Healing of leprosy-associated chronic plantar wounds with a novel biomembrane containing latex proteins from Calotropis procera.

Pre-clinical assays demonstrated that a 1% polyvinyl alcohol biomembrane containing latex proteins (10%) from the medicinal plant Calotropis procera was biocompatible and stimulated healing of incisional and excisional wounds in murine models, and the mechanistic aspects were established. The efficacy of the biomembrane (BioMemCpLP) to promote healing of chronic ulcers in leprosy patients was investigated. The study started with 28 volunteers. Five were excluded later due to different disconformities. Ulcers from 15 patients were continuously treated with BioMemCpLP for 56 days. Five patients were treated only with silver sulfadiazine and three patients received plain hydrocolloid wound dressings with high absorption capacity. In all cases, wound dressings were renewed three times a week for 56 days and ulcers were evaluated weekly for contraction and healing progress. The extent of the healed area in the ulcers treated with BioMemCpLP was greater than in the control groups. Approximately 88% of ulcers treated with BioMemCpLP were fully healed before day 56, against 6% in both control groups. This result was not correlated with age/gender, duration or location of ulcers, deformity or whether or not the patient was cured of leprosy. The results showed that BioMemCpLP was beneficial for treatment of ulcers suffered by leprosy patients without noticeable side effects.

Indigo Carmine Binding to Cu(II) in Aqueous Solution and Solid State: Full Structural Characterization Using NMR, FTIR and UV/Vis Spectroscopies and DFT Calculations.

The food industry uses indigo carmine (IC) extensively as a blue colorant to make processed food for young children and the general population more attractive. Given that IC can act as a ligand, this raises concerns about its interactions with essential metal ions in the human body. In view of this interest, in the present investigation, the copper(II)/indigo carmine system was thoroughly investigated in aqueous solution and in the solid state, and the detailed structural characterization of the complexes formed between copper(II) and the ligand was performed using spectroscopic methods, complemented with DFT and TD-DFT calculations. NMR and UV/Vis absorption spectroscopy studies of the ligand in the presence of copper(II) show changes that clearly reveal strong complexation. The results point to the formation of complexes of 1:1, 1:2 and 2:1 Cu(II)/IC stoichiometry in aqueous solution, favored in the pH range 6-10 and stable over time. DFT calculations indicate that the coordination of the ligand to the metal occurs through the adjacent carbonyl and amine groups and that the 1:1 and the 2:1 complexes have distorted tetrahedral metal centers, while the 1:2 structure is five-coordinate with a square pyramidal geometry. FTIR results, together with EDS data and DFT calculations, established that the complex obtained in the solid state likely consists of a polymeric arrangement involving repetition of the 1:2 complex unit. These results are relevant in the context of the study of the toxicity of IC and provide crucial data for future studies of its physiological effects. Although the general population does not normally exceed the maximum recommended daily intake, young children are highly exposed to products containing IC and can easily exceed the recommended dose. It is, therefore, extremely important to understand the interactions between the dye and the various metal ions present in the human body, copper(II) being one of the most relevant due to its essential nature and, as shown in this article, the high stability of the complexes it forms with IC at physiological pH.

Parental Assessment of Infantile Hemangioma Cosmetic Clinical Outcomes: Results of the Spanish Hemangioma Nationwide Prospective Cohort.

BACKGROUND: Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. OBJECTIVE: To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. PATIENTS AND METHODS: The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores - both before and after treatment - as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents' assessments. RESULTS: The median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. CONCLUSION: This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.

Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis.

Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis. We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from healthy controls and SSc patients stimulated by soluble factors that drive inflammation and fibrosis in SSc deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling. In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in response to repeated injury and in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.

[A descriptive overview of cases of congenital cytomegalovirus at a tertiary hospital between 2017 and 2023]. / Descriptivo de los casos de citomegalovirus congénitos en un hospital terciario entre 2017-2023.

