“Making Room”: A Thematic Analysis Study of the Process of Postpartum Maternal Adjustment

Maternal and Child Health Journal - Mothers are especially vulnerable to the onset or recurrence of psychological symptoms during the postpartum period. However, protective psychosocial factors may...     

Use of VA ECMO and percutaneous palliation of ductal dependent coarctation in a neonate with trisomy 21 and COVID-19 pneumonia

We present a case of a neonate with trisomy 21, ductal-dependent aortic coarctation, and severe respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia. The neonate was managed with venoarterial extracorporeal membrane oxygenation (VA ECMO), palliative stenting of the coarctation, and a vascular plug occlusion of a large patent ductus arteriosus. The patient was successfully weaned off extracorporeal membrane oxygenation (ECMO). The patient is currently awaiting a definitive surgical repair in the near future.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1

Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by the innate immune system. For LP, it has been shown that TLR2 is the essential receptor in cellular activation. However, molecular mechanisms of LP recognition are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (Pam(3)CSK(4)) to study the roles of CD14, TLR2 and TLR1 in binding and signaling of LP and their molecular interactions in human cells. The activity of Pam(3)CSK(4)-FLAG was TLR2 dependent, whereas the binding was enabled by CD14, as evaluated by flow cytometry and confocal microscopy. Using FRET and FRAP imaging techniques to study molecular associations, we could show that after Pam(3)CSK(4)-FLAG binding, CD14 and Pam(3)CSK(4)-FLAG associate with TLR2 and TLR1, and TLR2 is targeted to a low-mobility complex. Thus, LP binding to CD14 is the first step in the LP recognition, inducing physical proximity of CD14 and LP with TLR2/TLR1 and formation of the TLR2 signaling complex.     

Multiple sclerosis

Poster Session 3

Multiple sclerosis     

Physical activity and incident hypertension in black and white adults: the Atherosclerosis Risk in Communities Study

BACKGROUND: The epidemiologic observation that physical activity reduces the risk for hypertension has only been made for white men who self-reported hypertension. This study examined physical activity and clinically determined incident hypertension in black and white men and women of the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: ARIC is a population-based prospective study with four U.S. clinic centers. The present analyses included 7,459 black and white adults 45-65 years of age. Hypertension (systolic/diastolic blood pressure >/= 140/90 mm Hg) was defined by blood pressure measured by a random-zero device or medication use. Physical activity was assessed with the Baecke questionnaire. RESULTS: After adjustment for age, baseline blood pressure, ARIC center, education, body mass index, waist-hip ratio, parental history of hypertension, cigarette smoking, alcohol consumption, and diet, white men in the highest quartile of leisure activity (primarily cycling and walking) had a 34% lower odds of developing hypertension over 6 years compared to the least active (OR = 0.66, 95% CI = 0.47-0.94; P for quartile trend = 0.01). Baseline activity was not associated with incident hypertension in white women or blacks. CONCLUSIONS: Leisure-time physical activity reduces the odds of hypertension in middle-aged white men. Additional studies in women and blacks are needed.     

Identification of high and low responders to allografts

The immune response to an allograft varies from one individual to another. This individual variation is, at least in part, due to genetic variation in the regulation of cytokine gene expression. High and low cytokine responses in vitro for tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta1) and other cytokines can be predicted from an individual's cytokine genotype. Using the same genetic markers we have been able to show associations, in particular between TNF-alpha genotype of the recipient and acute allograft rejection and, similarly, between TGF-beta1 genotype and chronic rejection. The ability to identify high and low responders to allografts by a simple genetic test, and to predict who will suffer acute and chronic rejection, has implications for donor selection and recipient treatment as well as for the design and interpretation of clinical trials of new immunosuppressive agents.     

Prevalence and anatomic characteristics of infarct-like lesions on MR images of middle-aged adults: the atherosclerosis risk in communities study.

BACKGROUND AND PURPOSE: MR imaging has revealed putative evidence of subclinical cerebrovascular disease (CVD) as reflected by white matter signal changes and infarct-like lesions (ILLs). Nonetheless, the prevalence of this condition in the general population has been defined only to a limited extent. We herein report the prevalence and anatomic characteristics of ILLs seen on cranial MR images obtained as part of a population-based study of cardiovascular disease in middle-aged adults. These results are contrasted to those of previous similar studies, particularly those of an elderly population in the Cardiovascular Health Study (CHS). METHODS: This Atherosclerosis Risk in Communities (ARIC) cohort consists of a probability sample of community-living persons who were 55 to 72 years old at the time of MR examination. MR imaging of 1890 participants was performed at two ARIC field centers, based on a common protocol. MR studies were evaluated by trained readers at the MR Reading Center using original digital data displayed on a high-resolution workstation. The measures of lesion size, anatomic location, and signal intensity were collected. The definition for an ILL was a non-mass, hyperintense region with an arterial vascular distribution on spin-density and T2-weighted images. RESULTS: Two hundred ninety participants had ILLs, for an overall prevalence of 15.3%. Eighty-two percent of participants with ILLs had lesions that were 3 mm or larger in maximal dimension, although 87% of these lesions were 20 mm or smaller in maximal dimension. The prevalence of ILLs increased with age, from 7.9% in the 55- to 59-year-old age group to 22.9% in the 65- to 72-year-old age group (P < .001). Lesion prevalence was greater in black (20.7%) than in white persons (10.2% [P < .0001]), but did not differ significantly between male and female participants. The basal ganglia and thalamic region was the most commonly affected anatomic site, accounting for 78.9% of the lesions. CONCLUSION: Considering that the prevalence of self-reported stroke or transient ischemic attack in ARIC participants is 1.5%, these results suggest that there is significantly more subclinical than clinical CVD in the general population. Furthermore, the prevalence of this subclinical disease increases with age, and is greater in black persons. ILLs are dominated by "lacunae" in the basal ganglia and thalamus. These results are, in general, similar to those of a comparable study of elderly participants in the CHS, except for a 60% lower prevalence of ILLs in this younger population.     

Interleukin-10 (IL10) promoter polymorphisms and multiple sclerosis

Interleukin-10 (IL10) is an anti-inflammatory cytokine which may modulate disease expression in multiple sclerosis (MS). Three dimorphic polymorphisms within the IL10 promoter region at positions - 1082, -819 and -519 have previously been identified. The - 1082*A allele has been associated with low and the - 1082*G allele with high in vitro IL10 production. We have genotyped 185 Caucasian MS patients and 211 ethnically matched controls for each of these three dimorphisms. MS patients were stratified for severity of disease outcome. No associations were found for any IL10 promoter polymorphisms when the MS cases were compared with controls or with disease outcome with regards to disability. IL10 polymorphism does not appear to be associated with MS or to influence disease progression.