Diseases In Human History Research Articles

Ancient Mycobacterium leprae genome reveals medieval English red squirrels as animal leprosy host

Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year.1,2 Although ancient DNA (aDNA) approaches on the major causative agent, Mycobacterium leprae, have elucidated the disease's evolutionary history,3,4,5 the role of animal hosts and interspecies transmission in the past remains unexplored. Research has uncovered relationships between medieval strains isolated from archaeological human remains and modern animal hosts such as the red squirrel in England.6,7 However, the time frame, distribution, and direction of transmissions remains unknown. Here, we studied 25 human and 12 squirrel samples from two archaeological sites in Winchester, a medieval English city well known for its leprosarium and connections to the fur trade. We reconstructed four medieval M.leprae genomes, including one from a red squirrel, at a 2.2-fold average coverage. Our analysis revealed a phylogenetic placement of all strains on branch 3 as well as a close relationship between the squirrel strain and one newly reconstructed medieval human strain. In particular, the medieval squirrel strain is more closely related to some medieval human strains from Winchester than to modern red squirrel strains from England, indicating a yet-undetected circulation of M.leprae in non-human hosts in the Middle Ages. Our study represents the first One Health approach for M.leprae in archaeology, which is centered around a medieval animal host strain, and highlights the future capability of such approaches to understand the disease's zoonotic past and current potential.

Evaluation of the Antibacterial, Anti-Cervical Cancer Capacity, and Biocompatibility of Different Graphene Oxides.

Cancer stands as one of the deadliest diseases in human history, marked by an inferior prognosis. While traditional therapeutic methods like surgery, chemotherapy, and radiation have demonstrated success in inhibiting tumor cell growth, their side effects often limit overall benefits and patient acceptance. In this regard, three different graphene oxides (GO) with variations in their degrees of oxidation were studied chemically and tissue-wise. The accuracy of the synthesis of the different GO was verified by robust techniques using X-ray photoelectron spectroscopy (XPS), as well as conventional techniques such as infrared spectroscopy (FTIR), RAMAN spectroscopy, and X-ray diffraction (XRD). The presence of oxygenated groups was of great importance. It affected the physicochemical properties of each of the different graphene oxides demonstrated in the presence of new vibrational modes related to the formation of new bonds promoted by the graphitization of the materials. The toxicity analysis in the Hep-2 cell line of graphene oxide formulations at 250 µg/mL on the viability and proliferation of these tumor cells showed low activity. GO formulations did not show high antibacterial activity against Staphylococcus aureus and Escherichia coli strains. However, the different graphene oxides showed biocompatibility in the subdermal implantation model for 30, 60, and 90 days in the biomodels. This allowed healing by restoring hair and tissue architecture without triggering an aggressive immune response.

FGF21 increases the sensitivity of hepatocellular carcinoma to sorafenib under hypoxia

AbstractBackgroundHepatocellular carcinoma (HCC) is a common disease in human history and one of the main causes of cancer‐related death. Insufficient oxygen supply in the tumor microenvironment forces cancer cells to survive in a mild hypoxia environment. Fibroblast growth factor 21 (FGF21), a member of the FGF family, has become the focus of public attention due to its outstanding achievements in diabetes and lipid lowering. However, the mechanism of FGF21 in HCC remains unclear.ObjectiveThe aims of this study were to clarify whether or not FGF21 could increase the sensitivity of HCC to sorafenib (SORA) under hypoxia and explore the possible mechanism.MethodsIn this study, by using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide cell viability test, plate clone formation test, western blot analysis, Hoechst/propidium iodide double staining experiment, flow cytometry, quantitative reverse transcription polymerase chain reaction, and subcutaneous tumor transplantation in mice, we studied the effects of recombinant human FGF21 combined with SORA on hepatoma cells in vitro and in vivo. FGF21 could enhance the phosphorylation of mothers against decapentaplegic homolog 3 (Smad3) under anaerobic conditions. When combined with SORA, FGF21 could increase the sensitivity of hepatoma cells to SORA and inhibit the growth and migration of hepatoma cells.ResultsFGF21 may increase the sensitivity of HCC to SORA by enhancing the phosphorylation of Smad3 through the phosphatidylinositol 3‐kinase/protein kinase B pathway under hypoxia.ConclusionOur study suggested the possibility of combination therapy for SORA and FGF21 on HCC.

Genomic epidemiological analysis of county-scale Yersinia pestis spread pattern over 50 years in a Southwest Chinese prefecture.