OBJECTIVE: Cytomegalovirus infection (CMV) is the most common congenital infection in developed countries. The aim of our study was to describe the features of the children that have congenital CMV infection at our hospital for the last 6 years. METHODS: A retrospective descriptive study was designed that included all the children with CMV congenital infection that were diagnosed at tertiary hospital of Madrid Community between 2017 and 2023. RESULTS: Twenty-two children were included. 54.5% have a prenatal diagnosis, 50% of them were in the third trimester, 25% at first trimester and 25% at the second. 22.7% were preterm. CMV was isolated in all the samples with CV more than 1000 copies/ml. When CMV was made in blood, 11/22 (50%) had a high CV. Only one newborn had a high CV at CRL. 44% have affectation at transfontanellar ultrasound evidenced by vasculopathy (62%), intraventricular hemorrhage (IVH) or periventricular calcifications (20%). 68% were asymptomatic, al though 20% had a retarded intrauterine growth (RIG) at birth or clinical features or analytical were objectified (neutropenia, thrombocytopenia, cholestasis). 33% got treatment with val ganciclovir and 33% had sequelae (hearing loss). CONCLUSIONS: CMV congenital infection is still a severe public health issue in developed countries. Most of the cases are mild or asymptomatic even though we should have high clinical suspicion with compatible symptoms and consistent maternal history in order to make an early diagnosis and treatment to prevent or reduce sequelae.

COVID anomaly in the correlation analysis of S&P 500 market states.

Analyzing market states of the S&P 500 components on a time horizon January 3, 2006 to August 10, 2023, we found the appearance of a new market state not previously seen and we shall discuss its possible implications as an isolated state or as a beginning of a new general market condition. We study this in terms of the Pearson correlation matrix and relative correlation with respect to the S&P 500 index. In both cases the anomaly shows strongly.

Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy.

Tumors are highly complex and heterogenous ecosystems where malignant cells interact with healthy cells and the surrounding extracellular matrix (ECM). Solid tumors contain large ECM deposits that can constitute up to 60% of the tumor mass. This supports the survival and growth of cancerous cells and plays a critical role in the response to immune therapy. There is untapped potential in targeting the ECM and cell-ECM interactions to improve existing immune therapy and explore novel therapeutic strategies. The most abundant proteins in the ECM are the collagen family. There are 28 different collagen subtypes that can undergo several post-translational modifications (PTMs), which alter both their structure and functionality. Here, we review current knowledge on tumor collagen composition and the consequences of collagen PTMs affecting receptor binding, cell migration and tumor stiffness. Furthermore, we discuss how these alterations impact tumor immune responses and how collagen could be targeted to treat cancer.

The impact of dietary oregano essential oil supplementation on fatty acid composition and lipid stability in eggs stored at room temperature.

*1. In many countries, eggs are not refrigerated and must be stored at room temperature. The objective of this study was to explore the effects of dietary oregano oil (275 mg/kg; ORE) versus an unsupplemented control diet (CON) on laying hens on the shelf life and fatty acid profile of eggs.2. Treatments were randomly distributed into 10 pens containing 27 birds each. A total of 200 eggs were collected from both groups on the same day and were stored for either 0, 10, 21 and 35 d. At each storage time, egg yolks were analysed for fatty acid profile and lipid peroxidation.3. The main indicator of lipid peroxidation, malondialdehyde (MDA), was significantly lower in ORE eggs compared to CON eggs (p = 0.001). Storage time had a significant impact on MDA concentrations (p = 0.023), with the highest found after 35 d. Significant differences were found for individual fatty acids, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Palmitic acid, stearic acid, oleic acid, linoleic acid and arachidonic acid were significantly lower in ORE eggs compared to CON eggs (p < 0.05). Palmitoleic acid (p = 0.002), linolenic acid (p = 0.001) and docosahexaenoic acid (DHA, p = 0.001) were significantly higher in ORE eggs.4. Storage only affected oleic, linolenic, linoleic, arachidonic and docosahexaenoic acids (p < 0.05). Total SFA, MUFA, n-6 and ratio of n-3 to n-6 (n-3:n-6) PUFA were significantly higher in CON eggs (p < 0.05). The ratio of SFA to PUFA (SFA:PUFA, p = 0.005) and total n-3 PUFA (p = 0.001) were significantly higher in ORE eggs.5. The n-3:n-6 ratio was significantly impacted by treatment (p = 0.021) and storage (p = 0.031) with no significant interaction. This ratio is important for human health indication and could lead to the development of designer eggs.

