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1.
Nature ; 582(7810): 89-94, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32483373

RESUMO

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.


Assuntos
Proteína C9orf72/genética , Microbioma Gastrointestinal/fisiologia , Gliose/microbiologia , Gliose/patologia , Inflamação/genética , Inflamação/microbiologia , Medula Espinal/patologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Antibacterianos/farmacologia , Autoimunidade/efeitos dos fármacos , Autoimunidade/genética , Autoimunidade/imunologia , Movimento Celular/efeitos dos fármacos , Citocinas/imunologia , Transplante de Microbiota Fecal , Feminino , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Gliose/genética , Gliose/prevenção & controle , Inflamação/patologia , Inflamação/prevenção & controle , Mutação com Perda de Função/genética , Masculino , Camundongos , Microglia/imunologia , Microglia/microbiologia , Microglia/patologia , Medula Espinal/imunologia , Medula Espinal/microbiologia , Taxa de Sobrevida
2.
Genes Dev ; 32(13-14): 929-943, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29950492

RESUMO

While a mutation in C9ORF72 is the most common genetic contributor to amyotrophic lateral sclerosis (ALS), much remains to be learned concerning the function of the protein normally encoded at this locus. To elaborate further on functions for C9ORF72, we used quantitative mass spectrometry-based proteomics to identify interacting proteins in motor neurons and found that its long isoform complexes with and stabilizes SMCR8, which further enables interaction with WDR41. To study the organismal and cellular functions for this tripartite complex, we generated Smcr8 loss-of-function mutant mice and found that they developed phenotypes also observed in C9orf72 loss-of-function animals, including autoimmunity. Along with a loss of tolerance for many nervous system autoantigens, we found increased lysosomal exocytosis in Smcr8 mutant macrophages. In addition to elevated surface Lamp1 (lysosome-associated membrane protein 1) expression, we also observed enhanced secretion of lysosomal components-phenotypes that we subsequently observed in C9orf72 loss-of-function macrophages. Overall, our findings demonstrate that C9ORF72 and SMCR8 have interdependent functions in suppressing autoimmunity as well as negatively regulating lysosomal exocytosis-processes of potential importance to ALS.


Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/fisiopatologia , Autoimunidade/genética , Proteínas de Transporte/metabolismo , Exocitose/genética , Lisossomos/metabolismo , Animais , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Proteínas de Transporte/genética , Regulação da Expressão Gênica/genética , Humanos , Linfonodos/patologia , Proteína 1 de Membrana Associada ao Lisossomo/genética , Macrófagos/patologia , Camundongos , Camundongos Knockout , Mutação , Isoformas de Proteínas , Estabilidade Proteica , Esplenomegalia/genética
3.
Sensors (Basel) ; 24(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39001102

RESUMO

Visible light communication (VLC) is a promising complementary technology to its radio frequency (RF) counterpart to satisfy the high quality-of-service (QoS) requirements of intelligent vehicular communications by reusing LED street lights. In this paper, a hybrid handover scheme for vehicular VLC/RF communication networks is proposed to balance QoS and handover costs by considering the vertical handover and horizontal handover together judging from the mobile state of the vehicle. A Markov decision process (MDP) is formulated to describe this hybrid handover problem, with a cost function balancing the handover consumption, delay, and reliability. A value iteration algorithm was applied to solve the optimal handover policy. The simulation results demonstrated the performance of the proposed hybrid handover scheme in comparison to other benchmark schemes.

4.
Virol J ; 20(1): 264, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968757

RESUMO

The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.


Assuntos
Herpesvirus Suídeo 1 , Pseudorraiva , Suínos , Animais , Herpesvirus Suídeo 1/fisiologia , Actinas , Linhagem Celular , Replicação Viral
5.
Reprod Biol Endocrinol ; 20(1): 45, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35255928

