Clinical implications of single cell sequencing for bladder cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide, with about 0.5 million reported new cases and about 0.2 million deaths per year. In this scoping review, we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines. We searched PubMed, CENTRAL, Embase, and supplemented with manual searches through the Scopus, and Web of Science for published studies until February 2023. We included original studies that used at least one single-cell technology to study bladder cancer. Forty-one publications were included in the review. Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy. Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples. The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level. Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management. This nascent tool can advance the early diagnosis, prognosis judgment, and targeted therapy of bladder cancer.

Pregabalin synchronizes the regeneration of nerve and muscle fibers optimizing the gait recovery of MDX dystrophic mice.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder induced by mutations in the dystrophin gene, leading to a degeneration of muscle fibers, triggering retrograde immunomodulatory, and degenerative events in the central nervous system. Thus, neuroprotective drugs such as pregabalin (PGB) can improve motor function by modulating plasticity, together with anti-inflammatory effects. The present work aimed to study the effects of PGB on axonal regeneration after axotomy in dystrophic and non-dystrophic mice. For that, MDX and C57BL/10 mouse strains were subjected to peripheral nerve damage and were treated with PGB (30 mg/kg/day, i.p.) for 28 consecutive days. The treatment was carried out in mice as soon as they completed 5 weeks of life, 1 week before the lesion, corresponding to the peak period of muscle degeneration in the MDX strain. Six-week-old mice were submitted to unilateral sciatic nerve crush and were sacrificed in the 9th week of age. The ipsi and contralateral sciatic nerves were processed for immunohistochemistry and qRT-PCR, evaluating the expression of proteins and gene transcripts related to neuronal and Schwann cell activity. Cranial tibial muscles were dissected for evaluation of neuromuscular junctions using α-bungarotoxin, and the myelinated axons of the sciatic nerve were analyzed by morphometry. The recovery of motor function was monitored throughout the treatment through tests of forced locomotion (rotarod) and spontaneous walking track test (Catwalk system). The results show that treatment with PGB reduced the retrograde cyclic effects of muscle degeneration/regeneration on the nervous system. This fact was confirmed after peripheral nerve injury, showing better adaptation and response of neurons and glia for rapid axonal regeneration, with efficient muscle targeting and regain of function. No side effects of PGB treatment were observed, and the expression of pro-regenerative proteins in neurons and Schwann cells was upregulated. Morphometry of the axons was in line with the preservation of motor endplates, resulting in enhanced performance of dystrophic animals. Overall, the present data indicate that pregabalin is protective and enhances regeneration of the SNP during the development of DMD, improving motor function, which can, in turn, be translated to the clinic.

TNF-mimetic peptide mixed with fibrin glue improves peripheral nerve regeneration.

Surgical intervention is necessary following nerve trauma. Tubular prostheses can guide growing axons and inserting substances within these prostheses can be positive for the regeneration, making it an alternative for the current standard tools for nerve repair. Our aim was to investigate the effects of fibrin glue BthTL when combined with a synthetic TNF mimetic-action peptide on nerve regeneration. Male Wistar rats suffered left sciatic nerve transection. For repairing, we used empty silicon tubes (n = 10), tubes filled with fibrin glue BthTL (Tube + Glue group, n = 10) or tubes filled with fibrin glue BThTL mixed with TNF mimetic peptide (Tube + Glue + Pep group, n = 10). Animals were euthanized after 45 days. We collected nerves to perform immunostaining (neurofilament, GAP43, S100-ß, NGFRp75 and Iba-1), light and transmission electron microscopy (for counting myelinated, unmyelinated and degenerated fibers; and for the evaluation of morphometric aspects of regenerated fibers) and collagen staining. All procedures were approved by local ethics committee (protocol 063/17). Tube + Glue + Pep group showed intense inflammatory infiltrate, higher Iba-1 expression, increased immunostaining for NGFRp75 receptor (which characterizes Schwann cell regenerative phenotype), higher myelin thickness and fiber diameter and more type III collagen deposition. Tube + Glue group showed intermediate results between empty tube and Tube + Glue + Pep groups for anti-NGFRp75 immunostaining, inflammation and collagen; on fiber counts, this group showed more degenerate fibers and fewer unmyelinated axons than others. Empty tube group showed superiority only in GAP43 immunostaining. A combination of BthTL glue and TNF mimetic peptide induced greater axonal regrowth and remyelination.

