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1.
Int J Biol Macromol ; 265(Pt 1): 130811, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490399

RESUMO

Lipid Transfer Protein1 (LTP1) is a cationic, multifaceted protein belonging to the pathogenesis-related protein (PR14) family. Despite being involved in diverse physiological processes and defense mechanisms, the precise in-vivo role of LTP1 remains undiscovered. This work presents the characterization of recombinant Citrus sinensis LTP1 (CsLTP1) along with lipid binding studies through in-silico and in-vitro approaches. CsLTP1 demonstrated great thermal and pH stability with a huge biotechnological potential. It showed in-vitro binding capacity with jasmonic acid and lipids involved in regulating plant immune responses. Gene expression profiling indicated a significant upregulation of CsLTP1 in Candidatus-infected Citrus plants. CsLTP1 disrupted the cell membrane integrity of various pathogens, making it a potent antimicrobial agent. Further, in-vivo antimicrobial and insecticidal properties of CsLTP1 have been explored. The impact of exogenous CsLTP1 treatment on rice crop metabolism for managing blight disease has been studied using GC-MS. CsLTP1 triggered crucial metabolic pathways in rice plants while controlling the blight disease. CsLTP1 effectively inhibited Helicoverpa armigera larvae by impeding mid-gut α-amylase activity and obstructing its developmental stages. This study highlights the pivotal role of CsLTP1 in plant defense by offering insights for developing multi-target therapeutic agent or disease-resistant varieties to comprehensively tackle the challenges towards crop protection.


Assuntos
Anti-Infecciosos , Citrus sinensis , Citrus , Citrus sinensis/metabolismo , Proteínas de Transporte/metabolismo , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Citrus/metabolismo
2.
J Bone Joint Surg Am ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512988

RESUMO

BACKGROUND: Clinical guidelines for performing total joint arthroplasty (TJA) have not been uniformly adopted in practice because research has suggested that they may foster inequities in surgical access, potentially disadvantaging minority sociodemographic groups. The aim of this study was to assess whether undergoing TJA without meeting clinical guidelines affects complication risk and leads to disparities in postoperative outcomes. METHODS: This retrospective cohort study evaluated the records of 11,611 adult patients who underwent primary TJA from January 1, 2010, to December 31, 2020, at an academic hospital network. Based on self-reported race and ethnicity, 89.5% of patients were White, 3.5% were Black, 2.9% were Hispanic, 1.3% were Asian, and 2.8% were classified as other. Patients met institutional guidelines for undergoing TJA if they had a hemoglobin A1c of <8.0% and a body mass index of <40 kg/m2 and were not currently smoking. A logistic regression model was utilized to identify factors associated with complications, and a mixed-effects model was utilized to identify factors associated with not meeting guidelines for undergoing TJA. RESULTS: During the study period, 11% (1,274) of the 11,611 adults who underwent primary TJA did not meet clinical guidelines. Compared with the group who met guidelines, the group who did not had higher proportions of Black patients (3.2% versus 6.0%; p < 0.001) and Hispanic patients (2.7% versus 4.6%; p < 0.001). An increased risk of not meeting guidelines at the time of surgery was demonstrated among Black patients (odds ratio [OR], 1.60 [95% confidence interval (CI), 1.22 to 2.10]; p = 0.001) and patients insured by Medicaid (OR, 1.75 [95% CI, 1.26 to 2.44]; p = 0.001) or Medicare (OR, 1.22 [95% CI, 1.06 to 1.41]; p = 0.007). Patients who did not meet guidelines had a higher risk of reoperation than those who met guidelines (7.7% [98] versus 5.9% [615]; p = 0.017), including a higher risk of infection-related reoperation (3.1% [40] versus 1.4% [147]; p < 0.001). CONCLUSIONS: We found that patients who underwent TJA despite not meeting institutional preoperative criteria had a higher risk of postoperative complications. These patients were more likely to be from racial and ethnic minority groups, to have a lower socioeconomic status, and to have Medicare or Medicaid insurance. These findings underscore the need for surgery-related shared decision-making that is informed by evidence-based guidelines in order to reduce complication burden. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

3.
J Arthroplasty ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38309636

RESUMO

BACKGROUND: Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. RESULTS: A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. CONCLUSIONS: Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. LEVEL OF EVIDENCE: II.

