-
The Pan African Medical Journal 2022Purulent pericarditis is an infection of the pericardial space that produces pus that is found on gross examination of the pericardial sac or on the tissue microscopy....
Purulent pericarditis is an infection of the pericardial space that produces pus that is found on gross examination of the pericardial sac or on the tissue microscopy. In this case report, we will discuss a 31-year-old male who presented with a chief complaint of low-grade fevers, dry cough and difficulty breathing for about two weeks which preceded after removing of dental also two weeks prior. He was admitted and treated as COVID-19 in the isolation ward, he later developed cardiac tamponade and during pericardiocentesis thick pus was discharged. Pus culture and Gene Xpert tests were all negative. After his condition improved, the patient was transferred to the general ward with the pericardial window still discharging pus. Pericardiectomy was chosen as definitive management. The key takeaway in this report is that Empirical treatment with RHZE (rifampin, isoniazid, pyrazinamide, and ethambutol) in resource-limited settings is recommended due to difficulty in identifying the exact cause at a required moment.
Topics: Adult; COVID-19; Ethambutol; Humans; Isoniazid; Male; Mediastinitis; Pericarditis; Pericardium; Pyrazinamide; Rifampin; Sclerosis; Suppuration
PubMed: 36160276
DOI: 10.11604/pamj.2022.42.145.34018 -
Cell Reports Methods Apr 2023Although the differentiation of human induced pluripotent stem cells (hiPSCs) into various types of blood cells has been well established, approaches for clinical-scale...
Although the differentiation of human induced pluripotent stem cells (hiPSCs) into various types of blood cells has been well established, approaches for clinical-scale production of multipotent hematopoietic progenitor cells (HPCs) remain challenging. We found that hiPSCs cocultured with stromal cells as spheroids (hematopoietic spheroids [Hp-spheroids]) can grow in a stirred bioreactor and develop into yolk sac-like organoids without the addition of exogenous factors. Hp-spheroid-induced organoids recapitulated a yolk sac-characteristic cellular complement and structures as well as the functional ability to generate HPCs with lympho-myeloid potential. Moreover, sequential hemato-vascular ontogenesis could also be observed during organoid formation. We demonstrated that organoid-induced HPCs can be differentiated into erythroid cells, macrophages, and T lymphocytes with current maturation protocols. Notably, the Hp-spheroid system can be performed in an autologous and xeno-free manner, thereby improving the feasibility of bulk production of hiPSC-derived HPCs in clinical, therapeutic contexts.
Topics: Humans; Induced Pluripotent Stem Cells; Yolk Sac; Hematopoietic Stem Cells; Organoids; Activities of Daily Living
PubMed: 37159663
DOI: 10.1016/j.crmeth.2023.100460 -
Lancet (London, England) Sep 2020The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.
METHODS
MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/mvs ≥35 kg/m), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.
FINDINGS
Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.
INTERPRETATION
Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.
FUNDING
UK National Institute for Health Research Health Technology Assessment Programme.
Topics: Abortion, Missed; Adult; Double-Blind Method; Drug Therapy, Combination; Humans; Mifepristone; Misoprostol; Oxytocics; Treatment Outcome
PubMed: 32853559
DOI: 10.1016/S0140-6736(20)31788-8 -
Stem Cell Research & Therapy Sep 2022Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental... (Review)
Review
Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental follicle progenitor cells (DFPCs), which are stem cells found in dental follicles, differentiate into different kinds of cells that are necessary for tooth formation and eruption. Runt-related transcription factor 2 (Runx2) is a transcription factor that is essential for osteoblasts and osteoclasts differentiation, as well as bone remodeling. Mutation of Runx2 causing cleidocranial dysplasia negatively affects osteogenesis and the osteoclastic ability of dental follicles, resulting in tooth eruption difficulties. Among a variety of cells and molecules, Nel-like molecule type 1 (Nell-1) plays an important role in neural crest-derived tissues and is strongly expressed in dental follicles. Nell-1 was originally identified in pathologically fused and fusing sutures of patients with unilateral coronal synostosis, and it plays indispensable roles in bone remodeling, including roles in osteoblast differentiation, bone formation and regeneration, craniofacial skeleton development, and the differentiation of many kinds of stem cells. Runx2 was proven to directly target the Nell-1 gene and regulate its expression. These studies suggested that Runx2/Nell-1 axis may play an important role in the process of tooth eruption by affecting DFPCs. Studies on short and long regulatory noncoding RNAs have revealed the complexity of RNA-mediated regulation of gene expression at the posttranscriptional level. This ceRNA network participates in the regulation of Runx2 and Nell-1 gene expression in a complex way. However, non-study indicated the potential connection between Runx2 and Nell-1, and further researches are still needed.
