Bleeding disorders in the tribe: result of consanguineous in breeding

<p>Abstract</p> <p>Objective</p> <p>To determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages.</p> <p>Design</p> <p>Cross Sectional Study</p> <p>Introduction</p> <p>Countries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia.</p> <p>Patients & Methods</p> <p>Our team visited the village & developed the pedigree of the whole extended family, up to seven generations. Performa was filled by incorporating patients, family history of bleeding, signs & symptoms, and bleeding from any site. From them 144 individuals were screened with CBC, bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF assay and Factor VIII assay, samples were kept frozen at -70 degrees C until tested.</p> <p>Results</p> <p>The family tree of the seven generations comprises of 533 individuals, 63 subjects died over a period of 20 years and 470 were alive. Out of all those 144 subjects were selected on the basis of the bleeding history. Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients were male and 55.1% patients were female. Median age of all the patients was 20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was Von Willebrand disease and Platelet functional disorders.</p> <p>Conclusion</p> <p>Consanguineous marriages keep all the beneficial and adversely affecting recessive genes within the family; in homozygous states. These genes express themselves and result in life threatening diseases. Awareness, education & genetic counseling will be needed to prevent the spread of such common occurrence of these bleeding disorders in the community.</p

C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation

C3 glomerulopathies (C3G) are a group of severe renal diseases with distinct patterns of glomerular inflammation and C3 deposition caused by complement dysregulation. Here we report the identification of a familial C3G-associated genomic mutation in the gene complement factor H–related 1 (CFHR1), which encodes FHR1. The mutation resulted in the duplication of the N-terminal short consensus repeats (SCRs) that are conserved in FHR2 and FHR5. We determined that native FHR1, FHR2, and FHR5 circulate in plasma as homo- and hetero-oligomeric complexes, the formation of which is likely mediated by the conserved N-terminal domain. In mutant FHR1, duplication of the N-terminal domain resulted in the formation of unusually large multimeric FHR complexes that exhibited increased avidity for the FHR1 ligands C3b, iC3b, and C3dg and enhanced competition with complement factor H (FH) in surface plasmon resonance (SPR) studies and hemolytic assays. These data revealed that FHR1, FHR2, and FHR5 organize a combinatorial repertoire of oligomeric complexes and demonstrated that changes in FHR oligomerization influence the regulation of complement activation. In summary, our identification and characterization of a unique CFHR1 mutation provides insights into the biology of the FHRs and contributes to our understanding of the pathogenic mechanisms underlying C3G

Characteristics of difficult-to-treat rheumatoid arthritis: a real-life study

Objective: Despite therapeutic advances and the "treat-to-target" strategy, 5-20% of Rheuma- toid Arthritis (RA) patients fail to achieve treatment goals. The aim of this study was to identify the characteristics and risk factors associated with difficult-to-treat RA. Patients and Methods: This is a real-life study of patients with RA according to the ACR/EULAR 2010 clas- sification criteria. Sociodemographic, clinical, paraclinical and comorbidity data were collected, as well as the treatments used. Patients were divided into two groups: D2T RA and control group. The results were compared between the two groups. Logistic regression analysis was used to identify risk factors associated with D2T RA. Results: We included 25 D2T RA patients and 62 non-D2T RA patients. Mean age of patients and disease duration were higher in D2T RA group. Rheumatoid factor seropositivity was higher in the D2T RA group (p = 0.04). They had more active disease (p = 0.001) and more severe functional impairment (p < 0.001). Among ex- tra-articular manifestations, interstitial lung disease was more common in D2T RA patients (p = 0.018). Biologic disease-modifying antirheumatic drugs (bDMARDs) were prescribed more frequently in the D2T RA group and the glucocorticoid dose was higher in this group (p = 0.041). On multivariate analysis, disease activity, disease duration and lung involvement were identified as factors that were associated with D2T RA. Conclusions: D2T RA can be classified in about one-third of our RA patients. We observed an association be- tween longer disease duration, higher disease activity and rheumatoid factor seropositivity in D2T RA. In addition, lung involvement in the context of RA was more common in this group and may be a contributing factor to an inadequate response to treatment

Substrate Handling Strategies Thinned Multi-junction Solar-cell Wafers.

International audienc

Substrate Handling Strategies Thinned Multi-junction Solar-cell Wafers.

International audienc

Development and Validation of Key Microfabrication Processes for Through Cell Via Contacts Multi-Junction Solar Cell

International audienc

Behavioral manipulation—key to the successful global spread of the new coronavirus SARS‐CoV‐2?

International audienceAbstract Human‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) interaction can have an array of various outcomes—it could be mortal, morbid or merely carrying minor health consequences. The very rapid global spread has raised the issue whether there are further multi‐dimensional consequences of SARS‐CoV‐2 infection on human behavior, the key of its transmission. During the coronavirus crisis, odd, abnormal, and irresponsible behavior has been reported in coronavirus disease 2019 (COVID‐19) individuals, particularly in super‐spreaders, that is, persons with a high viral load, thus constituting also super‐emitters. Indeed, cases of infected persons ignoring self‐confinement orders, intentionally disregarding physical distancing and multiplying social interactions, or even deliberately sneezing, spitting or coughing were reported. While it is known that some other viruses, such as rabies and even influenza do change human behavior, this remains unclear for SARS‐CoV‐2. In this perspective, we highlight the possibility that COVID‐19 is facilitated by altered human social behavior that benefits SARS‐CoV‐2 transmission, through showcasing similar virus‐induced changed behavior by other pathogens and relating this to reports from the gray literature