Resistance to aztreonam-avibactam among clinical isolates of E. coli is primarily mediated by altered penicillin binding protein 3 and impermeability.

Herein, we investigated decreased susceptibility (DS; MICs 0.25-4 mg/L) and resistance (R; MICs >4 mg/L) to aztreonam-avibactam (ATM-AVI). Contemporary non-replicate clinical isolates of carbapenemase-producing Escherichia coli (n=90) (CP-EC) and ESBL-producing E. coli (n=12) (EP-EC) was used. CP-EC belonged to 25 distinct sequence types (STs) and all EP-EC belonged to ST405. All strains were isolated through 2019-2022 at the Karolinska University Laboratory, Stockholm, Sweden. ATM-AVI MICs were determined with broth microdilution and the EUCAST epidemiological cutoff value of 0.125 mg/L was used to define the wildtype (WT). Whole genome sequences (Illumina) were analyzed for detecting of resistance determinants among WT vs non-WT isolates. Among 102 isolates, 40 (39%) and 62 (61%) were WT and non-WT respectively. Among non-WT isolates 20 were R and 42 were DS. Resistance was observed among 14/47 NDM-producers, 5/43 OXA-48 group producers, and 1/12 EP-EC. DS was observed among 29/47 NDM, 13/43 OXA-48 group, and 3/12 EP-EC. Resistant isolates predominantly belonged to ST405 followed by STs 410, 361, 167, 617, and 1284. Presence of PBP3 inserts (YRIK/YRIN) were observed in 20/20 and presence of CMY-42 in 5/20 resistant isolates. Several mutations in the ftsI (encoding PBP3) and regulatory genes of outer membrane proteins (OmpC and OmpF) and efflux pumps (AcrAB-TolC) were detected. A ≥2-fold reduction in MICs were observed among 20/20 vs 7/20 isolates tested in the presence of the membrane permeabilizer PMBN and efflux inhibitor PAßN, respectively. In conclusion, resistance to ATM-AVI is a result of interplay of various determinants, including target alterations, deactivating enzymes, and decreased permeability.

A Multiresolution Approach with Method-Informed Statistical Analysis for Quantifying Lymphatic Pumping Dynamics.

Despite significant strides in lymphatic system imaging, the timely diagnosis of lymphatic disorders remains elusive. One main cause for this is the absence of standardized, quantitative methods for real-time analysis of lymphatic contractility. Here, we address this unmet need by combining near-infrared lymphangiography imaging with an innovative analytical workflow. We combined data acquisition, signal processing, and statistical analysis to integrate traditional peak and-valley with advanced wavelet time-frequency analyses. Decision theory was used to evaluate the primary drivers of attributable variance in lymphangiography measurements to generate a strategy for optimizing the number of repeat measurements needed per subject to increase measurement reliability. This approach not only offers detailed insights into lymphatic pumping behaviors across species, sex and age, but also significantly boosts the reliability of these measurements by incorporating multiple regions of interest and evaluating the lymphatic system under various gravitational loads. By addressing the critical need for improved imaging and quantification methods, our study offers a new standard approach for the imaging and analysis of lymphatic function that can improve our understanding, diagnosis, and treatment of lymphatic diseases. The results highlight the importance of comprehensive data acquisition strategies to fully capture the dynamic behavior of the lymphatic system.

Mechanics of Lymphatic Pumping and Lymphatic Function.

The lymphatic system plays a crucial role in maintaining tissue fluid balance, immune surveillance, and the transport of lipids and macromolecules. Lymph is absorbed by initial lymphatics and then driven through lymph nodes and to the blood circulation by the contraction of collecting lymphatic vessels. Intraluminal valves in collecting lymphatic vessels ensure the unidirectional flow of lymph centrally. The lymphatic muscle cells that invest in collecting lymphatic vessels impart energy to propel lymph against hydrostatic pressure gradients and gravity. A variety of mechanical and biochemical stimuli modulate the contractile activity of lymphatic vessels. This review focuses on the recent advances in our understanding of the mechanisms involved in regulating and collecting lymphatic vessel pumping in normal tissues and the association between lymphatic pumping, infection, inflammatory disease states, and lymphedema.

Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial.