RESUMO

Diabetes mellitus (DM), a high incidence metabolic disease, is related to the impairment of male spermatogenic function. Spermidine (SPM), one of the biogenic amines, was identified from human seminal plasma and believed to have multiple pharmacological functions. However, there exists little evidence that reported SPM's effects on moderating diabetic male spermatogenic function. Thus, the objective of this study was to investigate the SPM's protective effects on testicular spermatogenic function in streptozotocin (STZ)-induced type 1 diabetic mice. Therefore, 40 mature male C57BL/6 J mice were divided into four main groups: the control group (n = 10), the diabetic group (n = 10), the 2.5 mg/kg SPM-treated diabetic group (n = 10) and the 5 mg/kg SPM-treated diabetic group (n = 10), which was given intraperitoneally for 8 weeks. The type 1 diabetic mice model was established by a single intraperitoneal injection of STZ 120 mg/kg. The results showed that, compare to the control group, the body and testis weight, as well the number of sperm were decreased, while the rate of sperm malformation was significantly increased in STZ-induced diabetic mice. Then the testicular morphology was observed, which showed that seminiferous tubule of testis were arranged in mess, the area and diameter of which was decreased, along with downregulated anti-apoptotic factor (Bcl-2) expression, and upregulated pro-apoptotic factor (Bax) expression in the testes. Furthermore, testicular genetic expression levels of Sertoli cells (SCs) markers (WT1, GATA4 and Vimentin) detected that the pathological changes aggravated observably, such as the severity of tubule degeneration increased. Compared to the saline-treated DM mice, SPM treatment markedly improved testicular function, with an increment in the body and testis weight as well as sperm count. Pro-apoptotic factor (Bax) was down-regulated expression with the up-regulated expression of Bcl-2 and suppression of apoptosis in the testes. What's more, expression of WT1, GATA4, Vimentin and the expressions of glycolytic rate-limiting enzyme genes (HK2, PKM2, LDHA) in diabetic testes were also upregulated by SPM supplement. The evidence derived from this study indicated that the SMP's positive effect on moderating spermatogenic disorder in T1DM mice's testis. This positive effect is delivered via promoting spermatogenic cell proliferation and participating in the glycolytic pathway's activation.


Assuntos
Diabetes Mellitus Experimental , Glicólise/efeitos dos fármacos , Infertilidade Masculina , Espermatogênese/efeitos dos fármacos , Espermidina/farmacologia , Animais , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/etiologia , Infertilidade Masculina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise do Sêmen , Espermatogênese/fisiologia , Espermidina/uso terapêutico , Estreptozocina , Testículo/efeitos dos fármacos , Testículo/metabolismo
6.
J Opt Soc Am A Opt Image Sci Vis ; 39(10): 1839-1848, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36215556

RESUMO

The effective deployment of an intelligent reflecting mirror array (IRMA) can enhance channel quality and improve the system performance in visible light communications (VLC) systems. This paper focuses on the performance analysis and parameter optimization of an IRMA-aided VLC system. Initially, the channel gains of both line-of-sight (LoS) link and non-LoS links are analyzed. Then, considering the blockage probability of a LoS link, a theoretical expression of the average bit error rate (ABER) is derived. To further improve the system performance, the optimization problems about the parameters of the IRMA are formulated, and schemes are proposed to solve these problems. Moreover, a kind of hardware implementation of the IRMA is provided. Numerical results verify the accuracy of the derived ABER expression and the effectiveness of the proposed schemes.

7.
J Opt Soc Am A Opt Image Sci Vis ; 38(5): 654-662, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33983270

RESUMO

In previous studies, the receivers in indoor visible light communication (VLC) were usually fixed. However, in reality, the receivers in VLC have random locations and orientations. Therefore, it is important to consider these random factors for performance analysis in VLC. In this paper, we consider a typical VLC system with a fixed transmitter and a random receiver. Two types of receivers are investigated: (1) those with random location and (2) those with random orientation. Based on the established system model, the statistical characteristics of the channel were obtained, and closed-form expressions of the average channel capacity and the outage probability were derived, respectively. Finally, numerical results verified the accuracy of derived theoretical expressions. Moreover, the effects of the nominal optical intensity, the dimming target, the transmitter height, the receiver zone's radius, the outage threshold, and the Lambertian emission order on system performance were also provided.

8.
Entropy (Basel) ; 23(12)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34945902

RESUMO

This paper focuses on an unmanned aerial vehicle (UAV) assisted hybrid free-space optical (FSO)/radio frequency (RF) communication system. Considering the rate imbalance between the FSO and RF links, a buffer is employed at the UAV. Initially, theoretical models of energy consumption and throughput are obtained for the hybrid system. Based on these models, the theoretical expression of the energy efficiency is derived. Then, a nonconvex trajectory optimization problem is formulated by maximizing the energy efficiency of the hybrid system under the buffer constraint, velocity constraint, acceleration constraint, start-end position constraint, and start-end velocity constraint. By using the sequential convex optimization and first-order Taylor approximation, the nonconvex problem is transformed into a convex one. An iterative algorithm is proposed to solve the problem. Numerical results verify the efficiency of the proposed algorithm and also show the effects of buffer size on a UAV's trajectory.

