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1.
Aust J Gen Pract ; 53(7): 499-503, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38959520

RESUMO

BACKGROUND AND OBJECTIVES: There were 82.4 million new gonorrhoea cases worldwide in 2020. Dual treatment with ceftriaxone or cefixime and azithromycin or doxycycline is currently recommended for gonorrhoea in Indonesia. However, reduced susceptibility and resistance to cephalosporins and azithromycin are increasing. We evaluated the susceptibility pattern of Neisseria gonorrhoeae to cefixime, ceftriaxone, azithromycin and doxycycline. METHOD: N. gonorrhoeae isolates were obtained from 19 male participants with clinically and laboratory-confirmed gonorrhoea. Antibiotic susceptibility testing was conducted by disc diffusion and interpreted according to Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention criteria. RESULTS: Reduced susceptibility or resistance was observed against doxycycline in 19 isolates (100%), cefixime in six (31.6%), ceftriaxone in three (15.8%) and azithromycin in zero (0%) isolates. DISCUSSION: A dual treatment regimen with ceftriaxone and azithromycin can still be recommended as first-line therapy for gonorrhoea in Indonesia. Antibiotic susceptibility surveillance of N. gonorrhoeae should be routinely conducted.


Assuntos
Antibacterianos , Azitromicina , Ceftriaxona , Doxiciclina , Gonorreia , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Humanos , Indonésia , Neisseria gonorrhoeae/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Gonorreia/tratamento farmacológico , Masculino , Testes de Sensibilidade Microbiana/métodos , Azitromicina/uso terapêutico , Doxiciclina/uso terapêutico , Ceftriaxona/uso terapêutico , Ceftriaxona/farmacologia , Adulto , Cefixima/uso terapêutico , Cefixima/farmacologia , Atenção Primária à Saúde/estatística & dados numéricos , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada/métodos
2.
BMJ Case Rep ; 17(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960428

RESUMO

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection.


Assuntos
Antibacterianos , Doxiciclina , Tifo por Ácaros , Humanos , Tifo por Ácaros/complicações , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/tratamento farmacológico , Masculino , Doxiciclina/uso terapêutico , Antibacterianos/uso terapêutico , Anemia Hemolítica/etiologia , Anemia Hemolítica/diagnóstico , Adulto , Orientia tsutsugamushi/isolamento & purificação
3.
BMC Microbiol ; 24(1): 229, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943061

RESUMO

BACKGROUND: Lactobacillus plantarum has been found to play a significant role in maintaining the balance of intestinal flora in the human gut. However, it is sensitive to commonly used antibiotics and is often incidentally killed during treatment. We attempted to identify a means to protect L. plantarum ATCC14917 from the metabolic changes caused by two commonly used antibiotics, ampicillin, and doxycycline. We examined the metabolic changes under ampicillin and doxycycline treatment and assessed the protective effects of adding key exogenous metabolites. RESULTS: Using metabolomics, we found that under the stress of ampicillin or doxycycline, L. plantarum ATCC14917 exhibited reduced metabolic activity, with purine metabolism a key metabolic pathway involved in this change. We then screened the key biomarkers in this metabolic pathway, guanine and adenosine diphosphate (ADP). The exogenous addition of each of these two metabolites significantly reduced the lethality of ampicillin and doxycycline on L. plantarum ATCC14917. Because purine metabolism is closely related to the production of reactive oxygen species (ROS), the results showed that the addition of guanine or ADP reduced intracellular ROS levels in L. plantarum ATCC14917. Moreover, the killing effects of ampicillin and doxycycline on L. plantarum ATCC14917 were restored by the addition of a ROS accelerator in the presence of guanine or ADP. CONCLUSIONS: The metabolic changes of L. plantarum ATCC14917 under antibiotic treatments were determined. Moreover, the metabolome information that was elucidated can be used to help L. plantarum cope with adverse stress, which will help probiotics become less vulnerable to antibiotics during clinical treatment.


Assuntos
Ampicilina , Antibacterianos , Doxiciclina , Lactobacillus plantarum , Metabolômica , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/efeitos dos fármacos , Antibacterianos/farmacologia , Ampicilina/farmacologia , Doxiciclina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Purinas/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Difosfato de Adenosina/metabolismo , Humanos
4.
N Engl J Med ; 390(22): 2127-2128, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38865666
5.
Medicine (Baltimore) ; 103(25): e38613, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905360

RESUMO

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.


Assuntos
Antibacterianos , Tifo por Ácaros , Humanos , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/tratamento farmacológico , Tifo por Ácaros/complicações , Masculino , Adolescente , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Doxiciclina/uso terapêutico , Doxiciclina/administração & dosagem , Orientia tsutsugamushi/isolamento & purificação , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia
6.
ACS Appl Mater Interfaces ; 16(25): 31966-31982, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38829697

RESUMO

Currently, postoperative infection is a significant challenge in bone and dental surgical procedures, demanding the exploration of innovative approaches due to the prevalence of antibiotic-resistant bacteria. This study aims to develop a strategy for controlled and smart antibiotic release while accelerating osteogenesis to expedite bone healing. In this regard, temperature-responsive doxycycline (DOX) imprinted bioglass microspheres (BGMs) were synthesized. Following the formation of chitosan-modified BGMs, poly N-isopropylacrylamide (pNIPAm) was used for surface imprinting of DOX. The temperature-responsive molecularly imprinted polymers (MIPs) exhibited pH and temperature dual-responsive adsorption and controlled-release properties for DOX. The temperature-responsive MIP was optimized by investigating the molar ratio of N,N'-methylene bis(acrylamide) (MBA, the cross-linker) to NIPAm. Our results demonstrated that the MIPs showed superior adsorption capacity (96.85 mg/g at 35 °C, pH = 7) than nonimprinted polymers (NIPs) and manifested a favorable selectivity toward DOX. The adsorption behavior of DOX on the MIPs fit well with the Langmuir model and the pseudo-second-order kinetic model. Drug release studies demonstrated a controlled release of DOX due to imprinted cavities, which were fitted with the Korsmeyer-Peppas kinetic model. DOX-imprinted BGMs also revealed comparable antibacterial effects against Staphylococcus aureus and Escherichia coli to the DOX (control). In addition, MIPs promoted viability and osteogenic differentiation of MG63 osteoblast-like cells. Overall, the findings demonstrate the significant potential of DOX-imprinted BGMs for use in bone defects. Nonetheless, further in vitro investigations and subsequent in vivo experiments are warranted to advance this research.


Assuntos
Antibacterianos , Cerâmica , Doxiciclina , Microesferas , Osteogênese , Staphylococcus aureus , Doxiciclina/farmacologia , Doxiciclina/química , Antibacterianos/farmacologia , Antibacterianos/química , Cerâmica/química , Cerâmica/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Humanos , Impressão Molecular , Escherichia coli/efeitos dos fármacos , Liberação Controlada de Fármacos , Quitosana/química , Quitosana/farmacologia
7.
Vet Ital ; 60(1)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38898794

RESUMO

The aim of this study was to determine the concentration of TNF-alpha (TNF-α) in dogs naturally infected with Dirofilaria immitis (D. immitis) and to assess whether there are any changes in TNF-α concentration and their dependence during therapy for heartworm disease (HWD). For this study, 14 client-owned dogs with HWD were selected. Clinical and parasitological examinations (modified Knott test for circulating microfilariae and SNAP Test IDEXX for circulating D. immitis antigen) had been used for diagnosing D. immitis and HWD. All dogs were treated with an alternative therapy for HWD (oral doxycycline 10 mg/kg b.w., once daily for 6 weeks, then alternately 4 weeks without and 2 weeks with the medication, and oral ivermectin 6-14 µg/kg b.w., every 2 weeks). The dogs blood sera at the moment of HWD diagnosis, during and at the end of therapy were frozen for further quantifying of TNF-α (Canine TNF-alpha ELISA kit, Thermo scientific). At the moment of HWD diagnosis TNF-α was detected in 9 dogs (7.21±12.44 pg/ml). Concentration of TNF-α was not significantly change during the therapy, neither related to the level of D. immitis antigen nor to antigen level changes. The alternative therapy for HWD has no influence on TNF-α concentration dynamics.


