Influence of dengue virus serotypes on the abundance of Aedes aegypti insect-specific viruses (ISVs).

A comprehensive understanding of the virome in mosquito vectors is crucial for assessing the potential transmission of viral agents, designing effective vector control strategies, and advancing our knowledge of insect-specific viruses (ISVs). In this study, we utilized Oxford Nanopore Technologies metagenomics to characterize the virome of Aedes aegypti mosquitoes collected in various regions of Colombia, a country hyperendemic for dengue virus (DENV). Analyses were conducted on groups of insects with previous natural DENV infection (DENV-1 and DENV-2 serotypes), as well as mosquito samples that tested negative for virus infection (DENV-negative). Our findings indicate that the Ae. aegypti virome exhibits a similar viral composition at the ISV family and species levels in both DENV-positive and DENV-negative samples across all study sites. However, differences were observed in the relative abundance of viral families such as Phenuiviridae, Partitiviridae, Flaviviridae, Rhabdoviridae, Picornaviridae, Bromoviridae, and Virgaviridae, depending on the serotype of DENV-1 and DENV-2. In addition, ISVs are frequently found in the core virome of Ae. aegypti, such as Phasi Charoen-like phasivirus (PCLV), which was the most prevalent and showed variable abundance in relation to the presence of specific DENV serotypes. Phylogenetic analyses of the L, M, and S segments of the PCLV genome are associated with sequences from different regions of the world but show close clustering with sequences from Brazil and Guadeloupe, indicating a shared evolutionary relationship. The profiling of the Ae. aegypti virome in Colombia presented here improves our understanding of viral diversity within mosquito vectors and provides information that opens the way to possible connections between ISVs and arboviruses. Future studies aimed at deepening our understanding of the mechanisms underlying the interactions between ISVs and DENV serotypes in Ae. aegypti could provide valuable information for the design of effective vector-borne viral disease control and prevention strategies.IMPORTANCEIn this study, we employed a metagenomic approach to characterize the virome of Aedes aegypti mosquitoes, with and without natural DENV infection, in several regions of Colombia. Our findings indicate that the mosquito virome is predominantly composed of insect-specific viruses (ISVs) and that infection with different DENV serotypes (DENV-1 and DENV-2) could lead to alterations in the relative abundance of viral families and species constituting the core virome in Aedes spp. The study also sheds light on the identification of the genome and evolutionary relationships of the Phasi Charoen-like phasivirus in Ae. aegypti in Colombia, a widespread ISV in areas with high DENV incidence.

Development of a Risk Prediction Nomogram for Carotid Restenosis in the One Year RECAST Registry.

OBJECTIVE: Long term benefit of carotid angioplasty and stenting (CAS) can be reduced by recurrent stroke related to in stent restenosis (ISR). An individualised predictive tool is needed to identify ISR events. A nomogram for individual risk assessment of ISR ≥ 70% after CAS is proposed. METHODS: A national observational, prospective, multicentre registry was conducted between January 2015 and December 2020. Cohorts of patients with symptomatic or asymptomatic severe carotid stenosis who underwent CAS were included with a follow up of at least 1 year after CAS. Duplex ultrasound was used to assess in stent restenosis. Pre-operative factors were compared between the non-ISR and ISR groups. Kaplan-Meier and Cox regression were used for variable selection. The nomogram was formulated and validated by concordance indices and calibration curves. An in stent restenosis risk table was generated for risk stratification. RESULTS: A total of 354 patients were included in the analysis. The ISR rate of ≥ 70% was 7.6% (n = 27). Peripheral arterial disease (hazard ratio [HR] 3.18, 95% confidence interval [CI] 1.23 - 8.24, p = .017), anterior communicating artery absence (HR 3.38, 95% CI 1.27 - 8.94, p = .016), diabetes mellitus (HR 3.34, 95% CI 1.21 - 9.26, p = .020), female sex (HR 2.99, 95% CI 1.04 - 8.60, p = .041), and pre-procedure pathologic ultrasound vasoreactivity (HR 3.87, 95% CI 1.43 -10.50, p = .008), as independent risk factors for ISR of ≥ 70%, were included in the nomogram. Concordance index at 12 and 24 months was 0.83. In low risk groups, ISR of ≥ 70% occurred in 4.8% of patients during follow up compared with 56.2% of patients in the high risk groups (p < .001). CONCLUSION: The nomogram and risk evaluation score have good predictive ability for ISR. They can be used as practical clinical tools for individualised risk assessment.