9.
Opt Express ; 25(19): 22805-22819, 2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-29041587

RESUMO

This paper analyzes the received power distribution of a generalized indoor visible light communication (VLC) system. The generalization includes: both ceiling-mounted and wall-mounted layouts are considered on the transmitting end to cover some special scenarios; a generally applicable sum-of-sine luminous intensity pattern (SSLIP) is used to fit light emitting diodes (LEDs)' radiation curve; the receiver is considered to have a large light receiving area (LRA) with non-uniformly distributed received power. Through mathematical calculation, the expression of received power at any point of the room is derived. Using the expression, the impact of transmitting LEDs' radiation pattern on received power performance is investigated. It is suggested that in the ceiling-mounted scenario, the LED transmitters with sharp luminous intensity patterns have bigger received power variations and shorter optimal receiving distances. In the wall-mounted case in contrast, sharp luminous intensity patterns lead to smaller received power variations and longer optimal receiving distances.

10.
Opt Express ; 24(12): 13060-74, 2016 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-27410325

RESUMO

Multi-input multi-output (MIMO) technique is attractive for visible light communication (VLC), which exploits the high signal-to-noise ratio (SNR) of a single channel to overcome the capacity limitation due to the small modulation bandwidth of the light emitting diode. This paper establishes a MIMO VLC system under the non-negativity, peak power and dimmable average power constraints. Assume that perfect channel state information at the transmitter is known, the MIMO channel is changed to parallel, non-interfering sub-channels by using the singular value decomposition (SVD). Based on the SVD, the lower bound on the channel capacity for MIMO VLC is derived by employing entropy power inequality and variational method. Moreover, by maximizing the derived lower bound on the capacity under the given constraints, the receiver deployment optimization problem is formulated. The problem is solved by employing the principle of particle swarm optimization. Numerical results verify the derived capacity bound and the proposed deployment optimization scheme.

11.
Jpn J Clin Oncol ; 46(8): 727-34, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27207888

RESUMO

OBJECTIVE: This study aimed to investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life. METHODS: Clinical data of 28 cases of patients with orbital involvement of T4b squamous cell carcinoma of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between May 2008 and September 2015 were retrospectively analysed. The treatment efficacy and side effects were assessed. The study included 18 male and 10 female patients. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy and/or epidermal growth factor receptor inhibitor. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 4. The overall survival rate, local control rate and rate of effective orbital preservation were calculated using the Kaplan-Meier method. RESULTS: All patients completed the planned chemotherapy, and 27 (96.4%) of the patients completed the planned radiotherapy cycle. After the multimodal treatment, the 3-year overall survival, local control rate and rate of effective orbital preservation of the patients were 59.2%, 80.2% and 77.8%, respectively. CONCLUSIONS: Multimodal treatment could preserve the orbital organs of patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates and improve the quality of life of patients with advanced squamous cell carcinoma of the nasal cavity and paranasal sinus, thus providing a new treatment option for these patients.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Nasais/terapia , Preservação de Órgãos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Terapia Combinada/efeitos adversos , Feminino , Cabeça/diagnóstico por imagem , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Ceratoconjuntivite/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Nasais/mortalidade , Neoplasias Nasais/patologia , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Qualidade de Vida , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Med Sci Monit ; 22: 598-607, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26902177

RESUMO

BACKGROUND This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). MATERIAL AND METHODS Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0-5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. RESULTS PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. CONCLUSIONS Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively.


Assuntos
Fracionamento da Dose de Radiação , Radiocirurgia/métodos , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
13.
Infect Immun ; 83(1): 161-72, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25332120

RESUMO

Live attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. A major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without overattenuating the live vaccine. Here we used a live attenuated Salmonella enterica serovar Typhi strain to create a bivalent mucosal plague vaccine that produces both the protective F1 capsular antigen of Yersinia pestis and the LcrV protein required for secretion of virulence effector proteins. To reduce the metabolic burden associated with the coexpression of F1 and LcrV within the live vector, we balanced expression of both antigens by combining plasmid-based expression of F1 with chromosomal expression of LcrV from three independent loci. The immunogenicity and protective efficacy of this novel vaccine were assessed in mice by using a heterologous prime-boost immunization strategy and compared to those of a conventional strain in which F1 and LcrV were expressed from a single low-copy-number plasmid. The serum antibody responses to lipopolysaccharide (LPS) induced by the optimized bivalent vaccine were indistinguishable from those elicited by the parent strain, suggesting an adequate immunogenic capacity maintained through preservation of bacterial fitness; in contrast, LPS titers were 10-fold lower in mice immunized with the conventional vaccine strain. Importantly, mice receiving the optimized bivalent vaccine were fully protected against lethal pulmonary challenge. These results demonstrate the feasibility of distributing foreign antigen expression across both chromosomal and plasmid locations within a single vaccine organism for induction of protective immunity.


