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Vaccine Feb 2020Cholera still affects about three million people a year and kills approximately 100,000. Cholera can be effectively managed in the majority of cases with oral... (Review)
Review
Cholera still affects about three million people a year and kills approximately 100,000. Cholera can be effectively managed in the majority of cases with oral rehydration solution alone. Up to one third of patients present with severe dehydration, which can be diagnosed clinically, and will require rapid intravenous rehydration with Ringers Lactate or other appropriate fluid before being managed with oral rehydration solution. Antibiotics reduce the duration of illness and should be used in patients with severe dehydration. Resistance is common and local sensitivities should guide the choice of antibiotic. All children between six months and five years should receive zinc supplements. Effective case management with strict attention to detail including infection control and the use of protocolized approaches can reduce the mortality to around 1% even in resource poor settings.
Topics: Anti-Bacterial Agents; Child; Cholera; Dehydration; Diarrhea; Disease Management; Fluid Therapy; Humans; Practice Guidelines as Topic; Ringer's Lactate; Zinc
PubMed: 31668817
DOI: 10.1016/j.vaccine.2019.09.098 -
Current Protocols Oct 2022Inflammasomes are multiprotein complexes that play key roles in the host's innate immune response to insult. The assembly of an inflammatory complex is initiated with...
Inflammasomes are multiprotein complexes that play key roles in the host's innate immune response to insult. The assembly of an inflammatory complex is initiated with the oligomerization of the upstream inflammasome-forming sensor and then follows a well-orchestrated multi-step process leading to downstream effector functions that are critical in the innate immune response. The final assembly of these steps provides a detectable readout of inflammasome complex activation in the form of an apoptosis-associated speck-like protein containing a CARD (ASC) speck. Inflammasome activation-and the release of IL-1β and ASC specks from the microglia, the brain resident immune cell-have been implicated in various neurological and neurodegenerative disorders. Protocols exist for the generation of fluorescent inflammasome indicator peripheral macrophages. Building upon these protocols, we describe here a protocol that details the generation of fluorescent inflammasome indicator microglia cells using recombinant retroviruses to transduce murine BV-2 cells. In this protocol, the cells are established in a manner to allow for experimental control of the initial priming step of the inflammasome activation process. We then provide a series of steps for using these reporter cells within an inflammasome activation assay and use real-time imaging of ASC-speck formation as an indicator of inflammasome activation. In addition, we describe strategies for using these cells for examining the effects of a test substance on inflammasome activation. This protocol offers an effective approach conducive to screening for and examining modifications of microglia inflammasome activation due to exposure to chemicals or pharmacological agents. © Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Production of retroviruses to express inflammasome indicator Basic Protocol 2: Generation of inflammasome indicator BV-2 cells Basic Protocol 3: Priming and activation of BV-2-ASC-Cerulean cells for inflammasome activation assay Basic Protocol 4: Examining modifications to inflammasome activation by test substances Basic Protocol 5: Imaging and analysis of ASC speck formation.
Topics: Mice; Animals; Inflammasomes; CARD Signaling Adaptor Proteins; Microglia; Macrophages; Immunity, Innate; Retroviridae
PubMed: 36286528
DOI: 10.1002/cpz1.578 -
Quantitative Imaging in Medicine and... Nov 2019Liver magnetic resonance imaging (MRI) is subject to continuous technical innovations through advances in hardware, sequence and novel contrast agent development. In... (Review)
Review
Liver magnetic resonance imaging (MRI) is subject to continuous technical innovations through advances in hardware, sequence and novel contrast agent development. In order to utilize the abilities of liver MR to its full extent and perform high-quality efficient exams, it is mandatory to use the best imaging protocol, to minimize artifacts and to select the most adequate type of contrast agent. In this article, we review the routine clinical MR techniques applied currently and some latest developments of liver imaging techniques to help radiologists and technologists to better understand how to choose and optimize liver MRI protocols that can be used in clinical practice. This article covers topics on (I) fat signal suppression; (II) diffusion weighted imaging (DWI) and intravoxel incoherent motion (IVIM) analysis; (III) dynamic contrast-enhanced (DCE) MR imaging; (IV) liver fat quantification; (V) liver iron quantification; and (VI) scan speed acceleration.