Pregabalin-induced neuroprotection and gait improvement in dystrophic MDX mice.

Duchenne muscular dystrophy (DMD) is a genetic disease linked to the X chromosome induced by mutations in the dystrophin gene. Neuroprotective drugs, such as pregabalin (PGB), can improve motor function through the modulation of excitatory synapses, together with anti-apoptotic and anti-inflammatory effects. The present work studied the effects of PGB in the preservation of dystrophic peripheral nerves, allowing motor improvements in MDX mice. Five weeks old MDX and C57BL/10 mice were treated with PGB (30 mg/kg/day, i.p.) or vehicle, for 28 consecutive days. The mice were sacrificed on the 9th week, the sciatic nerves were dissected out and processed for immunohistochemistry and qRT-PCR, for evaluating the expression of proteins and gene transcripts related to neuronal activity and Schwann cell function. The lumbar spinal cords were also processed for qRT-PCR to evaluate the expression of neurotrophic factors and pro- and anti-inflammatory cytokines. Cranial tibial muscles were dissected out for endplate evaluation with α-bungarotoxin. The recovery of motor function was monitored throughout the treatment, using a spontaneous walking track test (Catwalk system) and a forced locomotion test (Rotarod). The results showed that treatment with PGB reduced the retrograde effects of muscle degeneration/regeneration on the nervous system from the 5th to the 9th week in MDX mice. Thus, PGB induced protein expression in neurons and Schwann cells, protecting myelinated fibers. In turn, better axonal morphology and close-to-normal motor endplates were observed. Indeed, such effects resulted in improved motor coordination of dystrophic animals. We believe that treatment with PGB improved the balance between excitatory and inhibitory inputs to spinal motoneurons, increasing motor control. In addition, PGB enhanced peripheral nerve homeostasis, by positively affecting Schwann cells. In general, the present results indicate that pregabalin is effective in protecting the PNS during the development of DMD, improving motor coordination, indicating possible translation to the clinic.

Evaluation of whole-body MRI with diffusion-weighted sequences in the staging of pediatric cancer patients.

BACKGROUND: The purpose of this study was to determine whether whole-body MRI (WBMRI) with diffusion-weighted sequences, which is free of ionizing radiation, can perform as well as traditional methods when used alone for staging or follow-up of pediatric cancer patients. METHODS: After obtaining approval from our institutional research ethics committee and appropriate informed consent, we performed 34 examinations in 32 pediatric patients. The examinations were anonymized and analyzed by two radiologists with at least 10 years' experience. RESULTS: The sensitivity and specificity findings, respectively, were as follows: 100% and 100% for primary tumor; 100% and 86% for bone metastasis; 33% and 100% for lung metastasis; 85% and 100% for lymph node metastasis; and 100% and 62% for global investigation of primary or secondary neoplasias. We observed excellent interobserver agreement for WBMRI and excellent agreement with standard staging examination results. CONCLUSIONS: Our results suggest that pediatric patients can be safely imaged with WBMRI, although not as the only tool but in association with low-dose chest CT (for subcentimeter pulmonary nodules). However, additional exams with ionizing radiation may be necessary for patients who tested positive to correctly quantify and locate the lesions.

Angiotensin-(1-7) receptor Mas antagonist (A779) influenced gliosis and reduced synaptic density in the spinal cord after peripheral axotomy.