Assuntos
Portadores de Fármacos , Vacina contra a Peste/imunologia , Peste/prevenção & controle , Salmonella typhi/genética , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Modelos Animais de Doenças , Vetores Genéticos , Camundongos Endogâmicos BALB C , Peste/imunologia , Vacina contra a Peste/administração & dosagem , Vacina contra a Peste/genética , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/imunologia , Análise de Sobrevida , Vacinação/métodos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
14.
J Opt Soc Am A Opt Image Sci Vis ; 31(3): 561-8, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24690654

RESUMO

This paper focuses on the capacity-approaching, nonuniform signaling for the pulse amplitude modulated (PAM) visible light communications under the non-negativity, peak power, and dimmable average power constraints. The input distribution is characterized by three parameters, i.e., the intensities, the probabilities, and the number of mass points in the PAM constellation. In the open literature, no analytical expression can be used to obtain the capacity-achieving input distribution. In this paper, a computationally simple but capacity-approaching input distribution is alternatively derived by determining the three aforementioned parameters. The resulting input distribution can serve as a useful tool not to approach the channel capacity but to guide the practical system design. Numerical results substantiate that the derived input distribution is a capacity-approaching distribution and can offer a better performance gain in comparison with the commonly employed uniform input distribution.

15.
Sci Transl Med ; 16(732): eadg7895, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38295187

RESUMO

A mutation in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Patients with ALS or FTD often develop autoimmunity and inflammation that precedes or coincides with the onset of neurological symptoms, but the underlying mechanisms are poorly understood. Here, we knocked out murine C9orf72 in seven hematopoietic progenitor compartments by conditional mutagenesis and found that myeloid lineage C9orf72 prevents splenomegaly, loss of tolerance, and premature mortality. Furthermore, we demonstrated that C9orf72 plays a role in lymphoid cells to prevent interleukin-17A (IL-17A) production and neutrophilia. Mass cytometry identified early and sustained elevation of the costimulatory molecule CD80 expressed on C9orf72-deficient mouse macrophages, monocytes, and microglia. Enrichment of CD80 was similarly observed in human spinal cord microglia from patients with C9ORF72-mediated ALS compared with non-ALS controls. Single-cell RNA sequencing of murine spinal cord, brain cortex, and spleen demonstrated coordinated induction of gene modules related to antigen processing and presentation and antiviral immunity in C9orf72-deficient endothelial cells, microglia, and macrophages. Mechanistically, C9ORF72 repressed the trafficking of CD80 to the cell surface in response to Toll-like receptor agonists, interferon-γ, and IL-17A. Deletion of Il17a in C9orf72-deficient mice prevented CD80 enrichment in the spinal cord, reduced neutrophilia, and reduced gut T helper type 17 cells. Last, systemic delivery of an IL-17A neutralizing antibody augmented motor performance and suppressed neuroinflammation in C9orf72-deficient mice. Altogether, we show that C9orf72 orchestrates myeloid costimulatory potency and provide support for IL-17A as a therapeutic target for neuroinflammation associated with ALS or FTD.


Assuntos
Esclerose Lateral Amiotrófica , Proteína C9orf72 , Demência Frontotemporal , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Proteína C9orf72/genética , Células Endoteliais/metabolismo , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Interleucina-17 , Doenças Neuroinflamatórias
16.
J Microbiol Immunol Infect ; 56(6): 1226-1235, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37758541

RESUMO

BACKGROUND AND PURPOSE: Pneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. METHODS: This retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. RESULTS: The cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = -0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = -0.006, p = 0.787 and rs = -0.156, p = 0.398). CONCLUSION: After the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia and pneumonia.


Assuntos
Anti-Infecciosos , Broncopneumonia , Pneumonia Pneumocócica , Pneumonia Viral , Criança , Humanos , Estudos Retrospectivos , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas Conjugadas/uso terapêutico , Antibacterianos/uso terapêutico , Macrolídeos
17.
J Microbiol Immunol Infect ; 56(1): 111-119, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36031532

