The Genetics Journey: A Case Report of a Genetic Diagnosis Made 30 Years Later

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant condition that was first described in 2006. The causative gene, EFTUD2, identified in 2012. We report on a family that initially presented to a pediatric genetics clinic in the 1980s for evaluation of multiple congenital anomalies. Re‐evaluation of one member thirty years later resulted in a phenotypic and molecularly confirmed diagnosis of MFDM. This family’s clinical histories and the novel EFTUD2 variant identified, c.1297_1298delAT (p.Met433Valfs*17), add to the literature about MFDM. This case presented several genetic counseling challenges and highlights that “the patient” can be multiple family members. We discuss testing considerations for an unknown disorder complicated by the time constraint of the patient’s daughter’s pregnancy and how the diagnosis changed previously provided recurrence risks. Of note, 1) the 1980s clinic visit letters provided critical information about affected family members and 2) the patient’s husband’s internet search of his wife’s clinical features also yielded the MFDM diagnosis, illustrating the power of the internet in the hands of patients. Ultimately, this case emphasizes the importance of re‐evaluation given advances in genetics and the value of a genetic diagnosis for both patient care and risk determination for family members.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147210/1/jgc40894.pd

Echocardiographic AV-interval optimization in patients with reduced left ventricular function

BACKGROUND: Ritter's method is a tool used to optimize AV delay in DDD pacemaker patients with normal left ventricular function only. The goal of our study was to evaluate Ritter's method in AV delay-interval optimization in patients with reduced left ventricular function. METHODS: Patients with implanted DDD pacemakers and AVB III° were assigned to one of two groups according to ejection fraction (EF): Group 1 (EF > 35%) and Group 2 (EF < 35%). AV delay optimization was performed by means of radionuclide ventriculography (RNV) and application of Ritter's method. RESULTS: For each of the patients examined, we succeeded in defining an optimal AV interval by means of both RNV and Ritter's method. The optimal AV delay determined by RNV correlated well with the delay found by Ritter's method, especially among those patients with reduced EF. The intra-class correlation coefficient was 0.8965 in Group 1 and 0.9228 in Group 2. The optimal AV interval in Group 1 was 190 ± 28.5 ms, and 180 ± 35 ms in Group 2. CONCLUSION: Ritter's method is also effective for optimization of AV intervals among patients with reduced left ventricular function (EF < 35%). The results obtained by RNV correlate well with those from Ritter's method. Individual programming of the AV interval is fundamentally essential in all cases

Causes of death and demographic characteristics of victims of meteorological disasters in Korea from 1990 to 2008

<p>Abstract</p> <p>Background</p> <p>Meteorological disasters are an important component when considering climate change issues that impact morbidity and mortality rates. However, there are few epidemiological studies assessing the causes and characteristics of deaths from meteorological disasters. The present study aimed to analyze the causes of death associated with meteorological disasters in Korea, as well as demographic and geographic vulnerabilities and their changing trends, to establish effective measures for the adaptation to meteorological disasters.</p> <p>Methods</p> <p>Deaths associated with meteorological disasters were examined from 2,045 cases in Victim Survey Reports prepared by 16 local governments from 1990 to 2008. Specific causes of death were categorized as drowning, structural collapse, electrocution, lightning, fall, collision, landslide, avalanche, deterioration of disease by disaster, and others. Death rates were analyzed according to the meteorological type, specific causes of death, and demographic and geographic characteristics.</p> <p>Results</p> <p>Drowning (60.3%) caused the greatest number of deaths in total, followed by landslide (19.7%) and structural collapse (10.1%). However, the causes of deaths differed between disaster types. The meteorological disaster associated with the greatest number of deaths has changed from flood to typhoon. Factors that raised vulnerability included living in coastal provinces (11.3 times higher than inland metropolitan), male gender (1.9 times higher than female), and older age.</p> <p>Conclusions</p> <p>Epidemiological analyses of the causes of death and vulnerability associated with meteorological disasters can provide the necessary information for establishing future adaptation measures against climate change. A more comprehensive system for assessing disaster epidemiology needs to be established.</p

Does directly observed therapy (DOT) reduce drug resistant tuberculosis?

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) is a widely recommended and promoted strategy to manage tuberculosis (TB), however, there is still disagreement about the role of DOT in TB control and the impact it has on reducing the acquisition and transmission of drug resistant TB. This study compares the portion of drug resistant genotype clusters, representing recent transmission, within and between communities implementing programs differing only in their directly observed therapy (DOT) practices.</p> <p>Methods</p> <p>Genotype clusters were defined as 2 or more patient members with matching IS<it>6110 </it>restriction fragment length polymorphism (RFLP) and spoligotype patterns from all culture-positive tuberculosis cases diagnosed between January 1, 1995 and December 31, 2001. Logistic regression was used to compute maximum-likelihood estimates of odds ratios (ORs) and 95% confidence intervals (CIs) comparing cluster members with and without drug resistant isolates. In the universal DOT county, all patients received doses under direct observation of health department staff; whereas in selective DOT county, the majority of received patients doses under direct observation of health department staff, while some were able to self-administer doses.</p> <p>Results</p> <p>Isolates from 1,706 persons collected during 1,721 episodes of tuberculosis were genotyped. Cluster members from the selective DOT county were more than twice as likely than cluster members from the universal DOT county to have at least one isolate resistant to isoniazid, rifampin, and/or ethambutol (OR = 2.3, 95% CI: 1.7, 3.1). Selective DOT county isolates were nearly 5 times more likely than universal DOT county isolates to belong to clusters with at least 2 resistant isolates having identical resistance patterns (OR = 4.7, 95% CI: 2.9, 7.6).</p> <p>Conclusions</p> <p>Universal DOT for tuberculosis is associated with a decrease in the acquisition and transmission of resistant tuberculosis.</p

