Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

The Transmission of Trauma from Mother to Infant: Radioactive Residues and Counter-Transference in the Case of a Haitian Mother and Her Two-Year-Old Son*

ABSTRACT

Close observation of the interactions between a traumatised mother and her infant son provides information on the modes of transmission of psychic trauma in the mother–infant dyad. Following the presentation of a current literature review on the theme, the subject of “radioactive residue” and counter-transference in the transmission of psychic trauma from mother to infant will be illustrated through a clinical case study that focuses on a Haitian mother and her two-year-old infant son who has been referred to a “transitional care nursery” in urban Paris. The encounter with this mother–infant dyad is analysed through observing the quality of the interactions that take place between the mother and infant in order to determine how a particularly traumatic narrative impacts the mother–infant relationship, in addition to relations with the clinician. Mother and infant respond to one another through the emission and reception of “radioactive residues” as hypothesized by Gampel. This clinical case study shows that there is a need to consider transcultural factors and collective experience and history when analysing traumatic events. Additionally, the case study shows that counter-transference can be an effective clinical tool for gaining access to an infant's experience as the recipient of a traumatic narrative.     

Bilateral optic nerve edema presenting as initial manifestation of thyroid eye disease

A 48-year-old smoker with a history of hyperthyroidism treated 10 years prior to presentation with radioactive iodine ablation of the thyroid gland presented to his ophthalmologist with a 2-week history of transient loss of vision in the right eye occurring for 1 to 2 hours each morning. He denied ocular pain, diplopia or change in the prominence of one or both eyes. Examination revealed 2 mm of relative proptosis on the right, bilateral temporal flare and lower lid retraction. There was minimal upper lid retraction and no evidence of lid lag. Ocular motility was full. Dilated fundoscopic examination revealed bilateral optic nerve edema, right more than left. CT of the orbit demonstrated enlargement of the extraocular muscles bilaterally with marked enlargement of the right medial rectus and left inferior rectus muscles resulting in crowding at the orbital apex bilaterally. Laboratory testing revealed the patient to be hyperthyroid. The patient was treated with high dose oral steroids followed by orbital radiation. Hyperthyroidism was managed by the patient’s primary care physician. Visual symptoms rapidly improved with oral steroids and orbital radiation. Optic nerve edema completely resolved. Repeat CT imaging demonstrated a reduction in the enlargement of the extraocular muscles with relief of bilateral optic nerve compression.     

Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series

BackgroundThe aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature.MethodsMedline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis.ResultsFifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes.ConclusionQuality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery.