Hearing results following endoscopic type I tympanoplasty in medium and large perforations.

OBJECTIVES: To clarify the hearing outcomes after endoscopic type I tympanoplasty for medium and large perforations due to chronic otitis media. METHODS: We examined the clinical records of patients who underwent endoscopic type I tympanoplasty for medium and large perforations of the eardrum resulting from chronic otitis media between January 2019 and December 2021. We analyzed the changes in hearing pre- and post-operation in patients with healed eardrums and assessed the impact of tympanosclerosis on hearing. Patients with incomplete follow-up data, middle ear cholesteatoma, stapes fixation, severe lesions in the tympanic antrum and mastoid necessitating mastoidectomy and/or ossicular chain reconstruction were excluded. RESULTS: A total of 156 patients underwent analysis for audiological outcomes. Among them, 63 had medium tympanic membrane perforations, with 18 cases showing calcification of the tympanic membrane and 20 cases with calcification in the tympanic cavity. Additionally, 93 cases had large tympanic membrane perforations, with 25 cases showing tympanic membrane calcification and 32 cases with tympanic cavity calcification. Prior to surgery, the Air Conduction threshold (AC) in the large perforation group was higher than in the medium perforation group, particularly at low frequencies, measuring (47.4 ± 13.3 dB) and (41.2 ± 14.7 dB), respectively (p-value < 0.05). Following surgery, both groups experienced an improvement in AC, measuring (33.6 ± 13.9 dB) and (32.6 ± 12.8 dB), respectively, with no significant difference noted (p-value > 0.05). There was no significant change in Bone Conduction threshold (BC) before and after surgery in either the large or medium perforation groups (all p-values > 0.05). Except for 4000 Hz an increase, bone conduction did not increase post-surgery, instead showing further improved. Pre-surgery, the Air-Bone Gap (ABG) in the large and medium perforation groups was (27.7 ± 8.5 dB) and (21.8 ± 8.3 dB), respectively, mainly affecting low frequencies, with a statistically significant difference noted (p-value < 0.05). Following surgery, ABG in both groups improved to (16.3 ± 7.6 dB) and (15.7 ± 8.4 dB), respectively, with no significant difference observed (p-value > 0.05). There was no significant difference in hearing pre-surgery among the groups with No calcification (No), Tympanic Membrane Calcification (TM), and Tympanic Cavity Calcification (TC). However, TC significantly impacted low frequency (250-500 Hz) AC and ABG. The differences in AC and ABG pre-surgery between TC and No group, and TC and TM group (at 250-500 Hz) were statistically significant (all p-values < 0.05). Preoperative ABG in TM group was better than in No group and TC group, suggesting minimal impact of tympanic membrane calcification on hearing. No interaction was observed between tympanic membrane perforation size and tympanosclerosis on hearing. Post-surgery, both large and medium tympanic membrane perforation groups, regardless of tympanosclerosis presence, showed good AC and ABG, with no statistically significant difference in △ABG (all p-values > 0.05). CONCLUSION: Preoperative AC and ABG were increase in cases of large tympanic membrane perforations and medium tympanic membrane perforations with tympanic cavity calcification. Surgical intervention led to more significant hearing improvement in these patients. However, irrespective of tympanic membrane perforation size and the presence of tympanosclerosis, as long as the ossicular chain remains intact and functional, postoperative AC and ABG outcomes are satisfactory. Endoscopic type I tympanoplasty proves effective in achieving improved hearing outcomes for patients with medium to large tympanic membrane perforations and tympanosclerosis, provided there is no ossicle chain fixation. LEVEL OF EVIDENCE: Level 4.

Secretion of the human parathyroid hormone through a microcin type I secretion system in Escherichia coli.

