OBJECTIVE: Corneal crosslinking (CXL) procedures are the treatment of choice in halting progressive corneal ectasia and preserving visual acuity due to keratoconus. Pulsed crosslinking (P-CXL) was developed using intermittent pulsing ultraviolet (UV) light to mitigate the depletion of oxygen levels that occurs with continuous UV exposure in standard crosslinking protocols (C-CXL). This study aimed to explore the use of P-CXL in the treatment of keratoconus and determine whether the availability of oxygen in P-CXL carries superior efficacy outcomes as an alternative to C-CXL modalities.
METHODS: This review was undertaken in accordance with PRISMA guidelines. A search of several databases conducted with two separate reviewers resulted in 29 papers meeting inclusion criteria for the review, 14 selected for meta-analysis. Primary outcomes assessed by the included papers included maximum keratometry (Kmax), corrected and uncorrected distance visual acuity (CDVA, UDVA), and secondary outcomes included central corneal thickness (CCT), endothelial cell count and demarcation line. Statistical analyses were carried out on Review Manager 5.4 and the meta-analysis employed a random-effects model, which estimated the weighted effect size of raw means using inverse variance weights.
RESULTS: At 12 months P-CXL showed statistically significant reductions in Kmax (-0.75 D; p < 0.001) and improvement in CDVA (-0.10 logMAR; p < 0.001) compared to baseline. The meta-analysis of comparative studies determined that mean differences in Kmax, CDVA, UDVA, Kmean and CCT after 12 months were not statistically significant between pulsed and continuous crosslinking groups.
CONCLUSIONS: Overall, P-CXL is effective in improving visual acuity and keratometry outcomes in keratoconus. The meta-analysis did not show a statistically significant difference in Kmax and CDVA between P-CXL and C-CXL, indicating a non-inferiority of P-CXL. However, findings of the meta-analysis are limited by the fact that different energy levels and exposure times were used for P-CXL in comparison to C-CXL in some studies, making it unsuitable to determine whether the efficacy of CXL is improved by the use of pulsed light.
CONCLUSIONS: What is Known • Pulsed crosslinking (P-CXL) uses intermittent UV light to prevent oxygen depletion when using higher energy protocols, unlike continuous UV exposure in standard continuous crosslinking (C-CXL). • This should theoretically enhance the efficacy of the treatment by maintaining higher oxygen levels that are crucial to the cross-linking process. • There are no systematic reviews or meta-analyses directly comparing the efficacy or safety of P-CXL to C-CXL. What is New • Meta-analysis revealed differences in keratometry between P-CXL and C-CXL groups with equivalent fluence (7.2 J/cm2) at 12 months were not statistically significant (Kmax -0.04 dioptres; p = 0.84). • Meta-analysis revealed differences in visual acuity between P-CXL and C-CXL groups with equivalent fluence (7.2 J/cm2) at 12 months were not statistically significant (CDVA -0.01 logMAR letters; p = 0.57). • The use of intermittent pulsing in higher energy CXL protocols renders statistically similar outcomes as continuous light exposure at equivalent fluence (7.2 J/cm2).

OBJECTIVE: To evaluate the stone ablation rate and direct thermal damage from thulium fiber laser (TFL) lithotripsy using continuous (C) and burst (B) lasing techniques on an in vitro ureteral model.
METHODS: The TFL Drive (Coloplast, Humlebaek, Denmark) was used in an in vitro saline-submerged ureteral model. Ten participants, including five junior and five experienced urologists, conducted the experimental setup with 7 different settings comparing two lasing techniques: steady-state lasing (0.5 J/10 Hz = 5W for 300 s and 0.5 J/20 Hz = 10W for 150 s) and burst, intermittent 5 s on/off lasing (0.5 J/20 Hz, 0.5 J/30 Hz, 0.5 J/60 Hz, 0.1 J/200 Hz, and 0.05 J/400 Hz) with a target cumulative energy of 1500 J using cubic 125 mm3 phantom BegoStonesTM. Ureteral damage was graded 1-3 based on the severity of burns and holes observed on the surface of the ureteral model.
RESULTS: The were no significant differences in stone ablation mass neither between C and B lasing techniques, nor between expertise levels. At C lasing technique had only mild ureteral lesions with no significant differences between expertise levels (p: 0.97) or laser settings (p: 0.71). At B lasing technique, different types of thermal lesions were found with no expertise (p: 0.11) or setting (p: 0.83) differences. However, B laser setting had higher grade direct thermal lesions than C (p: 0.048).
CONCLUSIONS: Regarding efficacy, C and B lasing techniques achieve comparable stone ablation rates. Safety-wise, B lasing mode showed higher grade of direct thermal lesions. These results should be further investigated to verify which of the lasing mode is the safest in vivo. Until then and unless proven otherwise, a C mode with low frequency should be recommended to avoid ureteral wall lesions.