BACKGROUND: Antimicrobials cause perturbations in the composition and diversity of the host microbiome. We aimed to compare gut microbiome perturbations caused by oral tebipenem pivoxil hydrobromide (a novel carbapenem) and by amoxicillin-clavulanic acid (an orally administered ß-lactam-ß-lactam inhibitor combination widely used in clinical practice). METHODS: We did a phase 1, single-centre, randomised, parallel-group, active-control trial to evaluate the effect of tebipenem pivoxil hydrobromide on the human gut microbiota. Healthy participants aged 18 years or older with no documented illnesses during recruitment were enrolled at Karolinska University Hospital (Stockholm, Sweden). Study participants were stratified by sex and block-randomised in a 1:1 ratio to treatment with either tebipenem pivoxil hydrobromide (600 mg orally every 8 h) or amoxicillin-clavulanic acid (500 mg amoxicillin and 125 mg clavulanic acid orally every 8 h). The study included 10 days of treatment (days 1-10) and four follow-up visits (days 14, 21, 90, and 180). The trial was open-label for clinical investigators and patients, but masked for microbiology investigators. Faecal samples were collected at all visits. Sequencing of 16S rDNA was used to measure the diversity metrics, and quantitative culture to quantify selected taxa. The primary outcomes were changes in the α and ß diversity and log count of colony-forming units for selected taxa between samples compared with baseline (day 1), and whether any changes reverted during the follow-up period. The analyses were done in the intention-to-treat population. This study was registered with ClinicalTrials.gov (NCT04376554). FINDINGS: The study was conducted between Jan 23, 2020, and April 6, 2021. 49 volunteers were screened for eligibility, among whom 30 evaluable participants (14 men and 16 women) were assigned: 15 (50%) to the tebipenem pivoxil hydrobromide group and 15 (50%) to the amoxicillin-clavulanic acid group. Baseline characteristics were similar between groups. Complete follow-up was available for all participants, and all participants except one completed treatment as assigned. The diversity metrics showed significant changes from baseline during the treatment period. Significant decreases in richness were observed on days 4-10 (p≤0·0011) in the amoxicillin-clavulanic acid group and on days 4-14 (p≤0·0019) in the tebipenem pivoxil hydrobromide group. Similarly, evenness was significantly decreased during treatment in the amoxicillin-clavulanic acid group (day 4, p=0·030) and the tebipenem pivoxil hydrobromide group (days 4-10, p<0·0001) compared with baseline. Quantitative cultures showed significant decreases in Enterobacterales (days 4-7, p≤0·0030), Enterococcus spp (days 4-14, p=0·025 to p<0·0001), Bifidobacterium spp (days 2-4, p≤0·026), and Bacteroides spp (days 4-10, p≤0·030) in the tebipenem pivoxil hydrobromide group. Similarly, in amoxicillin-clavulanic acid recipients, significant changes were observed in Enterobacterales (days 4-10, p≤0·048), Bifidobacterium spp (days 2-4, p≤0·013), and Lactobacillus spp (days 2-4, p≤0·020). Samples from the follow-up period were not significantly different from those at baseline in ß diversity analysis (PERMANOVA, p>0·99). By the end of the study, no significant change was observed compared with baseline in either group. There were no deaths or severe adverse events. INTERPRETATION: The impact of tebipenem pivoxil hydrobromide on the gut microbiome was similar to that of amoxicillin-clavulanic acid. The safety of antibiotic use with regard to the microbiome should be given attention, as dysbiosis is associated with health and disease. FUNDING: Spero Therapeutics.

Antimicrobial susceptibilities and genomic characteristics of methicillin-resistant Staphylococcus aureus resistant to mupirocin in Stockholm, Sweden.

