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1.
BMC Vet Res ; 20(1): 190, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734647

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a fatal zoonosis caused by ticks in East Asia. As SFTS virus (SFTSV) is maintained between wildlife and ticks, seroepidemiological studies in wildlife are important to understand the behavior of SFTSV in the environment. Miyazaki Prefecture, Japan, is an SFTS-endemic area, and approximately 100 feral horses, called Misaki horses (Equus caballus), inhabit Cape Toi in Miyazaki Prefecture. While these animals are managed in a wild-like manner, their ages are ascertainable due to individual identification. In the present study, we conducted a seroepidemiological survey of SFTSV in Misaki horses between 2015 and 2023. This study aimed to understand SFTSV infection in horses and its transmission to wildlife. A total of 707 samples from 180 feral horses were used to determine the seroprevalence of SFTSV using enzyme-linked immunosorbent assay (ELISA). Neutralization testing was performed on 118 samples. In addition, SFTS viral RNA was detected in ticks from Cape Toi and feral horses. The overall seroprevalence between 2015 and 2023 was 78.5% (555/707). The lowest seroprevalence was 55% (44/80) in 2016 and the highest was 92% (76/83) in 2018. Seroprevalence was significantly affected by age, with 11% (8/71) in those less than one year of age and 96.7% (435/450) in those four years of age and older (p < 0.0001). The concordance between ELISA and neutralization test results was 88.9% (105/118). SFTS viral RNA was not detected in ticks (n = 516) or feral horses. This study demonstrated that horses can be infected with SFTSV and that age is a significant factor in seroprevalence in wildlife. This study provides insights into SFTSV infection not only in horses but also in wildlife in SFTS-endemic areas.


Assuntos
Doenças dos Cavalos , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Cavalos , Estudos Soroepidemiológicos , Japão/epidemiologia , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/virologia , Doenças dos Cavalos/sangue , Phlebovirus/isolamento & purificação , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/veterinária , Febre Grave com Síndrome de Trombocitopenia/virologia , Feminino , Masculino , Anticorpos Antivirais/sangue , Carrapatos/virologia , Ensaio de Imunoadsorção Enzimática/veterinária , Animais Selvagens/virologia
2.
Int J Clin Oncol ; 29(7): 911-920, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38829471

RESUMO

BACKGROUND: Both cancer diagnosis/treatment modality and surgical technique for the spine have been developed recently. Nationwide trends in the surgical treatment for metastatic spinal tumors have not been reported in the last decades. This study aimed to examine recent trends in the surgical treatment for spinal metastasis and in-hospital patient outcomes using nationwide administrative hospital discharge data. METHODS: The Diagnosis Procedure Combination database from 2012 to 2020 was used to extract data from patients who underwent surgical procedures for spinal metastasis with the number of non-metastatic spinal surgery at the institutions that have performed metastatic spine surgeries at least one case in the same year. Trends in the surgical treatment for spinal metastasis, patients' demographics, and in-hospital mortality/outcomes were investigated. RESULTS: This study analyzed 10,321 eligible patients with spinal metastasis. The surgical treatment for spinal metastasis increased 1.68 times from 2012 to 2020, especially in fusion surgery, whereas the proportion of metastatic spinal surgery retained with a slight increase in the 2%s. Distributions of the primary site did not change, whereas age was getting older. In-hospital mortality and length of stay decreased over time (9.9-6.8%, p < 0.001; 37-30 days, p < 0.001). Postoperative complication and unfavorable ambulatory retained stable and slightly decreased, respectively. CONCLUSION: During the last decade, surgical treatment for spinal metastasis, especially fusion surgery, has increased in Japan. In-hospital mortality and length of stay decreased. Recent advances in cancer treatment and surgical techniques might influence this trend.


