an urgent need to understand the contributing factors for such outbreaks, especially in Mississippi (MS), an agricultural state with low socioeconomic status. Methods: Secondary data for the current study were obtained from the Mississippi State Department of Health (MSDH) Epidemiology department for the study period 2010–2018. Data were for individuals with reported foodborne diseases cases. The data were analyzed to determine the pathogens’ trend over time, the highest contributing pathogens to foodborne diseases, the significant geographical variation, and any significant differences in rates based on demographic variables. Results: Salmonella was the highest contributing pathogen to foodborne disease in MS. The study showed a seasonal variation in the trends of pathogens and a geographical variation, and no racial differences in the incidents of the foodborne diseases was observed. Conclusions: Incidence rates of foodborne illness remain high in the state of Mississippi. A better understanding of high levels of foodborne infections caused by Salmonella, Shigella, and Campylobacter resulting from cultural food handling practices or socioeconomic factors will allow to provide guidelines and food safety preventive measures. Full article
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Article
Anticancer Impact of Nitric Oxide (NO) and NO Combination with SMYD-3 Inhibitor on Breast Carcinomas
Diseases 2021, 9(4), 82; https://doi.org/10.3390/diseases9040082 - 12 Nov 2021
Viewed by 223
Abstract
Despite enormous advances in the detection and treatment of breast cancer, it still remains the leading cancer diagnosis and has the second highest mortality rate. Thus, breast cancer research is a high priority for academics and clinicians alike. Based on previous research indicating [...] Read more.
Despite enormous advances in the detection and treatment of breast cancer, it still remains the leading cancer diagnosis and has the second highest mortality rate. Thus, breast cancer research is a high priority for academics and clinicians alike. Based on previous research indicating the potential of nitric oxide (NO) and SMYD-3 inhibition, this work sought to expand upon these concepts and combine the two approaches. Both NO (from S-Nitrosoglutathione (GSNO)), termed Group 1, and a combination therapeutic, inhibitor-4 (SMYD-3 inhibitor) plus NO (from GSNO), termed Group 2, were evaluated for their efficacy on breast carcinoma cell lines MCF7 and MDA-MB-231, and the normal MCF10A breast cell line, using cellular viability, colony formation capacity, cytotoxicity, and cellular apoptosis analysis. These results indicated that, in Group 1, breast carcinoma lines MCF7 and MDA-MB-231, cells experienced a moderate reduction in cellular viability (~20–25%), a large reduction in colony formation capacity (~80–90%), a moderate increase in the relative number of dead cells, and a moderate increase in cellular apoptosis. Group 2 was significantly more impactful, with a ~50% knockdown in cellular viability, a 100% reduction in colony formation capacity, a large increase in the relative number of dead cells, and a large increase in cellular apoptosis. Additionally, Group 2 induced a very small impact on the normal MCF10A cell line. Cumulatively, this work revealed the exciting impact of this combination therapeutic, indicating its potential for clinical application and further research. Full article
(This article belongs to the Special Issue Epigenetics and Disease - 2021)
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Article
Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients—A Single-Center Case-Control Study
Diseases 2021, 9(4), 81; https://doi.org/10.3390/diseases9040081 - 03 Nov 2021
Viewed by 314
Abstract
Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS: A retrospective single-center case-control study was conducted with [...] Read more.
Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS: A retrospective single-center case-control study was conducted with the inclusion of 78 inoperable PDAC patients. Age-, sex-, chemotherapy-, stage-, and ascites formation-matched patients were assigned to two equal groups based on the application of modulated electro-hyperthermia (mEHT). The EHY2030 mEHT device was used. RESULTS: A trend in favor of mEHT was found in overall survival (p = 0.1420). To further evaluate the potential beneficial effects of mEHT, the presence of distant metastasis or ascites in the patients’ oncological history was investigated. Of note, mEHT treatment had a favorable effect on patients’ overall survival in metastatic disease (p = 0.0154), while less abdominal fluid responded to the mEHT treatment in a more efficient way (p ≤ 0.0138). CONCLUSION: mEHT treatment was associated with improved overall survival in PDAC in our single-center retrospective case-control study. The outcome measures encourage us to design a randomized prospective clinical study to further confirm the efficiency of mEHT in this patient cohort. Full article
(This article belongs to the Section Oncology)
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Article
Antibiotic Susceptibility, Biofilm Production, and Detection of mecA Gene among Staphylococcus aureus Isolates from Different Clinical Specimens
Diseases 2021, 9(4), 80; https://doi.org/10.3390/diseases9040080 - 01 Nov 2021
Viewed by 513
Abstract
The increasing incidence of methicillin-resistant and biofilm-forming S. aureus isolates in hospital settings is a gruesome concern today. The main objectives of this study were to determine the burden of S. aureus in clinical samples, assess their antibiotic susceptibility pattern and detect biofilm [...] Read more.
