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Volume 9, September

Diseases, Volume 9, Issue 4 (December 2021) – 10 articles

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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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040074 - 16 Oct 2021
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)
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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040073 - 15 Oct 2021
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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040072 - 15 Oct 2021
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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040071 (registering DOI) - 14 Oct 2021
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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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040070 - 13 Oct 2021
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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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040069 - 07 Oct 2021
Viewed by 180
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
Commentary
In Search of a Unifying Concept in Human Diseases
Diseases 2021, 9(4), 68; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040068 (registering DOI) - 04 Oct 2021
Viewed by 210
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 557
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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040066 - 23 Sep 2021
Viewed by 351
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://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040065 - 22 Sep 2021
Viewed by 502
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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