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تاريخ الأتراك العثمانيين
عن \"جامعة حمد بن خليفة\" و\"دار الأهلية\"، صدرت النسخة العربية من كتاب \"تاريخ الأتراك العثمانيين\" للمؤرخ والمستشرق الإنكليزي إدوارد شيفرد كريسي بترجمة أحمد سالم سالم. ينقسم العمل إلى خمسة وعشرين فصلا، اعتمد على تلخيص وشرح موسوعة \"التاريخ العثماني للمؤرخ والدبلوماسي الألماني جوزيف فون هامر (1774-1856) مع إضافة أحداث عديدة وقعت حتى نهاية القرن التاسع عشر، يستند المؤلف في توثيقها بشكل أساسي إلى خلفيته في دراسة القانون، متناولا صياغة السياسات العامة للدولة العثمانية، خاصة في علاقاتها مع القوى الأوروبية.
BOOK
MAPK phosphatases — regulating the immune response
Key Points
Mitogen-activated protein kinases (MAPKs) are essential regulators of both the innate and the adaptive immune responses. MAPK activity is regulated by reversible phosphorylation at threonine and tyrosine residues.
MAPK phosphatases (MKPs) are dual-specificity protein phosphatases that deactivate MAPKs by simultaneously removing the phosphate groups from both the threonine and tyrosine residues on active MAPKs. MKPs serve as a feedback control mechanism of MAPK pathways. There are at least ten MKPs in mammalian cells. These phosphatases have substantial differences in their subcellular localization, expression and biochemical properties, including substrate specificity and catalytic activation.
MKPs have been shown to have an important role in innate immune responses by regulating the production of inflammatory and anti-inflammatory cytokines, innate immune cell viability, and the function of antigen-presenting cells (APCs).
MKPs can also regulate the adaptive immune responses through regulation of cytokine biosynthesis and cell proliferation.
Different members of the MKP family have distinct roles in the immune responses. They can either positively or negatively regulate immune responses.
A number of immunomodulatory agents, including glucocorticoids and anti-inflammatory and pro-inflammatory cytokines can modulate the expression of
MKP1
.
Regulation of the immune response is crucial for avoiding an excessive inflammatory response. Here, recent advances in our understanding of the regulation of mitogen-activated protein kinase (MAPK) phosphatases and their emergence as key regulators of both innate and adaptive immunity are discussed.
Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are protein phosphatases that dephosphorylate both the phosphothreonine and phosphotyrosine residues on activated MAPKs. Removal of the phosphates renders MAPKs inactive, effectively halting their cellular function. In recent years, evidence has emerged that, similar to MAPKs, MKPs are pivotal in the regulation of immune responses. By deactivating MAPKs, MKPs can modulate both innate and adaptive immunity. A number of immunomodulatory agents have been found to influence the expression of MKP1 in particular, highlighting the central role of this phosphatase in immune regulation. This Review discusses the properties, function and regulation of MKPs during immune responses.
Journal Article
Thoracic magnetic resonance imaging in non-tuberculous mycobacterial pulmonary disease: Characteristics and potential implementation
Non-tuberculous mycobacteria (NTM) are pulmonary pathogens with increasing incidence and prevalence worldwide, with people with cystic fibrosis (pwCF) traditionally considered at high risk of disease development. The imaging assessment of NTM-pulmonary disease (NTM-PD) relies heavily on high-resolution computed tomography (HRCT). However, due to lengthy treatment regimens and the need for long-term follow-up, serial HRCT's result in progressive exposure to ionizing radiation; a particular concern in younger people.
We performed a retrospective cohort study of patients who had undergone serial thoracic magnetic resonance imaging (tMRI) scans to monitor NTM-PD as a novel tool to image the lung with a view to creating an algorithm for the utility of tMRI in the management of NTM-PD.
Thirty-six patients, of which twenty-four had a diagnosis of CF, with suspected or confirmed NTM-PD underwent serial tMRI between 1st January 2013 and 30th June 2018. A total of 117 serial tMRI's were performed (mean number per patient 3.25; range 2-6). The associated clinical impact that each serial MRI had on management, deemed as the utility of tMRI, found that all tMRI's were classified as aiding management with 60 (51.3%) altering management. tMRI's were more likely to alter management in the non-CF cohort than the CF cohort (69.4% vs. 43.2%). No imaging-related adverse events were reported across the 117 tMRI's.