Assuntos
Mortalidade Hospitalar , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/secundário , Feminino , Masculino , Idoso , Japão/epidemiologia , Pessoa de Meia-Idade , Mortalidade Hospitalar/tendências , Tempo de Internação/estatística & dados numéricos , Bases de Dados Factuais , Adulto , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Fusão Vertebral/métodos , Fusão Vertebral/estatística & dados numéricos , População do Leste Asiático
3.
J Orthop Sci ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38575427

RESUMO

BACKGROUND: Postoperative airway obstruction after anterior cervical spine surgery (ACSS) can be a fatal complication. Occasionally, it rapidly progresses to complete obstruction. There are no established standardized protocols on how medical staff should assess for signs and symptoms, seek help, or facilitate airway management after ACSS to prevent unfavorable events. This study aimed to primarily describe a systematic approach by assessing the signs and treatment outcomes of airway compromise in patients who underwent ACSS. Further, it recommended an action protocol after extubation for medical staff according to patients' symptoms to prevent unfavorable outcomes. METHODS: An extensive literature search was performed on PubMed, Web of Science, and the Cochrane Library to identify case reports, case series, and cohort studies restricted to English and published between January 1990 and March 2023. We included cases that described the signs, symptoms, and treatment of airway obstruction after ACSS. Meanwhile, cases involving complications of other known causes, cases of trauma or occipital-cervical fixation, or those using bone morphogenetic protein were excluded. RESULTS: Twenty cases from 17 studies were obtained, and their study quality was acceptable. Four patients died, and two presented with hypoxic ischemic encephalopathy. Further, five of six patients had fatal complications that initially developed within 7 h after surgery. Then, 9 (69%) of 13 patients with evidence of hematoma (69%) showed initial symptoms within 12 h after surgery. Finally, 9 of 11 patients with early-stage symptoms had favorable outcomes, and patients who developed late-stage symptoms commonly had unfavorable outcomes. CONCLUSION: The early identification of signs and symptoms and immediate treatment are important, particularly within 12 h postoperatively. We suggest a novel action protocol for medical staff according to symptom urgency, which includes the measurement of neck circumference using a string for evaluating neck swelling.

4.
Emerg Infect Dis ; 29(3): 614-617, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36823498

RESUMO

In Japan, 2 cats that underwent surgery in a room where a sick dog had been euthanized became ill within 9 days of surgery. Severe fever with thrombocytopenia syndrome virus was detected in all 3 animals; nucleotide sequence identity was 100%. Suspected cause was an uncleaned pulse oximeter probe used for all patients.


Assuntos
Infecções por Bunyaviridae , Infecção Hospitalar , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Cães , Animais de Estimação , Japão
5.
J Clin Microbiol ; 61(3): e0154322, 2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36840574

RESUMO

Molecular analysis of rabies virus can provide accurate diagnosis and information on its genetic diversity. The transportation of rabies brain samples from remote areas to a central laboratory is challenging owing to biohazard risks and decomposability. We investigated the utility of used lateral flow devices (LFDs) for subsequent molecular analysis and assessed the necessary storage temperatures. Using RNA extracted from used LFD strips, we performed conventional reverse transcription-PCR (RT-PCR) using an LN34 primer set to amplify short fragments (165 bp) for rabies virus detection and the P1-304 primer set to amplify long fragments of the entire N gene amplicon (1,506 bp) for phylogenetic analysis. Among 71 used LFDs stored in a refrigerator and 64 used LFDs stored at room temperature, the LN34 assay showed high sensitivities (96.2% and 100%, respectively) for the diagnosis of rabies, regardless of the storage temperature. A significant reduction in the sensitivity of rabies diagnosis was observed when using the P1-304 primer set for used LFDs stored at room temperature compared to those stored at refrigeration temperature (20.9% versus 100%; P < 0.05). Subsequent sequencing and phylogenetic analysis were successfully performed using the amplicons generated by the P1-304 RT-PCR assays. Used LFDs are thus promising resources for rabies virus RNA detection and sequence analysis. Virus detection via RT-PCR, amplifying a short fragment, was possible regardless of the storage temperature of the used LFDs. However, refrigerated storage is recommended for RT-PCR amplification of long fragments for phylogenetic analysis.


Assuntos
Vírus da Raiva , Raiva , Humanos , Vírus da Raiva/genética , Raiva/diagnóstico , Filogenia , RNA Viral/genética , RNA Viral/análise , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
6.
J Virol ; 96(18): e0081022, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36069552

