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Robust models of disease heterogeneity and control, with application to the SARS-CoV-2 epidemic
Full text linkIn light of the continuing emergence of new SARS-CoV-2 variants and vaccines, we create a robust simulation framework for exploring possible infection trajectories under various scenarios. The situations of primary interest involve the interaction between three components: vaccination campaigns, non-pharmaceutical interventions (NPIs), and the emergence of new SARS-CoV-2 variants. Additionally, immunity waning and vaccine boosters are modeled to account for their growing importance. New infections are generated according to a hierarchical model in which people have a random, individual infectiousness. The model thus includes super-spreading observed in the COVID-19 pandemic which is important for accurate uncertainty prediction. Our simulation functions as a dynamic compartment model in which an individual’s history of infection, vaccination, and possible reinfection all play a role in their resistance to further infections. We present a risk measure for each SARS-CoV-2 variant, , that accounts for the amount of resistance within a population and show how this risk changes as the vaccination rate increases. highlights that different variants may become dominant in different countries—and in different times—depending on the population compositions in terms of previous infections and vaccinations. We compare the efficacy of control strategies which act to both suppress COVID-19 outbreaks and relax restrictions when possible. We demonstrate that a controller that responds to the effective reproduction number in addition to case numbers is more efficient and effective in controlling new waves than monitoring case numbers alone. This not only reduces the median total infections and peak quarantine cases, but also controls outbreaks much more reliably: such a controller entirely prevents rare but large outbreaks. This is important as the majority of public discussions about efficient control of the epidemic have so far focused primarily on thresholds for case numbers
Surgical Treatment of Bone Sarcoma
Full text linkBone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic approach. While radiotherapy plays a role especially in Ewing sarcoma and chemotherapy in Ewing sarcoma and osteosarcoma, surgery remains the main pillar of treatment in all three entities. After complete tumor resection, the created bone defects need to be reconstructed. Possible strategies are implantation of allografts or autografts including vascularized bone grafts (e.g., of the fibula). Around the knee joint, rotationplasty can be performed or, as an alternative, the implantation of (expandable) megaprostheses can be performed. Challenges still associated with the implantation of foreign materials are aseptic loosening and infection. Future improvements may come with advances in 3D printing of individualized resection blades/implants, thus also securing safe tumor resection margins while at the same time shortening the required surgical time. Faster osseointegration and lower infection rates may possibly be achieved through more elaborate implant surface structure
The COVID-19 pandemic in the African continent
Full text linkIn December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus spread quickly and in March, 2020, it was declared a pandemic. Scientists predicted the worst scenario to occur in Africa since it was the least developed of the continents in terms of human development index, lagged behind others in achievement of the United Nations sustainable development goals (SDGs), has inadequate resources for provision of social services, and has many fragile states. In addition, there were relatively few research reporting findings on COVID-19 in Africa. On the contrary, the more developed countries reported higher disease incidences and mortality rates. However, for Africa, the earlier predictions and modelling into COVID-19 incidence and mortality did not fit into the reality. Therefore, the main objective of this forum is to bring together infectious diseases and public health experts to give an overview of COVID-19 in Africa and share their thoughts and opinions on why Africa behaved the way it did. Furthermore, the experts highlight what needs to be done to support Africa to consolidate the status quo and overcome the negative effects of COVID-19 so as to accelerate attainment of the SDGs
Occupational risk of cutaneous larva migrans: A case report and a systematic literature review
Full text linkutaneous larva migrans (CLM) is a parasitic zoonosis of warm tropical and subtropical areas, although autochthonous cases have been increasingly reported in Western European countries. Data on the prevalence of CLM as an occupational disease in workers exposed to potentially contaminated soil or in close contact with dogs and cats are scant. Herein, we report an autochthonous case of CLM in a dog breeder from southern Italy (Apulia region), along with a systematic literature review describing the risk of CLM infection, mainly according to job categories. The patient was referred to the dermatology unit presenting a serpiginous lesion on his hand, raising the suspected CLM diagnosis. In non-endemic areas, CLM might represent a challenge for physicians in terms of diagnosis, treatment, and prevention, particularly in workplaces. The multidisciplinary approach in the diagnosis of CLM with the involvement of different scientific competences (i.e., dermatologists, veterinarians, and occupational physicians) may contribute to further assess the distribution of human CLM and associated risk factors, toward reducing the risk for the infection.
