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Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular puncta. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and the control of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.

ObjectiveTo describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.DesignProspective observational study.SettingNeonatal intensive care unit (NICU).MethodsWe conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.ResultsA NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.ConclusionsIn comparison to fast outbreaks, outbreaks that are "slow and sustained" may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.

Eccrine angiomatous hamartoma is an uncommon, benign clinical entity constituting a nodular proliferation of eccrine glands and vascular structures localized to the dermis that typically present as unilateral, flesh-colored, erythematous, or violaceous papules on the extremities. These hamartomas may be associated with pain, hyperhidrosis, joint deformity, or functional impairment depending on the severity of the disease process. We present a case of bilaterally symmetric, asymptomatic eccrine angiomatous hamartomas involving all proximal interphalangeal joints of both hands. To date, there are only four prior cases of bilaterally symmetric eccrine angiomatous hamartomas reported in the literature, suggesting that the distribution experienced by our patient may represent a previously undescribed syndrome.

We report the two-photon absorption laser-induced fluorescence rotational spectrum of the CO B 1Σ+ ← X 1Σ+ Hopfield–Birge system (v′ = 0, v″ = 0) Q-branch in an ∼4850 K, atmospheric pressure plasma torch plume at thermal equilibrium in both the quenching-dominated (low laser intensity) and photoionization-dominated (high laser intensity) regimes. We provide a detailed analysis of the photophysics in these two regimes using a rate equation approach and propose modeling considerations for them as well. In the experimental spectra, distinct rotational transitions up to J″ = 83 are observed, allowing analysis over a very large range of rotational states. Evidence of predissociation is observed for J′ ≥ 64 and is likely due to the interaction with the D′1Σ+ electronic state, which has been proposed in the literature but never observed in the v′ = 0 state. The line positions of higher rotational states show disagreement with line positions calculated from molecular constants in the available literature, suggesting the need for modifications to the constants, which are reported here. A shift in the B 1Σ+ ← X 1Σ+ absorption spectrum toward higher two-photon energy as a result of the second-order Stark shift was observed in the photoionization-dominated spectrum, and the second-order Stark shift cross section was estimated to be 7 ± 3 × 10−18 cm2. The mean photoionization cross section of the excited upper state was inferred by comparing the line broadening of the two spectra and was estimated to be 11 ± 7 × 10−18 cm2. In addition, weak J′-dependent variations of the photoionization cross section were observed and are reported here. [ABSTRACT FROM AUTHOR]