The increasing incidence of methicillin-resistant and biofilm-forming S. aureus isolates in hospital settings is a gruesome concern today. The main objectives of this study were to determine the burden of S. aureus in clinical samples, assess their antibiotic susceptibility pattern and detect biofilm formation and mecA gene in them. A total of 1968 different clinical specimens were processed to isolate S. aureus following standard microbiological procedures. Antibiotic susceptibility test of the isolates was performed by Kirby–Bauer disc-diffusion method following CLSI guidelines. Biofilm was detected through tissue culture plate method. Methicillin-resistant S. aureus (MRSA) isolates were screened using cefoxitin (30 µg) discs and mecA gene was amplified by conventional polymerase chain reaction (PCR). Of 177 bacterial growth, the prevalence of S. aureus was 15.3% (n = 27). MRSA were 55.6% (15/27) and 44% (12/27) exhibited multidrug resistance (MDR). There was no significant association between methicillin resistance and MDR (p > 0.05). Both MRSA and MSSA were least sensitive to penicillin (100%, 75%) followed by erythromycin (86.6%, 66.6%). Most of the MRSA (93.4%) were susceptible to tetracycline. All S. aureus isolates were biofilm producers—19 (70%) were weak and only one (4%) was a strong biofilm producer. The strong biofilm-producing MSSA was resistant to most of the antibiotics except cefoxitin and clindamycin. None of the MSSA possessed mecA gene while 8 (53.3%) MRSA had it. More than half of S. aureus isolated were MRSA. High incidence of multidrug resistance along with capacity to form biofilm among clinical isolates of S.aureus is a matter of apprehension and prompt adoption of biosafety measures is suggested to curb their dissemination in the hospital environments. Full article
(This article belongs to the Section Infectious Disease)
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Review
Exploring the Inflammatory Pathogenesis of Colorectal Cancer
Diseases 2021, 9(4), 79; https://doi.org/10.3390/diseases9040079 - 30 Oct 2021
Viewed by 398
Abstract
Colorectal cancer is one of the most commonly diagnosed cancers worldwide. Traditionally, mechanisms of colorectal cancer formation have focused on genetic alterations including chromosomal damage and microsatellite instability. In recent years, there has been a growing body of evidence supporting the role of [...] Read more.
Colorectal cancer is one of the most commonly diagnosed cancers worldwide. Traditionally, mechanisms of colorectal cancer formation have focused on genetic alterations including chromosomal damage and microsatellite instability. In recent years, there has been a growing body of evidence supporting the role of inflammation in colorectal cancer formation. Multiple cytokines, immune cells such T cells and macrophages, and other immune mediators have been identified in pathways leading to the initiation, growth, and metastasis of colorectal cancer. Outside the previously explored mechanisms and pathways leading to colorectal cancer, initiatives have been shifted to further study the role of inflammation in pathogenesis. Inflammatory pathways have also been linked to some traditional risk factors of colorectal cancer such as obesity, smoking and diabetes, as well as more novel associations such as the gut microbiome, the gut mycobiome and exosomes. In this review, we will explore the roles of obesity and diet, smoking, diabetes, the microbiome, the mycobiome and exosomes in colorectal cancer, with a specific focus on the underlying inflammatory and metabolic pathways involved. We will also investigate how the study of colon cancer from an inflammatory background not only creates a more holistic and inclusive understanding of this disease, but also creates unique opportunities for prevention, early diagnosis and therapy. Full article
(This article belongs to the Special Issue Gastrointestinal Tract Inflammation and Cancers)
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Review
MYCN in Neuroblastoma: “Old Wine into New Wineskins”
Diseases 2021, 9(4), 78; https://doi.org/10.3390/diseases9040078 - 29 Oct 2021
Viewed by 360
Abstract
MYCN Proto-Oncogene, BHLH Transcription Factor (MYCN) has been one of the most studied genes in neuroblastoma. It is known for its oncogenetic mechanisms, as well as its role in the prognosis of the disease and it is considered one of the prominent targets [...] Read more.
