Displasia dentinaria tipo I: Manejo clínico y estudio histológico a propósito de dos casos

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.

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.

Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma

SUMMARY OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

Analysis of the distribution of microhardness, mineral, and organic content of human, bovine, and ovine teeth / Análisis de la distribución de microdureza, contenido mineral y orgánico de dientes humanos, bovinos y ovinos

Objetive. Human teeth have been commonly used for in vitro and in situ studies. Cu­rrently, other animals' teeth have been purposed for dental research to overcome human teeth' problematic availability. This study aimed to investigate the enamel and dentin from human, bovine, and ovine teeth concerning the microhardness, organic, and in­ organic contents via micro­Raman spectroscopy. Methods. Human, bovine, and ovine teeth were divided according to their type and age into seven groups: Ovine; Bovine­12 months; Bovine­24 months; Bovine­36 months; Bovine­48 months; Bovine­+60 months; Human (control). The enamel's microhardness (superficial and deep) and den­tin (superficial, middle, and deep) were analyzed. The calcium/phosphate ratio and am­ide contents were determined by micro­Raman spectroscopy. Results. Overall, the mi­crohardness of human enamel was superior to the other species. Dentin's microhardness was similar among groups. Ovine group showed lower values of calcium/phosphate ratio than human. Amide content was similar between bovine and human. The microhardness and calcium/phosphate ratio of enamel and dentin, respectively, decreased as the age of bovine teeth increased. Conclusions. Researchers must be aware and take into consider­ation the differences of ovine and bovine enamel compared to human enamel. Other al­ternatives that are more similar to the microhardness of human enamel should be sought. Bovine teeth of 12 and 24 months are suitable substitutes for dentin of human teeth. Researchers must also be aware of the age of the animals and specify it in the studies.

Objetivo. Los dientes humanos se han utilizado comúnmente para estudios in vitro e in situ. Actualmente, los dientes de otros animales se han destinado a la investiga­ción dental para superar la disponibilidad problemática de los dientes humanos. Este estudio tuvo como objetivo investigar el esmalte y la dentina de los dientes humanos, bovinos y ovinos en relación con la microdureza y los contenidos orgánicos e inor­gánicos a través de la espectroscopia micro­Raman. Métodos. Los dientes humanos, bovinos y ovinos se dividieron según su tipo y edad en siete grupos: Ovinos; Bovino­12 meses; Bovino­24 meses; Bovino­36 meses; Bovino­48 meses; Bovino­+60 meses; Hu­mano (control). Se analizó la microdureza del esmalte (superficial y profunda) y de la dentina (superficial, media y profunda). La relación calcio/fosfato y los contenidos de amida se determinaron mediante espectroscopía micro­Raman. Resultados. En general, la microdureza del esmalte humano fue superior a la de otras especies. La microdureza de la dentina fue similar entre los grupos. El grupo ovino mostró valores más bajos de la relación calcio/fosfato que el humano. El contenido de amida fue similar entre bovinos y humanos. La microdureza y la relación calcio/fosfato del esmalte y la dentina, respectiva­mente, disminuyeron a medida que aumentaba la edad de los dientes bovinos. Conclusiones. El esmalte de los dientes ovinos y bovinos no es un sustituto adecuado del de los dientes humanos. Se deben buscar otras alternativas que sean similares a la microdureza del esmalte humano. Sin embargo, los dientes bovinos de 12 y 24 meses son sustitutos adecuados de la dentina de los dientes humanos. Los investigadores deben conocer la edad de los animales y especificarla en los estudios.