PubMed: 31867237
DOI: 10.21037/qims.2019.09.18 -
Current Oncology (Toronto, Ont.) Feb 2020Soft-tissue sarcoma (sts) is rare and represents approximately 7% of cancers in children and in adolescents less than 20 years of age. Rhabdomyosarcoma (rms) is most... (Review)
Review
Soft-tissue sarcoma (sts) is rare and represents approximately 7% of cancers in children and in adolescents less than 20 years of age. Rhabdomyosarcoma (rms) is most prevalent in children less than 10 years of age and peaks again during adolescence (16-19 years of age). Multi-agent chemotherapy constitutes the mainstay of treatment for rms. In other non-rhabdomyosarcoma soft-tissue tumours, such as synovial sarcoma, evidence for routine use of chemotherapy is less robust, and alternative treatment options, including targeted agents and immunotherapy, are being explored. In this review, we focus on chemotherapy for pediatric-type rms and discuss the advances and challenges in systemic treatment for select non-rhabdomyosarcoma soft-tissue tumours in children and adolescents. We support an increasingly cooperative approach for treating pediatric and adult sts.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Humans; Sarcoma; Soft Tissue Neoplasms; Young Adult
PubMed: 32174753
DOI: 10.3747/co.27.5481 -
Journal of Hematology & Oncology Nov 2020The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal... (Review)
Review
The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development. These include new PIs such as ixazomib, marizomib, and oprozomib; new MoAbs such as isatuximab and MOR202; novel epigenetic agent ricolinostat and novel cytokines such as siltuximab. Recently, the first XPO-1 inhibitor, selinexor, was approved for RRMM. BCMA-targeted BiTE, antibody-drug conjugates and CAR-T cells have the potential to revolutionize the therapy for RRMM. In this review, we summarized the latest clinical development of these novel agents and regimens.
Topics: Animals; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Humans; Immune Checkpoint Inhibitors; Immunoconjugates; Immunotherapy, Adoptive; Multiple Myeloma; Proteasome Inhibitors
PubMed: 33168044
DOI: 10.1186/s13045-020-00980-5 -
Journal of Clinical Microbiology Oct 2023Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination is a treatment option for infections due to carbapenem-resistant...
Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination is a treatment option for infections due to carbapenem-resistant Enterobacterales (CRE), including metallo-ß-lactamase producers, regardless of additional production of broad-spectrum serine-ß-lactamases. However, AZA-resistance has already been reported in Enterobacterales and its early detection could be a valuable tool for faster and more accurate clinical decision-making. We therefore developed a rapid culture-based test for the identification of AZA resistance among multidrug-resistant Enterobacterales. The Rapid Aztreonam/Avibactam NP test is based on resazurin reduction when bacterial growth occurs in the presence of AZA at 8/4 µg/mL (protocol 1) or 12/4 µg/mL (protocol 2). Given the absence of guidelines on AZA susceptibility testing, two tentative breakpoints were indeed used to categorize AZA-susceptible isolates: ≤4 µg/mL in protocol 1 and ≤ 8 µg/mL in protocol 2. Bacterial growth was visually detectable by a blue-to-purple or blue-to-pink color change of the medium. A total of 78 enterobacterial isolates (among which 34 AZA-resistant and 13 AZA-resistant according to protocols 1 and 2, respectively) were used to evaluate the test performance using protocol 1 or protocol 2. The sensitivity and specificity of the test were found to be 100% and 97.7%, respectively, following protocol 1 and 100% and 100%, respectively, following protocol 2, in comparison with broth microdilution. All results were obtained within 4.5 hours corresponding to a time saving of ca. 14 hours compared with currently available methods for AZA susceptibility testing. The Rapid Aztreonam/Avibactam NP test is rapid, highly sensitive, specific, easily interpretable, and easy to implement in routine.
