scholarly journals Live imaging of the Cryptosporidium parvum lifecycle reveals direct development of male and female gametes from type one meronts

2021 ◽  
Author(s):  
Elizabeth D English ◽  
Amandine Guerin ◽  
Jayesh Tandel ◽  
Boris Striepen
Keyword(s):  
Treatment Options ◽  
Intermediate Stage ◽  
Original Description ◽  
Direct Development ◽  
Childhood Mortality ◽  
Type I ◽  
Cell Cycles ◽  
Parasite Plasmodium ◽  
Single Host ◽  
Intrinsic Program

Cryptosporidium is a leading infectious cause of diarrhea around the world associated with waterborne outbreaks, community spread, or zoonotic transmission. The parasite has significant impact on early childhood mortality, and infection is both consequence and cause of malnutrition and stunting. There is currently no vaccine, and treatment options are very limited. Cryptosporidium is a member of the Apicomplexa, and as typical for this protist phylum relies on asexual and sexual reproduction. In contrast to other Apicomplexa, like malaria parasite Plasmodium, Cryptosporidium's entire lifecycle unfolds in a single host in less than three days. Here we establish a model to image lifecycle progression in living cells, and observe, track, and compare nuclear division of asexual and sexual stage parasites. We establish the length and sequence of the cell cycles of all stages and map the developmental fate of parasites across multiple rounds of invasion and egress. We determine that the parasite executes an intrinsic program of three generations of asexual replication, followed by a single generation of sexual stages that is independent of environmental stimuli. We find no evidence for a morphologically distinct intermediate stage (the tetraploid type II meront) but demonstrate direct development of gametes from 8N type I meronts. The progeny of each meront is collectively committed to either asexual or sexual fate, but importantly, meronts committed to sexual fate give rise to both males and females. We define a Cryptosporidium lifecycle matching Tyzzer's original description and inconsistent with the coccidian lifecycle now shown in many textbooks.

Efficiency of diffusion-weighted MRI for differentiating radiologically similar simple and type I hydatid cysts of the liver

2021 ◽  
pp. 028418512098813
Author(s):  
Ilyas Dundar ◽  
Mesut Ozgokce ◽  
Fatma Durmaz ◽  
Sercan Ozkacmaz ◽  
Saim Turkoglu ◽  
...  
Keyword(s):  
Treatment Options ◽  
Type I ◽  
Hydatid Cysts ◽  
Liver Cysts ◽  
Diffusion Weighted ◽  
Significant Difference ◽  
Mean Diameter ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Hepatic Lesions

Background Determining the nature of purely cystic hepatic lesions is essential because different kinds have different follow-ups, treatment options, and complications. Purpose To explore the potential of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI) for the differentiation of type I hydatid cysts (HC) and simple liver cysts (SLC), which have similar radiological appearances. Material and Methods This single-center prospective study was conducted during 2016–2019. Round, homogenous, anechoic liver cysts >1 cm were classified according to at least two years of imaging follow-up, radiological features, serology, as well as puncture aspiration injection reaspiration procedure and pathology results. ADC values of 95 cysts (50 type I HCs and 45 SLCs) were calculated on DWI. The differences in ADC values were analyzed by independent t-test. Results Of 51 patients, 28 were female, 23 were male (mean age 32.07 ± 22.95 years; age range 5–82 years). Mean diameter of 45 SLCs was 2.59 ± 1.23 cm (range 1.2–7.6 cm) and ADCmean value was 3.03 ± 0.47 (range 2.64–5.85) while mean diameter of 50 type I HCs was 7.49 ± 2.95 cm (range 2.8–14 cm) and ADCmean value was 2.99 ± 0.29 (range 2.36–3.83). There was no statistically significant difference in ADC values between type I HCs and SLCs Conclusion Some studies report that ADC values of type I HCs are statistically significantly lower than those of SLCs. Others suggest no significant difference. In our study with a higher number of cases, using ADC parameters similar to those in previous studies, we did not find any statistically significant difference.

scholarly journals Management of Amelogenesis Imperfecta in Childhood: Two Case Reports