Tissue repair capacity of bioceramic endodontic sealers in rat subcutaneous tissue

Abstract This study aimed to evaluate the tissue repair capacity of four bioceramic endodontic sealers by quantifying type I and III collagen fibers. The following sealers were tested: EndoSequence BC Sealer (Brasseler, Brasseler, Savannah, USA), Bio C Sealer (Angelus, Londrina, Brazil), Bioroot RCS (Septodont, Santa Catarina, Brazil), and Sealer Plus BC (MKLife, Porto Alegre, Brazil). Polyethylene tubes 1.5 mm in diameter and 1 cm in length containing the endodontic sealers were implanted in the subcutaneous tissue of five rats (Rattus norvegicus albinus, Wistar lineage). After 14 days, the animals were euthanized, and collagen fibers were quantified from the histological tissue sections. Given a non-normal distribution of the data, a gamma regression with log link function was employed and implemented through the generalized linear models module, was used to test whether there was a significant difference between the sealers. The pairwise comparison was performed using Least significant difference. There were significant differences between the sealers for type I (p=0.001), type III (p=0.023), and total collagen (p=0.002). Overall, Bioroot sealer was statistically superior to the other sealers, except in the analysis of type III collagen, in which there was no difference between the Bioroot sealer and Bio C Sealer sealer and the control group (p>0.05). Bioroot RCS bioceramic endodontic sealer stimulates a greater production of collagen.

Resumo Este estudo visou avaliar a capacidade de reparação de tecidos de quatro cimentos endodônticos biocerâmicos através da quantificação de fibras colágenas de tipo I e III. Foram testados os seguintes cimentos: EndoSequence BC Sealer (Brasseler, Brasseler, Savannah, EUA), Bio C Sealer (Angelus, Londrina, Brasil), Bioroot RCS (Septodont, Santa Catarina, Brasil), e Sealer Plus BC (MKLife, Porto Alegre, Brasil). Foram implantados tubos de polietileno de 1,5 mm de diâmetro e 1 cm de comprimento contendo os cimentos endodônticos no tecido subcutâneo de cinco ratos (Rattus norvegicus albinus, linhagem Wistar). Após 14 dias, os animais foram eutanasiados e as fibras colágenas foram quantificadas a partir de cortes histológicos do tecido. Diante de uma distribuição não-normal dos dados, uma regressão gama com função de ligação log, implementada por meio do módulo de modelos lineares generalizados, foi empregada para testar se havia diferença significativa entre os cimentos. A comparação dois a dois foi realizada utilizando Least significant difference. Houve diferença significativa entre os cimentos para os colágenos tipo I (p=0,001), tipo III (p=0,023) e colágeno total (p=0,002). No geral, o cimento Bioroot foi estatisticamente superior aos demais cimentos, com exceção na análise do colágeno tipo III na qual não houve diferença entre o cimento Bioroot e o cimento Bio C Sealer e o grupo controle (p>0,05). O cimento endodôntico biocerâmico Bioroot RCS foi capaz de estimular uma maior produção de colágeno.

The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain / O efeito da dexmedetomidina na expressão do óxido nítrico sintase neuronal na medula espinhal dorsal em um modelo rato com dor neuropática crônica

Abstract Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. Methods Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4-6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. Results Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. Conclusion Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX.

Resumo Antecedentes A dor neuropática refere-se tipicamente à dor causada por lesões ou doenças do sistema somatossensorial. De modo geral, é caracterizada por dor à ambulação, alodinia e hiperalgesia. O óxido nítrico produzido pela enzima óxido nítrico sintase neuronal (nNOS) na medula espinhal dorsal pode ter um papel predominante na regulação da dor neuropática. A alta eficácia e segurança, bem como a plausível capacidade de proporcionar conforto, faz com que a dexmedetomidina (DEX) seja um adjuvante anestésico eficaz. O objetivo deste estudo foi investigar o efeito da DEX na expressão de nNOS na medula espinhal dorsal em um modelo de ratos com dor neuropática crônica. Métodos Ratos Sprague Dawley (SD) machos foram distribuídos aleatoriamente em três grupos: grupo de cirurgia simulada (sham), grupo de cirurgia (do nervo ciático; CCI) e grupo dexmedetomidina (DEX). Os modelos de dor neuropática crônica nos grupos CCI e DEX foram estabelecidos por ligadura do nervo ciático. A latência de retirada térmica (TWL) foi medida no dia 1 antes da cirurgia e nos dias 1, 3, 7 e 14 após o procedimento. Seis animais de cada grupo foram eutanasiados após a medida de TWL nos dias 7 e 14 após a cirurgia e o segmento L4-6 da medula espinhal foi extraído para determinação da expressão de nNOS por imuno-histoquímica. Resultados Em comparação ao grupo sham, o limiar de TWL diminuiu significativamente e a expressão de nNOS foi regulada de maneira positiva após a cirurgia nos grupos CCI e DEX. Comparado ao grupo CCI, o limiar de TWL aumentou de forma significativa e a expressão de nNOS caiu significativamente diminuída nos dia 7 e 14 após a cirurgia no grupo DEX. Conclusão A regulação negativa de nNOS na medula espinhal dorsal está envolvida na atenuação da dor neuropática pela DEX.

Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions / 医学前沿

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.

Glyceryl phenylbutyrate in the treatment of argininosuccinate synthetase deficiency: a case report / 中华实用儿科临床杂志

Clinical data of a child with high blood ammonia and suspected argininosuccinate synthetase deficiency (ASSD) in Hunan Children′s Hospital were retrospectively analyzed, including data of mass spectra for blood amino acids and acyl carnitine, urine organic acid analysis and whole exome sequencing.After the exact diagnosis of ASSD and being approved by the Administrative Regulation for Import Medical Devices Urgently Needed in Boao Lecheng International Medical Tourism Pilot Zone of Hainan Free Trade Port, the patient was medicated with Glyceryl phenylbutyrate (GPB) and followed up.The patient was a boy aged 7 years and 8 months, who presented at the Neurology Department of Hunan Children′s Hospital for sleepiness, abnormal mental behavior and personality change for 1 week on December 2, 2021.Before GPB treatment, the highest blood ammonia, alanine aminotransferase and aspartate transaminase were 325.2 μmol/L, 465.7 IU/L and 277.3 IU/L, respectively.Genetic metabolism assay of blood and urine showed a significantly increased citrulline at 697.42 μmol/L; urine organic acid analysis showed increased urinary orotic acid at 144.2 μmol/L, and increased uracil at 65.1 μmol/L.A pure heterozygous variant of the ASS1 gene (c.1087C>T, p.R363W) was detected.After GPB treatment, the blood ammonia levels were 21.3 μmol/L, 54.6 μmol/L and 62.4 μmol/L on the 41 st, 90 th and 146 th days, respectively.Until July 20, 2022 follow-up visit, the patient recovered well without adverse events.This was the first ASSD child in China who was treated with GPB.This case report provided therapeutic experience of ASSD in our country.ASSD has a high mortality rate and unexplained abnormal mental behavior.It is necessary to timely measure blood ammonia, and a series of urea cycle disorders should be well concerned.The diagnosis and management of ASSD rely on the data of metabolism examination and genetic testing.

Value of monitoring serum t-PINP/β-CTX ratio and 25 (OH) D levels in the prevention and treatment of osteoporosis after surgery for differentiated thyroid cancer in elderly women / 中华内分泌外科杂志