Topics: Humans; Aztreonam; Anti-Bacterial Agents; beta-Lactamases; Azabicyclo Compounds; beta-Lactamase Inhibitors; Microbial Sensitivity Tests; Drug Combinations; Ceftazidime
PubMed: 37791761
DOI: 10.1128/jcm.00588-23 -
Frontiers in Molecular Biosciences 2021Chagas disease, is a vector-mediated tropical disease whose causative agent is a parasitic protozoan named It is a very severe health issue in South America and Mexico... (Review)
Review
Chagas disease, is a vector-mediated tropical disease whose causative agent is a parasitic protozoan named It is a very severe health issue in South America and Mexico infecting millions of people every year. Protozoan gets transmitted to human through , a subfamily of the Reduviidae, and do not have any effective treatment or preventative available. The lack of economic gains from this tropical parasitic infection, has always been the reason behind its negligence by researchers and drug manufacturers for many decades. Hence there is an enormous requirement for more efficient and novel strategies to reduce the fatality associated with these diseases. Even, available diagnosis protocols are outdated and inefficient and there is an urgent need for rapid high throughput diagnostics as well as management protocol. The current advancement of nanotechnology in the field of healthcare has generated hope for better management of many tropical diseases including Chagas disease. Nanoparticulate systems for drug delivery like poloxamer coated nanosuspension of benzimidazole have shown promising results in reducing toxicity, elevating efficacy and bioavailability of the active compound against the pathogen, by prolonging release, thereby increasing the therapeutic index. Moreover, nanoparticle-based drug delivery has shown promising results in inducing the host's immune response against the pathogen with very few side effects. Besides, advances in diagnostic assays, such as nanosensors, aided in the accurate detection of the parasite. In this review, we provide an insight into the life cycle stages of the pathogen in both vertebrate host and the insect vector, along with an overview of the current therapy for Chagas disease and its limitations; nano carrier-based delivery systems for antichagasic agents, we also address the advancement of nano vaccines and nano-diagnostic techniques, for treatment of Chagas disease, majorly focusing on the novel perspectives in combating the disease.
PubMed: 34141721
DOI: 10.3389/fmolb.2021.655435 -
Frontiers in Pediatrics 2021The implementation of managed protocols contributes to a systematized approach to the patient and continuous evaluation of results, focusing on improving clinical... (Review)
Review
The implementation of managed protocols contributes to a systematized approach to the patient and continuous evaluation of results, focusing on improving clinical practice, early diagnosis, treatment, and outcomes. Advantages to the adoption of a pediatric sepsis recognition and treatment protocol include: a reduction in time to start fluid and antibiotic administration, decreased kidney dysfunction and organ dysfunction, reduction in length of stay, and even a decrease on mortality. Barriers are: absence of a written protocol, parental knowledge, early diagnosis by healthcare professionals, venous access, availability of antimicrobials and vasoactive drugs, conditions of work, engagement of healthcare professionals. There are challenges in low-middle-income countries (LMIC). The causes of sepsis and resources differ from high-income countries. Viral agent such as dengue, malaria are common in LMIC and initial approach differ from bacterial infections. Some authors found increased or no impact in mortality or increased length of stay associated with the implementation of the SCC sepsis bundle which reinforces the importance of adapting it to most frequent diseases, disposable resources, and characteristics of healthcare professionals. Conclusions: (1) be simple; (2) be precise; (3) education; (5) improve communication; (5) work as a team; (6) share and celebrate results.
PubMed: 34858905
DOI: 10.3389/fped.2021.755484 -
Current Protocols Jan 2022Entamoeba histolytica is a parasitic protozoan and the causative agent of amoebiasis in humans. Amoebiasis has a high incidence of disease, resulting in ∼67,900 deaths...
Entamoeba histolytica is a parasitic protozoan and the causative agent of amoebiasis in humans. Amoebiasis has a high incidence of disease, resulting in ∼67,900 deaths per year, and it poses a tremendous burden of morbidity and mortality in children. Despite its importance, E. histolytica is an understudied parasite. These protocols describe the in vitro growth, maintenance, cryopreservation, genetic manipulation, and cloning of axenic E. histolytica trophozoites. There has been significant progress in genetic manipulation of this organism over the past decade, and these protocols outline the ways in which these advances can be implemented. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Culturing E. histolytica trophozoites Support Protocol 1: Preparation of TYI-S-33 medium Support Protocol 2: Lot testing of Biosate peptone and adult bovine serum for TYI-S-33 medium Basic Protocol 2: Cryopreservation of E. histolytica trophozoites Support Protocol 3: Preparation of cryoprotectant solutions Basic Protocol 3: Transfection of E. histolytica trophozoites with Attractene reagent Basic Protocol 4: Creating clonal lines using limiting dilution Basic Protocol 5: Knockdown of one to two genes with trigger-induced RNA interference Support Protocol 4: Evaluation of RNA interference knockdown with reverse transcriptase PCR Basic Protocol 6: E. histolytica growth curves.
Topics: Adult; Animals; Child; Culture Media; Entamoeba histolytica; Genetic Techniques; Humans; RNA Interference; Trophozoites
PubMed: 35085418
DOI: 10.1002/cpz1.327