Plague, one of the most devastating infectious diseases in human history, is caused by the bacterium Yersinia pestis. Since the 1950s, the Dehong Dai-Jingpo Autonomous Prefecture (DH) in Yunnan Province, China, has recorded plague outbreaks that have resulted in 1,153 human cases and 379 deaths. The genetic diversity and transmission characteristics of Y. pestis strains in this region remain unknown. Here, we performed high-resolution genomic epidemiological analysis of 175 Y. pestis strains isolated from five counties and 19 towns in DH between 1953 and 2007. Phylogenetic analysis revealed that most DH strains were located in lineage 1.ORI2, which could be further subdivided into seven sub-phylogroups (SPG1-SPG7). The dominant sub-phylogroups of Y. pestis in DH varied during different periods and presented a population shift. Genomic evidence showed that plague might have emerged from the southwest of DH (e.g., Longchuan or Ruili counties) or its bordering countries, and subsequently spread to the northeast in multiple waves between 1982 and 2007. Our study infers a fine-scale phylogeny and spread pattern of the DH Y. pestis population, which extends our knowledge regarding its genetic diversity and provides clues for the future prevention and control of plague in this region.

Drug repurposing of FDA-approved anti-viral drugs via computational screening against novel 6M03 SARS-COVID-19.

The COVID-19 pandemic has been recognized as severe acute respiratory syndrome, one of the worst anddisastrous infectious diseases in human history. Until now, there is no cure to this contagious infection althoughsome multinational pharmaceutical companies have synthesized the vaccines and injecting them into humans, buta drug treatment regimen is yet to come. Among the multiple areas of SARS-CoV-2 that can be targeted, protease protein has significant values due to itsessential role in viral replication and life. The repurposing of FDA-approved drugs for the treatment of COVID-19has been a critical strategy during the pandemic due to the urgency of effective therapies. The novelty in this workrefers to the innovative use of existing drugs with greater safety, speed, cost-effectiveness, broad availability, anddiversity in the mechanism of action that have been approved and developed for other medical conditions. In this research work, we have engaged drug reprofiling or drug repurposing to recognize possible inhibitors ofprotease protein 6M03 in an instantaneous approach through computational docking studies. We screened 16 FDA-approved anti-viral drugs that were known for different viral infections to be tested againstthis contagious novel strain. Through these reprofiling studies, we come up with 5 drugs, namely, Delavirdine,Fosamprenavir, Imiquimod, Stavudine, and Zanamivir, showing excellent results with the negative binding energiesin Kcal/mol as - 8.5, - 7.0, - 6.8, - 6.8, and - 6.6, respectively, in the best binding posture. In silico studies allowedus to demonstrate the potential role of these drugs against COVID-19. In our study, we also observed the nucleotide sequence of protease protein consisting of 316 amino acid residuesand the influence of these pronouncing drugs over these sequences. The outcome of this research work providesresearchers with a track record for carrying out further investigational procedures by applying docking simulationsand in vitro and in vivo experimentation with these reprofile drugs so that a better drug can be formulated againstcoronavirus.

A Study on Role of Health Care Management Streams

Health care is the maintenance or improvement of health care via the prevention, diagnosis, treatment, amelioration, or cure of disease, illness, injury, and other physical and mental impairments in people. Health care is delivered by health care professionals and allied health care fields. Medicine, dentistry, pharmacy, midwifery, nursing, optometry, audiology, psychology, occupational therapy, physical therapy, athletic training, and other health professions are all part of health care. It includes work done in providing primary care, secondary care, and tertiary care, as well as in public healthcare. Access to health care may vary across countries, communities, and individuals, influenced by social and economic conditions as well as health care policies. Providing health care services means “the timely use of personal health care services to achieve the best possible health care outcomes. A limitation to health care services affects negatively the use of medical services, the efficacy of treatments, and overall outcome (well-being, mortality rates). An efficient health care system can contribute to a significant part of a country’s economy, development, and industrialization. Health care is conventionally regarded as an important determinant in promoting the general physical and mental health care and well-being of people around the world, An example of this was the worldwide eradication of smallpox in 1980, declared by the WHO as the first disease in human history to be eliminated by deliberate health care interventions.