Author summary
Cutaneous larva migrans (CLM) is a parasitic zoonosis caused by multiple types of hookworms, characterized by creeping migration of larva through the skin. Humans are infected through accidental penetration of their skin by free-living larvae at the filariform stage. CLM is typically acquired in warm tropical or subtropical areas, although reports of autochthonous cases have increased in Western European countries. There is little evidence on the prevalence of CLM as an occupational disease, although workers exposed to potentially contaminated soil or to animals that are the definitive hosts of these nematodes, as dogs and cats, could be considered at higher risk of infection. We report a case of autochthonous CLM in a dog breeder in southern Italy (Apulia) to highlight how the collaboration among specialists in a One Health perspective (e.g., dermatologists, occupational physicians, veterinarians, and parasitologists) is essential for the correct diagnosis of zoonotic infection
A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
Full text linkBone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear.
Methodology/Principal findings
Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformatic analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA–microRNA (miRNA)–mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP–treated mice, but decreased expression in osteocytes.
Conclusions/Significance
This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA–miRNA–mRNA triple network may offer a new target for leprosy therapeutics.
Author summary
Although the number of leprosy patients is gradually decreasing after the use of rifampin, those who have been cured still have bone damage. The Mycobacterium leprae is difficult to culture in vivo, and the potential biosafe problem should be considered. Thus, the minimal essential structure in Mycobacterium, N-glycosylated muramyl dipeptide, has been used to reveal the mechanism in leprosy. According to the analysis results, various differentially expressed genes have been filtered, and circadian Clock gene might be the key factor. We verified that Clock gene was upregulated in the process of osteogenesis. Osteocytes would maintain the balance between osteoblasts and osteoclasts in bone homeostasis. We noticed that the expression of Clock gene was decreased after treated with N-glycosylated muramyl dipeptide. This might be the reason why bone damage is still maintained in the cured patient, and regulating the expression of target at posttranscriptional level by microRNAs and circular RNAs can be the promising therapeutic method in leprosy bone damage
Self-Assembly of a Rare High Spin FeII/PdII Tetradecanuclear Cubic Cage Constructed via the Metalloligand Approach
Full text linkPolynuclear heterobimetallic coordination cages in which different metal cations are connected within a ligand scaffold are known to adopt a variety of polyhedral architectures, many of which display interesting functions. Within the extensive array of coordination cages incorporating Fe(II) centres reported so far, the majority contain low-spin (LS) Fe(II), with high-spin (HS) Fe(II) being less common. Herein, we present the synthesis and characterisation of a new tetradecanuclear heterobimetallic [Fe8Pd6L8](BF4]28 (1) cubic cage utilising the metalloligand approach. Use of the tripodal tris-imidazolimine derivative (2) permitted the formation of the tripodal HS Fe(II) metalloligand [FeL](BF4)2·CH3OH (3) that was subsequently used to form the coordination cage 1. Magnetic and structural analyses gave insight into the manner in which the HS environment of the metalloligand was transferred into the cage architecture along with the structural changes that accompanied its occupancy of the eight corners of the discrete cubic structure
Passiflora mollissima Seed Extract Induced Antiproliferative and Cytotoxic Effects on CAL 27 Spheroids
Full text linkMulticellular tumor spheroids are used as models in drug development due to their characteristics simulating in vivo tumors. Likewise, antiproliferative properties of extracts derived from fruits have been widely described. Peels and seeds can be used as a matrix to obtain different compounds. Recently, a study demonstrated the antiproliferative activity from a P. mollissima extract (PME) on human colon cancer cells; however, its effect on oral spheroids is unknown. Objective. To evaluate the antiproliferative potential of an extract obtained from P. mollissima seeds on the spheroid-type-3D culture model of CAL 27. Methods. CAL 27-spheroids were treated with three concentrations of PME (10, 50, and 100 μg/ml). After 72 hr incubation, morphology and cellular changes, cytotoxic and proapoptotic effect, gene expression, and metastasis were determined. Additionally, changes in the cell cycle phases responded to the PME concentrations. Comparisons between groups were made through a U Mann-Whitney test. Results. It was shown that 100 μg/ml PE affects CAL 27 cells proliferation grown in spheroids through cell cycle arrest and gene regulation of p53, HIF 1α, and CDH1. However, none of the treatments employed induced MMP9 gene expression. Conclusion. Our study shows that PME inhibits the growth and proliferation of oral tumor cells cultured in spheroids through the positive regulation of cell death and metastasis genes
Effect of Spacing and Boron Levels on Growth and Yield of Black Gram (Vigna mungo L.)