This study highlights that tMRI may hold promise as a monitoring tool in NTM-PD and should be prospectively evaluated in the monitoring of individuals with NTM-PD.
Journal Article
Blood cultures and predicting positivity in extremely preterm infants admitted to an outborn level IV NICU
Background
To determine if there were clinical factors that could identify patients with positive blood cultures in extremely preterm (EP) infants born at < 27 weeks gestation who underwent sepsis evaluation sometime after admission to a level IV NICU in an all referral children’s hospital.
Methods
An observational study using data from January 1, 2015 to December 31, 2020.
Results
Of the 530 EP infants admitted during the study, 345 EP infants (64%) had at least one blood culture drawn, of whom 64 (19%) had at least one positive blood culture. A total of 714 blood cultures were drawn at a median age of 41 days (IQR 15–87 days), of which 70 (9%) were positive. For the positive cultures, 47% grew gram positive bacteria, 44% grew gram negative bacteria, and 9% grew yeast. EP patients with positive blood cultures were more frequently on invasive mechanical ventilation and more often had a central line compared to EP patients with negative cultures. EP infants with positive blood cultures had greater mortality and surgical NEC than EP infants without positive cultures. Using logistic regression modeling, abnormal band counts (OR 1.03, 95% CI 1.003–1.06) and the initiation of vasopressors at the time of sepsis evaluation (OR 2.61, 95% CI 1.21–5.65) were the only clinical factors associated with a positive culture.
Conclusions
Most EP infants admitted to an all-referral Level IV NICU had a blood culture drawn. The rate of positive cultures was relatively low, although EP infants with positive blood cultures had higher rates of mortality and morbidities. Further work to develop biomarkers for the rapid identification of sepsis in EP infants is urgently needed.
Journal Article
Short-term complications and long-term morbidities associated with repeated unplanned extubations
ObjectiveTo describe characteristics associated with repeated unplanned extubations, short-term complications and outcomes, and longer-term morbidities including acquired subglottic stenosis.Study designCohort study including neonates admitted to a tertiary care neonatal intensive care unit who experienced an unplanned extubation in a 5-year period.ResultsWe reviewed 588 events involving 300 patients. Ten percent had airway trauma with reintubation, 42% required ≥2 reintubation attempts, and 39% led to increased baseline oxygen. Increased odds of repeated events were seen in patients with bronchopulmonary dysplasia and were associated with higher rates of tracheostomy and longer length of stay. The 9% of patients diagnosed with acquired subglottic stenosis had more unplanned extubations, higher rates of airway trauma and tracheitis, and were an older gestational age at birth.ConclusionUnplanned extubations lead to short- and long-term morbidities. Certain patient characteristics are associated with increased odds of repeated events and the development of acquired subglottic stenosis.
Journal Article
Development of a small baby unit to improve outcomes for the extremely premature infant
Survival and outcomes for extremely premature (EP) infants have improved and even infants born at 23 and 24 weeks that were previously considered non-viable are now routinely surviving. This review describes our particular institution’s basis for and process of creating and sustaining a small baby program for a quaternary, referral-based neonatal intensive care unit. Through multi-disciplinary collaboration, small baby guidelines were developed that established uniform care and optimized evidence-based practice for the care of this unique patient population. A focus on parent-centered care while removing noxious stimuli for the patient has improved neurodevelopmental outcomes. Data collection, quality improvement, and ongoing research are incorporated in the small baby program to establish and sustain best practices and outcomes for the EP patient. Through the establishment of a small baby unit, we have improved survival, decreased short-term morbidities, and improved neurodevelopmental outcomes for the EP infant in our region.
Journal Article
Outcomes following a comprehensive versus a selective approach for infants born at 22 weeks of gestation
ObjectiveTo examine outcomes at two institutions with different approaches to care among infants born at 22 weeks of gestation.Study designRetrospective, cohort study (2006–2015). Enrollment was limited to mother–infant dyads at 22 weeks of gestation. Proactive care was defined as provision of antenatal corticosteroids and neonatal resuscitation and intensive care. One center (Uppsala, Sweden; UUCH) provided proactive care to all mother–infant dyads (comprehensive center); the other center (Nationwide Children’s Hospital, USA; NCH) initiated or withheld treatment based on physician and family preferences (selective center). Differences in outcomes between the two centers were evaluated.ResultAmong 112 live-born infants at 22 weeks of gestation, those treated at UUCH had in-hospital survival rates higher than those at NCH (21/40, 53% vs. 6/72, 8%; P < 0.01). Among the subgroup of infants receiving proactive care (UUCH: 40/40, 100%; NCH: 16/72, 22%) survival was higher at UUCH than at NCH (21/40, 53% vs. 3/16, 19%; P < 0.05).ConclusionEven when mother–infant dyads were provided proactive care at NCH (selective center), survival was lower than infants provided proactive care at UUCH (comprehensive center). Differences between the approaches to care at the two centers at 22 weeks of gestation merits further investigation.
