Nasal Valve Lift in Nasal Valve Stenosis-A 2 Years Clinical Trial.

A clinical study was conducted to determine the effect of nasal valve lift treatment using absorbable, polylactic acid, self-retaining cone threads (Silhouette Soft) in patients with nasal valve stenosis. Sixty patients (n = 60) were included in this prospective study which was performed from January 2015 until December 2018, 19 patients dropped out due to noncompliance. Initially, participants were divided into two equal groups. One was treated by nasal valve lift only, the other additionally received turbinoplasty. A visual analog scale (VAS) was used to rate the sense of nasal ventilation. Patients' satisfaction was examined by a categorical scale, preoperatively, after 1 week, and after 1, 6, 12, 18, and 24 months. For statistical analysis, an univariant variance analysis was conducted to test the significance of differences in nasal breathing within one group at different points of postoperative controls, with the statistical significance set at p < 0.05. Moreover, the two groups were compared with each other regarding results of the categorical scale. After surgical treatment, an improvement is reported by all participants. Average VAS scores were significantly lower between preoperative and every postoperative rating. Although a decline in the effect of breathing improvement is recognizable as threads are dissolved, patients' satisfaction in improvement of nasal breathing is persistent in most cases, even at long-term observation. Overall, these results demonstrate that valve lift is an effective method to treat patients with nasal valve stenosis.

Role of Envelope Glycoprotein Complexes in Cell-Associated Spread of Human Cytomegalovirus.

The role of viral envelope glycoproteins, particularly the accessory proteins of trimeric and pentameric gH/gL-complexes, in cell-associated spread of human cytomegalovirus (HCMV) is unclear. We aimed to investigate their contribution in the context of HCMV variants that grow in a strictly cell-associated manner. In the genome of Merlin pAL1502, the glycoproteins gB, gH, gL, gM, and gN were deleted by introducing stop codons, and the mutants were analyzed for viral growth. Merlin and recent HCMV isolates were compared by quantitative immunoblotting for expression of accessory proteins of the trimeric and pentameric gH/gL-complexes, gO and pUL128. Isolates were treated with siRNAs against gO and pUL128 and analyzed regarding focal growth and release of infectious virus. All five tested glycoproteins were essential for growth of Merlin pAL1502. Compared with this model virus, higher gO levels were measured in recent isolates of HCMV, and its knockdown decreased viral growth. Knockdown of pUL128 abrogated the strict cell-association and led to release of infectivity, which allowed cell-free transfer to epithelial cells where the virus grew again strictly cell-associated. We conclude that both trimer and pentamer contribute to cell-associated spread of recent clinical HCMV isolates and downregulation of pentamer can release infectious virus into the supernatant.

Large-Scale Screening of HCMV-Seropositive Blood Donors Indicates that HCMV Effectively Escapes from Antibodies by Cell-Associated Spread.

Immunoglobulins are only moderately effective for the treatment of human cytomegalovirus (HCMV) infections, possibly due to ineffectiveness against cell-associated virus spread. To overcome this limitation, we aimed to identify individuals with exceptional antibodies in their plasma that can efficiently block the cell-associated spread of HCMV. A Gaussia luciferase-secreting mutant of the cell-associated HCMV strain Merlin was generated, and luciferase activity evaluated as a readout for the extent of cell-associated focal spread. This reporter virus-based assay was then applied to screen plasma samples from 8400 HCMV-seropositive individuals for their inhibitory effect, including direct-acting antiviral drugs as positive controls. None of the plasmas reduced virus spread to the level of these controls. Even the top-scoring samples that partially reduced luciferase activity in the screening assay failed to inhibit focal growth when reevaluated with a more accurate, immunofluorescence-based assay. Selected sera with high neutralizing capacity against free viruses were analyzed separately, and none of them prevented the focal spread of three recent clinical HCMV isolates nor reduced the number of particles transmitted, as demonstrated with a fluorescent Merlin mutant. We concluded that donors with cell-to-cell-spread-inhibiting plasma are nonexistent or extremely rare, emphasizing cell-associated spread as a highly efficient immune escape mechanism of HCMV.