Assuntos
Dirofilaria immitis , Dirofilariose , Doenças do Cão , Fator de Necrose Tumoral alfa , Animais , Cães , Dirofilariose/diagnóstico , Dirofilariose/tratamento farmacológico , Dirofilariose/sangue , Doenças do Cão/tratamento farmacológico , Doenças do Cão/diagnóstico , Doenças do Cão/sangue , Fator de Necrose Tumoral alfa/sangue , Masculino , Feminino , Doxiciclina/uso terapêutico , Ivermectina/uso terapêutico
8.
PLoS One ; 19(6): e0305720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38905249

RESUMO

Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T. pallidum subsp. pallidum has developed widespread macrolide resistance in the past decade. A study at the Peshawar Regional Blood Centre from June 2020-June 2021 analyzed serum samples from 32,812 blood donors in Khyber Pakhtunkhwa, Pakistan, to assess circulating T. pallidum strains and antibiotic resistance. Blood samples were initially screened for T. pallidum antibodies using a chemiluminescent microparticle immunoassay (CMIA). CMIA-reactive samples underwent polymerase chain reaction (PCR) targeted the polA, tpp47, bmp, and tp0319 genes. PCR-positive samples were further analyzed for molecular subtyping using a CDC-developed procedure and tp0548 gene examination. All PCR-positive samples were analyzed for the presence of point mutations A2058G and A2059G in 23S rRNA, as well as the G1058C mutation in 16S rRNA. These mutations are known to impart antimicrobial resistance to macrolides and doxycycline, respectively. Out of 32,812 serum samples, 272 (0.83%) were CMIA-reactive, with 46 being PCR-positive. Nine T. pallidum subtypes were identified, predominantly 14d/f. The A2058G mutation in 23S rRNA was found in 78% of cases, while G1058C in 16S rRNA and A2059G in 23S rRNA were absent. The research found donor blood useful for assessing T. pallidum molecular subtypes and antibiotic resistance, especially when chancres are not present. The prevalent subtype was 14d/f (51.85%), and the high macrolide resistance of 36 (78%) indicates caution in using macrolides for syphilis treatment in Khyber Pakhtunkhwa, Pakistan.


Assuntos
Antibacterianos , Doadores de Sangue , Farmacorresistência Bacteriana , Sífilis , Treponema pallidum , Treponema pallidum/genética , Treponema pallidum/efeitos dos fármacos , Treponema pallidum/isolamento & purificação , Humanos , Paquistão/epidemiologia , Sífilis/microbiologia , Sífilis/epidemiologia , Sífilis/sangue , Sífilis/tratamento farmacológico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Masculino , Feminino , Adulto , Macrolídeos/farmacologia , RNA Ribossômico 23S/genética , RNA Ribossômico 16S/genética , Pessoa de Meia-Idade , Doxiciclina/farmacologia , Doxiciclina/uso terapêutico , Adulto Jovem
9.
J Korean Med Sci ; 39(22): e186, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38859743

RESUMO

Herein, we report a case of uncomplicated falciparum malaria with late parasitological failure in a 45-year-old businessman returning from Ghana. The patient visited the emergency department with high fever, headache, and dizziness. He traveled without antimalarial chemoprophylaxis. Laboratory tests led to the diagnosis of uncomplicated falciparum malaria with an initial density of 37,669 parasites per µL of blood (p/µL). The patient was treated with intravenous artesunate followed by atovaquone/proguanil. He was discharged with improved condition and decreased parasite density of 887 p/µL. However, at follow-up, parasite density increased to 7,630 p/µL despite the absence of any symptoms. Suspecting treatment failure, the patient was administered intravenous artesunate and doxycycline for seven days and then artemether/lumefantrine for three days. Blood smear was negative for asexual parasitemia after re-treatment but positive for gametocytemia until day 101 from the initial diagnosis. Overall, this case highlights the risk of late parasitological failure in patients with imported uncomplicated falciparum malaria.


Assuntos
Antimaláricos , Atovaquona , Malária Falciparum , Plasmodium falciparum , Proguanil , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/diagnóstico , Gana , Antimaláricos/uso terapêutico , Pessoa de Meia-Idade , Masculino , Plasmodium falciparum/isolamento & purificação , Proguanil/uso terapêutico , Atovaquona/uso terapêutico , Viagem , Artemisininas/uso terapêutico , Artesunato/uso terapêutico , Parasitemia/tratamento farmacológico , Parasitemia/diagnóstico , Doxiciclina/uso terapêutico , Combinação de Medicamentos , Falha de Tratamento , Combinação Arteméter e Lumefantrina/uso terapêutico
10.
J Infect Dev Ctries ; 18(5): 834-838, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38865398