MYCN Proto-Oncogene, BHLH Transcription Factor (MYCN) has been one of the most studied genes in neuroblastoma. It is known for its oncogenetic mechanisms, as well as its role in the prognosis of the disease and it is considered one of the prominent targets for neuroblastoma therapy. In the present work, we attempted to review the literature, on the relation between MYCN and neuroblastoma from all possible mechanistic sites. We have searched the literature for the role of MYCN in neuroblastoma based on the following topics: the references of MYCN in the literature, the gene’s anatomy, along with its transcripts, the protein’s anatomy, the epigenetic mechanisms regulating MYCN expression and function, as well as MYCN amplification. MYCN plays a significant role in neuroblastoma biology. Its functions and properties range from the forming of G-quadraplexes, to the interaction with miRNAs, as well as the regulation of gene methylation and histone acetylation and deacetylation. Although MYCN is one of the most primary genes studied in neuroblastoma, there is still a lot to be learned. Our knowledge on the exact mechanisms of MYCN amplification, etiology and potential interventions is still limited. The knowledge on the molecular mechanisms of MYCN in neuroblastoma, could have potential prognostic and therapeutic advantages. Full article
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Review
Stem Cell Therapy for Post-Traumatic Stress Disorder: A Novel Therapeutic Approach
Diseases 2021, 9(4), 77; https://doi.org/10.3390/diseases9040077 - 29 Oct 2021
Viewed by 386
Abstract
Stem cell therapy is a rapidly evolving field of regenerative medicine being employed for the management of various central nervous system disorders. The ability to self-renew, differentiate into specialized cells, and integrate into neuronal networks has positioned stem cells as an ideal mechanism [...] Read more.
Stem cell therapy is a rapidly evolving field of regenerative medicine being employed for the management of various central nervous system disorders. The ability to self-renew, differentiate into specialized cells, and integrate into neuronal networks has positioned stem cells as an ideal mechanism for the treatment of epilepsy. Epilepsy is characterized by repetitive seizures caused by imbalance in the GABA and glutamate neurotransmission following neuronal damage. Stem cells provide benefit by reducing the glutamate excitotoxicity and strengthening the GABAergic inter-neuron connections. Similar to the abnormal neuroanatomic location in epilepsy, post-traumatic stress disorder (PTSD) is caused by hyperarousal in the amygdala and decreased activity of the hippocampus and medial prefrontal cortex. Thus, stem cells could be used to modulate neuronal interconnectivity. In this review, we provide a rationale for the use of stem cell therapy in the treatment of PTSD. Full article
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Review
The Role of an Anti-Inflammatory Diet in Conjunction to COVID-19
Diseases 2021, 9(4), 76; https://doi.org/10.3390/diseases9040076 - 29 Oct 2021
Viewed by 1297
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), otherwise known as COVID-19, has challenged healthcare systems at an international level. COVID-19 suppresses the immune system by causing a systemic inflammatory response, also known as cytokine release syndrome, leaving COVID-19 patients with high levels of proinflammatory [...] Read more.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), otherwise known as COVID-19, has challenged healthcare systems at an international level. COVID-19 suppresses the immune system by causing a systemic inflammatory response, also known as cytokine release syndrome, leaving COVID-19 patients with high levels of proinflammatory cytokines and chemokines. Nutrition’s function in the respiratory and immune systems has been investigated in much research, and its significance cannot be overstated, as the nutritional status of patients has been shown to be directly connected with the severity of the disease. Key dietary components such as vitamin C, D, omega-3 fatty acids, and zinc have shown potential in their anti-inflammatory effects, as well as the famous Mediterranean diet. This review aims to discuss the use of anti-inflammatory dietary approaches to prevent Sars-CoV-2 or lessen COVID-19 effects. Full article
(This article belongs to the Special Issue Lipids, Health, and Diseases: The Interplay)
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Editorial
Introduction and Tribute to Charlie Calisher
Diseases 2021, 9(4), 75; https://doi.org/10.3390/diseases9040075 - 20 Oct 2021
Viewed by 454
Abstract
It is a great pleasure to contribute a few words of introduction to this Special Issue of MDPI’s Diseases entitled “Recent Studies of Arthropod-, Bat-, and Rodent-Borne Viruses: A Theme Issue in Honor of Professor Charles H [...] Full article
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Article
Patient Heterogeneity in Acute Myeloid Leukemia: Leukemic Cell Communication by Release of Soluble Mediators and Its Effects on Mesenchymal Stem Cells
Diseases 2021, 9(4), 74; https://doi.org/10.3390/diseases9040074 - 16 Oct 2021
Viewed by 451
Abstract
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy, and non-leukemic stromal cells (including mesenchymal stem cells, MSCs) are involved in leukemogenesis and show AML-supporting effects. We investigated how constitutive extracellular mediator release by primary human AML cells alters proteomic profiles of [...] Read more.