Objective:To investigate the level change of serum total n-terminal propeptide of type Ⅰ precollagen (t-PINP) /type Ⅰ collagen carboxy-terminal peptide (beta-CTX) ratio, 25-hydroxyvitamin D (25-hydroxyvitamin D, 25 (OH) ) ratio, and 25-hydroxyvitamin D in elderly women with differentiated thyroid cancer (DTC) after surgery and its value in the prevention and treatment of osteoporosis (OP) .Methods:From Jan. 2020 to May. 2021, 112 elderly female postoperative DTC patients treated with thyroid stimulating hormone (TSH) suppression in Department of Endocrinology of Wenzhou Hospital of Integrative Medicine were collected for a prospective study, and the incidence of OP after 1 year of treatment was counted, and according to the incidence of OP, they were divided into incidence group ( n=78) and non-incidence group ( n=34). The general information, thyroid parameters [TSH, free triiodothyronine (FT3), free thyroxine (FT4) ], bone mineral density (BMD), and serum t-titrosine (BMD) were compared between the two groups. SPSS22.0 software was used, and the counting data was described by examples χ2 test. Grade data was expressed in u, Ridit test was used, measurement data was described in mean±standard deviation ( ±s), t test was used, Pearson correlation coefficient model was used to analyze postoperative thyroid index and serum t-PINP/β- Correlation between CTX ratio and 25 (OH) D level, and serum t-PINP after 1 year of treatment was analyzed through interaction/β- The role of CTX ratio and 25 (OH) D level in OP occurrence. Results:The incidence of OP after 1 year of TSH suppression treatment in 112 elderly female post-DTC patients in this study was 69.64% (78/112) ; serum TSH levels (0.63±0.19) mIU/ml after 1 year of treatment in patients who developed OP were lower than those in patients who did not develop OP (0.81±0.22) mIU/ml, and serum FT3 (6.15±1.71) pmol/ml and FT4 levels (24.63±4.28) pmol/ml were higher than those of patients without OP (4.32±1.29) pmol/ml and (20.36±3.70) pmol/ml ( t1=4.391, t2=5.581, t3=5.050,all P<0.05) .Serum t-PINP/β-CTX ratio (130.27±18.09) and 25 (OH) D level (20.18±4.15) ng/ml after 1 year of treatment in patients with OP were lower than those in patients without OP (148.56±20.37) and (23.36±4.36) ng/ml ( t1=4.733, t2=3.672, both P<0.05) ; serum TSH levels were positively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels, and serum FT3 and FT4 levels were negatively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels after 1 year of treatment in patients with OP ( P<0.05) ; low serum t-PINP/β-CTX ratio after 1 year of treatment expression, and low 25 (OH) D levels showed a positive interaction in OP occurrence in a superphase multiplicative model ( P<0.05) . Conclusion:Serum t-PINP/β-CTX ratio and 25 (OH) D level are closely associated with the occurrence of OP after DTC in elderly women, and postoperative monitoring can help prevent and treat OP.

Modulation of type I interferon signaling by natural products in the treatment of immune-related diseases / 中国天然药物

Type I interferon (IFN) is considered as a bridge between innate and adaptive immunity. Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion, tumor cell proliferation, and overactive immune responses. Due to intricate and diverse chemical structures, natural products and their derivatives have become an invaluable source inspiring innovative drug discovery. In addition, some natural products have been applied in clinical practice for infection, cancer, and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted. However, whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated. In the current review, we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity, including both agonism/activation and antagonism/inhibition, and their potential application as therapies. Furthermore, the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified. In conclusion, natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection, cancer, and autoimmune diseases.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Existence and morphology features of the myodural bridge in JapaLura Splendida / 解剖学报

Objective The dense fibrous connective tissue that connects sub-occipital muscles which consist of the rectus capitis posterior minor muscle (RCPmi), rectus capitis posterior major muscle (RCPma), obliquus capitis inferior muscle (OCI) and nuchal ligament (NL) to the spinal dura mater (SDM), is described as the myodural bridge (MDB) in humans. The MDB is perceived as an essential anatomical structure and has been a subject of interest for clinicians. Studies have revealed that MDB may be related to the dynamic circulation of the cerebrospinal fluid (CSF) and a chronic cervicogenic headache. To date, the MDB is identified as a universal, existing structure in mammals and it exists in other vertebrates as well, such as Gallus domesticus and Rock pigeons in Avifauna, Siamese crocodile and Trachemys scripta elegans in Reptile. The current study is to further analyze different structures features of the MDB in sundry classes and provide the anatomical basis for functional studies. The JapaLura Splendida is the most common species in Lacertiformes, Reptilia. So we chose it as the experimental object to supply the morphological study of the MDB in Reptilia. Methods The study was based on gross anatomical dissection, thick sheet section, histological staining to observe the structural characteristics of the post-occipital area of twenty JapaLura Splendidas and the existence of the MDB. Results The deep post-occipital muscles were composed of the rectus capitis dorsal muscle (RCD) and the obliquus capital posterior (OCP) muscle. The RCD was merged by the rectus capitis dorsal major muscle (RCDma), the rectus capitis dorsal minor muscle (RCDmi) and the obliquus capitis anterior muscle (OCA). In the atlanto-occipital space, the dense fibrous bundles were found to originate from the ventral aspect of the RCD and run ventral, closely inserting into the SDM. In the atlanto-axial space, the dense fibrous bundles were found to originate from the ventral aspect of the OCP and run ventral, closely contacted with the SDM. These dense fibrous bundles were the collagen type I fibers with strong double refraction. Conclusion The result of this study indicates that the MDB is located between the post-occipital muscles and the SDM in JapaLura Splendida. The MDB of Japalura splendida may be related to the activities of the head and neck, and exert a physiological function similar to the MDB in humans.

Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases / 中国药理学通报

The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

Tratamiento integral de una adolescente con dentinogénesis imperfecta tipo I / Comprehensive treatment of an adolescent with type I dentinogenesis imperfecta

La dentinogénesis imperfecta (DI) es un desorden hereditario de carácter autosómico dominante, que se origina durante la etapa de histodiferenciación en el desarrollo dental y altera la formación de la denti-na. Se considera una displasia dentinaria que puede afectar ambas denticiones con una incidencia de 1 en 6000 a 8000 nacimientos. El tratamiento del pa-ciente con DI es complejo y multidisciplinario, supone un desafío para el odontólogo, ya que por lo general están involucradas todas las piezas dentarias y afec-ta no solo la salud buco dental sino el aspecto emo-cional y psicológico de los pacientes. Objetivo: des-cribir el tratamiento integral y rehabilitador realiza-do en una paciente adolescente con diagnóstico de DI tipo I. Relato del caso: Paciente de sexo femenino de 14 años, que concurrió en demanda de atención a la Cátedra de Odontología Integral Niños de la FOU-BA derivada del Hospital "Prof. Dr. Juan P. Garrahan" con diagnóstico de osteogénesis imperfecta tipo III (OI). Nunca recibió atención odontológica y el motivo de consulta fue la apariencia estética de sus piezas dentarias. Se realizó el examen clínico y radiográfico arrojando el diagnóstico de DI tipo I asociada a OI. Conclusión: El tratamiento rehabilitador de la DI tipo I en los pacientes en crecimiento y desarrollo debe estar dirigido a intervenir de manera integral y tem-prana para resolver la apariencia estética y funcio-nal, evitar las repercusiones sociales y emocionales y acompañar a los pacientes y sus familias (AU)

Dentinogenesis imperfecta (DI) is an autosomal dominant inherited disorder that originates during the histodifferentiation stage of tooth development and alters dentin formation. It is considered a den-tin dysplasia that can affect both dentitions with an incidence of 1 in 6000 to 8000 births. The treatment of patients with DI is complex and multidisciplinary, it is a challenge for the dentist, since in general all the teeth are involved and it affects not only oral health but also the emotional and psychological aspect of the patients. Objective: To describe the comprehen-sive and rehabilitative treatment carried out in an adolescent patient with a diagnosis of DI type I. Case report: A 14-year-old female patient, who required dental attention at the Department of Pediatric Den-tistry of FOUBA and was referred from the Hospital "Prof. Dr. Juan P. Garrahan" with a diagnosis of os-teogenesis imperfecta type III (OI). The patient never received dental care and the reason for consultation was esthetic appearance of her teeth. A clinical and radiographic examination was performed, resulting in a diagnosis of DI type I associated with OI. Conclu-sion: Rehabilitative treatment of DI in growing and developing patients will be aimed at early and com-prehensive intervention to resolve esthetic and func-tional appearance, avoid social and emotional reper-cussions and accompany patients and their families (AU)

Estudio clínico y molecular en pacientes cubanos con neurofibromatosis tipo i / Clinical and molecular study in cuban patients with type I neurofibromatosis