The aim of this study was to investigate antimicrobial susceptibilities and genomic characteristics of mupirocin-resistant MRSA isolates in Stockholm, Sweden. In total, 44 non-duplicate mupirocin-resistant MRSA isolates detected in Stockholm during 2010-2022 were investigated. Antimicrobial susceptibility testing was performed using broth microdilution method and further tested for high-level mupirocin-resistance (MuH) and rifampicin by Etest®. All isolates were subjected to whole genome sequencing. 41 isolates presented MuH with MICs ≥1024 mg/L whilst three isolates displayed low-level mupirocin resistance (MuL). mupA-gene was detected in all MuH isolates. Point mutations in ileS gene leading to N213D and V588F were identified in the three MuL isolates. Mutation in rpoB (H481N) was detected in a rifampicin-resistant isolate. Among the isolates, 15 multi-locus sequence types (MLST) were identified, with the four most common sequence types (ST22, ST72, ST8, and ST125) accounting for 66% of the isolates. Mupirocin-resistant MRSA in Stockholm was uncommon, with a percentage of <0.5% among MRSA cases during 2010-2022. In the present study, most mupirocin-resistant isolates were MuH and mupA-positive, predominantly linked to ST22 or ST72 isolates. MuL-resistance was associated with a point mutation in the IleS protein. A multidrug-resistant ST1-MRSA-IV strain was resistant to both mupirocin and rifampicin.

Cancer immunotherapy responses persist after lymph node resection.

Surgical removal of lymph nodes (LNs) to prevent metastatic recurrence, including sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND), are performed in routine practice. However, it remains controversial whether removing LNs which are critical for adaptive immune responses impairs immune checkpoint blockade (ICB) efficacy. Here, our retrospective analysis demonstrated that stage III melanoma patients retain robust response to anti-PD1 inhibition after CLND. Using orthotopic murine mammary carcinoma and melanoma models, we show that responses to ICB persist in mice after TDLN resection. Mechanistically, after TDLN resection, antigen can be re-directed to distant LNs, which extends the responsiveness to ICB. Strikingly, by evaluating head and neck cancer patients treated by neoadjuvant durvalumab and irradiation, we show that distant LNs (metastases-free) remain reactive in ICB responders after tumor and disease-related LN resection, hence, persistent anti-cancer immune reactions in distant LNs. Additionally, after TDLN dissection in murine models, ICB delivered to distant LNs generated greater survival benefit, compared to systemic administration. In complete responders, anti-tumor immune memory induced by ICB was systemic rather than confined within lymphoid organs. Based on these findings, we constructed a computational model to predict free antigen trafficking in patients that will undergo LN dissection.

Lymphatic muscle cells are unique cells that undergo aging induced changes.

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. We have generated a comprehensive transcriptional single-cell atlas-including LMCs-of collecting lymphatic vessels in mouse dermis at various ages. We identified genes that distinguish LMCs from other types of muscle cells, characterized the phenotypical and transcriptomic changes in LMCs in aged vessels, and uncovered a pro-inflammatory microenvironment that suppresses the contractile apparatus in advanced-aged LMCs. Our findings provide a valuable resource to accelerate future research for the identification of potential drug targets on LMCs to preserve lymphatic vessel function as well as supporting studies to identify genetic causes of primary lymphedema currently with unknown molecular explanation.

Orbital Cholesterol Granuloma: Report of Two Cases.

Purpose: To report two rare cases of orbital cholesterol granuloma (CG) presenting with ptosis and proptosis. Methods: The first case was a 31-year-old male presented with progressive ptosis of the left eye (LE) during the past year and the second case was a 35-year-old male presented with proptosis of the right eye (RE) for 5 months ago. Orbital computed tomography revealed a cystic well-demarcated lesion in the superotemporal orbit with adjacent bone erosion in the LE of the first case and the RE of the second case. Results: In both cases, the tumor was excised completely through an anterolateral orbitotomy approach. Histopathological evaluation showed fibroconnective tissue with cholesterol clefts surrounded by granulomatous inflammation consistent with the diagnosis of CG. The symptoms of patients were resolved after surgery. Conclusions: CG of the orbit is a rare lesion that commonly occurred in the superotemporal area. Erosive bone expansion is the characteristic finding of this lesion that can be mistaken with lacrimal gland malignancies. Hence, it is essential to keep CG in mind in the differential diagnosis of lacrimal gland masses.

Regeneration of collecting lymphatic vessels following injury.