The peptide angiotensin-(1-7) [Ang (1-7)] and its receptor Mas are involved in controlling arterial pressure and display actions on the nervous system. In a previous study, our laboratory showed that A779 [(peptidyl antagonist of the Ang-(1-7)] treatment had a negative effect following a lesion of the sciatic nerve, possibly by delaying the responses of Schwann cells, resulting in a decreased axonal organization along with a slowed functional return. In the present work, we investigated the central cellular changes after sciatic nerve injury in rodents treated with A779 after two weeks. In the lumbar spinal cords, where the neuronal bodies that make up the sciatic are, the treatment with A779 showed reduced reactivity of astrocytes (p = 0.004, Mann-Whitney U test) and less synaptic density (p = 0.004, Mann-Whitney U test) after injury. Also, the treatment upregulated microglia activity in both sides (p = 0.004, Mann-Whitney U test), ipsilateral and contralateral to the lesion, of the spinal cord. In addition, the Mas expression in spine neurons was increased in response to axotomy especially after two weeks (p = 0.03, Mann-Whitney U test) following the nerve lesion in comparison to earlier stages after injury. Therefore, we can conclude that Ang-(1-7)/Mas axis plays a role during spinal cord recovery after peripheral nerve injury.

Pseudomyxoma peritonei in a pediatric patient: A case report and literature review.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare clinical condition, with an incidence of 1-2 cases per million, characterized by the dissemination of mucinous implants on the peritoneal surface and progressive gelatinous ascites. Although it usually presents an indolent behavior, its non-specific clinical presentation contributes to many cases remaining undiagnosed until a laparotomy is performed. With late diagnosis, performed after a long period of clinical deterioration and disease progression, it is common to find complications such as the formation of intestinal fistulas and obstruction. METHOD: Review of the medical record and search for references in the Medline, Lilacs, SciELO and MD Consult databases. RESULTS: There are rare case reports found in the literature demonstrating atypical PMP presentations. Our report is that of a 17-year-old adolescent with a sporadic tumor diagnosed in a primary site in the transverse colon, contrary to data commonly found in the literature that mention a more frequent occurrence in women in the fifth decade of life and with a primary site in the ovary and appendix. The development of mucinous adenocarcinoma is rare in the pediatric population, and topography in the transverse colon and non-familial sporadic pattern are unusual. CONCLUSION: The case reported not only raises awareness about the atypical presentations of the disease, but also emphasizes the use of imaging examinations for diagnosis, which has an important impact on prognosis and survival if performed timely.

Pseudomyxoma peritonei in a pediatric patient: A case report and literature review / Pseudomixoma peritoneal em paciente pediátrico: relato de caso e revisão de literatura

Summary Introduction: Pseudomyxoma peritonei (PMP) is a rare clinical condition, with an incidence of 1-2 cases per million, characterized by the dissemination of mucinous implants on the peritoneal surface and progressive gelatinous ascites. Although it usually presents an indolent behavior, its non-specific clinical presentation contributes to many cases remaining undiagnosed until a laparotomy is performed. With late diagnosis, performed after a long period of clinical deterioration and disease progression, it is common to find complications such as the formation of intestinal fistulas and obstruction. Method: Review of the medical record and search for references in the Medline, Lilacs, SciELO and MD Consult databases. Results: There are rare case reports found in the literature demonstrating atypical PMP presentations. Our report is that of a 17-year-old adolescent with a sporadic tumor diagnosed in a primary site in the transverse colon, contrary to data commonly found in the literature that mention a more frequent occurrence in women in the fifth decade of life and with a primary site in the ovary and appendix. The development of mucinous adenocarcinoma is rare in the pediatric population, and topography in the transverse colon and non-familial sporadic pattern are unusual. Conclusion: The case reported not only raises awareness about the atypical presentations of the disease, but also emphasizes the use of imaging examinations for diagnosis, which has an important impact on prognosis and survival if performed timely.