Introducción: La neurofibromatosis tipo i es una enfermedad hereditaria, autosómica dominante, multisistémica, progresiva con penetrancia completa y expresividad variable. El análisis de las familias con marcadores moleculares permite realizar el diagnóstico por métodos indirectos. Objetivos: Estudiar dos familias cubanas con al menos un caso de neurofibromatosis tipo i e identificar los alelos resultantes del polimorfismo para el diagnóstico molecular. Métodos: Se realizó un estudio descriptivo a dos familias con al menos un caso de neurofibromatosis tipo i. Se extrajo el ADN con la técnica de precipitación salina y fue utilizada la reacción en cadena de la polimerasa para la amplificación del fragmento de interés. Se realizó la digestión enzimática con la enzima Rsai para analizar los alelos del polimorfismo estudiado y posteriormente hacer la electroforesis en gel de agarosa al 2 por ciento. Resultados: Las manifestaciones clínicas más frecuentes fueron las manchas color café con leche, pecas axilares e inguinales y lesiones óseas. Se detectaron los alelos 1 y 2 al analizar el polimorfismo en las muestras. Las frecuencias alélicas fueron 38,5 por ciento y 61,5 por ciento respectivamente. Conclusiones: Fueron identificadas las principales manifestaciones clínicas en los pacientes. La técnica para el análisis del polimorfimo permitió el estudio molecular en las familias con neurofibromatosis tipo i. Se detectaron los alelos del marcador molecular y sus frecuencias. Se realizó el diagnóstico molecular de los individuos sospechosos (AU)

Introduction: Neurofibromatosis type i is a hereditary, autosomal dominant, multisystemic, progressive disease with complete penetrance and variable manifestation. The analysis of families with molecular markers allows diagnosis by indirect methods. Objectives: To study two Cuban families with at least one case of neurofibromatosis type i and to identify the alleles resulting from the polymorphism for molecular diagnosis. Methods: A descriptive study of two families with at least one case of neurofibromatosis type i was performed. DNA was extracted with the saline precipitation technique and polymerase chain reaction was used for amplification of the fragment of interest. Enzymatic digestion was performed with the RsaI enzyme to analyze the alleles of the polymorphism studied and then to perform electrophoresis in 2 percent agarose gel. Results: The most frequent clinical manifestations were café-au-lait spots, axillary and inguinal freckles and bone lesions. Alleles 1 and 2 were detected when analyzing the polymorphism in the samples. The allele frequencies were 38.5 percent and 61.5 percent respectively. Conclusions: The main clinical manifestations in patients were identified. The technique for polymorphism analysis allowed the molecular study in the families with neurofibromatosis type i. The alleles of the molecular marker and their frequencies were detected. Molecular diagnosis of suspected individuals was performed (AU)

Luschka and the carotid body / Luschka e o corpo carotídeo

The 'carotid body' is a small structure sited at the bifurcation of the common carotid artery. The macroscopic features of the carotid body, and items of the extrinsic nervous, and vascular supplies, were initially described by Taube (1743), complemented by a number of authors that followed, proceeding until Luschka (1962), who added the first microscopic study. The macroscopic features of the carotid body, including location, extrinsic innervation, and vascular supply, then provided, were described in a relatively satisfactory manner. However, despite Luschka's great and admirable effort, the microscopic findings seem to be flawed, what can be ascribed to the technical limitations at the time, and the artifacts due to the used procedures. Nevertheless, there is no doubt that Luschka and his forerunners provided an important step for forthcoming research on the carotid body, and its innervation.

O 'corpo carotídeo' é uma pequena estrutura situada na bifurcação da artéria carótida comum. Os aspectos macroscópicos do corpo carotídeo e itens sobre o suprimento nervoso e vascular extrínsecos foram descritos inicialmente por Taube (1743), complementados por um certo número de autores que seguiram, prosseguindo até Luschka (1962), que acrescentou o primeiro estudo microscópico. Os aspectos macroscópicos do corpo carotídeo, incluindo localização, inervação extrínseca e suprimento vascular, então providos, foram descritos de modo relativamente satisfatório. Entretanto, apesar do grande e admirável esforço de Luschka, os achados microscópicos aparecem falhos, o que pode ser atribuído às limitações técnicas daquele tempo e a artefatos devidos aos procedimentos utilizados. Todavia, não há dúvida que Luschka e seus precursores proveram um importante passo para pesquisas que vieram sobre o corpo carotídeo e da sua inervação.