BACKGROUND: Gram negative bacteria possess different secretion systems to export proteins to the extracellular medium. The simplest one, type I secretion system (T1SS), forms a channel across the cell envelope to export proteins in a single step. Peptides secreted by the T1SSs comprise a group of antibiotics, called class II microcins, which carry an amino terminal secretion domain that is processed concomitantly with export. Mature microcins range in size from 60 to 90 amino acids and differ in their sequences. Microcin T1SSs show a high versatility in relation to the peptides they are able to secrete, being mainly limited by the length of the substrates. Different bioactive peptides unrelated to bacteriocins could be secreted by microcin V (MccV) T1SS, while retaining their biological activity. RESULTS: In this work heterologous secretion of two variants of human parathyroid hormone (PTH) by MccV T1SS was evaluated. PTH is a bioactive peptide of 84 amino acids (PTH84), which is involved in the maintenance of bone homeostasis. Currently, a drug corresponding to the active fraction of the hormone, which resides in its first 34 amino acids (PTH34), is commercially produced as a recombinant peptide in Escherichia coli. However, research continues to improve this recombinant production. Here, gene fusions encoding hybrid peptides composed of the MccV secretion domain attached to each hormone variant were constructed and expressed in the presence of microcin T1SS in E. coli cells. Both PTH peptides (PTH34 and PTH84) were recovered from the culture supernatants and could be confirmed to lack the MccV secretion domain, i.e. microcin T1SS efficiently recognised, processed and secreted both PTH variants. Furthermore, the secreted peptides were stable in the extracellular medium unlike their unprocessed counterparts present in the intracellular space. CONCLUSION: The successful secretion of PTH variants using MccV T1SS could be considered as a new alternative for their production, since they would be recovered directly from the extracellular space without additional sequences. Furthermore, it would be a new example revealing the potential of microcin type I secretion systems to be conceived as a novel strategy for the production of recombinant peptides in E. coli.

Main oral characteristics and treatment of ligneous gingivitis and periodontitis in individuals with plasminogen deficiency: A systematic review.

OBJECTIVE: This systematic review evaluated the main clinical, radiographic, histopathological and treatment-related characteristics of ligneous gingivitis (LG) and periodontitis (LP) in individuals with plasminogen deficiency (PD). MATERIAL AND METHODS: Studies in humans diagnosed with PD, focusing on the evaluation of oral characteristics and treatment of the LG/LP were considered for inclusion criteria. Electronic searches were performed up to April 2024 in five databases and in the grey literature. Risk of bias was assessed according to the Joanna Briggs Institute Critical Appraisal Checklists for case reports. It was provided a narrative synthesis of the results. RESULTS: A total of 17 studies were included. All were case reports that analyzed 17 individuals with PD who presented with LG/LP. The relative frequency of PD type I was 56%, while type II constitutes the remaining 44%. In most studies, patients exhibited ulceration clinically, bone loss radiographically, and subepithelial eosinophilic material accumulation on histopathological evaluation. Conventional periodontal scaling was the most used management. All included studies provided well-described clinical characteristics and confirmed plasminogen deficiency through laboratory testing. Only three studies had a risk of bias values lower than 15%. CONCLUSIONS: Current evidence is limited and varied, complicating the diagnosis and treatment of GL/PL. Future studies should provide a more detailed account of treatments and include extended clinical and radiographic follow-up.

Use of Marsupialization as a Definitive Treatment for Large-sized Dentigerous Cysts in a Patient with Mucopolysaccharidosis Type I.

The correct diagnosis is fundamental for the appropriate treatment to be employed in a particular pathology. The best treatment is not the one that solves only local problems, fragmenting the patient, and therefore, it is necessary to integrate the entire systemic condition of the individual before initiating any local treatment. This context inevitably requires dentistry to participate in a multidisciplinary approach, where the role of the dentist is expanded in concepts that encompass ethics, human dignity, and professional valorization. This article describes a clinical case of a patient with mucopolysaccharidosis type I, whose treatment of cystic lesions present in the mandible was exclusively performed through marsupialisation. The objective of this study is to demonstrate, within the complexity of this rare syndrome, the difficulties of diagnosis and the need for evaluation of the patient beyond the limits of the oral cavity, as well as to report two cases of large dentigerous cysts, surgically treated conservatively through marsupialisation, without the need for re-approach for enucleation and without recurrences over a 20-year period.