Polarisation compensation in non-planar image-rotating OPO ring resonators.

Non-planar image-rotating OPO ring resonators necessitate polarisation compensation in contrast to their planar counterparts. This is essential for maintaining phase matching conditions for non-linear optical conversion in the resonator during each cavity round trip. In this study, we examine the polarisation compensation and its impact on the performance of two types of non-planar resonators: RISTRA with a π2 image rotation and FIRE with a fractional image rotation (π2 fraction). The RISTRA is insensitive to mirror phase shifts, while the FIRE has a more complex dependence of polarisation rotation on mirror phase shifts. There has been debate over whether a single birefringent element can provide adequate polarisation compensation for non-planar resonators beyond RISTRA-type. Our results show that under certain experimentally feasible conditions, even FIRE resonators can achieve adequate polarisation compensation with a single half-wave plate. We validate our theoretical analysis through numerical simulations and experimental studies of OPO output beam polarisation using ZnGeP2 non-linear crystals.

Cancer diagnosis in primary care after second pandemic year in Catalonia: a time-series analysis of primary care electronic health records covering about 5 million people.

BACKGROUND: During the COVID-19 pandemic, the incidence of chronic disease had drastically been reduced due to health care interruptions. The aim of this study is to analyse cancer diagnosis during the last 2 years of the COVID-19 pandemic. METHODS: Time-series study of cancer diagnoses recorded in primary care settings, using data from the primary care electronic health records from January 2014 to December 2021. We obtained the expected monthly rate per 100,000 inhabitants using a time regression adjusted by trend and seasonality. We additionally compared rates of cancer diagnoses in 2019 with those of 2020 and 2021 using the t-test. We performed the analysis globally, by sex and by type of cancer. RESULTS: In 2020, the rate of cancer diagnoses had reduced by -21% compared to 2019 (P < 0.05). Greater reductions were observed during the lockdown in early 2020 (>40%) and with some types of cancers, especially prostate and skin cancers (-29.6% and -26.9%, respectively, P < 0.05). Lung cancers presented statistically non-significant reductions in both years. Cancer diagnosis returned to expected around March 2021, and the rate in 2021 was similar to that of 2019 (overall difference of 0.21%, P = 0.967). However, an 11% reduction was still found when comparing the pandemic months of 2020-2021 with pre-pandemic months. CONCLUSIONS: Although primary care cancer diagnoses in 2021 have returned to pre-pandemic levels, missing diagnoses during the last 2 years have not been fully recovered.

End-of-life care for Filipino patients with cancer.

Providing end-of-life care within the cultural context of a Filipino patient in the United States is a complex process for clinicians, patients, and their families. An inclusive approach is crucial, especially because a significant proportion of patients belong to minority groups such as Filipinos, who represent the fourth largest group of immigrants in the United States as of data available in 2019. The case provided in this paper highlights the importance of family, religion, and finances in guiding the best possible way of providing end-of-life care for Filipino patients with cancer. At the end of this review, we discuss concrete action points that may give a non-Filipino physician a deeper understanding of end-of-life care for Filipinos.

Effects of pump pulse energy and repetition rate on beam quality in a high-power mid-infrared ZnGeP2 OPO.

We report on changes of beam quality with rising pump pulse energy and repetition rate in a high-power mid-infrared ZnGeP2 (ZGP) OPO in a non-planar cavity. The ZGP OPO generates 25 W in 3 - 5 µm pumped by a 10 kHz Q-switched Ho:LLF MOPA system at 2 µm. The beam quality factor increases from nearly diffraction-limited at OPO threshold to a M2 = 1.8 at maximum pump power. The degradation can be attributed to thermal lensing and gain guiding effects in the nonlinear crystal. To discriminate between those effects, we monitored the beam quality as a function of the repetition rate at the highest pump pulse energy using a Pockels cell as a pulse picker. Therefore, the heat load inducing thermal lensing increases linearly, whereas gain guiding remains nearly unaffected. M2 shows a minimum of 1.2 at 1 kHz, starting from 1.3 at 100 Hz and rising to 1.8 at 10 kHz. Those findings have been reproduced by numerical simulations. Further investigations show the transient evolution of beam quality, revealing the thermal lens build-up process to the steady-state.