Topics: Bone Remodeling; Calcium-Binding Proteins; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dental Sac; Humans; Osteogenesis; RNA; Stem Cells; Tooth Eruption; Transcription Factors
PubMed: 36175952
DOI: 10.1186/s13287-022-03140-3 -
Health Technology Assessment... Jun 2020Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage.
OBJECTIVES
(1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding.
DESIGN
A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding.
SETTING
A total of 48 hospitals in the UK.
PARTICIPANTS
Women aged 16-39 years with early pregnancy bleeding.
INTERVENTIONS
Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation.
MAIN OUTCOME MEASURES
The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective.
RESULTS
A total of 4153 women from 48 hospitals in the UK received either progesterone ( = 2079) or placebo ( = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; = 0.08). A significant subgroup effect (interaction test = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; = 0.004). A significant post hoc subgroup effect (interaction test = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation.
CONCLUSIONS
Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.
Topics: Abortion, Spontaneous; Adolescent; Adult; Cost-Benefit Analysis; Double-Blind Method; Female; Humans; Parturition; Pregnancy; Pregnancy Trimester, First; Progesterone; Suppositories; United Kingdom; Uterine Hemorrhage; Young Adult
PubMed: 32609084
DOI: 10.3310/hta24330 -
Nutrients Jan 2023Studies have suggested an important role of dyslipidemia, a condition with alterations in blood lipid levels, in promoting an additional effect on periodontal breakdown....
Studies have suggested an important role of dyslipidemia, a condition with alterations in blood lipid levels, in promoting an additional effect on periodontal breakdown. Thus, this study aimed to explore the theoretical pathways associated with dyslipidemia and periodontitis. We used data from 11,917 US adults with complete periodontal examinations participating in the Third National Health and Nutrition Examination Survey (NHANES III). Our hypothesis was tested using structural equation modelling (SEM). Dyslipidemia was defined according to the National Cholesterol Education Program (NCEP-ATP III) and periodontitis as a latent variable reflecting the shared variance of the number of surfaces with periodontal pocket depth [PPD] = 4 mm, PPD = 5 mm, PPD ≥ 6 mm, clinical attachment level [CAL] = 4 mm, CAL = 5mm, CAL ≥ 6 mm, and furcation involvement. The model also considered distal determinants (age, sex, and socioeconomic status) and proximal determinants (HbA1c, smoking and alcohol consumption, and obesity). The model showed sufficient global fit (Root Mean Squared Error of Approximation = 0.04, 90%CI = 0.04−0.05, Tucker−Lewis Index = 0.93, Comparative Fit Index = 0.95). Age, sex, socioeconomic status, obesity, and smoking were directly associated with periodontitis (p < 0.01). Dyslipidemia revealed a significant direct effect on periodontitis (standardized coefficient [SC] = 0.086, SE 0.027; p < 0.01), also mediated via an indirect pathway through HbA1c (SC = 0.021; SE 0.010; p = 0.02) and obesity (SC = 0.036; SE 0.012; p < 0.01) and resulted in a total effect on periodontitis. Dyslipidemia was associated with periodontitis through a direct pathway and indirectly through HbA1c and obesity in the US population. These results support the need for a multi-professional approach to tackling oral and noncommunicable diseases (NCDs), directed at their common risk factors.
Topics: Adult; Humans; Nutrition Surveys; Glycated Hemoglobin; Periodontitis; Dyslipidemias; Obesity
PubMed: 36678171
DOI: 10.3390/nu15020300 -
Journal of Visualized Experiments : JoVE Mar 2021The study of mutant mouse models of human hearing and balance disorders has unraveled many structural and functional changes which may contribute to the human...