RESUMO

Stress granules (SGs) are dynamic structures that store cytosolic messenger ribonucleoproteins. SGs have recently been shown to serve as a platform for activating antiviral innate immunity; however, several pathogenic viruses suppress SG formation to evade innate immunity. In this study, we investigated the relationship between rabies virus (RABV) virulence and SG formation, using viral strains with different levels of virulence. We found that the virulent Nishigahara strain did not induce SG formation, but its avirulent offshoot, the Ni-CE strain, strongly induced SG formation. Furthermore, we demonstrated that the amino acid at position 95 in the RABV matrix protein (M95), a pathogenic determinant for the Nishigahara strain, plays a key role in inhibiting SG formation, followed by protein kinase R (PKR)-dependent phosphorylation of the α subunit of eukaryotic initiation factor 2α (eIF2α). M95 was also implicated in the accumulation of RIG-I, a viral RNA sensor protein, in SGs and in the subsequent acceleration of interferon induction. Taken together, our findings strongly suggest that M95-related inhibition of SG formation contributes to the pathogenesis of RABV by allowing the virus to evade the innate immune responses of the host. IMPORTANCE Rabies virus (RABV) is a neglected zoonotic pathogen that causes lethal infections in almost all mammalian hosts, including humans. Recently, RABV has been reported to induce intracellular formation of stress granules (SGs), also known as platforms that activate innate immune responses. However, the relationship between SG formation capacity and pathogenicity of RABV has remained unclear. In this study, by comparing two RABV strains with completely different levels of virulence, we found that the amino acid mutation from valine to alanine at position 95 of matrix protein (M95), which is known to be one of the amino acid mutations that determine the difference in virulence between the strains, plays a major role in SG formation. Importantly, M95 was involved in the accumulation of RIG-I in SGs and in promoting interferon induction. These findings are the first report of the effect of a single amino acid substitution associated with SGs on viral virulence.


Assuntos
Vírus da Raiva , Grânulos de Estresse , Proteínas da Matriz Viral , Aminoácidos/metabolismo , Animais , Fator de Iniciação 2 em Eucariotos/metabolismo , Humanos , Interferons/imunologia , Proteínas Quinases/imunologia , RNA Viral/metabolismo , Vírus da Raiva/genética , Vírus da Raiva/patogenicidade , Ribonucleoproteínas/metabolismo , Grânulos de Estresse/genética , Grânulos de Estresse/imunologia , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
7.
Cell Immunol ; 385: 104675, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36746071

RESUMO

Active tolerance to ingested dietary antigens forms the basis for oral immunotherapy to food allergens or autoimmune self-antigens. Alternatively, oral administration of anti-CD3 monoclonal antibody can be effective in modulating systemic immune responses without T cell depletion. Here we assessed the efficacy of full length and the F(ab')2 fragment of oral anti-CD3 to prevent anti-drug antibody (ADA) formation to clotting factor VIII (FVIII) protein replacement therapy in hemophilia A mice. A short course of low dose oral anti-CD3 F(ab')2 reduced the production of neutralizing ADAs, and suppression was significantly enhanced when oral anti-CD3 was timed concurrently with FVIII administration. Tolerance was accompanied by the early induction of FoxP3+LAP-, FoxP3+LAP+, and FoxP3-LAP+ populations of CD4+ T cells in the spleen and mesenteric lymph nodes. FoxP3+LAP+ Tregs expressing CD69, CTLA-4, and PD1 persisted in spleens of treated mice, but did not produce IL-10. Finally, we attempted to combine the anti-CD3 approach with oral intake of FVIII antigen (using our previously established method of using lettuce plant cells transgenic for FVIII antigen fused to cholera toxin B (CTB) subunit, which suppresses ADAs in part through induction of IL-10 producing FoxP3-LAP+ Treg). However, combining these two approaches failed to improve suppression of ADAs. We conclude that oral anti-CD3 treatment is a promising approach to prevention of ADA formation in systemic protein replacement therapy, albeit via mechanisms distinct from and not synergistic with oral intake of bioencapsulated antigen.


Assuntos
Hemofilia A , Camundongos , Animais , Hemofilia A/tratamento farmacológico , Fator VIII , Interleucina-10/metabolismo , Formação de Anticorpos , Anticorpos Monoclonais , Fatores de Transcrição Forkhead/metabolismo , Tolerância Imunológica , Linfócitos T Reguladores
8.
J Vasc Interv Radiol ; 34(9): 1511-1515.e1, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37196821

RESUMO

Double-barrel stent placement across the iliocaval confluence is commonly used for the treatment of chronic bilateral iliocaval occlusion. The difference in the deployment outcomes of synchronous parallel stent deployment versus asynchronous or antiparallel deployment and the underlying stent interactions are poorly understood. In this study, 3 strategies of double-barrel nitinol self-expanding stent deployment across the iliocaval confluence (synchronous parallel, asynchronous parallel, and synchronous antiparallel) were contrasted in vivo in 3 swine followed by assessment of the explanted stent construct. Synchronous parallel stent deployment achieved a desired double-barrel configuration. The asynchronous parallel and antiparallel deployment strategies both resulted in a crushed stent despite subsequent simultaneous balloon angioplasty. These animal model results suggested that in patients who undergo double-barrel iliocaval reconstruction, synchronous parallel stent deployment may provide the desired stent conformation and increase the chance for clinical success.