2021 ◽  
Vol 18 (13) ◽  
pp. 7204
Author(s):  
Mirja Möhn ◽  
Julia Camilla Bulski ◽  
Norbert Krämer ◽  
Alexander Rahman ◽  
Nelly Schulz-Weidner
Keyword(s):  
Case Reports ◽  
Treatment Options ◽  
Permanent Dentition ◽  
Amelogenesis Imperfecta ◽  
Structural Defects ◽  
Type I ◽  
Oral Rehabilitation ◽  
Self Confidence ◽  
Health Quality ◽  
Masticatory System

Amelogenesis imperfecta (AI) is defined as an interruption of enamel formation due to genetic inheritance. To prevent malfunction of the masticatory system and an unaesthetic appearance, various treatment options are described. While restoration with a compomer in the anterior region and stainless steel crowns in the posterior region is recommended for deciduous dentition, the challenges when treating such structural defects in mixed or permanent dentition are changing teeth and growing jaw, allowing only temporary restoration. The purpose of this case report is to demonstrate oral rehabilitation from mixed to permanent dentition. The dentition of a 7-year-old patient with AI type I and a 12-year-old patient with AI type II was restored under general anesthesia to improve their poor aesthetics and increase vertical dimension, which are related to problems with self-confidence and reduced oral health quality of life. These two cases show the complexity of dental care for structural anomalies of genetic origin and the challenges in rehabilitating the different phases of dentition.

scholarly journals Mechanistic Inferences from Clinical Reports of SARS-CoV-2

2020 ◽  
Author(s):  
Meagan M Jenkins ◽  
Tyler R McCaw ◽  
Paul A Goepfert
Keyword(s):  
Randomized Clinical Trials ◽  
Severe Disease ◽  
Treatment Options ◽  
Management Strategies ◽  
Type I ◽  
Interferon Signaling ◽  
Adaptive Responses ◽  
Initial Clinical Trial ◽  
Inflammatory State ◽  
Clinical Trial Results

SARS-CoV-2 was identified as the causative pathogen in an outbreak of viral pneumonia cases originating in Wuhan, China, with an ensuing rapid global spread that led it to be declared a pandemic by the WHO on March 11, 2020. Given the threat to public health posed by sequelae of SARS-CoV-2 infection, the literature surrounding patient presentation in severe and non-severe cases, transmission rates and routes, management strategies, and initial clinical trial results have become available at an unprecedented pace. In this review we collate current clinical and immunologic reports, comparing these to reports of previous coronaviruses to identify mechanisms driving progression to severe disease in some patients. In brief, we propose a model wherein dysregulated type I interferon signaling leads to aberrant recruitment and accumulation of innate immune lineages in the lung, impairing establishment of productive adaptive responses, and permitting a pathologic pro-inflammatory state. Finally, we extend these findings to suggest possible treatment options that may merit investigation in randomized clinical trials.

scholarly journals Treatment options in type-2 low asthma

2020 ◽  
pp. 2000528 ◽  
Author(s):  
Timothy SC Hinks ◽  
Stewart J Levine ◽  
Guy G Brusselle
Keyword(s):  
Severe Asthma ◽  
Bacterial Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Occupational Exposures ◽  
Evidence Base ◽  
Type I ◽  
Eosinophilic Asthma ◽  
Ongoing Research

Monoclonal antibodies targeting IgE or the type-2 cytokines IL-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma respectively. However, these therapies are not appropriate for 30–50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, “type-2 low” asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, though poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity, occupational exposures and may be driven by persistent bacterial infections and by activation of a recently-described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits which can be identified and addressed. We particularly focus on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally we review ongoing research into other pathways including TNF, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems and is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.

scholarly journals Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late

2018 ◽  
Vol 19 (8) ◽  
pp. 2380 ◽  
Author(s):  
Michiel Remmerie ◽  
Veerle Janssens
Keyword(s):  
Clinical Trials ◽  
Endometrial Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Genetic Alterations ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Type Ii