Secondary lymphedema is a debilitating condition driven by impaired regeneration of lymphatic vasculature following lymphatic injury, surgical removal of lymph nodes in cancer patients or infection. However, the extent to which collecting lymphatic vessels regenerate following injury remains unclear. Here, we employed a novel mouse model of lymphatic injury in combination with state-of-the-art lymphatic imaging to demonstrate that the implantation of an optimized fibrin gel following lymphatic vessel injury leads to the growth and reconnection of the injured lymphatic vessel network, resulting in the restoration of lymph flow to the draining node. Intriguingly, we found that fibrin implantation elevates the tissue levels of CCL5, a potent macrophage-recruiting chemokine. Notably, CCL5-KO mice displayed a reduced ability to reconnect injured vessels following fibrin gel implantation. These novel findings shed light on the mechanisms underlying lymphatic regeneration and suggest that enhancing CCL5 signaling may be a promising therapeutic strategy for enhancing lymphatic regeneration.

The broad use of the Pm8 resistance gene in wheat resulted in hypermutation of the AvrPm8 gene in the powdery mildew pathogen.

BACKGROUND: Worldwide wheat production is under constant threat by fast-evolving fungal pathogens. In the last decades, wheat breeding for disease resistance heavily relied on the introgression of chromosomal segments from related species as genetic sources of new resistance. The Pm8 resistance gene against the powdery mildew disease has been introgressed from rye into wheat as part of a large 1BL.1RS chromosomal translocation encompassing multiple disease resistance genes and yield components. Due to its high agronomic value, this translocation has seen continuous global use since the 1960s on large growth areas, even after Pm8 resistance was overcome by the powdery mildew pathogen. The long-term use of Pm8 at a global scale provided the unique opportunity to study the consequences of such extensive resistance gene application on pathogen evolution. RESULTS: Using genome-wide association studies in a population of wheat mildew isolates, we identified the avirulence effector AvrPm8 specifically recognized by Pm8. Haplovariant mining in a global mildew population covering all major wheat growing areas of the world revealed 17 virulent haplotypes of the AvrPm8 gene that grouped into two functional categories. The first one comprised amino acid polymorphisms at a single position along the AvrPm8 protein, which we confirmed to be crucial for the recognition by Pm8. The second category consisted of numerous destructive mutations to the AvrPm8 open reading frame such as disruptions of the start codon, gene truncations, gene deletions, and interference with mRNA splicing. With the exception of a single, likely ancient, gain-of-virulence mutation found in mildew isolates around the world, all AvrPm8 virulence haplotypes were found in geographically restricted regions, indicating that they occurred recently as a consequence of the frequent Pm8 use. CONCLUSIONS: In this study, we show that the broad and prolonged use of the Pm8 gene in wheat production worldwide resulted in a multitude of gain-of-virulence mechanisms affecting the AvrPm8 gene in the wheat powdery mildew pathogen. Based on our findings, we conclude that both standing genetic variation as well as locally occurring new mutations contributed to the global breakdown of the Pm8 resistance gene introgression.

Minimal Invasive Procedures in Strabismus Surgery: A Narrative Review.

Purpose: To review the principles and different techniques of minimally invasive procedures in strabismus surgery. Methods: This is a narrative review on minimally invasive procedures in strabismus surgery including general aspects and different new modifications on conventional strabismus surgery. We reviewed 24 articles published between 1993 and 2020. Results: Minimal invasive procedures could be categorized into two subsets: one which minimizes conjunctival opening size and another which minimizes the muscle manipulations. Different conjunctival approaches have been introduced, such as Cul-de-sac and minimally invasive strabismus surgery incisions. Furthermore, there are different techniques for extraocular muscle weakening, strengthening, and transposition, such as mini-tenotomy, plication, mini-plication, Nishida, and modified Nishida procedures. Moreover, there are some techniques for handling strabismus in heavy eyes with high myopia and using adjustable sutures for strabismus correction. Conclusions: Minimally invasive procedures in strabismus surgery consist of surgical procedures that minimize tissue disruption, speed up rehabilitation, and often ultimate better outcomes. These techniques could be replaced traditional methods to reduce conjunctival and lid swelling in the direct postoperative period.

Three-dimensional (3D) Visualization Educational Modeling for Ophthalmology Residents' Training: Viewpoints.