Assuntos
Ligas , Stents , Animais , Suínos , Resultado do Tratamento , Grau de Desobstrução Vascular
9.
Mol Ther ; 30(12): 3552-3569, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-35821634

RESUMO

Hepatic adeno-associated viral (AAV) gene transfer has the potential to cure the X-linked bleeding disorder hemophilia A. However, declining therapeutic coagulation factor VIII (FVIII) expression has plagued clinical trials. To assess the mechanistic underpinnings of this loss of FVIII expression, we developed a hemophilia A mouse model that shares key features observed in clinical trials. Following liver-directed AAV8 gene transfer in the presence of rapamycin, initial FVIII protein expression declines over time in the absence of antibody formation. Surprisingly, loss of FVIII protein production occurs despite persistence of transgene and mRNA, suggesting a translational shutdown rather than a loss of transduced hepatocytes. Some of the animals develop ER stress, which may be linked to hepatic inflammatory cytokine expression. FVIII protein expression is preserved by interleukin-15/interleukin-15 receptor blockade, which suppresses CD8+ T and natural killer cell responses. Interestingly, mice with initial FVIII levels >100% of normal had diminishing expression while still under immune suppression. Taken together, our findings of interanimal variability of the response, and the ability of the immune system to shut down transgene expression without utilizing cytolytic or antibody-mediated mechanisms, illustrate the challenges associated with FVIII gene transfer. Our protocols based upon cytokine blockade should help to maintain efficient FVIII expression.


Assuntos
Fator VIII , Interleucina-15 , Camundongos , Animais , Fator VIII/genética , Interleucina-15/genética , Sirolimo/farmacologia
10.
J Reprod Dev ; 69(5): 261-269, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37599082

RESUMO

A high temperature-humidity index during summer has deleterious effects on mitochondrial function, reducing oocyte developmental competence. 5-Aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) are both known to support mitochondrial function and have strong anti-oxidant and anti-apoptotic activities. This study aimed to determine the mechanism of action of 5-ALA/SFC on oocyte quality. Bovine oocytes were collected from medium-sized follicles during summer (July-September, temperature-humidity index:76.6), cultured with 0, 1, 2, 4, and 8 µM 5-ALA with SFC at a molar ratio of 1:0.125, fertilized, and cultured for 10 days. The addition of 8/1 µM 5-ALA/SFC had a deleterious effect on oocyte cleavage rate in comparison with control oocytes, but did not affect the blastocyst rate, while 1/0.125 µM 5-ALA/SFC had a significantly higher increase in blastocyst rate than 8/1 µM 5-ALA/SFC. The addition of 1/0.125 and 2/0.25 µM 5-ALA/SFC improved oocyte quality by increasing the mitochondrial distribution pattern and metaphase-II oocytes, reducing reactive oxygen species and upregulating nuclear factor erythroid-2-related factor 2, heme oxygenase-1, and superoxide dismutase-1 in oocytes, and nuclear factor erythroid-2-related factor 2 and mitochondrial transcription factor A in cumulus cells. These results indicate that 1/0.125 and 2/0.25 µM 5-ALA/SFC may support oocyte quality and developmental competence and provide anti-oxidant actions in cumulus-oocyte complexes.


