Parent pain and catastrophizing are associated with pain, somatic symptoms, and pain-related disability among early adolescents

To examine associations between parental history of pain and catastrophizing and their adolescent's pain, somatic symptoms, catastrophizing, and disability. Participants included 178 youths aged 11-14 years recruited through public schools. Adolescents completed measures assessing pain characteristics, somatic symptoms, and pain catastrophizing. Parents reported on their own pain, and catastrophizing about their adolescent's pain. About one quarter of the adolescents and two thirds of parents reported having pain. Parent pain was associated with adolescent pain, somatic symptoms, and pain catastrophizing. Parent catastrophizing was a significant predictor of adolescent somatic symptoms and pain-related disability, beyond the contribution of parent pain. Adolescent catastrophizing mediated the association between parent catastrophizing and adolescent pain-related disability. Parent history of pain and pain-related cognitions may contribute to adolescent risk for chronic pain

Functional analysis of a novel mutation in the TIMM8A gene that causes deafness‐dystonia‐optic neuronopathy syndrome

Abstract Background The rare, X‐linked neurodegenerative disorder, Mohr–Tranebjaerg syndrome (also called deafness‐dystonia‐optic neuronopathy [DDON] syndrome), is caused by mutations in the TIMM8A gene. DDON syndrome is characterized by dystonia, early‐onset deafness, and various other neurological manifestations. The TIMM8A gene product localizes to the intermembrane space in mitochondria where it functions in the import of nuclear‐encoded proteins into the mitochondrial inner membrane. Frameshifts or premature stops represent the majority of mutations in TIMM8A that cause DDON syndrome. However, missense mutations have also been reported that result in loss of the TIMM8A gene product. Methods We report a novel TIMM8A variant in a patient with DDON syndrome that alters the initiation codon and employed functional analyses to determine the significance of the variant and its impact on mitochondrial morphology. Results The novel base change in the TIMM8A gene (c.1A>T, p.Met1Leu) results in no detectable protein and a reduction in TIMM8A transcript abundance. We observed a commensurate decrease in the steady‐state level of the Tim13 protein (the binding partner of Tim8a) but no decrease in TIMM13 transcripts. Patient fibroblasts exhibited elongation and/or increased fusion of mitochondria, consistent with prior reports. Conclusion This case expands the spectrum of mutations that cause DDON syndrome and demonstrates effects on mitochondrial morphology that are consistent with prior reports

Psychosocial and Financial Burden of Therapy in USA Patients with Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a devastating disease with significant morbidity and mortality. There are many psychosocial and financial implications of this disease; however, little is known how this affects the treatment of PAH patients. A questionnaire-based prospective cohort study was performed on 106 PAH patients from a Pulmonary Hypertension Center and the Pulmonary Hypertension Association national conference in 2018. The demographic, treatment, psychosocial, employment, financial impact on treatment data was obtained. The majority of patients had cardiopulmonary symptoms despite treatment. The symptoms affected their social and work lives, with about one in three applying for disability because of their PAH. The majority of PAH patients had insurance coverage, but still noted a significant financial burden of the disease, with nearly a half who needed financial assistance to pay for their PAH medications. Thirty (28.3%; 95% CI, 20.6–37.5%) patients mentioned they changed their medication regimen, with some skipping doses outright (28 [26.4%; 95% CI, 19–35.6%]) in order to save money. PAH continues to cause significant psychosocial and financial burden on patients despite advances in medications. This impact ranged from dissatisfaction with quality of life, to unemployment, to altering their medication regimen to save money

Comparing Diagnosis and Treatment of Pulmonary Hypertension Patients at a Pulmonary Hypertension Center versus Community Centers