The study of mutant mouse models of human hearing and balance disorders has unraveled many structural and functional changes which may contribute to the human phenotypes. Although important progress has been done in the understanding of the development and function of the neurosensory epithelia of the cochlea and vestibula, limited knowledge is available regarding the development, cellular composition, molecular pathways and functional characteristics of the endolymphatic sac. This is, in large part, due to the difficulty of visualizing and microdissecting this tissue, which is an epithelium comprised of only one cell layer. The study presented here describes an approach to access and microdissect the endolymphatic sac from the wild-type mouse inner ear at different ages. The result of a similar dissection is shown in a pendrin-deficient mouse model of enlargement of the vestibular aqueduct. A transgenic mouse with a fluorescent endolymphatic sac is presented. This reporter mouse can be used to readily visualize the endolymphatic sac with limited dissection and determine its size. It can also be used as an educational tool to teach how to dissect the endolymphatic sac. These dissection procedures should facilitate further characterization of this understudied part of the inner ear.
Topics: Animals; Disease Models, Animal; Endolymphatic Sac; Humans; Mice
PubMed: 33843930
DOI: 10.3791/62375 -
Journal of Clinical Medicine Jul 2021The eruption pathway from the dental follicle to the gingiva for permanent teeth is known as the gubernaculum tract (GT), a physiologic structure thought to play a role... (Review)
Review
The eruption pathway from the dental follicle to the gingiva for permanent teeth is known as the gubernaculum tract (GT), a physiologic structure thought to play a role in tooth eruption. Cone beam computed tomography and multi-detector computed tomography have recently been used to visualize the GT, with the results indicating that this structure might be related to the normal eruption of teeth. By contrast, curved and/or constricted GTs may lead to abnormal tooth eruption. In addition, complex odontomas have been reported from within the GT or dental sac of unerupted permanent teeth. If an odontoma occurs within the GT, the tooth will not erupt normally. Moreover, the imaging characteristics of the GT from the top of the odontogenic mass to the alveolar crest are extremely useful for making a differential pathological diagnosis and for differentiating between odontogenic and non-odontogenic masses. Therefore, radiological studies on the GT have been attracting increasing attention. Given this background, the present review aims to clarify the imaging characteristics and review recent studies on the GT considering the importance of the research.
PubMed: 34300216
DOI: 10.3390/jcm10143051 -
International Journal of Molecular... May 2022Human dental follicle cells (DFCs) as periodontal progenitor cells are used for studies and research in regenerative medicine and not only in dentistry. Even if... (Review)
Review
Human dental follicle cells (DFCs) as periodontal progenitor cells are used for studies and research in regenerative medicine and not only in dentistry. Even if innovative regenerative therapies in medicine are often considered the main research area for dental stem cells, these cells are also very useful in basic research and here, for example, for the elucidation of molecular processes in the differentiation into mineralizing cells. This article summarizes the molecular mechanisms driving osteogenic differentiation of DFCs. The positive feedback loop of bone morphogenetic protein (BMP) 2 and homeobox protein DLX3 and a signaling pathway associated with protein kinase B (AKT) and protein kinase C (PKC) are presented and further insights related to other signaling pathways such as the WNT signaling pathway are explained. Subsequently, some works are presented that have investigated epigenetic modifications and non-coding ncRNAs and their connection with the osteogenic differentiation of DFCs. In addition, studies are presented that have shown the influence of extracellular matrix molecules or fundamental biological processes such as cellular senescence on osteogenic differentiation. The putative role of factors associated with inflammatory processes, such as interleukin 8, in osteogenic differentiation is also briefly discussed. This article summarizes the most important insights into the mechanisms of osteogenic differentiation in DFCs and is intended to be a small help in the direction of new research projects in this area.
Topics: Cell Differentiation; Cells, Cultured; Dental Sac; Homeodomain Proteins; Humans; Osteogenesis; Wnt Signaling Pathway
PubMed: 35682637
DOI: 10.3390/ijms23115945