Deciphering the role of platelet alpha granules in alveolar-capillary breakdown in severe malaria

Abstract Malaria is considered the deadliest disease in human history, killing hundreds of thousands annually. A hallmark of severe malaria is the breakdown of blood-organ barriers, such as in the lungs and brain, but the precise mechanism of how this occurs remains unknown. We determined that, unlike wildtype mice (C57BL6), mice with platelet alpha-granule deficiencies (Nbeal2−/−) did not die of malaria-associated acute respiratory distress syndrome (MA-ARDS) when infected with Plasmodium berghei NK65-Edinburgh (PbE). While wildtype mice exhibited significant alveolar-capillary breakdown by 6 days post-infection, as measured by alveolar protein concentrations and Evans blue permeation, Nbeal2−/− mice did not develop severe pathology. Flow cytometric analysis revealed that PbE-infected Nbeal2−/− mice had reduced CD8 T cell lung recruitment and activation compared to wildtypes. From this data, we concluded that a component of platelet alpha granules is crucial for activating CD8 T cells that subsequently damage the alveolar barrier. We hypothesized that the enzyme hyaluronidase 2 (HYAL2) is that crucial component and plays a 2-fold role: 1) that it directly contributes to barrier breakdown by cleaving hyaluronan (HA) from the endothelial glycocalyx (eGC), and 2) that the HA fragments released after eGC cleavage promote inflammation via CD44-binding. We found that HA is elevated in the plasma of infected mice. Preliminary data suggest that CD44 splice variants are differentially expressed in the lungs of naïve vs. PbE-infected mice, which could alter the binding kinetics with HA. Together, these data support the hypothesis that platelet HYAL2 is a critical mediator of MA-ARDS.

Trends and prospects in spinal tuberculosis research: a future-oriented approach.

Tuberculosis is one of the oldest diseases in human history, and spinal tuberculosis (STB) is the most common form of extrapulmonary tuberculosis. A large number of research has been conducted in this field. However, there has been no bibliometric analysis performed in recent years in STB. The aim of this study was to analyze trends and hotspots in research on STB. Publications regarding STB between 1980 and 2022 were extracted from the Web of Science database. CiteSpace (V5.7.R2) and VOSviewer (1.6.10) were used to perform global analyses of the number of publications, countries, institutions, authors, journals, keywords, and cited references. A total of 1262 articles were published between 1980 and 2022. We observed rapid growth in the number of publications since 2010. Spine had the highest number of publications (47, 3.7%). Zhang HQ and Wang XY were key researchers. The Central South University published the most papers (90, 7.1%). China was the leading contributor in this field with 459 publications and 29 H-index. National partnerships are dominated by the USA, and there is a lack of active cooperation between other countries and authors. research on STB has achieved great progress, with an increasing number of publications since 2010. Surgical treatment and debridement are current research hots pots, and diagnosis, drug resistance, and kyphosis are likely research frontiers. Cooperation between countries and authors needs to be further strengthened.

571 Dendritic cell programming in vaccinia skin scarification

Smallpox is one of the deadliest viral diseases in human history, killing an estimated 300 million since 1900 alone. Edward Jenner’s 1796 discovery that skin inoculation with cowpox in a scarification method of delivery[i][ii] induced immunity against smallpox led to the global eradication of the disease by 1980[iii]. In recent years, the vaccinia virus model derived from cowpox was used to demonstrate that vaccinia virus skin scarification (VACVss) is a superior immunization strategy to other methods of vaccine delivery[iv].

The Role of Artificial Intelligence and Machine Learning During the Covid-19 Pandemic: A Review.

Covid-19 is one of the most significant infectious diseases that have faced humanity in the past century from clinical, economic, and social perspectives. Although the role of infectious diseases in human history has been vicious and is well known to humanity, Covid-19 is a special case since it is the first worldwide outbreak in the era of advanced computing and telecommunications. For this reason, it was only logical to see Artificial Intelligence (AI) and Machine Learning (ML) on the top of the list of controls to compact the spread of Covid-19. This paper goes through the applications of AI and ML that were reported in some of the major literature indexes and can be related to the main issues that face healthcare providers during the Covid-19 pandemic. This paper also discusses the applicability of these applications to healthcare organizations and points out the main prerequisites before they can be adopted.

Spanish Flu (Great Influenza) 1918: The Tale of The Most deadly Pandemic in History

The epidemic is an imminent danger that all humans fear, as it does not differentiate between anyone, whether small or old, rich or poor. It is characterized by its ability and super speed to conquer the world and its primary goal is to target humans and eradicate their lives. In this article, the authors decided to provide a brief historical overview of the Spanish flu pandemic, where it initiated and how it influenced the people of the earth and review a set of images about events that occurred in the United States of America in 1918. All facts in this article are collected from a group of published articles on websites. This article found that the Spanish flu is one of the deadliest diseases in human history, as it managed to kill 40 to 100 million people around the world in two years.