Beam quality and efficiency of ns-pulsed high-power mid-IR ZGP OPOs compared in linear and non-planar ring resonators.

We compare the performance of ns-pulsed mid-infrared optical parametric oscillators (OPOs) based on ZGP crystals in a simple linear cavity and two non-planar image-rotating resonators. Our 2 µm pump source is a 68 W 10 kHz diffraction limited Ho:LLF MOPA system. In a linear cavity, it allows us to generate up to 38 W of the total average power with M2<2.2 from the ZGP OPO in the 3-5 µm range. Beam quality and stability are significantly improved in both types of non-planar ring resonators (M2<1.8 in RISTRA and M2<1.4 in FIRE), while the total average power is above 21 W. Factors influencing the beam quality such as average power and pump repetition rate are studied in detail.

Divergences on expected pneumonia cases during the COVID-19 epidemic in Catalonia: a time-series analysis of primary care electronic health records covering about 6 million people.

BACKGROUND: Pneumonia is one of the complications of COVID-19. Primary care electronic health records (EHR) have shown the utility as a surveillance system. We therefore analyse the trends of pneumonia during two waves of COVID-19 pandemic in order to use it as a clinical surveillance system and an early indicator of severity. METHODS: Time series analysis of pneumonia cases, from January 2014 to December 2020. We collected pneumonia diagnoses from primary care EHR, a software system covering > 6 million people in Catalonia (Spain). We compared the trend of pneumonia in the season 2019-2020 with that in the previous years. We estimated the expected pneumonia cases with data from 2014 to 2018 using a time series regression adjusted by seasonality and influenza epidemics. RESULTS: Between 4 March and 5 May 2020, 11,704 excess pneumonia cases (95% CI: 9909 to 13,498) were identified. Previously, we identified an excess from January to March 2020 in the population older than 15 years of 20%. We observed another excess pneumonia period from 22 october to 15 november of 1377 excess cases (95% CI: 665 to 2089). In contrast, we observed two great periods with reductions of pneumonia cases in children, accounting for 131 days and 3534 less pneumonia cases (95% CI, 1005 to 6064) from March to July; and 54 days and 1960 less pneumonia cases (95% CI 917 to 3002) from October to December. CONCLUSIONS: Diagnoses of pneumonia from the EHR could be used as an early and low cost surveillance system to monitor the spread of COVID-19.

Influence of organization and demographic characteristics of primary care practices on continuity of care: analysis of a retrospective cohort from 287 primary care practices covering about 6 million people in Catalonia.

BACKGROUND: There is evidence that an ongoing patient-physician relationship is associated with improved health outcomes and more efficient health systems. The main objective of this study is to describe the continuity of care in primary healthcare in Catalonia (Spain) and to analyze whether the organization of primary care practices (PCP) or their patients' sociodemographic characteristics play a role in its continuity of care. METHODS: Four indices were used to measure continuity of care: Usual Provider Index (UPC), Modified Modified Continuity Index (MMCI), Continuity of Care Index (COC), and Sequential Continuity Index (SECON). The study was conducted on 287 PCP of the Catalan Institute of Health (Institut Català de la Salut-ICS). Each continuity of care index was calculated at the patient level (3.2 million patients and 35.5 million visits) and then aggregated at the PCP level. We adjusted linear regression models for each continuity index studied, considering the result of the index as an independent variable and demographic and organizational characteristics of the PCP as explanatory variables. Pearson correlation tests were used to compare the four continuity of care indices. RESULTS: Indices' results were: UPC: 70,5%; MMCI: 73%; COC: 53,7%; SECON: 60,5%. The continuity of care indices had the highest bivariate correlation with the percentage of appointments booked with an assigned health provider (VISUBA variable: the lower the value, the higher the visits without an assigned health provider, and thus an organization favoring immediate consultation). Its R2 ranged between 56 and 63%, depending on the index. The multivariate model which explained better the variability of continuity of care indices (from 49 to 56%) included the variables VISUBA and rurality with a direct relationship; while the variables primary care physician leave days and training practices showed an inverse relationship. CONCLUSION: Study results suggest that an organization of primary care favoring immediate consultation is related to a lower continuity of patient care.

