Notes

Scaleable creation of microbubbles having an ultrasound-modulated microfluidic unit.
Switching from standard to extended half-life FVIII prophylaxis resulted in increased mean dosing, while the mean number of weekly prophylactic injections (2.6±0.5 vs 1.8±0.3) decreased. Following rFVIIIFc initiation, a non-significant increase in median MPR occurred and the self-reported VERITAS-Pro
questionnaire demonstrated improved adherence to rFVIIIFc prophylaxis. Comparing adherent and non-adherent patients revealed age as the only factor likely to impact adherence (p=.07).

Our patient cohort exhibited high adherence levels before and after FVIII switching, based on MPR and VERITAS-Pro
questionnaire. The latter is likely a useful tool to quantity prophylaxis adherence from a patient's perspective in daily use.
Our patient cohort exhibited high adherence levels before and after FVIII switching, based on MPR and VERITAS-Pro® questionnaire. The latter is likely a useful tool to quantity prophylaxis adherence from a patient's perspective in daily use.
Medical consultations of family physicians play a key role in early diagnosis and proper management of hidradenitis suppurativa (HS).This study aimed to investigate family physicians' disease awareness, general attitudes, and knowledge of HS.

This cross-sectional descriptive study was conducted with 211 family physicians and residents through a web-based survey. The questionnaire consisted of 25 questions about the demographic characteristics of the participants as well as their awareness and general knowledge of HS.

While 90% of physicians know that the diagnosis of HS is made clinically without any need for a laboratory examination,only 23.7% of them felt confident performing such a diagnosis. About 63% of participants defined HS as an infectious disease of the apocrine glands, contradictive to the real pathophysiology. About 21% of them had not been medically trained in HS, and 3% of them even had never heard the name of HS. Only 33% were aware of the role of biological agents. Most of the family physicians (57.4%) were willing to participate in postgraduate education programmes about HS.

The family physicians' awareness of HS is limited. Increased practice in medical education and postgraduate education programmes may help increase the knowledge of family physicians.
The family physicians' awareness of HS is limited. Increased practice in medical education and postgraduate education programmes may help increase the knowledge of family physicians.Members of the Colletotrichum gloeosporioides species complex are causal agents of anthracnose in many commercially important plants. Closely related strains have different levels of pathogenicity on hosts despite their close phylogenetic relationship. To gain insight into the genetics underlying these differences, we generated and annotated whole-genome assemblies of multiple isolates of C. fructicola (Cf) and C. siamense (Cs), as well as three previously unsequenced species, C. aenigma (Ca), C. tropicale and C. viniferum with different pathogenicity on strawberry. Based on comparative genomics, we identified accessory regions with a high degree of conservation in strawberry-pathogenic Cf, Cs and Ca strains. These regions encode homologs of pathogenicity-related genes known as effectors, organized in syntenic gene clusters, with copy number variations in different strains of Cf, Cs and Ca. Analysis of highly contiguous assemblies of Cf, Cs and Ca revealed the association of related accessory effector gene clusters with telomeres and repeat-rich chromosomes and provided evidence of exchange between these two genomic compartments. In addition, expression analysis indicated that orthologues in syntenic gene clusters showed a tendency for correlated gene expression during infection. These data provide insight into mechanisms by which Colletotrichum genomes evolve, acquire and organize effectors.MicroRNAs (miRNAs) are small non-coding RNAs that direct post-transcriptional gene silencing in plant development and stress responses through cleavage or translational repression of target mRNAs. EGFR-IN-7 Here, we report the identification and functional characterization of a new member of the miR812 family in rice (named as miR812w) involved in disease resistance. miR812w is present in cultivated Oryza species, both japonica and indica subspecies, and wild rice species within the Oryza genus, but not in dicotyledonous species. miR812w is a 24nt-long that requires DCL3 for its biogenesis and is loaded into AGO4 proteins. Whereas overexpression of miR812w increased resistance to infection by the rice blast fungus Magnaporthe oryzae, CRISPR/Cas9-mediated MIR812w editing enhances disease susceptibility, supporting that miR812w plays a role in blast resistance. We show that miR812w derives from the Stowaway type of rice MITEs (Miniature Inverted-Repeat Transposable Elements). Moreover, miR812w directs DNA methylation in trans at target genes that have integrated a Stowaway MITE copy into their 3' or 5' untranslated region (ACO3, CIPK10, LRR genes), as well as in cis at the MIR812w locus. The target genes of miR812 were found to be hypo-methylated around the miR812 recognition site, their expression being up-regulated in transgene-free CRISPR/Cas9-edited miR812 plants. These findings further support that, in addition to post-transcriptional regulation of gene expression, miRNAs can exert their regulatory function at the transcriptional level. This relationship between miR812w and Stowaway MITEs integrated into multiple coding genes might eventually create a network for miR812w-mediated regulation of gene expression with implications in rice immunity.
The majority of clotting factor IX (FIX) resides extravascularly, in the subendothelial basement membrane, where it is important for haemostasis.

We summarize preclinical studies demonstrating extravascular FIX and its role in haemostasis and discuss clinical observations supporting this. We compare the in vivo binding of BeneFIX
and the extended half-life FIX, Alprolix
, to extravascular type IV collagen (Col4).

Three mouse models of haemophilia were used the FIX knockout as the CRM
model and two knock-in mice, representing a CRM
model of a commonly occurring patient mutation (FIX
) or a mutation that binds poorly to Col4 (FIX
). The murine saphenous vein bleeding model was used to assess haemostatic competency. Clinical publications were reviewed for relevance to extravascular FIX.

CRM status affects recovery and prophylactic efficacy. Prophylactic protection decreases ~5X faster in CRM
animals. Extravascular haemostasis can explain unexpected breakthrough bleeding in patients treated with some EHL-FIX therapeutics.
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