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy, and non-leukemic stromal cells (including mesenchymal stem cells, MSCs) are involved in leukemogenesis and show AML-supporting effects. We investigated how constitutive extracellular mediator release by primary human AML cells alters proteomic profiles of normal bone marrow MSCs. An average of 6814 proteins (range 6493−6918 proteins) were quantified for 41 MSC cultures supplemented with AML-cell conditioned medium, whereas an average of 6715 proteins (range 6703−6722) were quantified for untreated control MSCs. The AML effect on global MSC proteomic profiles varied between patients. Hierarchical clustering analysis identified 10 patients (5/10 secondary AML) showing more extensive AML-effects on the MSC proteome, whereas the other 31 patients clustered together with the untreated control MSCs and showed less extensive AML-induced effects. These two patient subsets differed especially with regard to MSC levels of extracellular matrix and mitochondrial/metabolic regulatory proteins. Less than 10% of MSC proteins were significantly altered by the exposure to AML-conditioned media; 301 proteins could only be quantified after exposure to conditioned medium and 201 additional proteins were significantly altered compared with the levels in control samples (153 increased, 48 decreased). The AML-modulated MSC proteins formed several interacting networks mainly reflecting intracellular organellar structure/trafficking but also extracellular matrix/cytokine signaling, and a single small network reflecting altered DNA replication. Our results suggest that targeting of intracellular trafficking and/or intercellular communication is a possible therapeutic strategy in AML. Full article
(This article belongs to the Section Oncology)
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Article
Viral Ecology and Natural Infection Dynamics of Kaeng Khoi Virus in Cave-Dwelling Wrinkle-Lipped Free-Tailed Bats (Chaerephon plicatus) in Thailand
Diseases 2021, 9(4), 73; https://doi.org/10.3390/diseases9040073 - 15 Oct 2021
Viewed by 398
Abstract
Kaeng Khoi virus (KKV; Order: Bunyavirales), is an endemic viral infection of the wrinkle-lipped free-tailed bat (Chaerephon plicatus aka Tadarida plicata plicata). Little is known about the ecology and maintenance of KKV within the bat population, nor the infection dynamics [...] Read more.
Kaeng Khoi virus (KKV; Order: Bunyavirales), is an endemic viral infection of the wrinkle-lipped free-tailed bat (Chaerephon plicatus aka Tadarida plicata plicata). Little is known about the ecology and maintenance of KKV within the bat population, nor the infection dynamics and transmission among bats or between bats and other vertebrates. Therefore, KKV was studied in Kaeng Khoi cave, Saraburi province, Thailand, during 1973–1974 with the objectives to (1) characterize the seasonal infection rates of KKV in the context of the bat population ecology, and (2) describe the infection dynamics and viral shedding by naturally- and experimentally-infected bats. To this end, the free-tailed bat population was estimated by a series of timed photographs taken during the evening exodus. The case population of 900,000 adult bats doubled at the time of weaning of the young and returned to its previous level soon thereafter. The newborn bats had neutralizing antibodies to KKV that were likely to be maternal in origin. The KKV antibody prevalence in adult bats was high (69–91%) in March–May and low (29–40%) in August and September. Kaeng Khoi virus was isolated from 75% of dead and 50% of moribund bats, but was not found in nearly 400 apparently healthy bats. Virus was present in saliva, urine and blood of most of the naturally-moribund bats tested. Consistent with observations from naturally-infected bats, experimental infection of bats with KKV revealed significant liver pathology, also suggestive that this is not a benign infection. Kaeng Khoi virus is an endemic, year-round infection maintained by the annual recruitment of a large number of immunologically-naïve juvenile bats. Moreover, it produces an acute infection in the bat, either leading to death by hepatitis, or immunity. Full article
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Article
Survey about the Quality of Life of Italian Patients with Fabry Disease
Diseases 2021, 9(4), 72; https://doi.org/10.3390/diseases9040072 - 15 Oct 2021
Viewed by 335
Abstract
Fabry disease (FD) is a genetic disease included in the group of lysosomal storage disorders, caused by X-linked deficiency of the enzyme alpha-galactosidase A. The aim of this study was to evaluate different aspects related to the quality of life (QoL) of a [...] Read more.
