Ehlers-Danlos Syndrome Hypermobility Type is Associated with Rheumatic Diseases

We retrospectively analyzed electronic medical records of patients with Ehlers-Danlos Syndrome hypermobility type (HEDS), including demographic information, workup, rheumatological diagnoses in order to determine its association with rheumatological conditions. HEDS Patients were stratified according to level of workup received (no additional work (physical exam only) = NWU, limited workup = LWU, comprehensive workup = CWU)). HEDS patients were predominantly female (21:4, F:M). The percentage of patients with at least one rheumatological condition was significantly correlated with level of workup (NWU, 9.2%; LWU, 33.3%, CWU, 67.1%; p-value \u3c 0.0001). The HLA-B27 antigen was more prevalent (p-value \u3c 2.2 × 10 –8 ) in the CWU HEDS patients (23.9%) than in the general population of the United States (6.1%). HEDS with CWU were associated with more rheumatological conditions (i.e. psoriasis, ankylosing spondylitis, rheumatoid arthritis, fibromyalgia) than those with NWU or LWU. In conclusion, HEDS is associated with complicated rheumatological conditions, which are uncovered by comprehensive workup. These conditions require different clinical management strategies than HEDS, and left untreated could contribute to the pain or even physical disability (i.e. joint erosions) in HEDS patients. While the mechanisms underlying these associations are unknown, it is important that all HEDS patients receive adequate workup to ensure a complete clinical understanding for the best care strategy possible

Management Practices and Productivity Level of Cebu City and Ozamiz City Eateries during COVID-19 Pandemic

The COVID-19 pandemic has made drastic changes in every country’s economy, affecting several businesses particularly in the restaurant industry and resulting in different obstacles that threaten the overall business productivity. Thus, the study is a quantitative non-experimental that aimed to determine if there is a significant relationship between the management practices and productivity among the 50 respondents from the randomly selected 10 eateries in Cebu City, Philippines through linear correlation analysis. Data were gathered online using an adapted and reliable questionnaire. Findings revealed that the management practices of the eateries have a very high average weighted mean and SD (x̄=3.34 SD=0.72). Meanwhile, the level of impact of the eateries’ overall productivity garnered a very high average weighted mean (x̄=3.50 SD=0.57). Therefore, the levels of management practices and the productivity of the eateries during the COVID-19 pandemic have significant relationship with a moderate positive correlation of 0.58 (r = 0.5846, = 0.00001, p < 0.05). This implies the great need for businesses to establish appropriate management practices and for employees to systematically apply these practices for the betterment of both the productivity of the employees and the business as a whole. Additionally, with the problems of operations, regulations imposed by the government, and adjustments to competitors being faced, respondents suggested fostering open communication and utilizing online platforms, and promotions for the improvement of management practices and productivity

FastPop: a rapid principal component derived method to infer intercontinental ancestry using genetic data.

BACKGROUND: Identifying subpopulations within a study and inferring intercontinental ancestry of the samples are important steps in genome wide association studies. Two software packages are widely used in analysis of substructure: Structure and Eigenstrat. Structure assigns each individual to a population by using a Bayesian method with multiple tuning parameters. It requires considerable computational time when dealing with thousands of samples and lacks the ability to create scores that could be used as covariates. Eigenstrat uses a principal component analysis method to model all sources of sampling variation. However, it does not readily provide information directly relevant to ancestral origin; the eigenvectors generated by Eigenstrat are sample specific and thus cannot be generalized to other individuals. RESULTS: We developed FastPop, an efficient R package that fills the gap between Structure and Eigenstrat. It can: 1, generate PCA scores that identify ancestral origins and can be used for multiple studies; 2, infer ancestry information for data arising from two or more intercontinental origins. We demonstrate the use of FastPop using 2318 SNP markers selected from the genome based on high variability among European, Asian and West African (African) populations. We conducted an analysis of 505 Hapmap samples with European, African or Asian ancestry along with 19661 additional samples of unknown ancestry. The results from FastPop are highly consistent with those obtained by Structure across the 19661 samples we studied. The correlations of the results between FastPop and Structure are 0.99, 0.97 and 0.99 for European, African and Asian ancestry scores, respectively. Compared with Structure, FastPop is more efficient as it finished ancestry inference for 19661 samples in 16 min compared with 21-24 h required by Structure. FastPop also provided scores based on SNP weights so the scores of reference population can be applied to other studies provided the same set of markers are used. We also present application of the method for studying four continental populations (European, Asian, African, and Native American). CONCLUSIONS: We developed an algorithm that can infer ancestries on data involving two or more intercontinental origins. It is efficient for analyzing large datasets. Additionally the PCA derived scores can be applied to multiple data sets to ensure the same ancestry analysis is applied to all studies