Continuous glucose monitors (CGMs) are an increasingly prevalent electronic medical device utilized by patients with diabetes, offering several advantages over \"finger sticks\". There is a resulting rise in patients with CGMs seen in radiation oncology clinics. Manufacturers specify that CGMs should not be exposed to radiation (both diagnostic and therapeutic), due to risk of device damage, creating challenges for patients and providers. We present a workflow for management of CGMs in radiation oncology patients, beginning with systematic screening by providers and staff. We propose options for CGM management together with the device prescriber, including removal of the CGM or keeping it in place with periodic finger sticks to confirm accuracy, and offer guidance to radiation oncology providers and staff.

BACKGROUND: The all-inside technique is now the most established treatment for meniscal repair, this usually involves a suture-based repair utilising interrupted sutures. A similar technique using continuous sutures can also be used; however there are no studies in the literature appraising this technique. This study aims to review outcomes for patients undergoing meniscal repair using a continuous suture all-inside technique.
METHODS: We reviewed patients undergoing meniscal repair using a continuous suture all-inside technique over a 5 year period. We recorded demographic details, injury type, surgical procedure, incidence of reoperation, functional outcomes (Tegner-Lysholm and International Knee Documentation Committee (IKDC) score) return to sport and failure of repair.
RESULTS: Data were collected for 37 patients. Mean age was 25.8 years, 81%, were male, median time to theatre was 169 days, mean follow-up time was 2.9 years. Concurrent ACL ruptures were present in 57%, all underwent ACL reconstruction in the same sitting. The mean Tegner-Lysholm score was 89. Mean IKDC score was 90.2. 78% were able to return to sport. Overall failure rate was 10.81%. Increasing age was associated with a decreased IKDC score (p = 0.02). Tegner-Lysholm score was significantly greater in patients with concurrent ACL injuries (p = 0.03) and patients with lateral meniscal tears (p = 0.04).
CONCLUSIONS: In the first study to review outcomes following continuous all-inside suture-based meniscal repair we demonstrate excellent clinical outcomes with IKDC, Tegner-Lysholm, return to play and failure rates comparable to other commonly used techniques. We conclude that this is an acceptable and cost-effective technique.

UNASSIGNED: This study aimed to evaluate the safety and efficacy of continuous propofol infusion for anesthesia during endoscopic ultrasonography (EUS).
UNASSIGNED: A total of 427 consecutive patients who underwent EUS between May 2018 and February 2019 were enrolled in this study. The patients were divided into two propofol infusion groups: continuous (n=207) and intermittent (n=220). The following parameters were compared: (1) propofol dose, (2) respiratory and circulatory depression, (3) body movement requiring discontinuation of the examination, (4) awakening score, and (5) patient satisfaction.
UNASSIGNED: The median total maintenance dose of propofol was significantly higher in the continuous group than in the intermittent group (160.0 mg vs. 130.0 mg, respectively); however, the reduction in SpO2 was significantly lower in the continuous group (2.9% vs. 13.2%). Body movements occurred less frequently in the continuous group than in the intermittent group (40.1% vs. 49.5%, respectively). The rate of complete awakening was significantly higher in the continuous group than in the intermittent group. Finally, there was a significant difference in the percentage of patients who answered \"absolutely yes\" when asked about receiving EUS again: 52.7% in the continuous group vs. 34.3% in the intermittent group.
UNASSIGNED: Continuous infusion resulted in stable sedation and reduced propofol-associated risks.

Peptide antibodies have become one of the most important classes of reagents in molecular biology and clinical diagnostics. For this reason, methods for their production and characterization continue to be developed, including basic peptide synthesis protocols, peptide-conjugate production and characterization, conformationally restricted peptides, immunization procedures, etc. Detailed mapping of peptide antibody epitopes has yielded important information on antibody-antigen interaction in general and specifically in relation to antibody cross-reactivity and theories of molecular mimicry. This information is essential for detailed understanding of paratope-epitope dynamics, design of antibodies for research, design of peptide-based vaccines, development of therapeutic peptide antibodies, and de novo design of antibodies with predetermined specificity.

OBJECTIVE: To determine the accuracy of a continuous glucose monitoring system (CGMS) device by comparing glucose concentrations measured over time as determined by the CGMS to those of the chemistry analyzer (reference method).
METHODS: 7 healthy goats and 7 dairy calves.
METHODS: A randomized, crossover design with 3 treatments: control, hypoglycemia, and hyperglycemia. The CGMS device was applied to the neck. Hypoglycemia and hyperglycemia were induced by insulin and xylazine, respectively. Glucose concentrations were measured by the chemistry analyzer CGMS, point-of-care glucometer, and intensive care unit machine at 0 (before treatment), 2, 4, 6, 8, 10, and 12 hours. Agreement between the CGMS and the chemistry analyzer was determined by Bland-Altman plots. The analytical and clinical accuracy of the CGMS was determined using the International Organization for Standardization (ISO) 15197:2013 criteria and the Parkes error grid analysis.
RESULTS: In goats, the CGMS overestimated glucose concentrations during the hypoglycemic, normoglycemia, and hyperglycemia treatments. In calves, the CGMS underestimated glucose concentrations during the hypoglycemic treatment but overestimated glucose concentrations in normoglycemia and hyperglycemic treatments. The CGMS met the ISO clinical accuracy criteria for goats and calves, with > 99% of the glucose measurements in zones A and B of the Parkes grid. However, the CGMS did not meet the ISO 15197:2013 criteria for analytical accuracy.
CONCLUSIONS: The CGMS evaluated in our study only met the ISO 15197:2013 clinical accuracy criteria, not the analytical accuracy. Therefore, the device might be considered for clinical use.