RESUMO

BACKGROUND AND PURPOSE: Urinary tract infections (UTIs) are the most common bacterial infection in young children. This study aimed to formulate nomogram plots for clinicians to predict UTIs in children aged <3 years by evaluating the risk factors for UTIs in these children. METHODS: This retrospective study was conducted at a tertiary medical center from December 2017 to November 2020. Children less than three years of age were eligible for the study if they had undergone both urine culture and urinalysis during the study period. Mixed-effects logistic regression models with a stepwise procedure were used to determine the relationship between outcome (positive/negative UTI) and covariates of interest (e.g., weight percentile, laboratory) for each patient. Nomogram plots were constructed on the basis of significant factors. We repeated the analysis thrice to adapt it to three different medical settings: medical centers, regional hospitals, and local clinics. RESULTS: In the medical center setting, the two most significant factors were urine leukocyte count ≥100 (OR =8.87; 95% CI (Confidence Interval), 4.135-19.027) and urine nitrite level (OR =8.809; 95% CI, 5.009-15.489). The two factors showed similar significance at the regional hospital and local clinic settings. Abnormal renal echo findings were positively correlated with UTI in the medical center setting (OR =2.534; 95% CI 1.757-3.655). Three nomogram plots for the prediction of UTIs were drawn for medical centers, regional hospitals, and local clinics. CONCLUSION: Using the three nomogram plots, frontline doctors can formulate the probabilities of pediatric UTIs for better decision-making.


Assuntos
Infecções Bacterianas , Infecções Urinárias , Criança , Humanos , Pré-Escolar , Estudos Retrospectivos , Nomogramas , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia , Urinálise/métodos
18.
Int J Ophthalmol ; 16(3): 427-433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935788

RESUMO

AIM: To investigate the risk and protective factors associated with the retinal nerve fiber layer defect (RNFLD) in a Chinese adult population. METHODS: This study was a cross-sectional population-based investigation including employees and retirees of a coal mining company in Kailuan City, Hebei Province. All the study participants underwent a comprehensive systemic and ophthalmic examination. RNFLD was diagnosed on fundus photographs. Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD. RESULTS: The community-based study included 14 440 participants. There were 10 473 participants in our study, including 7120 males (68.0%) and 3353 females (32.0%). The age range was 45-108y, averaging 59.56±8.66y. Totally 568 participants had RNFLD and the prevalence rate was 5.42%. A higher prevalence of RNFLD was associated with older age [P<0.001, odds ratio (OR): 1.032; 95% confidence interval (CI): 1.018-1.046], longer axial length (P=0.010, OR: 1.190; 95%CI: 1.042-1.359), hypertension (P=0.007, OR: 0.639; 95%CI: 0.460-0.887), and diabetes mellitus (P=0.019, OR: 0.684; 95%CI: 0.499-0.939). The protective factors of RNFLD were visual acuity (P=0.038, OR: 0.617; 95%CI: 0.391-0.975), and central anterior chamber depth (P=0.046, OR: 0.595; 95%CI: 0.358-0.990). CONCLUSION: In our cross-sectional community-based study, with an age range of 45-108y, RNFLD is associated with older age, longer axial length, hypertension, and diabetes mellitus. The protective factors of RNFLD are visual acuity and central anterior chamber depth. These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.

19.
J Microbiol Immunol Infect ; 55(5): 803-811, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35283046

RESUMO

PURPOSE: This study aimed to evaluate whether vitamin D supplementation can reduce the incidence of influenza and enterovirus infection in Taiwanese children. METHODS: This randomized, double-blind, controlled trial included children aged two to five years between April 2018 and October 2019 from daycare centers. All the participants were randomly assigned to a vitamin D supplementation group (2000 IU/day) or placebo group for one month. The primary outcome was the incidence of influenza and enterovirus infection in the following six months, and the secondary outcome was the incidence of influenza and enterovirus infection in the children's household members. RESULTS: Two hundred and forty-eight children participated. The vitamin D group showed a relative risk reduction of 84% against influenza compared to the placebo group but did not reach statistical significance. Kaplan-Meier curves revealed that the placebo group had a higher probability of influenza infection than the vitamin D group (log-rank test, p = 0.055), but the incidence of enterovirus infection was similar between the two groups (p = 0.946) among children. Among children's household members, the incidence of influenza (p = 0.586) and enterovirus infection (p = 0.528) were both similar between the two groups. All children who were tested for serum 25(OH)D levels after vitamin D intervention had 25(OH)D levels above 30 ng/ml CONCLUSION: Vitamin D supplementation may have a small preventative effect against influenza infection but does not affect enterovirus infection among preschool children. A high-dose short-term vitamin D intervention might be a way to elevate children's serum vitamin D levels in the first month of starting kindergarten.


Assuntos
Infecções por Enterovirus , Influenza Humana , Pré-Escolar , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estações do Ano , Suplementos Nutricionais , Vitamina D , Vitaminas , Método Duplo-Cego , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/prevenção & controle
20.
Biomed Environ Sci ; 35(7): 613-621, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35945176

RESUMO

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion: There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.


Assuntos
Diabetes Mellitus , Hiperlipidemias , Hipertensão , Degeneração Macular , Estudos Transversais , Diabetes Mellitus/epidemiologia , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Fatores de Risco
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