Resumo Introdução: O pseudomixoma peritoneal (PMP) é uma condição clinica rara, com incidência de 1-2 casos por milhão, caracterizada pela disseminação de implantes de natureza mucinosa pela superfície peritoneal e acúmulo progressivo de ascite gelatinosa. Embora apresente geralmente um comportamento indolente, a apresentação clínica inespecífica contribui para que muitos casos permaneçam sem diagnóstico até a realização de laparotomia. Com o diagnóstico tardio, realizado após um longo período de deterioração clínica e progressão de doença, é comum encontrar complicações, como a formação de fístulas e obstruções intestinais. Método: Revisão do prontuário médico e pesquisa bibliográfica nas bases de dados Medline, Lilacs, SciELO e MD Consult. Resultados: São raros os relatos de caso encontrados na literatura que demonstram apresentações atípicas do PMP. O presente estudo apresenta o caso de um adolescente com 17 anos ao diagnóstico e sítio primário no colón transverso com tumor esporádico, contrário aos dados comumente encontrados na literatura, que referem acometimento mais comum em mulheres na quinta década de vida e com sítio primário em ovário e apêndice. O desenvolvimento de adenocarcinoma mucinoso é raro na população pediátrica e a topografia no cólon transverso e padrão esporádico não familial também são pouco usuais. Conclusão: O caso relatado alerta para as apresentações atípicas da doença e enfatiza o uso de exames de imagem para o diagnóstico, que, se realizado precocemente, impacta de maneira importante o prognóstico e a sobrevida.

Pattern of Mas expression in acute and post-acute stage of nerve injury in mice.

Angiotensin-(1-7) (Ang [1-7]) and its receptor Mas are involved in a number of physiological processes, including control of arterial pressure and modulation of nervous system actions. However, the involvement of the Ang-(1-7)/Mas axis in peripheral nerve injury has not been investigated. Using a model of sciatic nerve injury in mice, we demonstrated opposing changes in Mas receptor expression at days 2 and 14 post-injury. Mas receptor expression was more intense 2days after the nerve lesion, compared with the intensity of the intact nerve. At this time point, the sciatic nerve functional index was -20. At day 14 after the lesion, the intensity of the immunostaining labeling in longitudinal sections of the nerve was reduced (∼30%) and the functional index increased +36 (gait improvement). In the axotomized group treated with A779 (a Mas receptor antagonist), the functional recovery index decreased in relation to the untreated axotomized group. The Mas receptor inhibitor also altered the intensity of labeling of S-100, GAP43, and IBA-1 (morphological features compatible with delayed axon growth). This study demonstrated that Ang-(1-7)/Mas axis activity was differentially modulated in the acute and post-acute stages of nerve injury.

Whole-body MRI in pediatric patients with cancer.

Cancer is the leading cause of natural death in the pediatric populations of developed countries, yet cure rates are greater than 70% when a cancer is diagnosed in its early stages. Recent advances in magnetic resonance imaging methods have markedly improved diagnostic and therapeutic approaches, while avoiding the risks of ionizing radiation that are associated with most conventional radiological methods, such as computed tomography and positron emission tomography/computed tomography. The advent of whole-body magnetic resonance imaging in association with the development of metabolic- and function-based techniques has led to the use of whole-body magnetic resonance imaging for the screening, diagnosis, staging, response assessment, and post-therapeutic follow-up of children with solid sporadic tumours or those with related genetic syndromes. Here, the advantages, techniques, indications, and limitations of whole-body magnetic resonance imaging in the management of pediatric oncology patients are presented.

Value of ultrasound in the imaging-guided transthoracic biopsy of lung lesions.

Transthoracic needle biopsy with fluoroscopic or computed tomographic guidance is a well-established and safe method for diagnosing malignant and benign thoracic lesions. Nonetheless, ultrasound is as effective as computed tomography for the guidance of transthoracic biopsies of peripheral pulmonary lesions and mediastinal tumors, and it offers some advantages. In this case report, we exemplify the proper use of ultrasound for the percutaneous biopsy of a lung lesion, aiming to show that it can be a safe, inexpensive, rapid, and effective alternative to computed tomography in appropriate cases.