Objectives The Clinical Practice Guidelines for the Management of Sepsis and Septic Shock weakly recommend steroids for septic shock resistant to fluid resuscitation and vasopressors. This study aimed to describe the clinical practices for septic shock in the real world and to compare the association between the intermittent or continuous infusion of steroids and the prognosis. Methods This was a retrospective cohort study based on the AMOR-VENUS, in which Japanese intensive care unit (ICU) inpatients were enrolled between January and March 2018. Adult patients with sepsis who received vasopressors within 72 h of ICU admission were included. The patients were divided into non-steroid and steroid groups, which were further divided into intermittent and continuous infusion groups. The patient characteristics and details of the steroids are described. To investigate the association between intermittent or continuous infusion, shock reversal, and mortality, logistic regression analyses were performed after adjusting for possible confounding factors. Results A total of180 patients with septic shock from 18 ICUs were enrolled. The mean age was 69.6 (SD, 14.3) years. Sixty-three patients (35.0%) received steroids (26 intermittently, 37 continuously). In the steroid group, hydrocortisone was used in 85.7%, the median daily dose was 192 mg, and the steroids were administered within 6 h of initiating vasopressor in 71.4%. The adjusted odds ratios of shock reversal on the 7th day and the ICU mortality for continuous versus intermittent infusion were 1.90 (95%CI, 0.43-8.40) and 0.61 (0.10-3.85), respectively. Conclusions There was considerable variation in the criteria for the selection of patients and in the decision to use continuous or intermittent steroid infusion.

In this study, a series of cobalt-based spinel ferrites catalysts, including nickel, cobalt, zinc, and copper ferrites, were synthesized using the sol-gel auto-combustion method followed by a chemical reduction process. These catalysts were employed for accelerating hydrogen generation via the sodium borohydride hydrolysis process. A continuous stirred tank reactor was used to perform catalytic reactor tests. All samples were subjected to analysis using XRD, FESEM, EDX, FTIR, and nitrogen adsorption-desorption techniques. The results revealed that the cobalt-based copper ferrite sample, Co/Cu-Ferrite, exhibited superior particle distribution, and porosity characteristics, as it achieved a high hydrogen generation rate of 2937 mL/min.gcat. In addition, the higher electrical donating property of Cu-Ferrite which leads to the increase in the electron density of the cobalt active sites can account for its superior performance towards hydrolysis of NaBH4. Using the Arrhenius equation and the zero-order reaction calculation, activation energy for the sodium borohydride hydrolysis reaction on the Co/Cu-Ferrite catalyst was determined to be 18.12 kJ/mol. This low activation energy compared to other cobalt-based spinel ferrite catalysts confirms the catalyst\'s superior performance as well. Additionally, the outcomes from the recycling experiments revealed a gradual decline in the catalyst\'s performance after each cycle during 4 repetitive cycles. The aforementioned properties render the Co/Cu-Ferrite catalyst an efficient catalyst for hydrogen generation through NaBH4 hydrolysis.

The hormone cortisol, released as the end-product of the hypothalamic-pituitary-adrenal (HPA) axis, has a well-characterized circadian rhythm that enables an allostatic response to external stressors. When the pattern of secretion is disrupted, cortisol levels are chronically elevated, contributing to diseases such as heart attacks, strokes, mental health disorders, and diabetes. The diagnosis of chronic stress and stress related disorders depends upon accurate measurement of cortisol levels; currently, it is quantified using mass spectroscopy or immunoassay, in specialized laboratories with trained personnel. However, these methods are time-consuming, expensive and are unable to capture the dynamic biorhythm of the hormone. This critical review traces the path of cortisol detection from traditional laboratory-based methods to decentralised cortisol monitoring biosensors. A complete picture of cortisol biology and pathophysiology is provided, and the importance of precision medicine style monitoring of cortisol is highlighted. Antibody-based immunoassays still dominate the pipeline of development of point-of-care biosensors; new capture molecules such as aptamers and molecularly imprinted polymers (MIPs) combined with technologies such as microfluidics, wearable electronics, and quantum dots offer improvements to limit of detection (LoD), specificity, and a shift toward rapid or continuous measurements. While a variety of different sensors and devices have been proposed, there still exists a need to produce quantitative tests for cortisol ─ using either rapid or continuous monitoring devices that can enable a personalized medicine approach to stress management. This can be addressed by synergistic combinations of technologies that can leverage low sample volumes, relevant limit of detection and rapid testing time, to better account for cortisol\'s shifting biorhythm. Trends in cortisol diagnostics toward rapid and continuous monitoring of hormones are highlighted, along with insights into choice of sample matrix.