RESUMO

INTRODUCTION: Q fever, a zoonotic disease caused by Coxiella burnetii (C. burnetii), presents diagnostic challenges due to its clinical and radiological nonspecificity, which often mimics community-acquired pneumonia, coupled with the limitations of traditional diagnostic methods. Metagenomic next-generation sequencing (mNGS) has become an indispensable tool in clinical diagnostics for its high-throughput pathogen identification capabilities. Herein, we detail a case of acute Q fever pneumonia diagnosed with mNGS. CASE PRESENTATION: The patient exhibited symptoms of fever, cough, expectoration, and diarrhea for three days, with the pathogen undetected in initial laboratory assessments. Bronchoscopy and bronchoalveolar lavage (BAL) were conducted, leading to the identification of C. burnetii in the lavage fluid via mNGS. Consequently, the patient was promptly initiated on a treatment regimen of 100 mg doxycycline, administered orally every 12 hours. RESULTS: Post-treatment, the patient's temperature normalized, and a full recovery was observed. The follow-up chest CT scan revealed complete resolution of the right lower lobe consolidation. CONCLUSIONS: The clinical presentation of Q fever pneumonia lacks specificity, making diagnosis based solely on symptoms and imaging challenging. mNGS offers a superior alternative for identifying elusive or rarely cultured pathogens.


Assuntos
Coxiella burnetii , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Febre Q , Humanos , Febre Q/diagnóstico , Febre Q/tratamento farmacológico , Febre Q/microbiologia , Coxiella burnetii/genética , Coxiella burnetii/isolamento & purificação , Metagenômica/métodos , Masculino , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
11.
MMWR Recomm Rep ; 73(2): 1-8, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38833414

RESUMO

No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.


Assuntos
Centers for Disease Control and Prevention, U.S. , Doxiciclina , Profilaxia Pós-Exposição , Doenças Bacterianas Sexualmente Transmissíveis , Humanos , Doxiciclina/uso terapêutico , Estados Unidos , Masculino , Feminino , Doenças Bacterianas Sexualmente Transmissíveis/prevenção & controle , Antibacterianos/uso terapêutico , Minorias Sexuais e de Gênero
13.
BMC Infect Dis ; 24(1): 591, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886677

RESUMO

BACKGROUND: Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges. CASE PRESENTATION: We present a case series of three patients diagnosed with persistent Q fever between 2022 and 2023. The average age of our three cases was 63.33 years old, consisting of two males and one female. The medical history of the individuals included previous valve replacement, aneurysm followed by aortic stent-graft placement and prosthetic hip joint replacement. At the onset of the disease, only one case exhibited acute fever, while the remaining two cases were devoid of any acute symptoms. The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. The epidemiological history uncovered that none of the three cases had direct exposure to domestic animals or consumption of unpasteurized dairy products. Case 1 and 2 resided in urban areas, while Case 3 was a rural resident engaged in farming. All patients received combination therapy of doxycycline and hydroxychloroquine, and no recurrence of the disease was observed during the follow-up period. CONCLUSION: Q fever is rarely diagnosed and reported in clinical practice in our country. We should be aware of persistent Q fever in high-risk population, even with unremarkable exposure history. Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii.


Assuntos
Coxiella burnetii , Diagnóstico Tardio , Febre Q , Febre Q/diagnóstico , Febre Q/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , China/epidemiologia , Coxiella burnetii/isolamento & purificação , Coxiella burnetii/genética , Idoso , Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala
14.
Sci Rep ; 14(1): 13608, 2024 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871849