An olaparib window-of-opportunity trial in patients with early-stage endometrial carcinoma: POLEN study.

OBJECTIVE: Olaparib is a potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1, 2, and 3 with potential activity in endometrial cancer (EC). METHODS: In this window-of-opportunity trial, women with operable type 1 EC received olaparib oral tablets (300mg) twice daily for 28days before surgery. The primary objective was to evaluate the effects of olaparib on EC in tissue samples taken at baseline and at treatment completion. Signal of activity was defined as significant changes in the expression of the cell cycle-related proteins cyclin D1, Ki67, and cleaved caspase-3. RESULTS: A total of 31 patients were included in the biomarker analysis. The median time of olaparib exposure was 24 days (1-39). Significant inhibition was found for cyclin D1 (p < 0.01), but not for Ki67 and active caspase 3 immunostaining. PARP-1 levels positively correlated with cyclin D1 levels (rho = 0.661, p = 0.0001). Both PARP-1 and cyclin D1 levels were significantly lower (p = 0.022 and p = 0.004, respectively) in patients with ARID1A[-] tumors than ARID1A[+] tumors. A significant relationship between plasma olaparib concentrations and decreased GLUT1 activity was observed (r = -0.5885; p < 0.05). Drug-related toxicity consisted mostly of gastrointestinal and grade 1 or 2 adverse events. CONCLUSIONS: Olaparib reduced expression of cyclin D1, which positively correlated with PARP-1 levels. This effect was more evident in ARID1A-deficient tumors. Olaparib further induced inhibition of GLUT1 plasma activity. Our findings could have noteworthy implications in predicting which patients with EC would benefit from olaparib-based strategies.

Primary care in the time of COVID-19: monitoring the effect of the pandemic and the lockdown measures on 34 quality of care indicators calculated for 288 primary care practices covering about 6 million people in Catalonia.

BACKGROUND: To analyse the impact of the COVID-19 epidemic and the lockdown measures on the follow-up and control of chronic diseases in primary care. METHODS: Retrospective study in 288 primary care practices (PCP) of the Catalan Institute of Health. We analysed the results of 34 indicators of the Healthcare quality standard (EQA), comprising different types: treatment (4), follow-up (5), control (10), screening (7), vaccinations (4) and quaternary prevention (4). For each PCP, we calculated each indicator's percentage of change in February, March and April 2020 respective to the results of the previous month; and used the T-Student test for paired data to compare them with the percentage of change in the same month of the previous year. We defined indicators with a negative effect those with a greater negative change or a lesser positive change in 2020 in comparison to 2019; and indicators with a positive effect those with a greater positive change or a lesser negative change. RESULTS: We observed a negative effect on 85% of the EQA indicators in March and 68% in April. 90% of the control indicators had a negative effect, highlighting the control of LDL cholesterol with a reduction of - 2.69% (95%CI - 3.17% to - 2.23%) in March and - 3.41% (95%CI - 3.82% to - 3.01%) in April; and the control of blood pressure with a reduction of - 2.13% (95%CI - 2.34% to - 1.9%) and - 2.59% (95%CI - 2.8% to - 2.37%). The indicators with the greatest negative effect were those of screening, such as the indicator of diabetic foot screening with a negative effect of - 2.86% (95%CI - 3.33% to - 2.39%) and - 4.13% (95%CI - 4.55% to - 3.71%) in March and April, respectively. Only one vaccination indicator, adult Measles-Mumps-Rubella vaccine, had a negative effect in both months. Finally, among the indicators of quaternary prevention, we observed negative effects in March and April although in that case a lower inadequacy that means better clinical outcome. CONCLUSIONS: The COVID-19 epidemic and the lockdown measures have significantly reduced the results of the follow-up, control, screening and vaccination indicators for patients in primary care. On the other hand, the indicators for quaternary prevention have been strengthened and their results have improved.