Inflammatory turmoil within: an exploration of autoinflammatory disease genetic underpinnings, clinical presentations, and therapeutic approaches.

Systemic autoinflammatory diseases (SAIDs) arise from dysregulated innate immune system activity, which leads to systemic inflammation. These disorders, encompassing a diverse array of genetic defects classified as inborn errors of immunity, are significant diagnostic challenges due to their genetic heterogeneity and varied clinical presentations. Although recent advances in genetic sequencing have facilitated pathogenic gene discovery, approximately 40% of SAIDs patients lack molecular diagnoses. SAIDs have distinct clinical phenotypes, and targeted therapeutic approaches are needed. This review aims to underscore the complexity and clinical significance of SAIDs, focusing on prototypical disorders grouped according to their pathophysiology as follows: (i) inflammasomopathies, characterized by excessive activation of inflammasomes, which induces notable IL-1ß release; (ii) relopathies, which are monogenic disorders characterized by dysregulation within the NF-κB signaling pathway; (iii) IL-18/IL-36 signaling pathway defect-induced SAIDs, autoinflammatory conditions defined by a dysregulated balance of IL-18/IL-36 cytokine signaling, leading to uncontrolled inflammation and tissue damage, mainly in the skin; (iv) type I interferonopathies, a diverse group of disorders characterized by uncontrolled production of type I interferons (IFNs), notably interferon α, ß, and ε; (v) anti-inflammatory signaling pathway impairment-induced SAIDs, a spectrum of conditions characterized by IL-10 and TGFß anti-inflammatory pathway disruption; and (vi) miscellaneous and polygenic SAIDs. The latter group includes VEXAS syndrome, chronic recurrent multifocal osteomyelitis/chronic nonbacterial osteomyelitis, Schnitzler syndrome, and Still's disease, among others, illustrating the heterogeneity of SAIDs and the difficulty in creating a comprehensive classification. Therapeutic strategies involving targeted agents, such as JAK inhibitors, IL-1 blockers, and TNF inhibitors, are tailored to the specific disease phenotypes.

In-vitro study on type I collagen synthesis in low-level laser therapy on the early ligament fibroblasts' healing process.

BACKGROUND: Low-level Laser Therapy (LLLT) has demonstrated its potential in promoting fiber matrix maturation, collagen synthesis, and fibroblast proliferation, contributing to tissue regeneration. Our study aimed to investigate the impact of LLLT on collagen type I synthesis, cell proliferation, and viability in human ligament fibroblasts derived from the Anterior Cruciate Ligament (ACL). METHODS: Tissue samples were obtained from individuals undergoing arthroscopic ACL reconstruction surgery. Primary human fibroblasts were isolated, and immunohistochemical assays confirmed their characteristics. LLLT at 850 nm was administered in three groups: Low dose (1.0 J/cm²), High dose (5.0 J/cm²), and Control (0.0 J/cm²). Cell viability was calculated using a membrane integrity assay, proliferation was determined by automated counting, and collagen type I concentration in cell culture was measured using an immunoassay. RESULTS: Fibroblasts showed decreased viability after low and high doses of LLLT, increased proliferation at the low dose, and increased collagen synthesis at the high dose on day 10 for both sexes after treatment. CONCLUSION: Our study demonstrated that LLLT may improve the early ligament healing process by increasing cell proliferation at the low dose and enhancing collagen type I synthesis at the high dose in human ligament fibroblasts.

Cerebral White Matter Alterations Associated With Oligodendrocyte Vulnerability in Organic Acidurias: Insights in Glutaric Aciduria Type I.

The white matter is an important constituent of the central nervous system, containing axons, oligodendrocytes, and its progenitor cells, astrocytes, and microglial cells. Oligodendrocytes are central for myelin synthesis, the insulating envelope that protects axons and allows normal neural conduction. Both, oligodendrocytes and myelin, are highly vulnerable to toxic factors in many neurodevelopmental and neurodegenerative disorders associated with disturbances of myelination. Here we review the main alterations in oligodendrocytes and myelin observed in some organic acidurias/acidemias, which correspond to inherited neurometabolic disorders biochemically characterized by accumulation of potentially neurotoxic organic acids and their derivatives. The yet incompletely understood mechanisms underlying the high vulnerability of OLs and/or myelin in glutaric acidemia type I, the most prototypical cerebral organic aciduria, are particularly discussed.