4.
J Knee Surg ; 37(1): 79-83, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36657464

RESUMO

Many studies have compared outcomes in total knee arthroplasty (TKA) versus unicompartmental knee arthroplasty (UKA); however, to the authors' knowledge, there is no study evaluating complication rates in patients with significant comorbidities. The purpose of this retrospective study was to compare the incidence of postoperative complications, readmission and reoperation rates, length of stay (LOS), and discharge location for patients with significant medical comorbidities undergoing TKA versus UKA. Using the NSQIP database from 2008 to 2018, patients were identified by CPT code (27447 or 27446) and admission diagnostic code of primary osteoarthritis and included in the study if they had an American Society of Anesthesia score greater than or equal to 3. Chi-square test was used to compare categorical variables and t-test for continuous variables. Multivariate regression was used to compare outcomes of interest between groups. A total of 167,054 patients were analyzed with 97.3% undergoing TKA. TKA patients had a greater overall complication rate than those undergoing UKA (p < 0.001). Readmission rates were approximately 1.5 times higher in TKA compared with UKA (p = 0.002), while no statistically significant difference was discovered in reoperation rates (p = 0.868). TKA was also associated with decreased rates of same day discharge, discharge within 24 hours of surgery, and discharge home (p < 0.001, <0.001, and <0.001, respectively). This study found an increase in complication rates, readmission rates, and LOS, along with a lower likelihood of discharge home when undergoing a TKA. These findings suggest that patients with significant medical comorbidities at baseline may benefit from UKA over TKA when anatomically indicated.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Pacientes , Tempo de Internação , Osteoartrite do Joelho/complicações , Resultado do Tratamento , Articulação do Joelho/cirurgia
5.
Clin Spine Surg ; 37(1): E37-E42, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37853571

RESUMO

STUDY DESIGN: Retrospective Cohort. OBJECTIVE: To evaluate patient-reported outcome measures (PROM) and minimal clinically important difference (MCID) achievement outcomes between anterior cervical discectomy and fusion (ACDF) and cervical disk replacement (CDR) in the Workers' Compensation (WC) population. SUMMARY OF BACKGROUND DATA: No studies to our knowledge have compared PROMs and MCID attainment between ACDF and CDR among patients with WC insurance undergoing surgery in an outpatient ambulatory surgical center (ASC). METHODS: WC insurance patients undergoing primary, single/double-level ACDF/CDR in an ASC were identified. Patients were divided into ACDF versus CDR. PROMs were collected at preoperative/6-week/12-week/6-month/1-year timepoints, including PROMIS-PF, SF-12 PCS/MCS, VAS neck/arm, and NDI. RESULTS: Seventy-nine patients were included, 51 ACDF/28 CDR. While operative time (56.4 vs. 54.4 min), estimated blood loss (29.2 vs. 25.9 mL), POD0 pain (4.9 vs. 3.8), and POD0 narcotic consumption (21.2 vs. 14.5 oral morphine equivalents) were higher in ACDF patients, none reached statistical significance ( P >0.050, all). One-year arthrodesis rate was 100.0% among ACDF recipients with available imaging (n=36). ACDF cohort improved from preoperative for PROMIS-PF from 12 weeks to 1 year, SF-12 PCS at 6 months, all timepoints for VAS neck/arm, and 12 weeks/6 months for NDI ( P ≤0.044, all). CDR cohort improved from preoperative for PROMIS-PF at 6 months, VAS neck/arm from 12 weeks to 1 year, and NDI at 12 weeks/6 months ( P ≤0.049, all). CDR cohort reported significantly lower VAS neck at 12 weeks/1 year and VAS arm at 12 weeks ( P ≤0.039, all). MCID achievement rates did not differ. CONCLUSION: While operative duration/estimated blood loss/acute postoperative pain/narcotic consumption were, on average, higher among ACDF recipients, these were not statistically significant, possibly due to the limited sample size. ACDF and CDR ASC patients generally demonstrated comparable arm pain/disability/physical function/mental health, though neck pain was significantly lower at multiple timepoints among CDR patients. Clinically meaningful PROM improvements were comparable. Larger, multicentered studies are required to confirm our results.