Effectiveness of electronic point-of-care reminders versus monthly feedback to improve adherence to 10 clinical recommendations in primary care: a cluster randomized clinical trial.

BACKGROUND: Numerous studies have analyzed the effectiveness of electronic reminder interventions to improve different clinical conditions, and most have reported a small to moderate effect. Few studies, however, have analyzed reminder systems targeting multiple conditions, and fewer still have compared electronic point-of-care reminders systems with other forms of feedback designed to improve delivery of care. METHODS: We performed an unblinded cluster randomized clinical trial to compare the effectiveness of an electronic point-of-care reminder system with that of a well-established system providing monthly feedback on adherence to clinical recommendations. The control group received monthly feedback only while the intervention group received monthly feedback in addition to on-screen point-of-care reminders for 10 clinical conditions. The study targeted all physicians and nurses at the 283 primary care centers managed by the Institut Català de la Salut (approximately 6600 professionals). RESULTS: Following exclusions and randomization, 132 primary care centers (328,728 patients with reminders) were assigned to the intervention group while 137 centers (317,117 patients with reminders) were randomized to the control group. A 20.6% improvement (OR 1.29, 95% CI: 1.25-1.34) in reminder resolution rates was observed in the intervention group. Results varied according to the clinical condition. The most effective reminder was screening for diabetic retinopathy (OR 1.51, 95% CI:1.46-1.57) while the least effective reminders were measurement of glycated hemoglobin (OR: 1.10, 95% CI: 1.07-1.13) and smoking cessation encouragement (OR 1.12, 95% CI: 1.09-1.16). CONCLUSIONS: Electronic point-of-care reminders were more effective than the existing monthly feedback system at resolving the 10 clinical situations. However, more studies are needed to investigate the variations of the effect observed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42391639, 08/10/2012. Retrospectively registered.

HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

[Evaluation of Fusarium spp. pathogenicity in plant and murine models]. / Evaluación de la capacidad patogénica de Fusarium spp. en modelos vegetal y murino.

The genus Fusarium is widely recognized for its phytopathogenic capacity. However, it has been reported as an opportunistic pathogen in immunocompetent and immunocompromised patients. Thus, it can be considered a microorganism of interest in pathogenicity studies on different hosts. Therefore, this work evaluated the pathogenicity of Fusarium spp. isolates from different origins in plants and animals (murine hosts). Twelve isolates of Fusarium spp. from plants, animal superficial mycoses, and human superficial and systemic mycoses were inoculated in tomato, passion fruit and carnation plants, and in immunocompetent and immunosuppressed BALB/c mice. Pathogenicity tests in plants did not show all the symptoms associated with vascular wilt in the three plant models; however, colonization and necrosis of the vascular bundles, regardless of the species and origin of the isolates, showed the infective potential of Fusarium spp. in different plant species. Moreover, the pathogenicity tests in the murine model revealed behavioral changes. It was noteworthy that only five isolates (different origin and species) caused mortality. Additionally, it was observed that all isolates infected and colonized different organs, regardless of the species and origin of the isolates or host immune status. In contrast, the superficial inoculation test showed no evidence of epidermal injury or colonization. The observed results in plant and murine models suggest the pathogenic potential of Fusarium spp. isolates in different types of hosts. However, further studies on pathogenicity are needed to confirm the multihost capacity of this genus.

Theoretical Study on the Photosensitizer Mechanism of Phenalenone in Aqueous and Lipid Media.