Once patients are diagnosed with pulmonary hypertension it is important to identify the correct diagnostic group as it will have implications on the disease state management. Pulmonary hypertension is increasingly diagnosed and treated in general medical practices; however, evidence-based guidelines recommend evaluation and treatment in pulmonary hypertension centers for accurate diagnosis and appropriate treatment recommendations. We conducted a retrospective cohort study of 509 random patients 18 years and older who were evaluated in our pulmonary hypertension clinic from January 2005 to December 2018. 68.4% (n = 348) had their diagnostic group clarified or changed. Pulmonary hypertension was deemed an incorrect diagnosis in 12.4% (n = 63). A total of 114 patients (22.4%) had been initiated on pulmonary hypertension specific treatment prior to presentation. Pulmonary hypertension specific medication was stopped in 57 (50.0%) cases. The estimated monthly saving of the stopped medication based on wholesale acquisition costs was USD 396,988.05–419,641.05, a monthly saving of USD 6964.70–7362.12 per patient. Evaluation outside of a pulmonary hypertension center may lead to misdiagnosis and inappropriate or inadequate treatment. Pulmonary arterial hypertension directed therapy improves median survival, but inappropriate therapy may cause harm; therefore, patients benefit from a specialized center with multiple resources to secure an accurate diagnosis and tailored treatment for their condition

De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity

Lamin B1 plays an important role in the nuclear envelope stability, the regulation of gene expression, and neural development. Duplication of LMNB1, or missense mutations increasing LMNB1 expression, are associated with autosomal-dominant leukodystrophy. On the basis of its role in neurogenesis, it has been postulated that LMNB1 variants could cause microcephaly. Here, we confirm this hypothesis with the identification of de novo mutations in LMNB1 in seven individuals with pronounced primary microcephaly (ranging from -3.6 to -12 SD) associated with relative short stature and variable degree of intellectual disability and neurological features as the core symptoms. Simplified gyral pattern of the cortex and abnormal corpus callosum were noted on MRI of three individuals, and these individuals also presented with a more severe phenotype. Functional analysis of the three missense mutations showed impaired formation of the LMNB1 nuclear lamina. The two variants located within the head group of LMNB1 result in a decrease in the nuclear localization of the protein and an increase in misshapen nuclei. We further demonstrate that another mutation, located in the coil region, leads to increased frequency of condensed nuclei and lower steady-state levels of lamin B1 in proband lymphoblasts. Our findings collectively indicate that de novo mutations in LMNB1 result in a dominant and damaging effect on nuclear envelope formation that correlates with microcephaly in humans. This adds LMNB1 to the growing list of genes implicated in severe autosomal-dominant microcephaly and broadens the phenotypic spectrum of the laminopathies.status: publishe

PREDICTIONS AND METHODS OF SEPARATION OF RACEMIC BIDENTATE LIGANDS VIA STEREOSELECTIVE LIGAND-EXCHANGE REACTIONS

The technique of molecular mechanics has been applied to the prediction of isomer distributions of several complexes of chiral quadridentate amine ligands in conjunction with some optically active bidentate substrates. Specifically, the systems reported comprise the cobalt(III) and nickel(II) complexes of N,N'-bis[2(S)-2-pyrrolidinylmethyl]ethane-1,2-diamine (S,S-epm) and N,N'-bis[2(S)-2-pyrrolidinylmethyl]propane-1,3-diamine (S,S-ppm) in combination with the chiral bidentate ligands propane-1,2-diamine, (pn) 2-pyrrolidinylmethanamine (pam), and alanine (ala). Agreement between all predicted and observed isomer ratios was within 5%. The experimentally determined enantiomer ratios were as follows: [Co(S,S-ppm)(pn)]3+, 49/51 R-pn/S-pn; [Ni(S,S-ppm)(pn)]2+, 57/43 R-pn/S-pn; [Ni(S,S-ppm)(pam)]2+, 44/56 R-pam/S-pam; [Ni(S,S-epm)(pn)]2+, 43/57 R-pn/S-pn; [Ni(S,S-epm)(pam)]2+, 70/30 R-pam/S-pam. Various experimental methods are reported for the determination of chiral separation