Correction: Inkjet-printed O2 gas sensors in intelligent packaging.

Correction for 'Inkjet-printed O2 gas sensors in intelligent packaging' by M. D. Fernández-Ramos et al., Analyst, 2021, 146, 3177-3184, https://doi.org/10.1039/D1AN00295C.

Correction: An optical sensor for the sensitive determination of formaldehyde gas based on chromotropic acid and 4-aminoazobenzene immobilized in a hydrophilic membrane.

Correction for 'An optical sensor for the sensitive determination of formaldehyde gas based on chromotropic acid and 4-aminoazobenzene immobilized in a hydrophilic membrane' by M. D. Fernández-Ramos et al., Analyst, 2023, 148, 4533-4538, https://doi.org/10.1039/D3AN01056B.

Oncolytic adenovirus coding for shedding-resistant MICA enhances immune responses against tumors.

Cancer immunotherapies strive to overcome tumor-induced immune suppression and activate antitumor immune responses. Although cytotoxic T lymphocytes (CTLs) play a pivotal role in this process, natural killer (NK) cells have also demonstrated remarkable tumor-killing abilities, given their ability to discriminate tumor cells from normal cells and mediate specific antitumoral cytotoxicity. NK cells activation depends on a balance between activation and inhibition signals from several ligands/receptors. Among them, MICA/NKG2D axis is a master regulator of NK activation. MHC class I chain-related polypeptide A (MICA) expression is upregulated by many tumor cell lines and primary tumors and serves as a ligand for the activating NK group 2D (NKG2D) receptor on NK cells and subpopulations of T cells. However, cancer cells can cleave MICA, making it soluble and de-targeting tumor cells from NK cells, leading to tumor immune escape.In this study, we present ICOVIR15KK-MICAMut, an oncolytic adenovirus (OAdv) armed with a transgene encoding a non-cleavable MICA to promote NK-mediated cell-killing capacity and activate the immune response against cancer cells. We first demonstrated the correct MICA overexpression from infected cells. Moreover, our MICA-expressing OAdv promotes higher NK activation and killing capacity than the non-armed virus in vitro. In addition, the armed virus also demonstrated significant antitumor activity in immunodeficient mice in the presence of human PBMCs, indicating the activation of human NK cells. Finally, OAdv-MICA overexpression in immunocompetent tumor-bearing mice elicits tumor-specific immune response resulting in a greater tumor growth control.In summary, this study highlights the significance of NK cells in cancer immunotherapy and presents an innovative approach using a modified oncolytic virus to enhance NK cell activation and antitumor immune response. These findings suggest promising potential for future research and clinical applications.

Leukocyte-associated immunoglobulin-like receptor-1 blockade in combination with programmed death-ligand 1 targeting therapy mediates increased tumour control in mice.

Collagen expression and structure in the tumour microenvironment are associated with tumour development and therapy response. Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a widely expressed inhibitory collagen receptor. LAIR-2 is a soluble homologue of LAIR-1 that competes for collagen binding. Multiple studies in mice implicate blockade of LAIR-1:collagen interaction in cancer as a promising therapeutic strategy. Here, we investigated the role of LAIR-1 in anti-tumour responses. We show that although LAIR-1 inhibits activation, proliferation, and cytokine production of mouse T cells in vitro, tumour outgrowth in LAIR-1-deficient mice did not differ from wild type mice in several in vivo tumour models. Furthermore, treatment with NC410, a LAIR-2-Fc fusion protein, did not result in increased tumour clearance in tested immunocompetent mice, which contrasts with previous data in humanized mouse models. This discrepancy may be explained by our finding that NC410 blocks human LAIR-1:collagen interaction more effectively than mouse LAIR-1:collagen interaction. Despite the lack of therapeutic impact of NC410 monotherapy, mice treated with a combination of NC410 and anti-programmed death-ligand 1 did show reduced tumour burden and increased survival. Using LAIR-1-deficient mice, we showed that this effect seemed to be dependent on the presence of LAIR-1. Taken together, our data demonstrate that the absence of LAIR-1 signalling alone is not sufficient to control tumour growth in multiple immunocompetent mouse models. However, combined targeting of LAIR-1 and PD-L1 results in increased tumour control. Thus, additional targeting of the LAIR-1:collagen pathway with NC410 is a promising approach to treating tumours where conventional immunotherapy is ineffective.

Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients.

BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.

Inhaled Litsea glaucescens K. (Lauraceae) leaves' essential oil has anxiolytic and antidepressant-like activity in mice by BDNF pathway activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Litsea glaucescens K. (Lauraceae) is a small tree from the Mexican and Central American temperate forests, named as "Laurel". Its aromatic leaves are ordinarily consumed as condiments, but also are important in Mexican Traditional Medicine, and among the most important non wood forest products in this area. The leaves are currently used in a decoction for the relief of sadness by the Mazahua ethnic group. Interestingly, "Laurel" has a long history. It was named as "Ehecapahtli" (wind medicine) in pre-Columbian times and applied to heal maladies correlated to the Central Nervous System, among them depression, according to botanical texts written in the American Continent almost five centuries ago. AIM OF THE STUDY: Depression is the first cause of incapacity in the world, and society demands alternative treatments, including aromatherapy. We have previously demonstrated the antidepressant-like activity of L. glaucescens leaves' essential oil (LEO), as well as their monoterpenes linalool, and beta-pinene by intraperitoneal route in a mice behavioral model. Here we now examined if LEO and linalool exhibit this property and anxiolytic activity when administered to mice by inhalation. We also investigated if these effects occur by BDNF pathway activation in the brain. MATERIALS AND METHODS: The LEO was prepared by distillation with water steam and analyzed by gas chromatography-mass spectrometry (GC-MS). The monoterpenes linalool, eucalyptol and ß-pinene were identified and quantified. Antidepressant type properties were determined with the Forced Swim Test (FST) on mice previously exposed to LEO or linalool in an inhalation chamber. The spontaneous locomotor activity and the sedative effect were assessed with the Open Field Test (OFT), and the Exploratory Cylinder (EC), respectively. The anxiolytic properties were investigated with the Elevated Plus Maze Apparatus (EPM) and the Hole Board Test (HBT). All experiments were video documented. The mice were subjected to euthanasia, and the brain hippocampus and prefrontal cortex were dissected. RESULTS: The L. glaucescens essential oil (LEO) contains 31 compounds according to GC/MS, including eucalyptol, linalool and beta-pinene. The LEO has anxiolytic effect by inhalation in mice, as well as linalool, and ß-pinene, as indicated by OFT and EC tests. The LEO and imipramine have antidepressant like activity in mice as revealed by the FST; however, linalool and ketamine treatments didn't modify the time of immobility. The BDNF was increased in FST in mice treated with LEO in both areas of the brain as revealed by Western blot; but did not decrease the level of corticosterone in plasma. The OFT indicated that LEO and imipramine didn't reduce the spontaneous motor activity, while linalool and ketamine caused a significant decrease. CONCLUSION: Here we report by the first time that L. glaucescens leaves essential oil has anxiolytic effect by inhalation in mice, as well as linalool, and ß-pinene. This oil also maintains its antidepressant-like activity by this administration way, similarly to the previously determined intraperitoneally. Since inhalation is a common administration route for humans, our results suggest L. glaucescens essential oil deserve future investigation due to its potential application in aromatherapy.

Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients. / [Artíulo traducido] Seguridad de minoxidil oral a dosis bajas en pacientes con hipertensión o arritmias: estudio multicéntrico de 264 pacientes.

BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.