Comparative Study of Outcome of Tympanoplasty between Endoscopic and Microscopic Approach

Background: Tympanoplasty is a common operation performed by ENT specialist. It is a challenging event to treat with a microscope when the external canal is narrow or overhang. The endoscopic permeatal approach gives the advantage of wide angle view and can avoid post-auricular approach and canaloplasty. The aim of the study was to compare the outcome of tympanoplasty in post-auricular microscopic and permeatal endoscopic approach.Material &Methods:A total of 100 patients between the age group 15 to 44 years who were attending the ENT OPD, suffering from Chronic Suppurative Otitis Media (CSOM) were selected on the basis of perforation type and their workup was done to assess the candidature for tympanoplasty. Comparative analysis between the two groups were done based on analysis using SPSS 24 software version. The level of significance was set to 5% (P<0.05).Results:A total of 100 patients were included in the study the overall graft take was 92.3% in cases of Endoscopic permeatal technique as compared to 88.88% in the case of Microscopic postaural underlay technique, with a majority of the failures in the large central perforation group rendering a p = 0.021 for patients operated for Large perforations, p=0.036 or moderate perforations and p = 0.0476 for small perforations. There was a difference in hearing improvement with majority of the cases improving to the range of 10-21 dB in permeatal endoscopic technique compared to 07-18 dB in postauralMicroscopic technique.Conclusion:In terms of graft take rate, hearing improvement and complications, the permeatal endoscopic method outperforms the postauricular microscopic approach.

Dermatofibrosarcoma protuberans with unusual presentation in vulva / Dermatofibrosarcoma protuberans con presentación inusual en vulva

Abstract Gynecological sarcomas are uncommon and their location in the vulva and vagina has an incidence of 5% of all malignant neoplasms of the female genital tract. We present the case of a 54-year-old patient with a diagnosis of dermatofibrosarcoma protuberans in the vulva, an infrequent pathology, with less than 60 cases reported worldwide in this anatomical location. Clinically it has a locally aggressive behavior, due to the proliferation of spindle cells with pleomorphism and frequent figures of mitosis that infiltrate the reticular dermis and subcutaneous cellular tissue, giving rise to tumor lesions of variable size and with high rates of local recurrence. The treatment of first choice is surgical excision of the tumor with Mohs micrographic surgery or other surgical techniques for complete evaluation of the circumferential and deep peripheral margin. However, the identification of carcinogenesis mechanis ms where the chromosomal translocation t (17; 22) (q22; q13) is recognized, forming the COL1A1-PDGFB fusion gene, which participates in stimulating tumor cell proliferation, allowing treatment with tyrosine kinase inhibitors such as imatinib for neoadjuvant therapy of surgically unresectable tumors and local recurrences.

Resumen Los sarcomas ginecológicos son infrecuentes y la localización de estos en vulva y vagina tienen una incidencia del 5% de todas las neoplasias malignas del tracto genital femenino. Presentamos el caso de una paciente de 54 años con diagnóstico de dermatofibrosarcoma protuberans en vulva, una patología infrecuente, con menos de 60 casos reportados a nivel mundial en esta localización anatómica. Clínicamente tiene un comportamiento localmente agresivo, debido a la proliferación de células fusiformes con pleomorfismo y frecuentes figuras de mitosis que infiltran la dermis reticular y tejido celular subcutáneo, dando origen a lesiones tumorales de tamaño variable y con altas tasas de recurrencia local. El tratamiento en primera elección es la escisión quirúrgica del tumor con cirugía micrográfica de Mohs u otras técnicas quirúrgicas para evaluación completa del margen periférico circunferencial y profundo. Sin embargo, la identificación de mecanismos de carcinogénesis donde se reconoce la translocación cromosómica t (17; 22) (q22; q13), formando al gen de fusión COL1A1-PDGFB, el cual participa estimulando la proliferación celular tumoral, ha permitido la utilización de los inhibidores de la tirosina quinasa como el imatinib para la realización de terapia neoadyuvante en casos de tumores irresecables quirúrgicamente y en recurrencias locales.