Content and tissue expression of Collagen I, Collagen IV, and Laminin in the Extracellular Matrix in Prostate Adenocarcinoma.

Prostate cancer is one of the most common neoplasm in the male population. It is not known why some tumors become more aggressive than others. Although most studies show changes in the expression of cell adhesion molecules and the extracellular matrix correlated with the Gleason score, no study has objectively measured the tissue content of these molecules. This study aims to measure the content and tissue expression of collagen type I and IV and laminin in the extracellular matrix of patients with prostate adenocarcinoma and correlate these findings with the Gleason score and clinical characteristics. Forty-one patients who underwent radical prostate surgery at the Urology Department of a reference Hospital in Brazil between January 2015 and December 2020 were studied. The tissue protein content was estimated under light microscopy at a final magnification of 200 × . The mean collagen I score in prostate adenocarcinoma tissue samples was 7.16 ± 1.03 pixels/field. The mean type IV collagen score was 3.44 ± 0.61 pixels/field. The mean laminin score was 5.19 ± 0.79 pixels/field. The total Gleason score was correlated with both collagen and laminin. All the correlations were negative, which shows that the higher the collagen/laminin expression was, the lower the total Gleason score (p-value < 0,05). According to the Pearson correlation analysis, age has no statistical relationship with collagen and laminin content. PSA, in turn, showed a correlation only with laminin, but r = -0.378 (p = 0.015). Among the associated diseases and lifestyle habits, there is only statistical significance in the comparison of alcoholism for collagen I. For collagen IV and laminin, no statistical significance was obtained with the clinical variables analyzed.

Displasia dentinaria tipo I: Manejo clínico y estudio histológico a propósito de dos casos / Dentin dysplasia type I: clinical management and histological study based on two cases

La displasia dentinaria tipo I (DD-I) corresponde a una alteración dentinaria de heterogeneidad genética y penetrancia completa, en donde se presenta un defecto en el desarrollo de las raíces de los dientes tanto temporales como definitivos. Clínicamente se observan dientes con extrema movilidad junto con antecedentes de exfoliación prematura o espontánea. Los defectos estructurales de los tejidos dentarios, tales como DD-I; implican un desafío ya que son pocos los casos documentados en la literatura que hablan de esta condición. Además implican un tratamiento multidisciplinario y altamente invasivo. El objetivo de este artículo es presentar dos casos de DD-I, enfatizando en su tratamiento y características histopatológicas.

Dentin Dysplasia Type I (DD-I) consists of a pathological dentinary alteration with genetic heterogeneity that results in a defectuous development of dental roots both in primary and secondary dentition. Clinically we can appreciate teeth with extreme pathological mobility and premature or spontaneous exfoliation. Alterations within normal dental structure, such as DD-I imply a challenge for the common practitioner, because of the scarce number of case reports with in the scientific literature regarding this condition and also, because of the need for a highly invasive and multidisciplinary approach they require. The aim of this article is to present two DD-I cases, emphasizing on their treatment and histopathological features.

Type I interferon pathway genetic variants in severe COVID-19.

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. According to the World Health Organization (WHO), there have been over 760 million reported cases and over 6 million deaths caused by this disease worldwide. The severity of COVID-19 is based on symptoms presented by the patient and is divided as asymptomatic, mild, moderate, severe, and critical. The manifestations are interconnected with genetic variations. The innate immunity is the quickest response mechanism of an organism against viruses. Type I interferon pathway plays a key role in antiviral responses due to viral replication inhibition in infected cells and adaptive immunity stimulation induced by interferon molecules. Thus, variants in type I interferon pathway's genes are being studied in different COVID-19 manifestations. This review summarizes the role of variants in type I interferon pathway's genes on prognosis and severity progression of COVID-19.