Fabry disease (FD) is a genetic disease included in the group of lysosomal storage disorders, caused by X-linked deficiency of the enzyme alpha-galactosidase A. The aim of this study was to evaluate different aspects related to the quality of life (QoL) of a multicentre cohort of Italian patients with FD. An observational survey was conducted to measure health-related quality of life (HR-QoL) in FD patients using the CAPI (Computer-Assisted Personal Interview) method: 106 patients (mostly women) responded to the questionnaire. Geographically, 53.7% of patients lived in northern Italy, 18.9% in central Italy and 27.4% in southern Italy or the Islands. All data were collected through a five-dimensional EuroQoL questionnaire referring to functional aspects (mobility, personal care, routine activities) and perception of physical/mental well-being (pain or discomfort, anxiety or depression). A descriptive analysis of responses was performed; FD patients were compared in terms of QoL with subjects suffering from other chronic diseases, such as Crohn’s disease, chronic hepatitis, cirrhosis and multiple sclerosis. Difficulty in normal daily activities was reported by 47.2% of FD patients. About one third of subjects also had mobility difficulties. Feelings of loneliness and isolation were reported by 33.3% of those being 60–69 years old. Anxiety was equally reported in both oldest and youngest patients (66.7%), while depression, relational problems, fear of other people’s judgement increased along with age, reaching 66.7% in the over-70-years group. Male patients were largely troubled about the risk of physical disability, particularly those aged 60 years or over. Furthermore, FD patients had a poorer QoL than people suffering from other chronic inflammatory disorders. Our study upholds that FD patients have a poor QoL, as already known, negatively impacting psychic well-being and social activities. Our survey has also found a worse QoL in FD patients compared with other severe chronic disorders. Full article
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Review
A Review of Immunocryosurgery and a Practical Guide to Its Applications
Diseases 2021, 9(4), 71; https://doi.org/10.3390/diseases9040071 - 14 Oct 2021
Viewed by 342
Abstract
Immunocryosurgery is a minimally invasive combinational therapeutic procedure that has been designed, developed, and evaluated in the Dermatology Department of the University of Ioannina from 2004. In a fixed time protocol, this approach combines immune stimulatory therapy with imiquimod and cryosurgery, i.e., cryosurgery [...] Read more.
Immunocryosurgery is a minimally invasive combinational therapeutic procedure that has been designed, developed, and evaluated in the Dermatology Department of the University of Ioannina from 2004. In a fixed time protocol, this approach combines immune stimulatory therapy with imiquimod and cryosurgery, i.e., cryosurgery is applied during continuous imiquimod treatment. Laboratory findings in tissue and blood level credit the efficacy to the synergy of imiquimod and cryosurgery. The synergy has been established through clinical trials and the excellent feasibility and efficacy demonstrated in clinical practice. Immunocryosurgery has extensive proof of excellent efficacy, comparable to surgery, in the treatment of basal cell carcinoma. It has also been evaluated in cases of Bowen’s disease, keratoacanthoma, Merkel cell carcinoma, lentigo maligna, and cutaneous squamous cell carcinoma with or without the addition of adjuvants. The aims of this review are to detail the immunocryosurgery protocol with the addition of daily practice clinical tips, compile data on the mechanism of action of immunocryosurgery, and delineate indications and possible future applications. Most of the available data originate from the treatment of BCC, of all histological types and localizations, and the principles reported mainly reflect on evidence related to the treatment of this common skin cancer. Full article
(This article belongs to the Section Oncology)
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Article
Neglected Needs of Family Caregivers during the COVID-19 Pandemic and What They Need Now: A Qualitative Study
Diseases 2021, 9(4), 70; https://doi.org/10.3390/diseases9040070 - 13 Oct 2021
Viewed by 777
Abstract
COVID-19 has had a negative impact on family caregivers, whether the care receivers lived with the caregiver, in a separate community home, in supportive living, or in long-term care. This qualitative study examines the points of view of family caregivers who care in [...] Read more.