Contribution of human recombinant Interferon-Alpha 2b treatment in symptomatic and asymptomatic patients with SARS-CoV-2 virus infection / Contribución del tratamiento con Interferón-Alpha 2b humano recombinante en pacientes sintomáticos y asintomáticos con infección por el virus SARS-CoV2

Introduction: Subjects with asymptomatic infections are not generally admitted to health care facilities, however, they may benefit from antiviral therapy. Objective: To evaluate the contribution to treatment with combined therapy based on recombinant human interferon alpha 2b + Lopinavir/Ritonavir + Chloroquine versus Lopinavir/Ritonavir + Chloroquine in asymptomatic and symptomatic patients. Material and Methods: An observational study was carried out in patients with a positive diagnosis of COVID-19 from April 1st to July 30th, 2020. From a total of 308 patients treated with interferon + Lopinavir/Ritonavir + Chloroquine, we selected a statistically representative sample of 40 patients using a simple randomization process. As a control group, 27 patients who only received treatment with Lopinavir/Ritonavir + Chloroquine were selected. These patients underwent determinations of anti-SARS-CoV-2 antibodies, determinations of inflammatory markers, and follow-up by RT-PCR to evaluate the time length of negativization. Results: The group treated with interferon had a significantly shorter time to negativization. Patients treated with interferon showed a significant decrease in inflammatory markers at the time of hospital discharge and they had an increase in antibody titers at two and four months after hospital discharge, compared to the group of patients who did not receive interferon. Conclusions: The treatment with exogenous interferon in patients with COVID-19 had a significant contribution to the regulation of the immune response of the patients(AU)

Introducción: Los sujetos con infección asintomática generalmente no son admitidos en centros de asistencia médica, sin embargo, pueden beneficiarse de la terapia antiviral. Objetivo: evaluar la contribución al tratamiento de la terapia combinada basada en interferón alfa 2b recombinante humano + Lopinavir/Ritonavir + Cloroquina contra Lopinavir/Ritonavir + Cloroquina en pacientes asintomáticos y sintomáticos. Material y Métodos: Se realizó un estudio observacional en pacientes con diagnóstico positivo de COVID-19, durante los días del 1 de abril al 30 de julio de 2020. De un total de 308 pacientes tratados con interferón + Lopinavir/Ritonavir + Cloroquina, se seleccionaron mediante un proceso de aleatorización simple, una muestra estadísticamente representativa de 40 pacientes. Como grupo control se seleccionaron 27 pacientes que solo recibieron tratamiento con Lopinavir/Ritonavir + Cloroquina. Estos pacientes se sometieron a determinaciones de anticuerpos anti-SARS-CoV-2, determinaciones de marcadores inflamatorios y seguimiento por RT-PCR para evaluar el tiempo de negativización. Resultados: El grupo tratado con interferón tuvo un tiempo significativamente más corto de negativización. Los pacientes tratados con interferón mostraron una disminución significativa de los marcadores inflamatorios en el momento del alta hospitalaria y tuvieron un incremento de los títulos de anticuerpos a los dos y cuatro meses posteriores al alta hospitalaria, en comparación con el grupo de pacientes que no recibió interferón. Conclusiones: El tratamiento con interferón exógeno en pacientes con COVID-19 tuvo una contribución significativa en la regulación de la respuesta inmune de los pacientes(AU)

Neurofibromatosis laríngea: a propósito de un caso / Laryngeal neurofibromatosis: a case report

Resumen El neurofibroma laríngeo es poco frecuente, representa menos del 0,1% de las neoplasias benignas de la laringe. Puede presentarse aislado, o más comúnmente asociado a neurofibromatosis tipo I. Se presenta el caso de un paciente varón de 40 años, ya diagnosticado de neurofibromatosis tipo I, que presenta masa supraglótica submucosa asintomática, diagnosticada como hallazgo casual en una intubación por una cirugía previa programada.

Abstract Laryngeal neurofibroma is rare, representing less than 0.1% of benign tumors of the larynx. It can occur in isolation or more commonly associated with type I neurofibromatosis. The case of a 40-year-old male patient, already diagnosed with type I neurofibromatosis, is presented with an asymptomatic submucosal supraglottic mass, diagnosed as a chance finding in intubation due to a previous scheduled surgery.