Prevalence of brucellosis in cattle at Potengi region, Rio Grande do Norte state, Brazil / Prevalência de brucelose em bovinos na região do potengi, estado do rio grande do norte

Brucellosis is an infectious disease that can infect production animals on the risk of causing economic damages, as well as human health. In Brazil there is a low number of studies on the prevalence of brucellosis, therefore this study had the objective of investigating the occurrence of it in the Potengi region, RN, Brazil it"s distribution related to sex, age, time of the year and municipality of origin. This study was a quantiative design on the type of epidemiological survey and the data was collected along with the Institute of Farm"s Defense and Inspection of Rio Grande do Norte (IDIARN), from august 2007 to august 2008. The results showed that Brucellosis was present in the region in study with a prevalence of 6,02%. Most of the cases happened in female sex animals (82,2%), and with age between four and five and a half years (70%). The prevalence was relatively decreasing in 2008 when compared to 2007 and most of the municipality of the region (64%) presented cases. Keywords: Animal health, epidemiology, Brucella sp, cattle

A brucelose é uma enfermidade infecto-contagiosa que pode afetar os animais de produção a ponto de causar danos econômicos, bem como à saúde da população. No Brasil os estudos para se conhecer a sua prevalência ainda são deficientes, para tanto, o presente trabalho teve como objetivo investigar a ocorrência da brucelose na região do Potengi, RN, sua distribuição com relação ao sexo, faixa etária, época do ano e município de procedência. O estudo compreendeu um delineamento quantitativo do tipo levantamento epidemiológico e os dados foram coletados junto ao Instituto de Defesa e Inspeção Agropecuária do Rio Grande do Norte (IDIARN), no período de agosto de 2007 a agosto de 2008. Os resultados evidenciaram que a brucelose estava presente na região estudada com uma prevalência de 6,02%. A maioria dos casos acontecia em animais do sexo feminino (82,2%), e com idade entre quatro anos e meio e cinco anos (70%). A prevalência foi relativamente decrescente em 2008 quando comparado com 2007 e a maioria dos municípios da região (64%) apresentaram casos. Palavras-Chave: Sanidade, epidemiologia, Brucella sp, bovinos

Prevalence of brucellosis in cattle at Potengi region, Rio Grande do Norte state, Brazil / PREVALÊNCIA DE BRUCELOSE EM BOVINOS NA REGIÃO DO POTENGI, ESTADO DO RIO GRANDE DO NORTE

Brucellosis is an infectious disease that can infect production animals on the risk of causing economic damages, as well as human health. In Brazil there is a low number of studies on the prevalence of brucellosis, therefore this study had the objective of investigating the occurrence of it in the Potengi region, RN, Brazil it"s distribution related to sex, age, time of the year and municipality of origin. This study was a quantiative design on the type of epidemiological survey and the data was collected along with the Institute of Farm"s Defense and Inspection of Rio Grande do Norte (IDIARN), from august 2007 to august 2008. The results showed that Brucellosis was present in the region in study with a prevalence of 6,02%. Most of the cases happened in female sex animals (82,2%), and with age between four and five and a half years (70%). The prevalence was relatively decreasing in 2008 when compared to 2007 and most of the municipality of the region (64%) presented cases. Keywords: Animal health, epidemiology, Brucella sp, cattle