Background: Three-dimensional models are used to guide residents and physicians in accessing specific anatomical areas and types of fractures and better diagnosis of anomalies. These models are useful for illuminating complex anatomical areas, such as orbit, especially limited space with sensitive access. The aim of this study was to design a three-dimensional visualization educational modeling for ophthalmology residents' training. Methods: This study is a product-oriented application that uses radiological images of anatomy, anomalies, and orbital fractures based on actual CT scans of patients. These CT scans were carefully selected from the Picture Archiving and Communication System of Ghaem Hospital of Mashhad University of Medical Sciences. Results: To produce twelve 3D models, the CT scan files were converted to 3D printer output. Then, the models were presented to residents at a training session by an ophthalmologist. These models created all major fractures associated with the orbit area and most disorders, anomalies of this area and several normal anatomical. The features of 3D models were mentioned. The strengths and weaknesses of the educational modeling, the level of satisfaction with the use of three-dimensional models, suggestions and criticisms were assessed qualitatively by the residents. Satisfaction was reported 100% by residents. Suggestions for future 3D models were presented, and the only criticism was fear of exams and grades. Conclusion: Real-size 3D modeling help to understand the spatial and mental imagery of anatomy and orbital pathology and to touch different anatomical areas creates a clear image in the minds of residents, especially in the orbit.

Effect of Polycitra-K and Bicitra in the Treatment of Pediatric Nephrolithiasis: A Double-Blind Randomized Trial.

Background: Urolithiasis is a common, sever, painful, and costly disease with a high probability of relapse. This study was performed to compare the effect of Polycitra-K containing potassium citrate and Bicitra containing sodium citrate in the treatment of kidney stones in children who referred to Hazrat Masoumeh hospital in Qom. Methods: This double-blind randomized clinical trial study was carried out on 176 patients aged between 5 and 18 years old with kidney stones, hypocitraturia, and negative urine who referred to Hazrat Masoumeh hospital in Qom (Iran). Patients were divided into 2 groups of treatment (a dose of 1 mL/kg or 1-1.5 mg/ kg Polycitra-K) and control (Bicitra in the same dose). The results of kidney ureter bladder X ray (KUB ) was followed and the 2 groups were compared. The chi-square test or the Fisher exact test was used to analyze qualitative values in the treated groups. Results: Regarding bladder stones, there was a significant difference between the 2 treatment groups (p = 0.025), in which16 patients (18.2%) in the Polycitrat-K group and 29 patients (33%) in the Bicitra group had bladder stones. With respect to stone passage, 58 patients (65.9%) in the Polycitra-K group and 36 patients (40.9%) in the Bicitra group were recorded. Conclusion: Oral Polycitrat-K is an effective preferential supplement against kidney stones in children due to urine alkalization, but the results of our study showed that both Polycitrat-K and Bicitra drugs have similar effects as therapeutic agents. Registration code in the Iranian Registry of Clinical Trials: IRCT20190619043945N1.

Synthesis of TiC@C-anatase/rutile@polyvinyl alcohol/xylan: a powerful photocatalyst for degradation of organic pollutant under visible light.

In this study, a composite bearing titanium carbide (TiC), titanium dioxide (TiO2), polyvinyl alcohol and xylan (TiC@C-anatase/rutile@polyvinyl alcohol/xylan) was synthesized and applied as a photocatalyst for the degradation of bromophenol blue (BPB) solution through several steps. Nanostructure of TiC and TiO2 in the anatase and rutile phases was obtained through heat treatment of TiC at different times and temperatures (TiC@AR) which led to a reduction in energy bandgap from UV to visible light, in addition to the enhancement of the surface activity. After TiC@AR polymerization by xylan and polyvinyl alcohol and obtaining TiC@AR/PX, the energy bandgap reduced to IR range (52% of the sunlight) while showing an enhancement in the surface activity. The photocatalytic activity of the compounds was tested by studying the decomposition of BPB solution under visible light. The result illustrated the ability of TiC and TiC@AR to decrease the concentration of BPB after 150 min by 35% and 37%, respectively, while this reduction was 72% for TiC@AR/PX. Considering the effective parameters, the energy bandgap and the surface layer played key roles in photocatalytic degradation.

Visual outcomes of photorefractive keratectomy in non-children with anisometropic amblyopia: One-year Follow-up Outcomes.

