Characterization of environmental airborne hydrocarbon contaminants by surface-enhanced Raman scattering.

This paper explores the unintentional contamination of Surface-Enhanced Raman Scattering (SERS) substrates by ambient hydrocarbon contaminants and their contribution to SERS spectra. Previous studies have identified amorphous carbon as a potential complicating factor in data analysis in SERS experiments, although its origin has been elusive. Our work showed that ambient hydrocarbon contamination and its decomposition products can be detected by SERS on a gold substrate. We propose that ambient air itself is a source of amorphous carbon contamination on SERS substrates. This understanding is crucial for the correct interpretation of SERS data and highlights the need for careful consideration of potential environmental contaminants in SERS analysis.

Phase 3 randomized trial of mavorixafor, CXCR4 antagonist, in WHIM syndrome.

We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist for participants with Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by CXCR4 gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC) ≤400/µL. Participants received once-daily mavorixafor or placebo for 52 weeks. Primary endpoint was time (hours) above ANC threshold ≥500/µL (TATANC; over 24 hours). Secondary endpoints included TAT absolute lymphocyte count ≥1000/µL (TATALC; defined similar to TATANC); absolute changes in white blood cell (WBC), ANC, and ALC from baseline; annualized infection rate; infection duration and total infection score (combined infection number/severity). In 31 participants (mavorixafor, n=14; placebo, n=17), mavorixafor least squares (LS) mean TATANC was 15.0 hours, placebo 2.8 hours (P<0.001). Mavorixafor LS mean TATALC was 15.8 hours, placebo 4.6 hours (P<0.001). Higher absolute WBC, ANC, and ALC levels were seen with mavorixafor than placebo at each timepoint assessed. Annualized infection rates were 60% lower with mavorixafor versus placebo (LS mean 1.7 versus 4.2; nominal P=0.007) and total infection scores were 40% lower (7.4 [95% CI, 1.6-13.2] versus 12.3 [95% CI, 7.2-17.3]). Treatment with mavorixafor reduced infection frequency, severity, duration, and antibiotic use. No discontinuations occurred due to treatment-emergent adverse events (TEAEs); no related serious TEAEs were observed. Overall, mavorixafor-treated participants showed significant increases in LS mean TATANC and TATALC, reduced infection frequency, severity/duration. Mavorixafor was well tolerated in participants with WHIM syndrome. Trial was registered at ClinicalTrials.gov NCT03995108.

Rabies virus-based labeling of layer 6 corticothalamic neurons for two-photon imaging in vivo.

Neocortical layer 6 (L6) is less understood than other more superficial layers, largely owing to limitations of performing high-resolution investigations in vivo. Here, we show that labeling with the Challenge Virus Standard (CVS) rabies virus strain enables high-quality imaging of L6 neurons by conventional two-photon microscopes. CVS virus injection into the medial geniculate body can selectively label L6 neurons in the auditory cortex. Only three days after injection, dendrites and cell bodies of L6 neurons could be imaged across all cortical layers. Ca2+ imaging in awake mice showed that sound stimulation evokes neuronal responses from cell bodies with minimal contamination from neuropil signals. In addition, dendritic Ca2+ imaging revealed significant responses from spines and trunks across all layers. These results demonstrate a reliable method capable of rapid, high-quality labeling of L6 neurons that can be readily extended to other brain regions.

Evaluation and validation of an RT-PCR assay for specific detection of monkeypox virus (MPXV).

Monkeypox virus (MPXV) is a zoonotic orthopoxvirus within the Poxviridae family. MPXV is endemic to Central and West Africa. However, the world is currently witnessing an international outbreak with no clear epidemiological links to travel or animal exposure and with ever-increasing numbers of reported cases worldwide. Here, we evaluated and validated a new, sensitive, and specific real-time PCR-assay for MPXV diagnosis in humans and compare the performance of this novel assay against a Food & Drug Administration-cleared pan-Orthopox RT-PCR assay. We determined specificity, sensitivity, and analytic performance of the PKamp™ Monkeypox Virus RT-PCR assay targeting the viral F3L-gene. In addition, we further evaluated MPXV-PCR-positive specimens by viral culture, electron microscopy, and viral inactivation assays. The limit of detection was established at 7.2 genome copies/reaction, and MPXV was successfully identified in 20 clinical specimens with 100% correlation against the reference method with 100% sensitivity and specificity. Our results demonstrated the validity of this rapid, robust, and reliable RT-PCR assay for specific and accurate diagnosis of MPXV infection in human specimens collected both as dry swabs and in viral transport media. This assay has been approved by NYS Department of Health for clinical use.