COVID-19 has had a negative impact on family caregivers, whether the care receivers lived with the caregiver, in a separate community home, in supportive living, or in long-term care. This qualitative study examines the points of view of family caregivers who care in diverse settings. Family caregivers were asked to describe what could have been done to support them during the COVID-19 pandemic and to suggest supports they need in the future as the pandemic wanes. Thorne’s interpretive qualitative methodology was employed to examine current caregiver concerns. Thirty-two family caregivers participated. Family caregivers thought the under-resourced, continuing care system delayed pandemic planning, and that silos in health and community systems made caregiving more difficult. Family caregivers want their roles to be recognized in policy, and they cite the need for improvements in communication and navigation. The growth in demand for family caregivers and their contributions to the healthcare system make it critical that the family caregiver role be recognized in policy, funding, and practice. Full article
(This article belongs to the Special Issue COVID-19 and Global Chronic Disease)
Article
Short- and Long-Term Effects of Rehabilitation after Perimesencephalic Subarachnoid Hemorrhage
Diseases 2021, 9(4), 69; https://doi.org/10.3390/diseases9040069 - 07 Oct 2021
Viewed by 386
Abstract
In about 25% of patients with spontaneous subarachnoid hemorrhage (SAH), a bleeding source cannot be identified during radiological diagnostics. Generally, the outcome of perimesencephalic or prepontine (PM) SAH is known to be significantly better than after non-PM SAH. Data about long-term follow-up concerning [...] Read more.
In about 25% of patients with spontaneous subarachnoid hemorrhage (SAH), a bleeding source cannot be identified during radiological diagnostics. Generally, the outcome of perimesencephalic or prepontine (PM) SAH is known to be significantly better than after non-PM SAH. Data about long-term follow-up concerning physical and mental health are scarce, so this study is reports on long-term results. We measured the influence of PM SAH on a quality-of-life modified Rankin (mRs) scale after six months. For long-term follow-up, a SF-36 questionnaire was used. Questionnaires were sent out between 18 and 168 months after ictus. In 37 patients, a long-term follow-up was available (up to 14 years after SAH). Data detected with the SF-36 questionnaire are compared to reference applicability to the standard population. In total, 37 patients were included for further analysis and divided in 2 subgroups; 13 patients (35%) received subsequent rehabilitation after clinical stay and 24 (65%) did not. In the short-term outcome, a significant improvement from discharge until follow-up was identified in patients with subsequent rehabilitation, but not in the matched pair group without rehabilitation. When PM SAH was compared to the standard population, a reduction in quality of life was identified in physical items (role limitations because of physical health problems, physical functioning) as well as in psychological items (role limitations because of emotional problems). Subsequent rehabilitation on PM SAH patients probably leads to an increase in independence and better mRs. While better mRs was shown at discharge in patients without subsequent rehabilitation, the mRs of rehabilitants was nearly identical after rehabilitation. Patients with good mRs also reached high levels of health-related quality of life (HRQoL) without rehabilitation. Thus, subsequent rehabilitation needs to be encouraged on an individual basis. Indication criteria for subsequent rehabilitation should be defined in further studies to improve patient treatment and efficiency in health care. Full article
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Commentary
In Search of a Unifying Concept in Human Diseases
Diseases 2021, 9(4), 68; https://doi.org/10.3390/diseases9040068 - 04 Oct 2021
Viewed by 462
Abstract
Throughout the history of biological/medicine sciences, there has been opposing strategies to find solutions to complex human disease problems. Both empirical and deductive approaches have led to major insights and concepts that have led to practical preventive and therapeutic benefits for the human [...] Read more.