OBJECTIVE: To evaluate the safety, efficiency, short term stability, and sensory results of photorefractive keratectomy (PRK) in anisometropic in non-compliant children with correction. METHODS: Twelve eyes of 12 children with an age range: 6-17 years and anisometropic amblyopia who underwent PRK under general anesthesia to correct the dioptric difference between the eyes were included in this study. A complete ophthalmic assessment including refractive status, uncorrected and corrected distance visual acuity (UDVA & CDVA), and binocular vision status using the Worth 4-dot test and stereopsis were performed before and 1, 3, 6, and 12 months after PRK. RESULTS: The mean preoperative CDVA was 0.34 ± 0.24 LogMAR which showed a statistically significant improvement at 12 months (0.20 ± 0.19, p = 0.024) after surgery compared to the preoperative assessment. (p = 0.003) The mean preoperative UDVA was 0.63 ± 0.24 LogMAR that increased to 0.44 ± 0.24, 0.32 ± 0.16, 0.25 ± 0.19, and 0.25 ± 0.19 LogMAR at 1, 3, 6, and 12 months after PRK, respectively. One to three lines improvement in UDVA and CDVA was seen in 10 (83.4%) and 8 eyes (66.7%); while one line UDVA and CDVA loss was seen in one (8.3%) and one (8.3%) eye and unchanged UDVA and CDVA was seen in 1 (8.3%) and 3 eyes (25%), respectively. The mean preoperative stereoacuity was 341.9 ± 245.7 s of arc, which significantly improved to 166.6 ± 87.5 s of arc 12 months after PRK. (p = 0.012). CONCLUSION: PRK was an effective surgical alternative to improve visual acuity and stereopsis in anisometropic children who did not cooperate with conventional methods of amblyopia therapy.

The Effect of the Protein Synthesis Entropy Reduction on the Cell Size Regulation and Division Size of Unicellular Organisms.

The underlying mechanism determining the size of a particular cell is one of the fundamental unknowns in cell biology. Here, using a new approach that could be used for most of unicellular species, we show that the protein synthesis and cell size are interconnected biophysically and that protein synthesis may be the chief mechanism in establishing size limitations of unicellular organisms. This result is obtained based on the free energy balance equation of protein synthesis and the second law of thermodynamics. Our calculations show that protein synthesis involves a considerable amount of entropy reduction due to polymerization of amino acids depending on the cytoplasmic volume of the cell. The amount of entropy reduction will increase with cell growth and eventually makes the free energy variations of the protein synthesis positive (that is, forbidden thermodynamically). Within the limits of the second law of thermodynamics we propose a framework to estimate the optimal cell size at division.

3D Printed Models for Teaching Orbital Anatomy, Anomalies and Fractures.

PURPOSE: The aim of this study was to determine the efficacy of using 3D printing models in the learning process of orbital anatomy and pathology by ophthalmology residents. METHODS: A quasi-experimental study was performed with 24 residents of ophthalmology at Mashhad University of Medical Sciences. Each stratum was randomized into two groups. The educational booklets were distributed, and various forms of orbital 3D models were printed from orbital computed tomography (CT) scans. Knowledge enhancement on the topics was measured by comparing pretest and posttest scores. RESULTS: Thirteen residents who were trained using traditional methods were deemed the control group; while 11 residents who were trained using the 3D printed models were classed as the intervention group. The control group was younger than the intervention group (P = 0.047). The results showed that there was a statistically significant difference in the total posttest scores between the two groups. Based on the repeated measures of the analysis of variance (ANOVA), score variables were significant between the two groups (P = 0.008). Interestingly, the use of the 3D educational model was more effective and statistically significant with the year one residents as compared to the year two residents (P = 0.002). CONCLUSION: This study is the first one in Iran quantifying the effects of learning using 3D printed models in medical education. In fact, 3D modeling training is seemingly effective in teaching ophthalmic residents. As residents have never encountered such technology before, their experience using 3D models proved to be satisfactory and had a surprising positive effect on the learning process through visual training.

Spectral- and Polarization-Dependent Scattering of Gold Nanobipyramids for Exogenous Contrast in Optical Coherence Tomography.