Out of the East (or North or South): A Response to Philip Slavin

Abstract This article responds to Philip Slavin’s ‘Out of the West: Formation of a Permanent Plague Reservoir in South-Central Germany (1349–1356) and Its Implications’. Genetics has transformed the study of plague, one of the most lethal diseases in human history. But this technically demanding science raises questions of what constitutes valid evidence and supportable argument when examining historical phenomena at a microscopic level. Slavin argues that two new lineages of Yersinia pestis, the causative organism of plague, were seeded in central Germany following the Black Death; appearing sequentially, one lineage caused plague outbreaks in the 1350s and early 1360s, only to retreat and be replaced by a second lineage. Here, evidence is adduced to support the early central European proliferation of one lineage of Y. pestis, but also to suggest that the second lineage arose simultaneously in a different locale, outside Europe and within different epidemiological parameters. Because of the inherent rarity of biological evidence, the reconstruction of epidemiological phenomena will always require consilience with archaeological and documentary sources. Establishing ‘best practices’ of analysis and verification in this emerging multidisciplinary field has implications not only for Europe’s four hundred-year experience with plague, but for all fields of global health history.

The Plague (Black Death) Is Still Around and May Come Back

Plague has been among the most devastating infectious diseases in human history. The decrease in the plague in recently reported cases and studies implies that the plague should not recur, but the fact is that it (Black Death) is still around and may appear again. The disease can be occult for many years. The reemergence of the plague epidemic with unusual clinical form, magnitude, and rapid expansion at any place and time without prior notice could pose a serious risk to public health. Plague outbreaks most likely result from the reactivation of organisms in local foci. The reemergence of foci suggests that environmental or climatic changes could be favorable for an epidemiological cycle of Yersinia pestis. Thus, countries harboring plague foci can be at risk of outbreaks in the future. Different epidemiological aspects of the plague must be emphasized in prophylactic medical plans and health education systems, and healthcare workers should be alert and aware of the natural cycle, as well as clinical symptoms and signs of plague. Finally, surveillance, education, and research are also suggested regarding this fatal infection and other emerging diseases.

Social Media Efficacy in Crisis Management: Effectiveness of Non-pharmaceutical Interventions to Manage COVID-19 Challenges.

The new identified virus COVID-19 has become one of the most contagious diseases in human history. The ongoing coronavirus has created severe threats to global mental health, which have resulted in crisis management challenges and international concerns related to health issues. As of September 9, 2021, there were over 223.4 million patients with COVID-19, including 4.6 million deaths and over 200 million recovered patients reported worldwide, which has made the COVID-19 outbreak one of the deadliest pandemics in human history. The aggressive public health implementations endorsed various precautionary safety and preventive strategies to suppress and minimize COVID-19 disease transmission. The second, third, and fourth waves of COVID-19 continue to pose global challenges to crisis management, as its evolution and implications are still unfolding. This study posits that examining the strategic ripostes and pandemic experiences sheds light on combatting this global emergency. This study recommends two model strategies that help reduce the adverse effects of the pandemic on the immune systems of the general population. This present paper recommends NPI interventions (non-pharmaceutical intervention) to combine various measures, such as the suppression strategy (lockdown and restrictions) and mitigation model to decrease the burden on health systems. The current COVID-19 health crisis has influenced all vital economic sectors and developed crisis management problems. The global supply of vaccines is still not sufficient to manage this global health emergency. In this crisis, NPIs are helpful to manage the spillover impacts of the pandemic. It articulates the prominence of resilience and economic and strategic agility to resume economic activities and resolve healthcare issues. This study primarily focuses on the role of social media to tackle challenges and crises posed by COVID-19 on economies, business activities, healthcare burdens, and government support for societies to resume businesses, and implications for global economic and healthcare provision disruptions. This study suggests that intervention strategies can control the rapid spread of COVID-19 with hands-on crisis management measures, and the healthcare system will resume normal conditions quickly. Global economies will revitalize scientific contributions and collaborations, including social science and business industries, through government support.

Limonin, an AMPK Activator, Inhibits Hepatic Lipid Accumulation in High Fat Diet Fed Mice.