Assuntos
Ácido Aminolevulínico , Antioxidantes , Animais , Bovinos , Ácido Aminolevulínico/farmacologia , Antioxidantes/farmacologia , Temperatura Alta , Oócitos/fisiologia , Estresse Oxidativo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos
11.
BMC Nephrol ; 24(1): 237, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582721

RESUMO

BACKGROUND: Renal tubular acidosis is the principal clinical feature associated with tubulointerstitial nephritis in patients with primary Sjögren's syndrome. Renal tubular dysfunction due to interstitial nephritis has been considered the underlying pathophysiology connecting renal tubular acidosis and primary Sjögren's syndrome. However, the detailed mechanisms underlying the pathophysiology of renal tubular acidosis in primary Sjögren's syndrome is not fully understood. CASE PRESENTATION: A 30-year-old woman was admitted with complaints of weakness in the extremities. The patient was hospitalized thirteen years earlier for similar issues and was diagnosed with hypokalemic paralysis due to distal renal tubular acidosis with primary Sjögren's syndrome. This diagnosis was based on a positive Schirmer's test. Besides, anti-Sjögren's syndrome-related antigen A was also detected. Laboratory tests indicated distal RTA; however, a renal biopsy showed no obvious interstitial nephritis. Laboratory tests conducted during the second admission indicated distal renal tubular acidosis. Therefore, a renal biopsy was performed again, which revealed interstitial nephritis. Histological analysis of acid-base transporters revealed the absence of vacuolar type H+-ATPases in the collecting duct. The vacuolar type H+-ATPase was also absent in the past renal biopsy, suggesting that the alteration in acid-base transporters is independent of interstitial nephritis. CONCLUSIONS: This case study demonstrates that vacuolar-type H+-ATPases are associated with distal renal tubular acidosis, and distal renal tubular acidosis precedes interstitial nephritis in patients with primary Sjögren's syndrome.


Assuntos
Acidose Tubular Renal , Hipopotassemia , Nefrite Intersticial , Síndrome de Sjogren , ATPases Vacuolares Próton-Translocadoras , Feminino , Humanos , Adulto , Acidose Tubular Renal/complicações , Acidose Tubular Renal/diagnóstico , Nefrite Intersticial/complicações , Nefrite Intersticial/diagnóstico , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Paralisia/complicações , Hipopotassemia/etiologia , Proteínas de Membrana Transportadoras , Anticorpos
12.
Eur Spine J ; 32(2): 505-516, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36567342

RESUMO

PURPOSE: Clinical outcomes after decompression procedures are reportedly worse for lumbar spinal stenosis (LSS) with diffuse idiopathic skeletal hyperostosis (DISH), especially DISH extended to the lumbar segment (L-DISH). However, no studies have compared the effect of less-invasive surgery versus conventional decompression techniques for LSS with DISH. The purpose of this study was to compare the long-term risk of reoperation after decompression surgery focusing on LSS with L-DISH. METHODS: This study compared open procedure cohort (open conventional fenestration) and less-invasive procedure cohort (bilateral decompression via a unilateral approach) with ≥ 5 years of follow-up. After stratified analysis by L-DISH, patients with L-DISH were propensity score-matched by age and sex. RESULTS: There were 57 patients with L-DISH among 489 patients in the open procedure cohort and 41 patients with L-DISH among 297 patients in the less-invasive procedure cohort. The reoperation rates in L-DISH were higher in the open than less-invasive procedure cohort for overall reoperations (25% and 7%, p = 0.026) and reoperations at index levels (18% and 5%, p = 0.059). Propensity score-matched analysis in L-DISH demonstrated that open procedures were significantly associated with increased overall reoperations (hazard ratio [HR], 6.18; 95% confidence interval [CI], 1.37-27.93) and reoperations at index levels (HR, 4.80; 95% CI, 1.04-22.23); there was no difference in reoperation at other lumbar levels. CONCLUSIONS: Less-invasive procedures had a lower risk of reoperation, especially at index levels for LSS with L-DISH. Preserving midline-lumbar posterior elements could be desirable as a decompression procedure for LSS with L-DISH.


Assuntos
Hiperostose Esquelética Difusa Idiopática , Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Estudos Retrospectivos , Reoperação , Hiperostose Esquelética Difusa Idiopática/complicações , Descompressão Cirúrgica/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Resultado do Tratamento
13.
J Med Syst ; 47(1): 42, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36995484

RESUMO

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an endovascular procedure for hemorrhage control. In REBOA, the balloon must be placed in the precise place, but it may be performed without X-ray fluoroscopy. This study aimed to estimate the REBOA zones from the body surface using deep learning for safe balloon placement. A total of 198 abdominal computed tomography (CT) datasets containing the regions of the REBOA zones were collected from open data libraries. Then, depth images of the body surface generated from the CT datasets and the images corresponding to the zones were labeled for deep learning training and validation. DeepLabV3+, a deep learning semantic segmentation model, was employed to estimate the zones. We used 176 depth images as training data and 22 images as validation data. A nine-fold cross-validation was performed to generalize the performance of the network. The median Dice coefficients for Zones 1-3 were 0.94 (inter-quarter range: 0.90-0.96), 0.77 (0.60-0.86), and 0.83 (0.74-0.89), respectively. The median displacements of the zone boundaries were 11.34 mm (5.90-19.45), 11.40 mm (4.88-20.23), and 14.17 mm (6.89-23.70) for the boundary between Zones 1 and 2, between Zones 2 and 3, and between Zone 3 and out of zone, respectively. This study examined the feasibility of REBOA zone estimation from the body surface only using deep learning-based segmentation without aortography.