Congenital Acute Myeloid Leukemia with t(8;16) and t(17;19) Double Translocation: Case Presentation and Literature Review

Congenital leukemia is uncommon and excluding transient myeloproliferation associated with Down syndrome, makes up approximately 1% of childhood leukemias. A newborn boy was born with multiple subcutaneous nodules and large purpuric papules. Skin biopsy revealed proliferation of atypical hematologic cells in the dermis. Bone marrow morphology was consistent with acute myeloid leukemia (M5) and cytogenetic studies revealed t(8;16) and t(17;19) double translocation. Although prognosis of congenital leukemia is known to be dismal, recent reports showed spontaneous remissions. With the fear of chemotherapy-related toxicity, to treat or not to treat may be a dilemma both to parents and pediatricians. We report our experience and review the literature

Acute acalculous cholecystitis during the course of primary Epstein-Barr virus infection: a new case and a review of the literature

OBJECTIVE: The aim of this study was to describe a case of acute acalculous cholecystitis occurring in the course of primary Epstein-Barr virus (EBV) infection. METHODS: The clinical features of the case were analyzed and compared to those of three other similar cases reported in the international literature. RESULTS: All cases occurred in European females with cholestatic hepatitis, presented with gallbladder wall thickening, and recovered uneventfully without the need for surgical intervention. CONCLUSIONS: Acute acalculous cholecystitis may occur during the course of acute EBV infection, especially in patients with cholestatic hepatitis. Clinicians should be aware of the possible involvement of the gallbladder during EBV infection to avoid unnecessary invasive procedures or the overuse of antibiotics

Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes.

PURPOSE: Several clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level. METHODS: Ten index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity. RESULTS: Pathogenicity was demonstrated for six of the seven novel EPHB4 VUS investigated. A heterogeneity of molecular disease mechanisms was identified, from loss of protein production or aberrant subcellular localization to total reduction of the phosphorylation capability of the receptor. There was some phenotype-genotype correlation; however, previously unreported intrafamilial overlapping phenotypes such as lymphatic-related fetal hydrops (LRFH) and CM-AVM2 in the same family were observed. CONCLUSION: This study highlights the usefulness of protein expression and subcellular localization studies to predict EPHB4 variant pathogenesis. Our accurate clinical phenotyping expands our interpretation of the Janus-faced spectrum of EPHB4-related disorders, introducing the discovery of cases with overlapping phenotypes

Investigation of NRXN1 deletions: Clinical and molecular characterization

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P  = 6.08 × 10 −7 ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97220/1/35780_ftp.pd

Membrane Damage Elicits an Immunomodulatory Program in Staphylococcus aureus

The Staphylococcus aureus HrtAB system is a hemin-regulated ABC transporter composed of an ATPase (HrtA) and a permease (HrtB) that protect S. aureus against hemin toxicity. S. aureus strains lacking hrtA exhibit liver-specific hyper-virulence and upon hemin exposure over-express and secrete immunomodulatory factors that interfere with neutrophil recruitment to the site of infection. It has been proposed that heme accumulation in strains lacking hrtAB is the signal which triggers S. aureus to elaborate this anti-neutrophil response. However, we report here that S. aureus strains expressing catalytically inactive HrtA do not elaborate the same secreted protein profile. This result indicates that the physical absence of HrtA is responsible for the increased expression of immunomodulatory factors, whereas deficiencies in the ATPase activity of HrtA do not contribute to this process. Furthermore, HrtB expression in strains lacking hrtA decreases membrane integrity consistent with dysregulated permease function. Based on these findings, we propose a model whereby hemin-mediated over-expression of HrtB in the absence of HrtA damages the staphylococcal membrane through pore formation. In turn, S. aureus senses this membrane damage, triggering the increased expression of immunomodulatory factors. In support of this model, wildtype S. aureus treated with anti-staphylococcal channel-forming peptides produce a secreted protein profile that mimics the effect of treating ΔhrtA with hemin. These results suggest that S. aureus senses membrane damage and elaborates a gene expression program that protects the organism from the innate immune response of the host