Type II endometrial carcinomas (ECs) are responsible for most endometrial cancer-related deaths due to their aggressive nature, late stage detection and high tolerance for standard therapies. However, there are no targeted therapies for type II ECs, and they are still treated the same way as the clinically indolent and easily treatable type I ECs. Therefore, type II ECs are in need of new treatment options. More recently, molecular analysis of endometrial cancer revealed phosphorylation-dependent oncogenic signalling in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways to be most frequently altered in type II ECs. Consequently, clinical trials tested pharmacologic kinase inhibitors targeting these pathways, although mostly with rather disappointing results. In this review, we highlight the most common genetic alterations in type II ECs. Additionally, we reason why most clinical trials for ECs using targeted kinase inhibitors had unsatisfying results and what should be changed in future clinical trial setups. Furthermore, we argue that, besides kinases, phosphatases should no longer be ignored in clinical trials, particularly in type II ECs, where the tumour suppressive phosphatase protein phosphatase type 2A (PP2A) is frequently mutated. Lastly, we discuss the therapeutic potential of targeting PP2A for (re)activation, possibly in combination with pharmacologic kinase inhibitors.

scholarly journals Diagnosis, Staging, and Patient Selection for Locoregional Therapy to Treat Hepatocellular Carcinoma

2020 ◽  
Vol 37 (05) ◽  
pp. 441-447
Author(s):  
Zachary T. Berman ◽  
Isabel Newton
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Family Education ◽  
Locoregional Therapy ◽  
Stage Disease ◽  
Incidence And Mortality ◽  
Tumor Boards ◽  
Diagnostic Approaches ◽  
Locoregional Therapies

AbstractHepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality and the only cancer for which the incidence and mortality are on the rise. Sensitive and specific screening and diagnostic approaches, robust staging regimens, multidisciplinary tumor boards, and patient/family education and engagement in the shared decision-making process help to identify a patient's optimal treatment options. Locoregional therapies have been the mainstay for treating intermediate-stage disease, but they are finding special applications for early and advanced disease. This review discusses the diagnosis of HCC, current accepted staging models, and treatment of HCC, with a focus on locoregional therapies.

scholarly journals Antiviral immunity is impaired in COPD patients with frequent exacerbations

2019 ◽  
Vol 317 (6) ◽  
pp. L893-L903 ◽  
Author(s):  
Aran Singanayagam ◽  
Su-Ling Loo ◽  
Maria Calderazzo ◽  
Lydia J. Finney ◽  
Maria-Belen Trujillo Torralbo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Treatment Options ◽  
Stable State ◽  
Innate Immune ◽  
Chronic Obstructive ◽  
Type I ◽  
Obstructive Pulmonary Disease ◽  
Immune Mediators ◽  
Copd Patients

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.

A single-arm phase II trial of afatinib in pretreated patients with advanced NSCLC harboring a HER2 mutation: The ETOP NICHE trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9070-9070 ◽  
Author(s):  
Egbert F. Smit ◽  
Solange Peters ◽  
Rafal Dziadziuszko ◽  
Urania Dafni ◽  
Juergen Wolf ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Type I ◽  
Toxicity Profile ◽  
Lung Carcinogenesis ◽  
Serious Adverse Events ◽  
Control Disease

9070 Background: HER2mutations are identified in about 2% of lung adenocarcinomas and are critical for lung carcinogenesis. Afatinib is a selective and irreversible erbB family blocker with a manageable toxicity profile and promising results in small retrospective studies targeting HER2 in NSCLC. Methods: NICHE is a single-arm phase II trial exploring the potential of afatinib to control disease (complete or partial response or disease stabilization for ≥12 weeks) in pre-treated patients with advanced NSCLC harboring HER2 exon 20 mutations. Patients were treated with afatinib 40 mg/day p.o. until tumor progression or lack of tolerability. A Simon’s two stage phase II design was adopted, to explore whether afatinib can achieve a DCR of 75%, as opposed to a DCR of 50% under the current treatment options. For a 1-sided type I error of 10% and power of 80%, a total of 22 patients were needed. Results: As of 24 November 2016, 13 patients were recruited into the trial. Median age was 60 years, 69% female and 62% never smokers. The overall toxicity profile was in the expected range, with 5 patients experiencing serious adverse events (dyspnea, diarrhea, dehydration, epistaxis, pleural, pericardial and renal insufficiency). The median follow-up was 23 weeks (IQR 12 – 39). Three patients died and 10 were still on follow-up, among them five were still on treatment. Total of 7 patients (54%) achieved DC at 12-weeks, 3 patients had PD before and 3 at 12-weeks. The 12-week PFS was 51% (95% CI: 22 - 75) and the median PFS 13 weeks (95% CI 6 - NE). In the 1st stage analysis of the Simon’s design, with 9 patients included, the stopping boundary was crossed. Therefore and upon recommendations of the ETOP IDMC, recruitment into the trial was stopped prematurely in December 2016. Treatment and follow-up of the enrolled patients continues as planned. Conclusions: Based on the interim results, afatinib did not show the expected potential to control disease in this patient population. However in the full analysis set with 13 patients, clear signs of activity were seen. A comprehensive biomolecular analysis of the tumors is currently ongoing in order to identify a subgroup of patients who might still derive benefit from afatinib treatment. Clinical trial information: NCT02369484.

