A genetic approach to the de novo identification of targets of strain-specific immunity in malaria parasites

Vaccine research in malaria has a high priority. However, identification of specific antigens as candidates for vaccines against asexual blood stages of malaria parasites has been based on largely circumstantial evidence. We describe here how genes encoding target antigens of strain-specific immunity in malaria can be directly located in the parasite's genome without prior information concerning their identity, by the method we call linkage group selection. Two genetically distinct clones of the rodent malaria parasite Plasmodium chabaudi chabaudi, each of which induces an immunity in laboratory mice that is more protective against challenge with itself than with the heterologous strain, were genetically crossed, and the uncloned cross progeny selected in mice that had been made partially immune by infection and drug cure with one or the other parental strain. Proportions of parental alleles in the selected and unselected cross progeny were compared by using quantitative genome-wide molecular markers. A small number, including groups of linked markers forming so-called selection valleys, were markedly reduced under strain-specific immune pressure. A very prominent selection valley was found to contain the gene for merozoite surface protein-1, a major candidate antigen for malaria vaccine development, at the locus at which the strongest reduction under strain-specific immune selection was detected. Closely linked to the merozoite surface protein-1 gene was a gene containing the signature motif of the ring-infected erythrocyte surface antigen family. Another affected locus, unlinked to this selection valley, contained a member of the serine repeat antigen gene family.     

Thromboembolic disease in surgery for malignancy-rationale for prolonged thromboprophylaxis

Patients undergoing surgery for malignancy are at increased risk of initial and recurrent venous thromboembolism (VTE). Several factors have been found to increase the risk of deep vein thrombosis (DVT) in cancer patients both during the first days after the operation and after discharge from hospital. Although, in general, thromboprophylaxis is provided to cancer patients after surgery, the length of time these patients require prophylaxis has not yet been established. Autopsy series, clinical series, and clinical trials indicate that up to about 40% of VTE occurs post discharge. General surgical patients undergoing major abdominal surgery require VTE prophylaxis, and prolonged thromboprophylaxis should be considered in the post-discharge period in high-risk patients, particularly those with cancer. Evidence from studies in general and orthopedic surgery show that prolonged prophylaxis reduces the number of thromboembolic events after discharge from hospital. Prophylaxis should be simple, safe, and effective and should be administered easily to allow continuation of therapy after discharge. Low-molecular-weight heparins are potentially the most suitable agents for long-term thromboprophylaxis in cancer patients.     

Impact of TennCare reform on care of patients with rheumatic diseases

BACKGROUND: As a consequence of cost-cutting changes, termed "TennCare reform," to Tennessee's state-funded health care plan, a number of beneficiaries have either had their benefits substantially reduced or have been disenrolled entirely. The purpose of this study was to determine the impact of these reforms on the health of patients with chronic rheumatic diseases. METHODS: We determined differences with adherence to scheduled appointments in an urban academic rheumatology clinic in the 3 months before and in the 3 months after TennCare reform. A telephone survey was conducted to determine plans for future rheumatic care among those patients scheduled to be seen in this clinic in the 3 months after TennCare reform. RESULTS: Overall, 402 of the 601 patients scheduled for a rheumatology clinic appointment before TennCare reform (67%) adhered to their scheduled rheumatology appointment, compared with 362 of 595 patients (61%) scheduled for an appointment after TennCare reform, a difference that was statistically significant (P = 0.034). After TennCare reform, patients who did not adhere with clinic follow-up were more likely to have been disenrolled from TennCare (P < 0.001). By telephone survey, among those who were disenrolled from TennCare, almost half indicated that they did not know where they were going to receive future rheumatic disease care. Among those who retained TennCare, less than half indicated that they could afford to purchase all of their medications. CONCLUSIONS: TennCare reform has significantly limited care for patients with rheumatic diseases. The long-term consequences of this merit future study.     

Primary Synovial Sarcoma of the Pharynx: A Series of Five Cases and Literature Review

Synovial sarcoma comprises approximately 10 % of all soft tissue sarcomas. Although synovial sarcoma has been reported in practically every organ, the extremities are the commonest site of occurrence followed by the head and neck. Primary synovial sarcoma of the pharynx is rare and only case reports have been published. We report a series of five cases of primary synovial sarcoma involving the pharynx.     