RESUMO

Transplantation of stem cell-derived ß-cells is a promising therapeutic advancement in the treatment of type 1 diabetes mellitus. A current limitation of this approach is the long differentiation timeline that generates a heterogeneous population of pancreatic endocrine cells. To address this limitation, an inducible lentiviral overexpression system of mature ß-cell markers was introduced into human induced-pluripotent stem cells (hiPSCs). Following the selection of the successfully transduced hiPSCs, the cells were treated with doxycycline in the pancreatic progenitor induction medium to support their transition toward the pancreatic lineage. Cells cultured with doxycycline presented the markers of interest, NGN3, PDX1, and MAFA, after five days of culture, and glucose-stimulated insulin secretion assays demonstrated that the cells were glucose-responsive in a monolayer culture. When cultured as a spheroid, the markers of interest and insulin secretion in a static glucose-stimulated insulin secretion assay were maintained; however, insulin secretion upon consecutive glucose challenges was limited. Comparison to human fetal and adult donor tissues identified that although the hiPSC-derived spheroids present similar markers to adult insulin-producing cells, they are functionally representative of fetal development. Together, these results suggest that with optimization of the temporal expression of these markers, forward programming of hiPSCs towards insulin-producing cells could be a possible alternative for islet transplantation.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diferenciação Celular , Proteínas de Homeodomínio , Células-Tronco Pluripotentes Induzidas , Células Secretoras de Insulina , Fatores de Transcrição Maf Maior , Proteínas do Tecido Nervoso , Transativadores , Humanos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/citologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Transativadores/metabolismo , Transativadores/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição Maf Maior/metabolismo , Fatores de Transcrição Maf Maior/genética , Insulina/metabolismo , Glucose/metabolismo , Glucose/farmacologia , Secreção de Insulina/efeitos dos fármacos , Células Cultivadas , Doxiciclina/farmacologia
15.
J Hazard Mater ; 475: 134931, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38889467

RESUMO

In this study, oversized microplastics (OMPs) were intentionally introduced into soil containing manure-borne doxycycline (DOX). This strategic approach was used to systematically examine the effects of combined OMP and DOX pollution on the growth of pak choi, analyze alterations in soil environmental metabolites, and explore the potential migration of antibiotic resistance genes (ARGs). The results revealed a more pronounced impact of DOX than of OMPs. Slender-fiber OMPs (SF OMPs) had a more substantial influence on the growth of pak choi than did coarse-fiber OMPs (CF OMPs). Conversely, CF OMPs had a more significant effect on the migration of ARGs within the system. When DOX was combined with OMPs, the negative effects of DOX on pak choi growth were mitigated through the synthesis of indole through the adjustment of carbon metabolism and amino acid metabolism in pak choi roots. In this process, Pseudohongiellaceae and Xanthomonadaceae were key bacteria. During the migration of ARGs, the potential host bacterium Limnobacter should be considered. Additionally, the majority of potential host bacteria in the pak choi endophytic environment were associated with tetG. This study provides insights into the intricate interplay among DOX, OMPs, ARGs, plant growth, soil metabolism, and the microbiome.


Assuntos
Antibacterianos , Doxiciclina , Esterco , Microplásticos , Poluentes do Solo , Doxiciclina/farmacologia , Doxiciclina/toxicidade , Antibacterianos/toxicidade , Antibacterianos/farmacologia , Esterco/microbiologia , Poluentes do Solo/toxicidade , Microplásticos/toxicidade , Resistência Microbiana a Medicamentos/genética , Microbiologia do Solo , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Genes Bacterianos/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Multiômica
16.
J Econ Entomol ; 117(3): 733-749, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38701242

RESUMO

Wolbachia pipientis is a maternally inherited intracellular bacterium that infects a wide range of arthropods. Wolbachia can have a significant impact on host biology and development, often due to its effects on reproduction. We investigated Wolbachia-mediated effects in the Asian citrus psyllid, Diaphorina citri Kuwayama, which transmits Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening disease. Diaphorina citri are naturally infected with Wolbachia; therefore, investigating Wolbachia-mediated effects on D. citri fitness and CLas transmission required artificial reduction of this endosymbiont with the application of doxycycline. Doxycycline treatment of psyllids reduced Wolbachia infection by approximately 60% in both male and female D. citri. Psyllids treated with doxycycline exhibited higher CLas acquisition in both adults and nymphs as compared with negative controls. In addition, doxycycline-treated psyllids exhibited decreased fitness as measured by reduced egg and nymph production as well as adult emergence as compared with control lines without the doxycycline treatment. Our results indicate that Wolbachia benefits D. citri by improving fitness and potentially competes with CLas by interfering with phytopathogen acquisition. Targeted manipulation of endosymbionts in this phytopathogen vector may yield disease management tools.