Assuntos
Oclusão com Balão , Semântica , Humanos , Aorta , Hemorragia , Abdome , Oclusão com Balão/métodos
14.
Mod Rheumatol ; 33(3): 503-508, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35588242

RESUMO

OBJECTIVES: In rheumatoid arthritis, neck pain can be caused by inflammatory reactions or cervical lesions, but the prevalence and associated factors have not been well studied. This study aimed to investigate the prevalence of neck pain in patients with rheumatoid arthritis and elucidate the related factors. METHODS: This study included 146 patients with rheumatoid arthritis. Neck pain, quality of life, and levels of anxiety and depression were evaluated using a questionnaire. Cervical lesions and spinal alignment were evaluated using plain radiograph and magnetic resonance imaging. Factors associated with neck pain were analysed using a logistic regression model. RESULTS: Fifty-six per cent of the patients had neck pain, and the quality of life scores were significantly worse in these patients. Multivariate analysis revealed age, C7 sagittal vertical axis, upper cervical lesion, and endplate erosion as factors associated with neck pain in patients with rheumatoid arthritis. CONCLUSIONS: More than half the patients with rheumatoid arthritis suffer from neck pain, and neck pain affects the quality of life and activities of daily living. Neck pain was associated with upper cervical lesion and endplate erosion suggesting the importance of radiological examination in patients with rheumatoid arthritis and neck pain.


Assuntos
Artrite Reumatoide , Articulação Atlantoaxial , Humanos , Vértebras Cervicais/diagnóstico por imagem , Cervicalgia/diagnóstico por imagem , Cervicalgia/epidemiologia , Cervicalgia/etiologia , Qualidade de Vida , Atividades Cotidianas , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/patologia , Articulação Atlantoaxial/patologia
15.
Am J Hum Genet ; 104(2): 287-298, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30661771

RESUMO

Hypusine is formed post-translationally from lysine and is found in a single cellular protein, eukaryotic translation initiation factor-5A (eIF5A), and its homolog eIF5A2. Biosynthesis of hypusine is a two-step reaction involving the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). eIF5A is highly conserved throughout eukaryotic evolution and plays a role in mRNA translation, cellular proliferation, cellular differentiation, and inflammation. DHPS is also highly conserved and is essential for life, as Dhps-null mice are embryonic lethal. Using exome sequencing, we identified rare biallelic, recurrent, predicted likely pathogenic variants in DHPS segregating with disease in five affected individuals from four unrelated families. These individuals have similar neurodevelopmental features that include global developmental delay and seizures. Two of four affected females have short stature. All five affected individuals share a recurrent missense variant (c.518A>G [p.Asn173Ser]) in trans with a likely gene disrupting variant (c.1014+1G>A, c.912_917delTTACAT [p.Tyr305_Ile306del], or c.1A>G [p.Met1?]). cDNA studies demonstrated that the c.1014+1G>A variant causes aberrant splicing. Recombinant DHPS enzyme harboring either the p.Asn173Ser or p.Tyr305_Ile306del variant showed reduced (20%) or absent in vitro activity, respectively. We co-transfected constructs overexpressing HA-tagged DHPS (wild-type or mutant) and GFP-tagged eIF5A into HEK293T cells to determine the effect of these variants on hypusine biosynthesis and observed that the p.Tyr305_Ile306del and p.Asn173Ser variants resulted in reduced hypusination of eIF5A compared to wild-type DHPS enzyme. Our data suggest that rare biallelic variants in DHPS result in reduced enzyme activity that limits the hypusination of eIF5A and are associated with a neurodevelopmental disorder.