Hyperadiponectinemia enhances bone formation in mice

<p>Abstract</p> <p>Background</p> <p>There is growing evidence that adiponectin, a physiologically active polypeptide secreted by adipocytes, controls not only adipose tissue but also bone metabolism. However, a role for adiponectin in bone development remains controversial.</p> <p>Methods</p> <p>We therefore investigated the endocrine effects of adiponectin on bone metabolism using 12-week-old male transgenic (Ad-Tg) mice with significant hyperadiponectinemia overexpressing human full-length adiponectin in the liver.</p> <p>Results</p> <p>In Ad-Tg mice, the serum level of osteocalcin was significantly increased, but the levels of RANKL, osteoprotegerin, and TRAP5b were not. Bone mass was significantly greater in Ad-Tg mice with increased bone formation. In contrast, bone resorption parameters including the number of osteoclasts and eroded surface area did not differ between Ad-Tg and their littermates.</p> <p>Conclusions</p> <p>These findings demonstrate that hyperadiponectinemia enhances bone formation in mice.</p

Equine post-breeding endometritis: A review

The deposition of semen, bacteria and debris in the uterus of the mare after breeding normally induces a self-limiting endometritis. The resultant fluid and inflammatory products are cleared by 48 hours post cover. Mares that are susceptible to persistent post-breeding endometritis (PPBEM) have impaired uterine defence and clearance mechanisms, making them unable to resolve this inflammation within the normal time. This persists beyond 48 hours post-breeding and causes persistent fluid accumulation within the uterus. Mares with PPBEM have an increased rate of embryonic loss and a lower overall pregnancy rate than those without the condition. To enhance conception rates, mares at high risk need optimal breeding management as well as early diagnosis, followed by the most appropriate treatment. This article reviews the pathogenesis, diagnosis and treatment of PPBEM and the management of affected mares

Formulation of a Medical Food Cocktail for Alzheimer's Disease: Beneficial Effects on Cognition and Neuropathology in a Mouse Model of the Disease

Dietary supplements have been extensively studied for their beneficial effects on cognition and AD neuropathology. The current study examines the effect of a medical food cocktail consisting of the dietary supplements curcumin, piperine, epigallocatechin gallate, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate on cognitive functioning and the AD hallmark features and amyloid-beta (Aβ) in the Tg2576 mouse model of the disease.The study found that administering the medical food cocktail for 6 months improved cortical- and hippocampal- dependent learning in the transgenic mice, rendering their performance indistinguishable from non-transgenic controls. Coinciding with this improvement in learning and memory, we found that treatment resulted in decreased soluble Aβ, including Aβ oligomers, previously found to be linked to cognitive functioning.In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD

Bioaccessibility of selenium after human ingestion in relation to its chemical species and compartmentalization in maize

International audienceSelenium is a micronutrient needed by all living organisms including humans, but often present in low concentration in food with possible deficiency. From another side, at higher concentrations in soils as observed in seleniferous regions of the world, and in function of its chemical species, Se can also induce (eco)toxicity. Root Se uptake was therefore studied in function of its initial form for maize (Zea mays L.), a plant widely cultivated for human and animal food over the world. Se phytotoxicity and compartmentalization were studied in different aerial plant tissues. For the first time, Se oral human bioaccessibility after ingestion was assessed for the main Se species (SeIV and SeVI) with the BARGE ex vivo test in maize seeds (consumed by humans), and in stems and leaves consumed by animals. Corn seedlings were cultivated in hydroponic conditions supplemented with 1 mg L−1 of selenium (SeIV, SeVI, Control) for 4 months. Biomass, Se concentration, and bioaccessibility were measured on harvested plants. A reduction in plant biomass was observed under Se treatments compared to control, suggesting its phytotoxicity. This plant biomass reduction was higher for selenite species than selenate, and seed was the main affected compartment compared to control. Selenium compartmentalization study showed that for selenate species, a preferential accumulation was observed in leaves, whereas selenite translocation was very limited toward maize aerial parts, except in the seeds where selenite concentrations are generally high. Selenium oral bioaccessibility after ingestion fluctuated from 49 to 89 % according to the considered plant tissue and Se species. Whatever the tissue, selenate appeared as the most human bioaccessible form. A potential Se toxicity was highlighted for people living in seleniferous regions, this risk being enhanced by the high Se bioaccessibility

Inhibition of 26S Protease Regulatory Subunit 7 (MSS1) Suppresses Neuroinflammation

Recently, researchers have focused on immunosuppression induced by rifampicin. Our previous investigation found that rifampicin was neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In this study, using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we discovered that 26S protease regulatory subunit 7 (MSS1) was decreased in rifampicin-treated microglia. Western blot analysis verified the downregulation of MSS1 expression by rifampicin. As it is indicated that the modulation of the ubiquitin-26S proteasome system (UPS) with proteasome inhibitors is efficacious for the treatment of neuro-inflammatory disorders, we next hypothesized that silencing MSS1 gene expression might inhibit microglial inflammation. Using RNA interference (RNAi), we showed significant reduction of IkBα degradation and NF-kB activation. The production of lipopolysaccharides-induced pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide, cyclooxygenase-2, and prostaglandin E2 were also reduced by MSS1 gene knockdown. Taken together, our findings suggested that rifampicin inhibited microglial inflammation by suppressing MSS1 protein production. Silencing MSS1 gene expression decreased neuroinflammation. We concluded that MSS1 inhibition, in addition to anti-inflammatory rifampicin, might represent a novel mechanism for the treatment of neuroinflammatory disorders