Therapeutic dilemma in the repression of severe acute respiratory syndrome coronavirus-2 proteome

Currently, the pandemic coronavirus disease 2019 (COVID-19) has unprecedentedly captivated its human hosts by causing respiratory illnesses because of evolution of the genetic makeup of novel coronavirus (CoV) known as severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). As much as the researchers are inundated for the quest of effective treatments from available drugs, the discovery and trials of new experimental drugs are also at a threshold for clinical trials. There has been much concern regarding the new and targeted drugs considering the comprehensive ambiguity regarding the mechanism and pathway of the drug action with respect to the new and unpredictable structural and nonstructural proteins (NSPs) of SARS CoV-2. This study was aimed to discuss functional pathways related to NSPs in CoVs with updated knowledge regarding SARS CoV-2, mechanisms of action of certain approved and investigational drugs for correct orientation regarding the treatment strategies, including nucleotide analog mechanism, receptor analog mechanism, and peptide–peptide interactions, along with the impact of COVID-19 on a global scale. Although there is a dire need for targeted drugs against SARS CoV-2, the practical achievement of its cure is possible by only using effective drugs with appropriate mechanisms to eliminate the disease.     

Exosomes: A new frontier under the spotlight for diagnosis and treatment of gastrointestinal diseases

Exosomes are small plasma membrane-bound multivesicular bodies ranging in size from 20-100 nm. Exosomes are degraded fragments of mRNA, microRNA, and enriched in proteins, lipids, and nucleic acid. They are produced in the endosomes of most eukaryotic cells and once secreted, exosomes are involved in cell to cell communication and remodeling of the matrix in the extracellular compartment. Exosome biogenesis plays a crucial role in cellular development, inflammation, immunity, hemostasis, carcinogenesis, and degeneration. Due to their unique biochemical and biophysical properties, exosomes serve a variety of functions including biomarkers of diagnostic and prognostic significance. Besides, there is an increasing level of evidence to expand our understanding of the exosomes as novel therapeutic agents. Inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis, hepatic fibrosis, and gastrointestinal malignancies such as colorectal cancer are the potential avenues where exosomes can be applied as cell therapy and immunotherapy and have shown promising results in several in-vitro and animal models. The purpose of this review article is to highlight the emerging role of exosomes as the diagnostic and therapeutic tool in various diseases involving the gastrointestinal tract like IBD, hepatocellular carcinoma, and colon cancer. A thorough literature search was performed on databases such as PubMed, Ovid Medline, and EMBASE to achieve the objectives of this review article.     

Melatonin levels and microRNA (miRNA) relative expression profile in the follicular ambient microenvironment in patients undergoing in vitro fertilization process

PurposeIntrafollicular fluid (IFF) melatonin plays a decisive role in maintaining granulosa cells’ DNA integrity and protects them against apoptosis. It reduces oxidative stress and improves the oocyte quality with a higher fertilization rate.MethodThis prospective study investigated the antioxidant property of IFF melatonin and its impact on IVF outcome parameters. We also explored the relative expression of five microRNAs (miR-663b, miR-320a, miR-766-3p, miR-132-3p, miR-16-5p) and levels of cell-free DNA (cfDNA) by real-time PCR in unexplained infertile patients. We collected 425 follicular fluid (FF) samples containing mature oocytes from 295 patients undergoing IVF.ResultsPatients were subgrouped based on IFF melatonin concentration (group A ≤ 30 pg/mL, group B > 70 to ≤ 110 pg/mL, group C > 111 to ≤ 385 pg/mL). Our results showed that patients with ≤ 30 pg/mL IFF melatonin levels have significantly higher oxidative stress markers, cfDNA levels, and lower relative expression of miR-663b, miR-320a, miR-766-3p, miR-132-3p, and miR-16-5p compared to other subgroups (p < 0.001). Similarly, they have a low fertilization rate and a reduced number of high-quality day 3 embryos.ConclusionFindings suggest that the therapeutic use of melatonin produces a considerable rise in the number of mature oocytes retrieved, fertilization rate, and good-quality embryo selection. Furthermore, miRNA signature enhances the quality of embryo selection, thus, may allow us to classify them as non-invasive biomarkers to identify good-quality embryos.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-020-02010-2.