Assuntos
Genes Recessivos/genética , Lisina/análogos & derivados , Mutação , Transtornos do Neurodesenvolvimento/enzimologia , Transtornos do Neurodesenvolvimento/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Alelos , Sequência de Aminoácidos , Criança , Pré-Escolar , Deficiências do Desenvolvimento/enzimologia , Deficiências do Desenvolvimento/genética , Feminino , Haplótipos , Humanos , Lisina/biossíntese , Masculino , Erros Inatos do Metabolismo/enzimologia , Erros Inatos do Metabolismo/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/química , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Linhagem , Fatores de Iniciação de Peptídeos/química , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Convulsões/enzimologia , Convulsões/genética , Adulto Jovem , Fator de Iniciação de Tradução Eucariótico 5A
16.
J Bone Miner Metab ; 40(1): 120-131, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34424413

RESUMO

INTRODUCTION: Although lumbar lesions such as spondylolisthesis, scoliosis, and vertebral fracture are not specific to rheumatoid arthritis (RA), the prevalence is high in RA patients. However, no longitudinal study has evaluated lumbar lesions in RA. This study aimed to investigate the incidence of and risk factors for lumbar lesions in RA by a prospective longitudinal cohort study. MATERIALS AND METHODS: The study cohort comprised 110 patients with RA from the 'analysis of factors for RA spinal disorders (AFFORD)' study who completed the secondary survey at a single orthopaedic outpatient RA clinic. Radiological examination included standing radiographs and magnetic resonance imaging (MRI) of the lumbar spine. New development of spondylolisthesis, scoliosis, and vertebral fracture were assessed between baseline and secondary survey. RESULTS: The incidences of spondylolisthesis, scoliosis, and vertebral fracture were 42%, 16%, and 12%, respectively, during a mean follow-up of 7 years. The independent risk factor for de novo scoliosis was poor control of RA (adjusted odds ratio [aOR] 4.81, p = 0.011), while the independent risk factors for new vertebral fracture was use of glucocorticoid at secondary survey (aOR 14.87, p = 0.012). Patients with de novo scoliosis exhibited more severe low back pain and lower quality of life than those without. CONCLUSION: The incidence of scoliosis was related in patients with poor control of RA, while new vertebral fracture was more common in patients with use of glucocorticoid. Control of disease activity might be important in preventing radiological lumbar disorders in RA.


Assuntos
Artrite Reumatoide , Escoliose , Fraturas da Coluna Vertebral , Espondilolistese , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Humanos , Incidência , Estudos Longitudinais , Vértebras Lombares/diagnóstico por imagem , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Escoliose/diagnóstico por imagem , Escoliose/epidemiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Espondilolistese/diagnóstico por imagem , Espondilolistese/epidemiologia
17.
Clin Exp Nephrol ; 26(3): 272-277, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34591238

RESUMO

BACKGROUND: Sarcopenia is strongly associated with long-term mortality in patients undergoing hemodialysis. The diagnostic modalities used to assess muscle mass, such as bioimpedance analysis and dual-energy X-ray absorption measurement, have limitations for application in patients on hemodialysis. Therefore, there is a need to establish a simple index for assessing muscle mass that can be universally performed in patients on hemodialysis. METHODS: Patients on maintenance hemodialysis were included in this study. Laboratory tests, skeletal muscle mass measured by bioimpedance analysis, and clinical records were obtained retrospectively. The creatinine generation rate (CGR) was calculated from the pre- and postdialysis blood tests using a kinetic model as the index for whole-body muscle mass. Correlations between the CGR and skeletal muscle mass were investigated, and the cut-off value for muscle wasting was determined. Kaplan-Meier survival analysis was performed to investigate the feasibility of the CGR for predicting long-term survival. RESULTS: Among the 130 patients included, eight were diagnosed with sarcopenia by bioimpedance analysis. The CGR was positively correlated with skeletal muscle mass (r = 0.454, p < 0.001). Multiple linear regression analysis revealed that age and sex independently influenced the CGR. The patients were classified into two groups according to age- and sex-adjusted CGRs. During a median follow-up period of 32 months, the Kaplan-Meier survival analysis showed that patients with low CGR showed significantly poor long-term prognosis (p = 0.002). CONCLUSION: The CGR is a simple index for muscle mass and can predict long-term mortality in patients on hemodialysis.


