Digital Tip Amputations from the Perspective of the Nail

The management strategy proposed herein for fingertip amputations advocates secondary healing with preservation of appearance as well as function. Conservative healing is more likely to result in a sensate, nontender, and cosmetically acceptable fingertip compared to surgical management in many clinical scenarios. This manuscript examines in detail the extent of fingertip injury and defines the relationship of injury to final fingertip outcome. A classification is presented, which allows adequate initial counseling regarding prognosis, and predicts the need for secondary corrective surgery

Seroepidemiology of Human Bocavirus Infection in Jamaica

Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean.In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA).HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica.HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world

Interactions of Ar(9+) and metastable Ar(8+) with a Si(100) surface at velocities near the image acceleration limit

Auger LMM spectra and preliminary model simulations of Ar(9+) and metastable Ar(8+) ions interacting with a clean monocrystalline n-doped Si(100) surface are presented. By varying the experimental parameters, several yet undiscovered spectroscopic features have been observed providing valuable hints for the development of an adequate interaction model. On our apparatus the ion beam energy can be lowered to almost mere image charge attraction. High data acquisition rates could still be maintained yielding an unprecedented statistical quality of the Auger spectra.Comment: 34 pages, 11 figures, http://pikp28.uni-muenster.de/~ducree

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification

CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response

Here, we report that genome editing by CRISPR-Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR-Cas9.Peer reviewe

The microphytobenthos of Königshafen — spatial and seasonal distribution on a sandy tidal flat

A microphytobenthic species composition of a tidal flat in the northern Wadden Sea was analysed regarding cell numbers and biomass (in carbon units). The three sampling sites differed in tidal inundation from 15 cm to about 90 cm water depth at high tide. The sediment was sandy at all three stations. A cluster analysis revealed a separation of the benthic diatoms into three areas: aNereis-Corophium-belt, a seagrass-bed and theArenicola-flat. Small epipsammic diatoms were most abundant and dominated the microalgal biomass. A microphytobenthic “spring bloom” even started beneath the ice cover of the flat in January. Lowest values of cell numbers and biomass of benthic microalgae were found in summer. Highest values were measured in the uppermost area (Nereis-Corophium-belt), and only here was an autumnal increase of benthic microalgae found. Further cluster analysis within each of the three areas revealed seasonal differences although the majority of species were present all year round. Many species were most abundant in spring, and some showed a bimodal distribution (spring-autumn) in the year of investigatio

Reactive community-based self-administered treatment against residual malaria transmission: study protocol for a randomized controlled trial

Background: Systematic treatment of all individuals living in the same compound of a clinical malaria case may clear asymptomatic infections and possibly reduce malaria transmission, where this is focal. High and sustained coverage is extremely important and requires active community engagement. This study explores a communitybased approach to treating malaria case contacts. Methods/design: This is a cluster-randomized trial to determine whether, in low-transmission areas, treating individuals living in the same compound of a clinical malaria case with dihydroartemisinin-piperaquine can reduce parasite carriage and thus residual malaria transmission. Treatment will be administered through the local health system with the approach of encouraging community participation designed and monitored through formative research. The trial goal is to show that this approach can reduce in intervention villages the prevalence of Plasmodium falciparum infection toward the end of the malaria transmission season. Discussion: Adherence and cooperation of the local communities are critical for the success of mass treatment campaigns aimed at reducing malaria transmission. By exploring community perceptions of the changing trends in malaria burden, existing health systems, and reaction to self-administered treatment, this study will develop and adapt a model for community engagement toward malaria elimination that is cost-effective and fits within the existing health system. Trial registration: Clinical trials.gov, NCT02878200. Registered on 25 August 2016

Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1

Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts parallel to homologous recombination (HR) in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling. Yen1, but not the HJ resolvases Slx1-Slx4 and Mus81-Mms4, safeguards chromosome segregation by removing replication intermediates that escape Dna2. Post-replicative DNA damage checkpoint activation in Dna2 helicase-defective cells causes terminal G2/M arrest by precluding Yen1-dependent repair, whose activation requires progression into anaphase. These findings explain the exquisite replication stress sensitivity of Dna2 helicase-defective cells, and identify a non-canonical role for Yen1 in the processing of replication intermediates that is distinct from HJ resolution. The involvement of Dna2 helicase activity in completing replication may have implications for DNA2-associated pathologies, including cancer and Seckel syndrome