A physicochemical evaluation of ossein-hydroxyapatite within the bovine bone matrix revealed demineralization and making type I collagen available as a result of processing and solubilization by acids.

Bovine bone is an animal-origin matrix rich in type I collagen (COL I) and it necessitates prior demineralization and makes COL I available. This study investigated the ossein-hydroxyapatite physicochemical properties evaluation as a result of processing and solubilization by acids and revealed the bone matrix demineralization and making COL I available. The tibia residue from bovine sources was processed, ground, and transformed into bone matrix powder. The bone matrix was solubilized in acetic acid followed by lactic acid. The bone matrix was evaluated as a result of processing and solubilization by acids: ossein and hydroxyapatite percentages by nitrogen and ash content, mineral content, particle size distribution, Fourier-transformation infrared spectroscopy, x-ray diffraction, and scanning electron microscope. For the obtained residual extracts, pH and mineral content were evaluated. The solubilization by acids affected the ossein-hydroxyapatite physicochemical properties, and the bone matrix solubilized by acetic and lactic acid showed the preservation of the ossein alongside the loss of hydroxyapatite. The processing and the solubilization by acids were revealed to be a  alternative to bone matrix demineralization and enabling the accessibility of bone COL I. PRACTICAL APPLICATION: Bovine bone is an abundant type I collagen source, but processing maneuvers and demineralization effect present limitations due to the rigidity of the structural components. Exploring methodologies to process and demineralize will allow type I collagen to be obtained from the bone source, and direct and amplify the potentialities in the chemical and food industries. The research focused on bone sources and collagen availability holds paramount significance, and promotes repurposing agribusiness residues and development of protein-base products.

Mechanism of action and treatment of type I interferon in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) caused by HBV, HCV infection, and other factors is one of the most common malignancies in the world. Although, percutaneous treatments such as surgery, ethanol injection, radiofrequency ablation, and transcatheter treatments such as arterial chemoembolization are useful for local tumor control, they are not sufficient to improve the prognosis of patients with HCC. External interferon agents that induce interferon-related genes or type I interferon in combination with other drugs can reduce the recurrence rate and improve survival in HCC patients after surgery. Therefore, in this review, we focus on recent advances in the mechanism of action of type I interferons, emerging therapies, and potential therapeutic strategies for the treatment of HCC using IFNs.

Molecular weight-dependent antitumor effects of prunes-derived type I arabinogalactan on human and murine triple wild-type melanomas.

The regulation of metastasis-related cellular aspects of two structurally similar AGIs from prunes tea infusion, with different molar masses, was studied in vitro against Triple Wild-Type metastatic melanoma (TWM) from murine and human origin. The higher molar mass AGI (AGI-78KDa) induced TWMs cells death and, in murine cell line, it decreased some metastasis-related cellular processes: invasiveness capacity, cell-extracellular matrix interaction, and colonies sizes. The lower molar mass AGI (AGI-12KDa) did not induce cell death but decreased TWMs proliferation rate and, in murine cell line, it decreased cell adhesion and colonies sizes. Both AGIs alter the clonogenic capacity of human cell line. In spite to understand why we saw so many differences between AGIs effects on murine and human cell lines we performed in silico analysis that demonstrated differential gene expression profiles between them. Complementary network topological predictions suggested that AGIs can modulate multiple pathways in a specie-dependent manner, which explain differential results obtained in vitro between cell lines. Our results pointed to therapeutic potential of AGIs from prunes tea against TWMs and showed that molecular weight of AGIs may influence their antitumor effects.

On the mechanism of visible-light sensitized photosulfoxidation of toluidine blue O.

