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Acalvaria is a rare congenital malformation of unknown etiopathogenesis that affects the development of the skull and surrounding muscular structures. There is scant literature regarding the pathophysiology, and no standardized guidelines exist for patient management. Herein, we present a case of acalvaria in a newborn and our multidisciplinary approach from diagnosis to 1 year of age. [ABSTRACT FROM AUTHOR]

Before 2000, children PCV7 was the first pneumococcal conjugate vaccine (PCV) approved for use in children 80% of IPD cases among children in North America (i.e., serotypes 4, 6B, 9V, [...]

Objective To determine the frequency of self-reported occupational exposure to silica in SSc patients enrolled in the Australian Scleroderma Cohort Study, and to compare the disease characteristics of the silica-exposed patients with those of the non-exposed patients. Method Data collected over a 12-year period from 1670 SSc patients were analysed. We compared the demographic and clinical characteristics of those who reported occupational silica exposure with those who did not. A subgroup analysis of male patients was performed, as well as a multivariable analysis of correlates of silica exposure. Results Overall, 126 (7.5%) of the cohort reported occupational silica exposure. These individuals were more likely to be male (73 of 231, i.e. 31.6% males exposed) and to have worked in mining and construction industries. Those who reported silica exposure were younger at the onset of SSc skin involvement [odds ratio (OR) 0.9, P  = 0.02], of male gender (OR 14.9, P  < 0.001), have joint contractures (OR 1.8, P  = 0.05) and have higher physical disability as defined by scleroderma HAQ (OR 1.4, P  = 0.01). Conclusion The highest percentage of silica exposure was found in males. These patients were more likely to have the presence of certain clinical manifestations and Scl-70 antibody, which is known to confer a poor prognosis. These findings support the association between occupational silica exposure and the subsequent development of SSc. Further investigation is required to describe the range of clinical manifestations and disease course, including prognosis and treatment response, in those diagnosed with occupationally induced SSc compared with idiopathic SSc. [ABSTRACT FROM AUTHOR]

Objective To quantify the burden of interstitial lung disease (ILD) in SSc. Methods Clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with healthcare databases for the period 2008–2015. ILD was defined by characteristic fibrotic changes on high-resolution CT (HRCT) lung, while severity was defined by the extent lung involvement on HRCT (mild <10%, moderate 10–30%, severe >30%). Determinants of healthcare cost were estimated using logistic regression. Results SSc-ILD patients utilized more healthcare resources, including hospitalization, emergency department presentation and ambulatory care services, than those without ILD with a total cost per patient of AUD$48 368 (26 230–93 615) vs AUD$33 657 (15 144–66 905), P <0.001) between 2008–2015. Healthcare utilization was associated with an annual median (25th–75th) excess cost per SSc-ILD patient compared with those without ILD of AUD$1192 (807–1212), P <0.001. Increasing ILD severity was associated with significantly more healthcare utilization and costs with an annual excess cost per patient with severe ILD compared with mild ILD of AUD$2321 (645–1846), P <0.001. ILD severity and the presence of coexistent PAH were the main determinants of overall healthcare cost above median for this SSc-ILD cohort (OR 5.1, P <0.001, and OR 2.6, P =0.01, respectively). Furthermore, SSc-ILD patients reported worse physical HRQoL compared with those without ILD [34.3 (10.5) vs 39.1 (10.8), P <0.001], with a progressive decline with increasing ILD severity (P =0.002). Conclusion SSc-ILD places a large burden on the healthcare system and the patient through poor HRQoL in addition to incremental healthcare resource utilization and associated direct cost. [ABSTRACT FROM AUTHOR]

The article discusses the medical case of a 62-year-old man diagnosed with systemic sclerosis (SSc), an autoimmune disease, after a manifestation by chronic constrictive pericarditis (CP). The patient's medical history is provided including lethargy and exertional dyspnoea. Results of various tests performed on the patient are described including signs of cardiac failure and dense fibrotic thickening of the pericardium. Also mentioned are typical features of SSc.

Genomic instability and inflammation are distinct hallmarks of aging, but the connection between them is poorly understood. Understanding their interrelationship will help unravel new mechanisms and therapeutic targets of aging and age-associated diseases. Here we report a novel mechanism directly linking genomic instability and inflammation in senescent cells through a mitochondria-regulated molecular circuit driven by p53 and cytoplasmic chromatin fragments (CCF). We show, through activation or inactivation of p53 by genetic and pharmacologic approaches, that p53 suppresses CCF accumulation and the downstream inflammatory senescence-associated secretory phenotype (SASP), without affecting cell cycle arrest. p53 activation suppressed CCF formation by promoting DNA repair, and this is reflected in maintenance of genomic integrity, particularly in subtelomeric regions, as shown by single cell genome resequencing. Activation of p53 in aged mice by pharmacological inhibition of MDM2 reversed signatures of aging, including age- and senescence-associated transcriptomic signatures of inflammation and age-associated accumulation of monocytes and macrophages in liver. Remarkably, mitochondria in senescent cells suppressed p53 activity by promoting CCF formation and thereby restricting ATM-dependent nuclear DNA damage signaling. These data provide evidence for a mitochondria-regulated p53 signaling circuit in senescent cells that controls DNA repair, genome integrity, and senescence- and age-associated inflammation. This pathway is immunomodulatory in mice and a potential target for healthy aging interventions by small molecules already shown to activate p53.

Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women., Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer., Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million., Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.