A brucelose é uma enfermidade infecto-contagiosa que pode afetar os animais de produção a ponto de causar danos econômicos, bem como à saúde da população. No Brasil os estudos para se conhecer a sua prevalência ainda são deficientes, para tanto, o presente trabalho teve como objetivo investigar a ocorrência da brucelose na região do Potengi, RN, sua distribuição com relação ao sexo, faixa etária, época do ano e município de procedência. O estudo compreendeu um delineamento quantitativo do tipo levantamento epidemiológico e os dados foram coletados junto ao Instituto de Defesa e Inspeção Agropecuária do Rio Grande do Norte (IDIARN), no período de agosto de 2007 a agosto de 2008. Os resultados evidenciaram que a brucelose estava presente na região estudada com uma prevalência de 6,02%. A maioria dos casos acontecia em animais do sexo feminino (82,2%), e com idade entre quatro anos e meio e cinco anos (70%). A prevalência foi relativamente decrescente em 2008 quando comparado com 2007 e a maioria dos municípios da região (64%) apresentaram casos. Palavras-Chave: Sanidade, epidemiologia, Brucella sp, bovinos

Tumor de células gigantes ósseo: aspectos clínicos e radiográficos de 115 casos / Giant cell tumor of bone: clinical and radiographic aspects of 115 cases

OBJETIVO: Analisar os aspectos clínicos e radiográficos em pacientes com diagnóstico de tumor de células gigantes ósseo, confirmado por histopatologia. MATERIAIS E MÉTODOS: Os dados clínicos e radiológicos (quando disponíveis) de 115 pacientes com diagnóstico de tumor de células gigantes ósseo foram analisados no presente estudo. RESULTADOS: Dos casos avaliados, 57,4 por cento (66) eram do sexo feminino e 80 por cento (92) eram da raça branca. A média de idade dos pacientes foi de 30 anos e a topografia mais freqüente das lesões foi a metáfise distal do fêmur, em 22,6 por cento (26) dos casos. O aspecto radiográfico mais comum foi o de lesão puramente lítica, em 63,7 por cento (51) dos casos. CONCLUSAO: O tumor de células gigantes é uma neoplasia óssea relativamente comum, com predomínio em indivíduos da raça branca e com aspecto radiológico bem definido.

Sarcoma de Ewing: aspectos clínicos e radiográficos de 226 casos / Ewing's sarcoma: clinical and radiographic aspects of 226 cases

OBJETIVO: Avaliar os aspectos radiográficos e clínicos presentes em pacientes com o diagnóstico de sarcoma de Ewing confirmado por histopatologia. MATERIAIS E MÉTODOS: Foram analisados, neste trabalho, os dados clínicos e radiográficos (quando disponíveis) de 226 pacientes com o diagnóstico de sarcoma de Ewing ósseo. RESULTADOS: Dos casos avaliados, 61,5 por cento (139) eram do sexo masculino e 83,7 por cento (189) eram brancos. A mediana de idade dos pacientes foi de 14 anos e a topografia mais freqüente das lesões foi o osso ilíaco, em 13,7 por cento (31) dos casos. O aspecto radiográfico mais comum foi o de lesão lítica com reação periosteal (padrões variados), em 32,7 por cento (74) dos casos. CONCLUSÃO: O sarcoma de Ewing ósseo é uma neoplasia bastante agressiva, ocorrendo mais comumente em indivíduos na segunda década de vida e cujo aspecto radiográfico mais comum é o de lesão lítica com reação periosteal típica de lesão agressiva.

OBJECTIVE: To review the clinical and radiographic findings in patients with histologically confirmed Ewing's sarcoma. MATERIALS AND METHODS: Clinical and radiological (whenever available) data of 226 patients with Ewing's sarcoma of the bone were analyzed. RESULTS: Of the evaluated cases, 61.5% (139) were male and 83.7% (189) were white. The average age was 14 years old and the most common site of the lesions was the iliac bone, seen in 13.7% (31) of the cases. The most common radiological findings were lytic lesion with periosteal reaction, seen in 32.7% (74) of the patients. CONCLUSION: Ewing's sarcoma of bone is an aggressive neoplasm, occurring mainly in the second decade of life, which main radiological findings are lytic lesions with periosteal reaction, typical characteristic of aggressive lesions.