Journal Article
Established severe BPD: is there a way out? Change of ventilatory paradigms
Improved survival of extremely preterm newborn infants has increased the number of infants at risk for developing bronchopulmonary dysplasia (BPD). Despite efforts to prevent BPD, many of these infants still develop severe BPD (sBPD) and require long-term invasive mechanical ventilation. The focus of research and clinical management has been on the prevention of BPD, which has had only modest success. On the other hand, research on the management of the established sBPD patient has received minimal attention even though this condition poses large economic and health problems with extensive morbidities and late mortality. Patients with sBPD, however, have been shown to respond to treatments focused not only on ventilatory strategies but also on multidisciplinary approaches where neurodevelopmental support, growth promoting strategies, and aggressive treatment of pulmonary hypertension improve their long-term outcomes. In this review we will try to present a physiology-based ventilatory strategy for established sBPD, emphasizing a possible paradigm shift from acute efforts to wean infants at all costs to a more chronic approach of stabilizing the infant. This chronic approach, herein referred to as chronic phase ventilation, aims at allowing active patient engagement, reducing air trapping, and improving ventilation-perfusion matching, while providing sufficient support to optimize late outcomes.
Impact
Based on pathophysiological aspects of evolving and established severe BPD in premature infants, this review presents some lung mechanical properties of the most severe phenotype and proposes a chronic phase ventilatory strategy that aims at reducing air trapping, improving ventilation-perfusion matching and optimizing late outcomes.
Journal Article
Preterm Birth, Bronchopulmonary Dysplasia, and Long-Term Respiratory Disease
[...]given the strong association between maternal smoking and the outcomes presented here, and the well-documented racial disparities in both preterm birth and infant mortality in the United States, questions regarding the role of potential social determinants of health must be addressed in future studies. [...]we wish to highlight two critical insights from the article by Morrow and colleagues: first, that maternal smoking during pregnancy puts preterm infants at significant risk for developing BPD and/or late respiratory diseases; and second, that the current definitions of BPD are inadequate to predict longer-term respiratory disease in preterm infants (4). Given that there are currently no widely available and effective preventative therapies for BPD or late respiratory disease, data from studies like this one are critical for developing the insights needed to design precision methods to avoid abnormal lung development and its lifelong consequences in preterm infants.
Journal Article
Non-tuberculous mycobacterial infection in cystic fibrosis before and after initiation of elexacaftor/tezacaftor/ivacaftor: now is not the time to lower the guard
BackgroundThe prevalence of infection with non-tuberculous mycobacteria (NTM) has been increasing in people with cystic fibrosis (pwCF) over the past 30 years. Emerging reports of beneficial effects of CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), on the rates of NTM acquisition and persistence are encouraging. In this observational study, we evaluate the impact of the introduction of ETI on the prevalence of NTM infection within a cohort of pwCF living in sub-tropical Queensland, Australia.MethodsWe examined the impact of ETI introduction on rates of NTM isolation in pwCF attending an adult CF centre and two large regional clinics providing CF care. Data on NTM infection were collected for a minimum of 2 years pre- and post-initiation of ETI.ResultsIn total, 271 (84.2%) were commenced on ETI with 33 (12.2%) of these pwCF isolating an NTM species on one or more occasion. The number of pwCF isolating Mycobacterium abscessus (Mabs) remained static across the 4-year period of analysis. However, there was a trend towards declining numbers of pwCF isolating either Mycobacterium intracellulare or other NTM species across the surveillance period.ConclusionsETI therapy was not associated with reduced rates of NTM isolation from sputum over the first 2 years of treatment. However, at a species level, two distinct patterns of change were seen with a trend towards a reduction in the isolation of M. intracellulare, while the rates of Mabs isolation remained unchanged. The reasons for this remain unclear at present but highlight the need for ongoing vigilance with screening for NTM in the setting of ETI therapy.
Journal Article