Assuntos
Doxiciclina , Aptidão Genética , Hemípteros , Wolbachia , Animais , Wolbachia/fisiologia , Hemípteros/microbiologia , Feminino , Doxiciclina/farmacologia , Masculino , Ninfa/microbiologia , Ninfa/crescimento & desenvolvimento , Liberibacter , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Simbiose , Antibacterianos/farmacologia , Citrus/microbiologia
17.
Prev Med ; 183: 107977, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692309

RESUMO

OBJECTIVE: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.S., nor how best to engage those most vulnerable to STIs in taking up this nascent prevention strategy. METHOD: Between July and September of 2023, 24 GBM from across the U.S. completed qualitative interviews about their perceptions regarding Doxy-PEP. Interviews were analyzed using a codebook approach to thematic analysis. RESULTS: Participants were generally interested in using Doxy-PEP, but were concerned about the potential for antibiotic resistance, side-effects, medication interactions to occur, along with stigmatizing discourse around its use. Meanwhile, participants were motivated by the simplicity of Doxy-PEP and the protection it could confer on both an individual and community-level- as well as its potential to reduce STI-related anxiety. Finally, participants desired additional information on Doxy-PEP to address their concerns. CONCLUSIONS: There is a need for clear guidelines and expanded public health messaging on Doxy-PEP in the U.S.


Assuntos
Doxiciclina , Homossexualidade Masculina , Profilaxia Pós-Exposição , Pesquisa Qualitativa , Minorias Sexuais e de Gênero , Humanos , Masculino , Estados Unidos , Adulto , Homossexualidade Masculina/psicologia , Minorias Sexuais e de Gênero/psicologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Percepção , Entrevistas como Assunto
18.
Lancet Glob Health ; 12(7): e1149-e1158, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754459

RESUMO

BACKGROUND: Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913. FINDINGS: Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups. INTERPRETATION: Nodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections. FUNDING: Medical Research Council (UK). TRANSLATION: For the Luo translation of the abstract see Supplementary Materials section.


Assuntos
Doxiciclina , Síndrome do Cabeceio , Humanos , Criança , Adolescente , Feminino , Masculino , Doxiciclina/uso terapêutico , Síndrome do Cabeceio/tratamento farmacológico , Método Duplo-Cego , Uganda , Resultado do Tratamento , Antibacterianos/uso terapêutico , Onchocerca volvulus/efeitos dos fármacos
20.
Am J Emerg Med ; 81: 136-139, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38728936

RESUMO

BACKGROUND: The updated 2021 CDC treatment guidelines recommend a single dose of 500 mg intramuscular ceftriaxone for Neisseria gonorrhea and doxycycline 100 mg by mouth twice daily for 7 days for Chlamydia trachomatis coinfection. However, there is a significant public health concern regarding patient non-adherence to the 7-day course of doxycycline. To date, there are no studies assessing this concern. Therefore, the objective of this study was to evaluate a patient's adherence to doxycycline for chlamydial infections after discharge from the Emergency Department (ED). METHODS: This was an IRB-approved, single-center, retrospective cohort study evaluating the adherence to doxycycline for Chlamydia trachomatis infections. Patients who received treatment and were discharged from the ED with a doxycycline e-prescription between May 2021 and September 2022 were included. Patients were excluded if <18 years of age, pregnant, a sexual assault victim, or admitted inpatient. The primary endpoint was the incidence of doxycycline prescription pick-up after discharge from the ED. The secondary endpoint was the incidence of repeat ED visits for the same chief complaint within 28 days. Descriptive statistics were computed for all study variables and Fisher's Exact tests were used to assess the outcomes. RESULTS: A review of 144 patients who tested positive for chlamydia and were discharged from the ED with an e-prescription for doxycycline revealed that 18% of patients did not pick up their prescription (N = 26). Non-adherent patients were more likely to return to the ED with the same chief complaint within 28 days (23.1% vs 7.6%, OR 3.6 [1.2-11.3], p = 0.026). No differences were detected in baseline demographics, housing status, insurance type, sexual orientation, or Sexually Transmitted Infection history. CONCLUSION: For patients with a positive chlamydia infection who were discharged from the ED on doxycycline, an 18% non-adherence rate was found and a 3.6-fold higher likelihood of returning to the ED with the same chief complaint if the prescription was not picked up.


Assuntos
Antibacterianos , Infecções por Chlamydia , Chlamydia trachomatis , Doxiciclina , Serviço Hospitalar de Emergência , Adesão à Medicação , Humanos , Doxiciclina/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Feminino , Estudos Retrospectivos , Masculino , Antibacterianos/uso terapêutico , Adulto , Adesão à Medicação/estatística & dados numéricos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente
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