Assuntos
Sarcopenia , Creatinina , Humanos , Músculo Esquelético , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Sarcopenia/diagnóstico , Sarcopenia/etiologia
18.
Int J Mol Sci ; 23(15)2022 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-35897725

RESUMO

A clear identification of the etiology of glomerular disease is essential in patients with diabetes. Renal biopsy is the gold standard for assessing the underlying nephrotic pathology; however, it has the risk for potential complications. Here, we aimed to investigate the feasibility of urinary fluorescence imaging using an enzyme-activatable probe for differentiating diabetic kidney disease and the other glomerular diseases. Hydroxymethyl rhodamine green (HMRG)-based fluorescent probes targeting gamma-glutamyl transpeptidase (GGT) and dipeptidyl-peptidase (DPP) were used. Urinary fluorescence was compared between groups which were classified by their histopathological diagnoses (diabetic kidney disease, glomerulonephritis, and nephrosclerosis) as obtained by ultrasound-guided renal biopsy. Urinary fluorescence was significantly stronger in patients with diabetic kidney disease compared to those with glomerulonephritis/nephrosclerosis after DPP-HMRG, whereas it was stronger in patients with nephrosclerosis than in patients with glomerulonephritis after GGT-HMRG. Subgroup analyses of the fluorescence performed for patients with diabetes showed consistent results. Urinary fluorescence imaging using enzyme-activatable fluorescence probes thus represents a potential noninvasive assessment technique for kidney diseases in patients with diabetes.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Glomerulonefrite , Nefroesclerose , Nefropatias Diabéticas/diagnóstico por imagem , Corantes Fluorescentes , Glomerulonefrite/diagnóstico por imagem , Humanos , Imagem Óptica/métodos , Rodaminas , gama-Glutamiltransferase
19.
J Stroke Cerebrovasc Dis ; 31(1): 106178, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34794030

RESUMO

Bow hunter's syndrome is the mechanical compression of the vertebral artery due to cervical rotation, resulting in ischemic symptoms in the vertebrobasilar artery territory. However, some cases present without typical symptoms and exhibit compression of the non-dominant side of the vertebral artery. We encountered a case of posterior circulation embolism due to a subtype of bow hunter's syndrome in a 74-year-old man. Although the right vertebral artery was not visualized on time-of-flight magnetic resonance angiography in the neutral position, duplex ultrasonography and time-of-flight magnetic resonance angiography in the left cervical rotation position showed blood flow in the right vertebral artery. In this case, blood flow in the contralateral vertebral artery was normal, and typical bow hunter's syndrome symptoms did not occur. In a case of posterior circulation embolism with undetermined etiology, wherein the routine duplex ultrasonography and time-of-flight magnetic resonance angiography results were inconclusive, additional testing with head positioning led to the diagnosis of a subtype of bow hunter's syndrome.


Assuntos
Embolia , Mucopolissacaridose II , Idoso , Embolia/diagnóstico , Humanos , Masculino , Mucopolissacaridose II/complicações
20.
Mod Rheumatol ; 32(6): 1027-1034, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34878544

RESUMO

OBJECTIVE: Several studies have demonstrated that low back pain (LBP) is related to disease activity in patients with rheumatoid arthritis (RA). However, there is no longitudinal research. This study aimed to determine the impacts and risk factors for LBP increase in RA in a longitudinal cohort study. METHODS: The study evaluated 113 patients with RA who completed the secondary survey. LBP increase was defined as ≥1 standard deviation of mean change in visual analogue scale (VAS) between the baseline and secondary surveys. The impacts of LBP increase on quality of life (QOL) and psychological status were evaluated. Risk factors were assessed among patient demographic characteristics and radiological changes. RESULTS: Mean change in VAS for LBP was -0.8 ± 30.4 mm during a mean 7-year follow-up. LBP increase was defined as ≥30-mm increase in VAS for LBP. Patients with LBP increase had significantly lower QOL and worse mental status than patients without it. Poor control of RA was identified as an independent risk factor for LBP increase (odds ratio, 9.82, p = .001). CONCLUSION: Patients with poor control of RA were likely to experience LBP increase in the long term. Control of RA disease activity is important for control of LBP, QOL, and mental status.


Assuntos
Artrite Reumatoide , Dor Lombar , Artrite Reumatoide/complicações , Artrite Reumatoide/psicologia , Seguimentos , Humanos , Estudos Longitudinais , Dor Lombar/complicações , Dor Lombar/epidemiologia , Qualidade de Vida , Fatores de Risco , Inquéritos e Questionários
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