We report on the formation of toluidine blue O (TBO) sulfoxide by a self-sensitized photooxidation of TBO. Here, the photosulfoxidation process was studied by mass spectrometry (MS) and discussed in the context of photodemethylation processes which both contribute to TBO consumption over time. Analysis of solvent effects with D2O, H2O, and CH3CN along with product yields and MS fragmentation patterns provided mechanistic insight into TBO sulfoxide's formation. The formation of TBO sulfoxide is minor and detectable up to 12% after irradiation of 3 h. The photosulfoxidation process is dependent on oxygen wherein instead of a type II (singlet oxygen, 1O2) reaction, a type I reaction involving TBO to reach the TBO sulfoxide is consistent with the results. Density functional theory results point to the formation of the TBO sulfoxide by the oxidation of TBO via transiently formed peroxyl radical or thiadioxirane intermediates. We discover that the TBO photosulfoxidation arises competitively with TBO photodemethylation with the latter leading to formaldehyde formation.

Glaucoma neovascular e esclerite necrosante com inflamação. Há uma relação? / Neovascular glaucoma and necrotizing scleritis with inflammation. Is there a relationship?

RESUMO O objetivo deste trabalho foi relatar um caso raro de glaucoma neovascular em paciente portador de diabetes mellitus tipo 1 que evoluiu para esclerite necrosante com inflamação. Homem, 22 anos e com diabetes mellitus tipo 1 mal controlada apresentou perda visual dolorosa súbita no olho direito. Acuidade visual em olho direito sem percepção luminosa e 20/80 em olho esquerdo. Pressão intraocular de 35mmHg e exame compatível com glaucoma neovascular em olho direito. Foi iniciado tratamento com colírios hipotensores no olho direito e panfotocoagulação a laser no olho esquerdo. Após 3 semanas, houve piora da dor, hiperemia e aparecimento de afinamento escleral na região superior de olho direito, com posterior protrusão uveal. Quadro compatível com esclerite anterior necrosante com inflamação, apesar das sorologias para doenças autoimunes negativas. Ainda que raro, este relato de associação de glaucoma neovascular e esclerite justifica a discussão dos mecanismos inflamatórios em comum nessas doenças, para melhor compreensão da patogênese dessas graves apresentações clínicas.

ABSTRACT The aim of this study was to report a rare case of neovascular glaucoma in a patient with type 1 diabetes mellitus that progressed to necrotizing scleritis with inflammation. A 22-year-old male with poorly controlled type 1 diabetes mellitus experienced sudden painful vision loss on the right eye. Visual acuity on the right eye was no light perception, while it was 20/80 in the left eye. Intraocular pressure was measured at 35 mmHg, and the examination was consistent with neovascular glaucoma on the right eye. Treatment with hypotensive eye drops was initiated in the right eye, and panphotocoagulation laser therapy was performed on the left eye. After three weeks, there was worsening pain, redness, and the appearance of scleral thinning in the upper region of the right eye, followed by uveal protrusion. This presentation was consistent with necrotizing anterior scleritis with inflammation, despite negative serology for autoimmune diseases. Although rare, this report of the association between neovascular glaucoma and scleritis justifies the discussion of common inflammatory mechanisms in these diseases to enhance the understanding of the pathogenesis of these severe clinical presentations.

Long-Term Cardiorespiratory, Endocrine, Ophthalmic, and Functional Outcomes in Adult Patients with Mucopolysaccharidosis Type I (Hurler Syndrome) Post Haematopoietic Stem Cell Transplantation: The Irish Experience

Abstract Mucopolysaccharidosis type IH (MPS IH) is caused by homozygous IDUA gene pathogenic variants. This results in deficiency of the enzyme α-L-iduronidase (IDUA), which is necessary for the degradation of glycosaminoglycans (GAGs). This study outlines the long-term outcomes in adult Irish patients affected with MPS IH, who were followed up for mean 28 years post Haematopoietic Stem Cell Transplantation. Nineteen adult MPS IH patients underwent HSCT in childhood. The participant cohort represents 6 families. Among the 13 patients with Irish Traveller ethnicity, 6 patients were either siblings or first cousins. All these related patients were homozygous for p. Trp402Ter (W402X). Mean age at the first transplantation was 8 months (range 3-21). Five patients had undergone a second transplantation (n=5, 26%) in childhood, due to graft failure. None of the patients had a cardiac valve surgery at the time of the study. 14/19 patients had mild to moderate aortic or mitral valve insufficiency or stenosis. 3/19 patients used non-invasive ventilation at night. Two patients had tracheostomy in situ. Both sensorineural as well as conductive hearing defects. No corneal clouding post corneal transplantation (n=8) was observed. Six patients attended regular secondary school. Multidisciplinary follow-up is needed to address the disease specific complications in adulthood.

