Epigenetic and transcriptional regulation of cytokine production by Plasmodium falciparum-exposed monocytes.

Plasmodium falciparum infection causes the most severe form of malaria, where excessive production of proinflammatory cytokines can drive the pathogenesis of the disease. Monocytes play key roles in host defense against malaria through cytokine production and phagocytosis; however, they are also implicated in pathogenesis through excessive proinflammatory cytokine production. Understanding the underlying molecular mechanisms that contribute to inflammatory cytokine production in P. falciparum-exposed monocytes is key towards developing better treatments. Here, we provide molecular evidence that histone 3 lysine 4 (H3K4) methylation is key for inflammatory cytokine production in P. falciparum-exposed monocytes. In an established in vitro system that mimics blood stage infection, elevated proinflammatory TNF and IL-6 cytokine production is correlated with increased mono- and tri-methylated H3K4 levels. Significantly, we demonstrate through utilizing a pharmacological inhibitor of H3K4 methylation that TNF and IL-6 expression can be suppressed in P. falciparum-exposed monocytes. This elucidated epigenetic regulatory mechanism, controlling inflammatory cytokine production, potentially provides new therapeutic options for future malaria treatment.

Chest wall deformities and their possible associations with different genetic syndromes.

OBJECTIVE: Our primary objective was to identify discrete and syndromic cases of Pectus excavatum (PE) and Pectus carinatum (PC). We also intended to highlight the significance of further genetic exploration in clinically suspected syndromic cases of PC and PE. Pectus excavatum (PE) and Pectus carinatum (PC) are the most common morphological chest wall deformities. Although various hypotheses have been put forth, the pathogenesis of both entities is largely unknown. Clinicians often refer such cases for further genetic evaluation to exclude an associated underlying connective tissue disorder or a syndrome. Additionally, a detailed anamnesis with focused family history and thorough dysmorphological physical examination was done. PE and PC are considered isolated abnormalities if there is the absence of features of other syndromes, eliminating the need for further genetic evaluations. It is believed that the pattern of inheritance of these non-syndromic isolated PE and PC cases with positive family history could be multifactorial in nature. The recurrence risk of such isolated cases is thought to be low. Further diagnostic studies are indicated as PE and PC could be a part of a syndrome. Among the many syndromes, the most common monogenic syndromes associated with PE and PC are Marfan's and Noonan's. PATIENTS AND METHODS: After obtaining the consent, we compiled a database of the patients who presented with chest wall deformities during the period 2017-2019. We selected 70 cases with PC and PE deformities to identify the discrete and syndromic PC and PE cases. During the study, we perused the cytogenetic and/or molecular analyses, that had been conducted to confirm the clinically suspected syndromic cases. We also scrutinized for the presence of PC and PE cases that are associated with the rare syndrome (s). RESULTS: Various genetic abnormalities were identified in 28 (40%) of the 70 cases that had been diagnosed with chest wall abnormalities. Along with PE and PC, other thoracic wall abnormalities were also identified, such as the broad chest, bell-shaped thorax, and elongated or enlarged thorax. One case of a rare genetic disorder of Morquio syndrome associated with PC was also identified. Novel (previously unpublished) genomic variants are reported here. CONCLUSIONS: It is important to delve deeper when encountering cases of PE and PC by conducting a further genetic exploration of such cases to identify syndromic associations that cause other structural and functional disorders, diagnosis of which might be missed during the early developmental period. Early identification of such disorders may help us correcting the defects, slowing the progression of disease processes, and preparing better to deal with the potential outcome.

2D speckle tracking: a diagnostic and prognostic tool of paramount importance.

OBJECTIVE: We aimed to conduct a review of the literature relevant to cardiac imaging techniques and summarize the use of different non-invasive imaging modalities in the assessment of ventricular size, function, and mechanics. The current review emphasizes the benefits of speckle tracking imaging (STI), highlighting its use in demonstrating myocardial strain. This robust technique is a recent addition to the existing imaging techniques that are used to assess the myocardium. In terms of effectively determining the left ventricle ejection fraction, it is a comparable technique to cardiac magnetic resonance. The use of STI method for image acquisition relies on semiautomatic identification of the border and deformation of the region of interest, and is also independent of the angle of insonation, thus it increases the inter-and intra-observer reproducibility in contrast to the conventional tissue doppler imaging. MATERIALS AND METHODS: The databases of PubMed, Scopus, and Embase were thoroughly searched for the following keywords: 2- dimensional/ two-dimensional/ 2-D, speckle/strain tracking, systolic dysfunction, and heart failure. The studies selected described image acquisition techniques and the application of this imaging modality in various clinical settings. The selected journal articles were perused to provide the best possible analysis of STI. RESULTS: Our comparative analysis demonstrated that the STI, when compared with the conventional echocardiography, is a more sensitive image acquiring technique for detecting subclinical myocardial dysfunction. Based on the analysis it can be stated that the STI can provide valuable information on both regional and global myocardial function, and it can also quantify cardiac synchronicity and rotation. Additionally, it serves as a better prognostic indicator. CONCLUSIONS: The change in longitudinal strain can serve as an early marker of the left ventricular systolic dysfunction, and therefore, monitoring via STI has both diagnostic and prognostic value in heart failure, ischemic heart disease, valvulopathies, chemotherapy-induced cardiotoxicity, and cardiac resynchronization therapy. Despite the lack of standardization, the method is also effective in assessing the right ventricle and left atrial function and arterial rigidity.