The photosensitizer ability of phenalenone was studied in aqueous and lipid media through the single electron transfer reactions, employing the density functional theory. Although phenalenone is a well-known photosensitizer and is widely used as an (1)O2 reference sensitizer, little is known about the reaction mechanism involved. In this study we carried out a single electron transfer reaction between the basal, excited, oxidized and reduced state of phenalenone with oxygen molecules such as (3)O2 and O2(•-). In aqueous media the photosensitizer capacity of phenalenone was measured through both type I and type II mechanisms. In lipid media the photosensitizer ability of phenalenone was attributed to the type II mechanism. The results indicated that the photosensitizer ability of phenalenone shows a heavy reliance on the media where the reaction occurs whether this is an aqueous or lipid media. Finally, this study supports the idea about that electron transfer reactions can be used to study the photosensitizer ability of molecules.

Myofibroblasts contribute to but are not necessary for wound contraction.

Wound contraction facilitates tissue repair. The correct balance between too little contraction, which leads to non-healing wounds, and too much contraction, which leads to contractures, is important for optimal healing. Thus, understanding which cells cause wound contraction is necessary to optimize repair. Wound contraction is hypothesized to develop from myofibroblast (cells which express alpha-smooth muscle actin; ACTA2) contractility, while the role of fibroblast contractility is unknown. In this study, we utilized ACTA2 null mice to determine what role fibroblasts play in wound contraction. Human scar contractures were immunostained for ACTA2, beta-cytoplasmic actin (ACTB), and gamma-cytoplasmic actin (ACTG1). Full-thickness cutaneous wounds were created on dorsum of ACTA2(+/+) mice and strain-matching ACTA2(+/-) and ACTA2(-/-) mice. Wound contraction was quantified. Tissue was harvested for histologic, immunohistochemical and protein analysis. Compared with surrounding unwounded skin, human scar tissue showed increased expression of ACTA2, ACTB, and ACTG1. ACTA2 was focally expressed in clusters. ACTB and ACTG1 were widely, highly expressed throughout scar tissue. Wound contraction was significantly retarded in ACTA2(-/-) mice, as compared to ACTA2(+/+) controls. Control mice had increased epithelialization, cell proliferation, and neovascularization. ACTA2(-/-) mice had lower levels of apoptosis, and fewer total numbers of cells. Smaller amount of collagen deposition and immature collagen organization in ACTA2(-/-) mice demonstrate that wounds were more immature. These data demonstrate that myofibroblasts contribute to but are not necessary for wound contraction. Mechanisms by which fibroblasts promote wound contraction may include activation of contractile signaling pathways, which promote interaction between non-muscle myosin II and ACTB and ACTG1.

Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis.

The copper sequestering ability of melatonin and its metabolites cyclic 3-hydroxymelatonin (3OHM), N(1) -acetyl-N(2) -formyl-5-methoxykynuramine (AFMK), and N(1) -acetyl-5-methoxykynuramine (AMK) was investigated within the frame of the Density Functional Theory. It was demonstrated that these compounds are capable of chelating copper ions, yielding stable complexes. The most likely chelation sites were identified. Two different mechanisms were modeled, the direct-chelation mechanism (DCM) and the coupled-deprotonation-chelation mechanism (CDCM). It is proposed that, under physiological conditions, CDCM would be the main chelation route for Cu(II). It was found that melatonin and its metabolites fully inhibited the oxidative stress induced by Cu(II)-ascorbate mixtures, via Cu(II) chelation. In the same way, melatonin, AFMK, and 3OHM also prevented the first step of the Haber-Weiss reaction, consequently turning off the ˙OH production via the Fenton reaction. Therefore, it is proposed that, in addition to the previously reported free radical scavenging cascade, melatonin is also involved in a concurrent 'chelating cascade', thereby contributing to a reduction in oxidative stress. 3OHM was identified as the most efficient of the studied compounds for that purpose, supporting the important role of this metabolite in the beneficial effects of melatonin against oxidative stress.

In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography.

Spectroscopic analysis of biological tissues can provide insight into changes in structure and function due to disease or injury. Depth-resolved spectroscopic measurements can be implemented for tissue imaging using optical coherence tomography (OCT). Here, spectroscopic OCT is applied to in vivo measurement of burn injury in a mouse model. Data processing and analysis methods are compared for their accuracy. Overall accuracy in classifying burned tissue was found to be as high as 91%, producing an area under the curve of a receiver operating characteristic curve of 0.97. The origins of the spectral changes are identified by correlation with histopathology.