Unveiling the Role of Donor Impurity Position on the Electronic Properties in Strained Type I and Type II Core/Shell Quantum Dots under Magnetic Field.

In this theoretical investigation, we delve into the significant effects of donor impurity position within core/shell quantum dot structures: type I (CdTe/ZnS) and type II (CdTe/CdS). The donor impurity's precise location within both the core and the shell regions is explored to unveil its profound influence on the electronic properties of these nanostructures. Our study investigates the diamagnetic susceptibility and binding energy of the donor impurity while considering the presence of an external magnetic field. Moreover, the lattice mismatch-induced strain between the core and shell materials is carefully examined as it profoundly influences the electronic structure of the quantum dot system. Through detailed calculations, we analyze the strain effects on the conduction and valence bands, as well as the electron and hole energy spectrum within the core/shell quantum dots. The results highlight the significance of donor impurity position as a key factor in shaping the behaviors of impurity binding energy and diamagnetic susceptibility. Furthermore, our findings shed light on the potential for tuning the electronic properties of core/shell quantum dots through precise impurity positioning and strain engineering.

Complex Regional Pain Syndrome Type I: Evidence for the CB1 and CB2 Receptors Immunocontent and Beneficial Effect of Local Administration of Cannabidiol in Mice.

Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.

Assessing transformation methods for group comparisons under violated assumptions: type I error rate and test power / [Avaliação de métodos de transformação para comparações de grupos sobre pressupostos violados: taxa de erro tipo I e poder do teste]

ABSTRACT In this study, some transformation methods that are applied when the assumptions of analysis of variance are not met are evaluated in terms of type I error rate and the test power, under circumstances with different distributions, number of groups, number of observations, variance ratios, and different standard deviation differences. The data set used in the study consisted of random numbers generated from N (0,1), and χ2(3) distributions using the random function of the Numpy library in the Python programming language. The logarithmic, square root and root transformations were evaluated on ANOVA based on simulation combinations. It was observed that the transformation techniques of taking the square root after adding 0.5 and 0.375 to the data were relatively more reliable compared to other transformations in terms of type I error rate. However, in every case, type I error rate determined at the beginning of the experiment increased both before and after the transformation was applied. In particular, interestingly, the third and fourth degree root transformations gave better results of test power in the right skewed distribution. In addition, we compared the transformation techniques in question to determine the normality of the data and the homogeneity of variances by a real data.

RESUMO Neste estudo, alguns métodos de transformação, aplicados quando as premissas da análise de variância não são cumpridas, são avaliados em termos de taxa de erro tipo I e poder de teste, em circunstâncias com diferentes distribuições, número de grupos, número de observações, razões de variância e diferenças de desvio-padrão. O conjunto de dados utilizados no estudo consistiu em números aleatórios gerados a partir das distribuições N(0,1) e χ2(3), utilizando a função aleatória da biblioteca Numpy, na linguagem de programação Python. As técnicas de transformação logarítmica, raiz quadrada e raiz foram avaliadas na ANOVA, com base em combinações de simulação. Observou-se que as técnicas de transformação de tomar a raiz quadrada após adicionar 0,5 e 0,375 aos dados foram relativamente mais confiáveis em comparação com outras transformações em termos de taxa de erro tipo I. No entanto, em todos os casos, a taxa de erro tipo I determinada no início do experimento aumentou tanto antes quanto depois da aplicação da transformação. Em particular, curiosamente, as transformações de raiz de terceiro e de quarto grau deram melhores resultados de poder de teste na distribuição assimétrica à direita. Além disso, foram comparadas as técnicas de transformação em questão para determinar a normalidade dos dados e a homogeneidade das variâncias por meio de dados reais.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants.

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.