Telephone follow-up one day post-cataract surgery.

CLINICAL RELEVANCE: With the increasing use of technology and an emerging need for virtual clinical reviews, particularly following the recent pandemic, it is essential to evaluate the safety of these clinical tools. BACKGROUND: This retrospective study aims to determine the safety of virtual follow-up day one after cataract surgery. METHODS: All patients who underwent cataract surgery at Auckland District Health Board, New Zealand (Aotearoa), and were triaged for telephone review the day after surgery, from 5th November 2018 to 31st January 2020, were eligible. Outcomes measured: presentations to the acute eye clinic prior to the post-operative visit (number and reasons) and complications at the one-month follow-up (persistent inflammation, cystoid macular oedema, raised intra-ocular pressure). RESULTS: Nine hundred and eighty-seven cataract surgeries were triaged for virtual follow-up over the retrospective study period. Nine hundred and eighty-five cases in 928 patients met the inclusion criteria. The median duration of phone calls was 5 minutes (range 2-30). Prior to the one-month post-operative visit, there were 66 presentations to the acute eye clinic, most commonly due to ocular surface irritation (33.3%) and persisting inflammation (25.8%). At the one-month post-operative review, 110 cases (11.2%) had complications; 62 (6.3%) had persisting inflammation, 46 (4.7%) had cystoid macular oedema, and two (0.2%) had raised intraocular pressure. CONCLUSIONS: This is the largest study of a virtual day one post-operative follow-up following cataract surgery, and demonstrates that, in carefully selected subjects, virtual follow-up is a safe alternative to a clinic review. This method could significantly reduce healthcare costs and serve to be more efficient and favourable for patients and clinicians.

SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs. METHODS: In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile-positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed. RESULTS: 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11-2.81), while the <65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P < .05) and increased secondary bile acid concentrations (P < .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity. CONCLUSIONS: Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial. CLINICAL TRIALS REGISTRATION: NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw= 2&rank=4.

Patient-reported quality of life for cataract surgery: prospective validation of the 'Impact on Life' and Catquest-9SF questionnaires in New Zealand.

AIMS: The 'Impact on Life' (IoL) questionnaire is used to prioritise publicly funded cataract surgery in New Zealand, however, it has not been formally validated for ophthalmic use. The Catquest-9SF questionnaire is widely used to assess vision-related quality of life (VRQoL) but has not been validated in New Zealand. This study evaluates the validity of the IoL and Catquest-9SF questionnaires for measuring VRQoL in New Zealand. METHOD: Formal ethics approval was obtained. Participants completed the IoL and Catquest-9SF questionnaires before and three months after routine cataract surgery. Rasch analysis was used to investigate all qualitative questionnaire responses. Results were correlated with the change in patient visual acuity. RESULTS: There was a 100% response rate at follow-up (41 participants). Disordered probability thresholds were observed for all IoL questions but no Catquest-9SF questions. All IoL questions demonstrated unsatisfactory mean-square fit statistics. Differences in visual acuity following surgery correlated with the change in total F-score for the Catquest-9SF (P=0.04), but not IoL responses (P=0.17). CONCLUSIONS: Disordered probability thresholds, poor question-model fit and correlation with visual acuity changes indicate the current IoL questionnaire is poorly suited for assessment of VRQoL. In contrast, the Catquest-9SF demonstrated credible results for assessment of VRQoL in New Zealand.

Biomechanical changes in the cornea following cataract surgery: A prospective assessment with the Corneal Visualisation Scheimpflug Technology.

IMPORTANCE: Intraocular pressure (IOP) is often reduced following cataract surgery. Postoperative changes in corneal stiffness are likely to be at least partly responsible for any reduction in IOP measured with applanation tonometry. BACKGROUND: To determine the effect of cataract surgery and corneal incision size on corneal biomechanics. DESIGN: Prospective randomized trial. PARTICIPANTS: One hundred prospectively enrolled patients qualifying for cataract surgery. METHODS: Participants were randomized to clear corneal incisions with a 2.20 or 2.85 mm keratome. Corneal Visualisation Scheimpflug Technology (Corvis-ST) tonometry and dynamic corneal response measurements were obtained preoperatively, and 3 mo postoperatively. Multiple regression analysis was completed using R software. MAIN OUTCOME MEASURES: Corvis-ST biomechanical parameters. RESULTS: Ninety-three eyes of 93 patients were included in the final analysis. Mean Corvis-ST biomechanically corrected IOP decreased by 3.63 mmHg postoperatively (95% confidence interval = 2.97-4.35, P ≤ 0.01), and central pachymetry increased by 6.96 µm (4.33-9.59, P ≤ 0.01). Independent of IOP and pachymetry changes, mean (±SE) corneal first applanation stiffness parameter reduced by 9.761 ± 3.729 (P = 0.01) postoperatively. First applanation velocity increased by 0.007 ± 0.002 ms, second applanation velocity increased by 0.012 ± 0.004 ms (P ≤ 0.01), the first applanation deformation amplitude increased by 0.008 ± 0.002 mm (P ≤ 0.01) and the deflection amplitude at highest concavity increased by 0.030 ± 0.069 (P ≤ 0.01). There were no significant differences between different incision size groups. CONCLUSIONS AND RELEVANCE: Corneal stiffness is reduced 3 mo following cataract surgery and is associated with falsely low IOP measurements. This finding may be important for glaucoma patients and in particular when assessing the effectivity of minimally invasive glaucoma surgery devices.