Antley-Bixler syndrome: surgical management of ambiguous genitalia - a case report.

OBJECTIVE: To report a case of type 2 Antley-Bixler syndrome (ABS). SUBJECT AND METHODS: A 3-year-old boy who had been raised male, with facial dimorphism and malformations of both elbows and forearms, was referred to our unit for ambiguous genitalia. Genetic testing confirmed the diagnosis of ABS. A surgical intervention was performed to correct the ambiguous genitalia through a combined perineal and transabdominal approach. RESULTS: The postoperative course was uneventful and the patient was released from the hospital 10 days after the surgery. CONCLUSION: Repair of the ambiguous genitalia in this patient was possible, but definitive inferences on the benefit of this intervention cannot be made without long-term follow-up.

An effective method to release anastomotic tension after repair of esophageal atresia using a Foley catheter.

Esophageal atresia (EA) is the most common malformation of the esophagus. Primary anastomosis is achievable in more than 90% of the cases and the milestone of the surgical intervention is achieving a watertight, low-tension anastomosis of the esophageal pouches. The purpose of this paper is to present a new method for releasing tension in the anastomosis and also to provide a safe way for enteral feeding in children with primarily repaired EA. From 2000 to 2012 twenty-one patients underwent primary esophageal anastomosis for EA in our department. During the surgical intervention, a 12-french Foley catheter is inserted through one of the nostrils, through the esophagus down to the site of the anastomosis and passed by into the stomach. After surgery, continuous gentile traction is maintained on the catheter for several days. We had no postoperative disruption of the anastomosis and anastomotic leaks occurred in 1 of the 21 cases. Overall survival rate was 67%. Using the Foley catheter to protect the anastomosis and to release the tension of the sutures provides a cheap and effective means to improve the outcomes of the treatment of EA.

Morphologic, morphometrical and histochemical proprieties of the costal cartilage in children with pectus excavatum.

Pectus excavatum (PE) is the most frequent anterior chest deformity occurring in approximately one of 1000 live births. Despite the excellent achievements in the treatment of the disease, the etiology of PE is yet to be clarified. It is believed that the cause for PE is an intrinsic costal cartilage abnormality leading to an overgrowth of the cartilage, which pushes the sternum backward. Several histological studies revealed contradictory results and failed to identify a clear structural abnormality of the costal cartilage responsible for the apparition of PE. In this article, we focused on identifying the microscopic disturbances of the costal cartilage in patients with PE. We obtained cartilage samples from 29 children with PE and 18 control cartilage samples. The samples were subjected to morphologic, morphometrical and histochemical assess. The results indicate a young, immature pattern of the cartilage matrix with a normal cell/matrix ratio. These results sustain the theory that the cause of PE is to be found inside the costal cartilage and the most plausible cause is a global overgrowth of the costal cartilage.

Preliminary results after Nuss procedure.

INTRODUCTION: Pectus excavatum (PE) is the most frequent anterior chest deformity and occurs in approximately 1 in 1000 live births. In 1998 Donald Nuss introduced a new minimal invasive operative technique for PE which avoids any cartilage resection or sternum osteotomy. PURPOSE: The purpose of this study is to assess the short and medium time results after minimal invasive correction of pectus excavatum and to present our improvements to the original Nuss technique. MATERIAL AND METHODS: During a two years period seven PE patients were treated by us using Nuss technique. The intervention represents a premiere because it was the first Nuss operation performed by a team composed exclusively by Romanian surgeons. We present you the seven cases, our operative technique and the short and medium term outcomes. MAIN RESULTS: No itraoperative incidences were recorded. Postoperative course was good for all patients. Complication occurred in three cases: two pleural effusions and a wound dehiscence. They have been all successfully resolved with no further events. Overall the therapeutic and cosmetic results were considered good by patients and their parents. CONCLUSION: Preliminary results indicate that Nuss operation for PE correction is a safe surgical technique with excellent cosmetic outcomes. More cases and long time results are necessary to fully evaluate this technique.