Polarization-sensitive optical coherence tomography (PS-OCT) reveals the subsurface microstructure of biological tissue and provides information regarding the polarization state of light backscattered from tissue. Complementing OCT's structural signal with molecular imaging requires strategies to simultaneously detect multiple exogenous contrast agents with high specificity in tissue. Specific detection of molecular probes enables the parallel visualization of physiological, cellular, and molecular processes. Here we demonstrate that, by combining PS-OCT and spectral contrast (SC)-OCT measurements, we can distinguish signatures of different gold nanobipyramids (GNBPs) in lymphatic vessels from the surrounding tissue and blood vessels in live mouse models. This technique could well be extended to other anisotropic nanoparticle-based OCT contrast agents and presents significant progress toward enabling OCT molecular imaging.

Comparison of binocular game and patching in treating mild to moderate anisometropic amblyopia: a study protocol for a randomized controlled trial.

BACKGROUND: Amblyopia, as a neurodevelopmental preventable visual disorder, affects approximately 1.1 % in Asia. A binocular approach to treating amblyopia has been recently proposed. Whether the binocular playing game treatment is comparable to patching treatment needs further randomized clinical trials. To address this, the present research, designs, develops, and evaluates a new binocular game to treat amblyopia. METHODS: This study has been designed as a non-inferiority, randomized, two parallel-group, controlled trial. Forty-four patients between 4 and 12 years diagnosed with amblyopia will be randomly assigned to the control and intervention groups. In the intervention group, amblyopia treatment is provided with red-green anaglyphic glasses and a red filter placed in front of the amblyopic eye, along with a game to be played for 30 min twice a day. Those in the control group will receive patch therapy according to amblyopia treatment study protocol. The primary outcome is to change visual acuity in the amblyopic eye from the baseline to 3 months after randomization. ETHICS AND DISSEMINATION: The Ethics Committee of Mashhad University of Medical sciences' approval date was February 28, 2018, with a reference code of IR.MUMS.fm.REC.1396.783. Thus far, the recruitment of participants has not been completed and is scheduled to end in September 2021. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20180217038768N1 . Registered on 22 April 2019.

Monitoring of hospital sewage shows both promise and limitations as an early-warning system for carbapenemase-producing Enterobacterales in a low-prevalence setting.

Carbapenemase-producing Enterobacterales (CPE) constitute a significant threat to healthcare systems. Continuous surveillance is important for the management and early warning of these bacteria. Sewage monitoring has been suggested as a possible resource-efficient complement to traditional clinical surveillance. It should not least be suitable for rare forms of resistance since a single sewage sample contains bacteria from a large number of individuals. Here, the value of sewage monitoring in early warning of CPE was assessed at the Sahlgrenska University Hospital in Gothenburg, Sweden, a setting with low prevalence of CPE. Twenty composite hospital sewage samples were collected during a two-year period. Carbapenemase genes in the complex samples were analyzed by quantitative PCR and the CPE loads were assessed through cultures on CPE-selective agar followed by species determination as well as phenotypic and genotypic tests targeting carbapenemases of presumed CPE. The findings were related to CPE detected in hospitalized patients. A subset of CPE isolates from sewage and patients were subjected to whole genome sequencing. For three of the investigated carbapenemase genes, blaNDM, blaOXA-48-like and blaKPC, there was concordance between gene levels and abundance of corresponding CPE in sewage. For the other two analyzed genes, blaVIM and blaIMP, there was no such concordance, most likely due to the presence of those genes in non-Enterobacterales populating the sewage samples. In line with the detection of OXA-48-like- and NDM-producing CPE in sewage, these were also the most commonly detected CPE in patients. NDM-producing CPE were detected on a single occasion in sewage and isolated strains were shown to match strains detected in a patient. A marked peak in CPE producing OXA-48-like enzymes was observed in sewage during a few months. When levels started to increase there were no known cases of such CPE at the hospital but soon after a few cases were detected in samples from patients. The OXA-48-like-producing CPE from sewage and patients represented different strains, but they carried similar blaOXA-48-like-harbouring mobile genetic elements. In conclusion, sewage analyses show both promise and limitations as a complement to traditional clinical resistance surveillance for early warning of rare forms of resistance. Further evaluation and careful interpretation are needed to fully assess the value of such a sewage monitoring system.