NAFLD is the most prevalent liver disease in human history. The treatment is still limited yet. In the current study, we reported that limonin inhibited hepatic lipid accumulation and fatty acid synthesis in HFD fed mice. Using AMPK inhibitor and AMPK deficient C. elegans, we revealed the effect was dependent on the activation of AMPK. We found that limonin activated AMPK through inhibition of cellular energy metabolism and increasing ADP:ATP ratio. Furthermore, the treatment of limonin induced AMPK mediated suppression of the transcriptional activity of SREBP1/2. Our study suggests that limonin may a promising therapeutic agent for the treatment of NAFLD.

COVID-19, the Pandemic of the Century and Its Impact on Cardiovascular Diseases.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely ranks among the deadliest diseases in human history. As with other coronaviruses, SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2. COVID-19 has upended lives worldwide. Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications, while patients have avoided hospital visits because of limited resources and the fear of infection, thereby increasing out-hospital mortality due to delayed diagnosis and treatment. Clinical observations show that sex, age, and race all influence the risk for SARS-CoV-2 infection, as do hypertension, obesity, and pre-existing cardiovascular conditions. Many hospitalized COVID-19 patients suffer cardiac injury, acute coronary syndromes, or cardiac arrhythmia. SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis, endothelial cell damage and dysfunction, oxidative stress and reactive oxygen species production, vasoconstriction, fibrotic and thrombotic protein expression, vascular permeability and microvascular dysfunction, heart inflammatory cell accumulation and activation, and a cytokine storm. Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors, angiotensin receptor blockers, steroids, aspirin, statins, and PCSK9 inhibitors. This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.

COVID-19-related knowledge, risk perception, information seeking, and adherence to preventive behaviors among undergraduate students, southern Iran.

Globally, the novel COVID-19 has been recognized as one of the most important pandemics and devastating diseases in human history, with many deaths and morbidities. In the absence of effective treatment and limited supply of COVID-19 vaccine, people must adhere to recommended preventive measures. This study aimed to determine the level of COVID-19 knowledge, perceived susceptibility, perceived severity, and health information-seeking and preventive behaviors as well as associated factors with preventive behaviors in a sample of Iranian students at Persian Gulf University. Data was collected using an online structured and validated questionnaire. Descriptive statistics, the Mann-Whitney U, Chi-square, and Spearman correlation tests were applied to analyze data. The significance level was set at P < 0.05. In total, 98% (319/325) of the participants completed the survey. A majority of participants were aware of the three main COVID-19 symptoms: fever, dry cough, and shortness of breath, while half of them were unaware of gastrointestinal problems caused by COVID-19. More than half of the subjects had a low perceived susceptibility and severity toward COVID-19. Most of the participants engaged in preventive behaviors and got COVID-19 information from social media and the Internet. Preventive behavior was associated with perceived susceptibility (P = 0.015), perceived severity (P = 0.014), and health information seeking (P < 0.001) of individuals toward COVID-19. The results of our research can help health authorities develop health promotion programs for student populations by providing baseline data.

Origins of a killer

Discovering the beginnings of tuberculosis, the most lethal infectious disease in human history, is crucial to beating it, finds Rebecca Batley

Prevention of Rabies by Application of Lytta vesicatoria (Ḏarārīḥ) in Persian Medicine Texts in Islamic Civilization

Rabies is one of the most lethal diseases in human history. From the past, various drugs have been used to prevent the contraction of the disease when being bitten by a rabid animal. An insect called Ḏarārīḥ (Lytta vesicatoria), although poisonous, has in some cases been medically used. Greeks and Romans have used venomousness of this insect to treat skin diseases, but it has not been used to prevent rabies. This is a summative qualitative content analysis that focused on Persian Medicine (PM) texts from 2th to 13th AH centuries. Literature was searched during centuries 4th to 13th AH, by using this key words: ذراریـح) Ḏarārīḥ), قنثاریـدس) Cantharis/cantharides), and ئشـفث Lytta vesicatoria and after extracting the data and analyzing them, the results were presented. In TPM texts, this insect was used to prevent rabies. This study has shown that the use of ḏarārīḥ (Lytta vesicatoria) in the prevention of rabies has been one of the innovations of the practitioners of Islamic civilization. The innovation proves that scholars in the period of Islamic civilization were not merely consumers or custodians of Roman, Greek, Indian, and Iranian knowledge, but added to it while preserving that knowledge.

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy.

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities—such as surgery, chemotherapy, and radiation therapy—have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.