Myopenia as a significant prognostic factor in BCLC-B intermediate-stage hepatocellular carcinoma treated with sorafenib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15639-e15639
Author(s):  
Mao Okada ◽  
Hiroyuki Nakanishi ◽  
Masayuki Kurosaki ◽  
Sakura Kirino ◽  
Leona Osawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Significant Prognostic Factor ◽  
Poor Prognostic Factor ◽  
Skeletal Muscle Index ◽  
The Impact

e15639 Background: Tyrosine kinase inhibitors (TKI) are important treatment options for unresectable hepatocellular carcinoma (HCC). The survival benefit of sorafernib was demonstrated not only in advanced stage but also for BCLC-B intermediate stage who are refractory to transcatheter arterial chemoembolization by OPTIMIS study. Skeletal muscle mass depletion (Myopenia) is a poor prognostic factor in HCC treated by resection or loco-reginal ablation, but its effect on survival in TKI treated patients, especially in those within BCLC-B stage remains unclear. The aim of the present study is to elucidate the impact of myopenia on survival among HCC treated with sorafenib, especially in BCLC-B stage. Methods: In 213 patients who started treatment with sorafenib between 2009 and 2016, myopenia at baseline was determined by using skeletal muscle index calculated from CT images of the third lumber vertebra level. The impact of myopenia on survival was analyzed in whole patients, after stratification by BCLC stage, and after matching for backgrounds within BCLC-B patients. Results: The median survival in whole, BCLC-C, and –B was 13.7, 8.7 and 15.2 months, respectively. Myopenia was not a significant prognostic factor in whole patients and in BCLC-C stage. However, among BCLC-B patients (n = 104), survival was significantly better in patients with no myopenia (p = 0.05). Among them, 85 patients who continued sorafenib for more than 8 weeks were extracted and those with or without myopenia were matched for backgrounds by propensity score. Backgrounds including etiology, Child-Pugh score, BMI, AFP and PIVKA-Ⅱwas not different between myopenia (n = 30) and no myopenia group (n = 30) after matching. The overall survival at 6-, 12-, and 24-months was 96%, 74%, and 62% in no myopenia group which was significantly better compared to 89%, 64%, and 28% in myopenia group (p = 0.019). The hazard ratio was 2.12 (95% CI 1.11-4.03). Conclusions: Absence of myopenia predicts favorable outcome in sorafenib treated HCC patients within BCLC-B intermediate stage.

scholarly journals Spontaneous Renal Artery Dissection in a Patient with Neurofibromatosis Type I

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Nicolas W. Shammas ◽  
Majid Z. Chammas ◽  
Jon Robken ◽  
Edmund Coyne
Keyword(s):  
Renal Artery ◽  
Treatment Options ◽  
Diagnostic Testing ◽  
Neurofibromatosis Type ◽  
Artery Dissection ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Endovascular Stenting ◽  
History Of ◽  
Endovascular Approach

We present a case of spontaneous renal artery dissection (SRAD) in a 28-year-old female with history of neurofibromatosis type I (NF-1) treated successfully with endovascular stenting. The clinical presentation, diagnostic testing, and treatment options are discussed. An endovascular approach with stenting was successfully performed after failure of medical treatment with subcutaneous low molecular weight heparin. Patient’s blood pressure and symptoms improved significantly. This may be the first reported case of SRAD in a patient with NF-1 successfully treated with endovascular stenting.

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