Effect of phacoemulsification incision size on incision repair and remodeling: Optical coherence tomography assessment.

PURPOSE: To characterize the effect of incision size on corneal incision repair and remodeling over 3 months after cataract surgery. SETTING: Department of Ophthalmology, Auckland District Health Board, Auckland, New Zealand. DESIGN: Prospective case series. METHODS: Eyes having routine cataract surgery were randomized to receive 2.20 mm or 2.85 mm uniplanar clear corneal incisions. Anterior segment optical coherence tomography of incision thickness, length, width, gaping, and angle and specular microscopy of endothelial cell density (ECD), polymegathism, and pleomorphism were completed at baseline and 1, 7, 30, and 90 days postoperatively. RESULTS: Each incision group comprised 50 eyes (50 patients). Ninety-nine patients (99%) attended all assessments. The Descemet membrane detachment rate was greater than 50% with 2.20 mm incisions (P = .01). Patients with Descemet membrane detachments had increased endothelial wound gaping, slower visual recovery, and increased corneal thickness at the incision site at all visits (φ = 0.54, P < .01). The 2.20 mm group had greater polymegathism despite no difference in the mean phacoemulsification energy between groups (2.20 mm: 32.3% ± 6.2% [SD]; 2.85 mm: 30.8% ± 6.5%) (P = .02). Ninety days postoperatively, the 2.20 mm group had a lower mean ECD (2195 ± 360 cells/mm2) than the 2.85 mm group (2397 ± 335 cells/mm2) (P = .01). Final visual acuity, gaping, and angles were not significantly different between the groups. CONCLUSIONS: The 2.20 mm wide corneal incisions were more prone to trauma than 2.85 mm incisions during routine cataract surgery. Corneal incisions with signs of trauma were associated with prolonged visual recovery and slower healing postoperatively.

Predicting pseudophakic refractive error: Interplay of biometry prediction error, anterior chamber depth, and changes in corneal curvature.

PURPOSE: To quantify pseudophakic refractive error prediction with the Hill-RBF, Barrett Universal II, and SRK/T formulas and to evaluate the temporal effects of anterior chamber depth (ACD) and keratometric changes on postoperative refraction. SETTING: Department of Ophthalmology, University of Auckland and Auckland District Health Board, Auckland, New Zealand. DESIGN: Prospective case series. METHODS: Patients listed for cataract surgery were prospectively recruited. Optimum intraocular lens (IOL) power and predicted refractive outcomes were calculated, and the predicted refraction was compared with objective refractive outcomes at 1-week and 1-month and 3-month follow-ups. RESULTS: The study comprised 100 patients (100 eyes). The mean axial length was 23.4 mm ± 1.1 (SD). The mean keratometry was 43.9 ± 1.3 diopters (D). The mean absolute prediction errors at 3-months were: Universal II: 0.50 ± 0.46 D, RBF: 0.49 ± 0.43 D, and SRK/T: 0.52 ± 0.49 D. The Universal II formula was better than all other methods at 1 week (P = .02); no method was superior at 1 month (P = .46) or 3 months (P = .37). The RBF method predicted the highest proportion of eyes within ±0.25 D at 3 months. Keratometric changes primarily occurred 1 to 4 weeks postoperatively (P = .03) and trended toward corneal steepening (+0.11 D, P < .01). A significant mean hyperopic shift occurred 4 to 12 weeks postoperatively (+0.18 D, P < .01), accompanied by a trend toward increasing ACD (+0.04 mm, P = .03). CONCLUSIONS: The Universal II and RBF methods were better than SRK/T in medium length eyes (22 to 24.5 mm). It might be prudent to expect a progressive hyperopic shift in the 3 months after surgery because of posterior IOL migration.