No full textA field experiment was conducted aiming to study the effect of Spacing and Boron levels on growth and yield of black gram during Zaid season 2022. The treatments comprised of row spacing (25, 30, 35 cm) and boron (1.0, 1.5, 2.0 kg/ha). The results showed that application of boron 2.0 kg/ha at 35 cm × 10 cm spacing has recorded significantly higher plant height (44.53 cm), number of branches per plant (9.27), number of nodules (35.53) and dry weight (10.44 g). However higher number of pods per plant (30.73), seeds per pod (6.40), test weight (42.48 g), seed yield (930.33 kg/ha) and stover yield (2040.33 kg/ha) were recorded with the application of boron 2.0 kg/ha at 25 cm ×10 cm spacing. Therefore, the spacing of 25 cm × 10 cm and application of Boron 2.0 kg/ha could be a promising option for the yield enhancement in black gram
Effect of Spacing and Boron Levels on Growth and Yield of Black Gram (Vigna mungo L.)
Full text linkA field experiment was conducted aiming to study the effect of Spacing and Boron levels on growth and yield of black gram during Zaid season 2022. The treatments comprised of row spacing (25, 30, 35 cm) and boron (1.0, 1.5, 2.0 kg/ha). The results showed that application of boron 2.0 kg/ha at 35 cm × 10 cm spacing has recorded significantly higher plant height (44.53 cm), number of branches per plant (9.27), number of nodules (35.53) and dry weight (10.44 g). However higher number of pods per plant (30.73), seeds per pod (6.40), test weight (42.48 g), seed yield (930.33 kg/ha) and stover yield (2040.33 kg/ha) were recorded with the application of boron 2.0 kg/ha at 25 cm ×10 cm spacing. Therefore, the spacing of 25 cm × 10 cm and application of Boron 2.0 kg/ha could be a promising option for the yield enhancement in black gram
What Should We Do after the COVID-19 Vaccination? Vaccine-Associated Diseases and Precautionary Measures against Adverse Reactions
Full text linkCOVID-19 vaccines have been used to counteract the global COVID-19 pandemic. While these are effective, adverse reactions have been reported, such as injection-site pain, muscle ache, fever, palpitation, and chest discomfort. The release of inflammatory cytokines, such as interleukin (IL)-6 and IL-1β, is a potential mechanism for post-vaccine side-effects. Chest discomfort after the vaccination, including myocarditis and acute coronary syndrome, is a particularly serious adverse reaction. It is important to be familiar with the differential diagnoses of chest discomfort and organ-specific diseases associated with COVID-19 vaccines as the preparation for booster shots and vaccinations among children aged 5–11 years begins. High-intensity exercise, alcohol, tobacco smoking, and baths promote inflammatory cytokines, such as IL-6, which may exacerbate the adverse reactions after vaccination. Japanese data show that deaths during baths are the most common for several days after mRNA vaccination. Additionally, alcohol and tobacco smoking were identified as predictive factors of lower antibody titers after vaccination. In this review, we aimed to provide a few recommendations to prevent vaccine-associated disease