Evaluation of chemical contamination of crops produced in greenhouse by irrigation with reclaimed water.

Using reclaimed water for agricultural irrigation is increasing worldwide to compensate for water scarcity. The aim of this work was to evaluate the uptake of some of the most commonly detected organic contaminants of emerging concern (CECs) and pesticides in regenerated water in a field study. Furthermore, it was studied their distribution and accumulation in the different parts of a crop (soil, plant and fruit). Three crops (cucumber, pepper and melon) were grown under controlled agronomic conditions in a greenhouse. In order to make an accurate evaluation of the process, "regenerated blank water" was spiked with 70 chemicals (including antibiotics, anti-inflammatories, analgesics, anaesthetics, anxiolytics, anticonvulsants, pesticides) at environmental concentrations (∼1 µg/L) and used for continuous crop irrigation. After crop season, the average total concentration of contaminants detected in the soil samples ranged from 132 to 232 µg/kg d.w depending of the crops type. Between 7 and 10 different contaminants were found in the harvested fruits, up to levels of 27.8 µg/kg f.w. cucumber, 12.4 µg/kg f.w. melon and 7.8 µg/kg f.w pepper. In general, cucumber fruit showed higher accumulation levels of contaminants than pepper and melon for most target analytes. The accumulation rates followed the order: root (0.2 %) < stem/leaf (1-4 %) < fruit (1-6 %) < soil (17-30 %). The experimental data obtained in this study were also used to assess the risk associated with the reuse of reclaimed water for crop irrigation as well to identify those contaminants that, due to their physicochemical properties, show higher accumulation rates and environmental impact.

Gamma-ray sources imaging and test-beam results with MACACO III Compton camera.

Hadron therapy is a radiotherapy modality which offers a precise energy deposition to the tumors and a dose reduction to healthy tissue as compared to conventional methods. However, methods for real-time monitoring are required to ensure that the radiation dose is deposited on the target. The IRIS group of IFIC-Valencia developed a Compton camera prototype for this purpose, intending to image the Prompt Gammas emitted by the tissue during irradiation. The system detectors are composed of Lanthanum (III) bromide scintillator crystals coupled to silicon photomultipliers. After an initial characterization in the laboratory, in order to assess the system capabilities for future experiments in proton therapy centers, different tests were carried out in two facilities: PARTREC (Groningen, The Netherlands) and the CNA cyclotron (Sevilla, Spain). Characterization studies performed at PARTREC indicated that the detectors linearity was improved with respect to the previous version and an energy resolution of 5.2 % FWHM at 511 keV was achieved. Moreover, the imaging capabilities of the system were evaluated with a line source of 68Ge and a point-like source of 241Am-9Be. Images at 4.439 MeV were obtained from irradiation of a graphite target with an 18 MeV proton beam at CNA, to perform a study of the system potential to detect shifts at different intensities. In this sense, the system was able to distinguish 1 mm variations in the target position at different beam current intensities for measurement times of 1800 and 600 s.

V-Shaped Tröger Oligothiophenes Boost Triplet Formation by CT Mediation and Symmetry Breaking.

A new family of molecules obtained by coupling Tröger's base unit with dicyanovinylene-terminated oligothiophenes of different lengths has been synthesized and characterized by steady-state stationary and transient time-resolved spectroscopies. Quantum chemical calculations allow us to interpret and recognize the properties of the stationary excited states as well as the time-dependent mechanisms of singlet-to-triplet coupling. The presence of the diazocine unit in Tröger's base derivatives is key to efficiently producing singlet-to-triplet intersystem crossing mediated by the role of the nitrogen atoms and of the almost orthogonal disposition of the two thiophene arms. Spin-orbit coupling-mediated interstate intersystem crossing (ISC) is activated by a symmetry-breaking process in the first singlet excited state with partial charge transfer character. This mechanism is a characteristic of these molecular triads since the independent dicyanovinylene-oligothiophene branches do not display appreciable ISC. These results show how Tröger's base coupling of organic chromophores can be used to improve the ISC efficiency and tune their photophysics.