Throughout the history of biological/medicine sciences, there has been opposing strategies to find solutions to complex human disease problems. Both empirical and deductive approaches have led to major insights and concepts that have led to practical preventive and therapeutic benefits for the human population. The classic definitions of “science” (to know) has been paired with the classic definition of technology (to do). One knew more as the technology developed, and that development was often based on science. In other words, one could do more if science could improve the technology. In turn, this made possible to know more science with improved technology. However, with the development of new technologies of today in biology and medicine, major advances have been made, such as the information from the Human Genome Project, genetic engineering techniques and the use of bioinformatic uses of sophisticated computer analyses. This has led to the renewed idea that Precision Medicine, while raising some serious ethical concerns, also raises the expectation of improved potential of risk predictions for prevention and treatment of various genetically and environmentally influenced human diseases. This new field Artificial Intelligence, as a major handmaiden to Precision Medicine, is significantly altering the fundamental means of biological discovery. However, can today’s fundamental premise of “Artificial Intelligence”, based on identifying DNA, as the primary nexus of human health and disease, provide the practical solutions to complex human diseases that involve the interaction of those genes with the broad spectrum of “environmental factors”? Will it be “precise” enough to provide practical solutions for prevention and treatments of diseases? In this “Commentary”, with the example of human carcinogenesis, it will be challenged that, without the integration of mechanistic and hypothesis-driven approaches with the “unbiased” empirical analyses of large numbers of data, the Artificial Intelligence approach with fall short. Full article
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Review
Empowering Melatonin Therapeutics with Drosophila Models
Diseases 2021, 9(4), 67; https://doi.org/10.3390/diseases9040067 - 26 Sep 2021
Viewed by 938
Abstract
Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function [...] Read more.
Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases. Full article
(This article belongs to the Special Issue Novel Melatonin Based Therapies)
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Review
Overview of Helicobacter pylori Infection: Clinical Features, Treatment, and Nutritional Aspects
Diseases 2021, 9(4), 66; https://doi.org/10.3390/diseases9040066 - 23 Sep 2021
Viewed by 688
Abstract
Helicobacter pylori (H. pylori) is a 0.5–1 µm wide, 2–4 µm long, short helical, S-shaped Gram-negative microorganism. It is mostly found in the pyloric region of the stomach and causes chronic gastric infection. It is estimated that these bacteria infect more [...] Read more.
Helicobacter pylori (H. pylori) is a 0.5–1 µm wide, 2–4 µm long, short helical, S-shaped Gram-negative microorganism. It is mostly found in the pyloric region of the stomach and causes chronic gastric infection. It is estimated that these bacteria infect more than half of the world’s population. The mode of transmission and infection of H. pylori is still not known exactly, but the faecal–oral and oral–oral routes via water or food consumption are thought to be a very common cause. In the last three decades, research interest has increased regarding the pathogenicity, microbial activity, genetic predisposition, and clinical treatments to understand the severity of gastric atrophy and gastric cancer caused by H. pylori. Studies have suggested a relationship between H. pylori infection and malabsorption of essential micronutrients, and noted that H. pylori infection may affect the prevalence of malnutrition in some risk groups. On the other hand, dietary factors may play a considerably important role in H. pylori infection, and it has been reported that an adequate and balanced diet, especially high fruit and vegetable consumption and low processed salty food consumption, has a protective effect against the outcomes of H. pylori infection. The present review provides an overview of all aspects of H. pylori infection, such as clinical features, treatment, and nutrition. Full article
(This article belongs to the Special Issue The Relationship between Nutrition and Diseases)
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Review
COVID-19 Associated Mucormycosis: A Systematic Review from Diagnostic Challenges to Management
Diseases 2021, 9(4), 65; https://doi.org/10.3390/diseases9040065 - 22 Sep 2021
Cited by 2 | Viewed by 1010
Abstract
The coronavirus disease 2019 (COVID-19) outbreak has caused significant destruction, claiming over three million lives worldwide. Post SARS-COV-2 invasion, immunosuppression with hyperglycemia and elevated ferritin levels along with steroidal treatment creates a perfect storm for opportunistic infections. There is increasing evidence of mucormycosis [...] Read more.
The coronavirus disease 2019 (COVID-19) outbreak has caused significant destruction, claiming over three million lives worldwide. Post SARS-COV-2 invasion, immunosuppression with hyperglycemia and elevated ferritin levels along with steroidal treatment creates a perfect storm for opportunistic infections. There is increasing evidence of mucormycosis co-infection in COVID-19 patients, during or post-treatment. A worse prognosis, a late diagnosis, and limited guidelines of screening and management of COVID-19 associated mucormycosis have made healthcare professionals fear an epidemic alongside a pandemic. This review geographically reports cases of COVID-19 associated mucormycosis (CAM), evaluates characteristics, clinical manifestations, and outcomes of mucormycosis in COVID-19 active or recovered patients. It further describes preventive strategies and recommendations for optimal management therapy that can be adopted worldwide to curtail an impending threat to the healthcare system. Full article
(This article belongs to the Section Infectious Disease)
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