Assuntos
Fusão Vertebral , Indenização aos Trabalhadores , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Fusão Vertebral/métodos , Medição da Dor , Discotomia/métodos , Cervicalgia/cirurgia , Entorpecentes
6.
BMC Public Health ; 23(1): 2549, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129850

RESUMO

BACKGROUND: Black and Latinx populations are disproportionately affected by stroke and are likely to experience gaps in health care. Within fragmented care systems, remote digital solutions hold promise in reversing this pattern. However, there is a digital divide that follows historical disparities in health. Without deliberate attempts to address this digital divide, rapid advances in digital health will only perpetuate systemic biases. This study aimed to characterize the range of digital health interventions for stroke care, summarize their efficacy, and examine the inclusion of Black and Latinx populations in the evidence base. METHODS: We searched PubMed, the Web of Science, and EMBASE for publications between 2015 and 2021. Inclusion criteria include peer-reviewed systematic reviews or meta-analyses of experimental studies focusing on the impact of digital health interventions on stroke risk factors and outcomes in adults. Detailed information was extracted on intervention modality and functionality, clinical/behavioral outcome, study location, sample demographics, and intervention results. RESULTS: Thirty-eight systematic reviews met inclusion criteria and yielded 519 individual studies. We identified six functional categories and eight digital health modalities. Case management (63%) and health monitoring (50%) were the most common intervention functionalities. Mobile apps and web-based interventions were the two most commonly studied modalities. Evidence of efficacy was strongest for web-based, text-messaging, and phone-based approaches. Although mobile applications have been widely studied, the evidence on efficacy is mixed. Blood pressure and medication adherence were the most commonly studied outcomes. However, evidence on the efficacy of the various intervention modalities on these outcomes was variable. Among all individual studies, only 38.0% were conducted in the United States (n = 197). Of these U.S. studies, 54.8% adequately reported racial or ethnic group distribution. On average, samples were 27.0% Black, 17.1% Latinx, and 63.4% White. CONCLUSION: While evidence of the efficacy of selected digital health interventions, particularly those designed to improve blood pressure management and medication adherence, show promise, evidence of how these interventions can be generalized to historically underrepresented groups is insufficient. Including these underrepresented populations in both digital health experimental and feasibility studies is critical to advancing digital health science and achieving health equity.


Assuntos
Saúde Digital , Acidente Vascular Cerebral , Envio de Mensagens de Texto , Adulto , Humanos , Hispânico ou Latino , Acidente Vascular Cerebral/prevenção & controle , Telefone , Negro ou Afro-Americano , Estados Unidos
7.
EMBO Rep ; 24(11): e57250, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37712432

RESUMO

MicroRNAs (miRNAs) together with Argonaute (AGO) proteins form the core of the RNA-induced silencing complex (RISC) to regulate gene expression of their target RNAs post-transcriptionally. Argonaute proteins are subjected to intensive regulation via various post-translational modifications that can affect their stability, silencing efficacy and specificity for targeted gene regulation. We report here that in Caenorhabditis elegans, two conserved serine/threonine kinases - casein kinase 1 alpha 1 (CK1A1) and casein kinase 2 (CK2) - regulate a highly conserved phosphorylation cluster of 4 Serine residues (S988:S998) on the miRNA-specific AGO protein ALG-1. We show that CK1A1 phosphorylates ALG-1 at sites S992 and S995, while CK2 phosphorylates ALG-1 at sites S988 and S998. Furthermore, we demonstrate that phospho-mimicking mutants of the entire S988:S998 cluster rescue the various developmental defects observed upon depleting CK1A1 and CK2. In humans, we show that CK1A1 also acts as a priming kinase of this cluster on AGO2. Altogether, our data suggest that phosphorylation of AGO within the cluster by CK1A1 and CK2 is required for efficient miRISC-target RNA binding and silencing.


Assuntos
Proteínas de Caenorhabditis elegans , MicroRNAs , Animais , Humanos , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caseína Quinase I/genética , Caseína Quinase I/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Complexo de Inativação Induzido por RNA/genética , Complexo de Inativação Induzido por RNA/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Inativação Gênica , Serina/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
8.
J Immigr Minor Health ; 25(5): 1202-1206, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37314608

RESUMO

Though immigrants from Bangladesh are a fast-growing and under-resourced immigrant community in the United States, little has been studied about their overall health and social needs. Older immigrant adults from Bangladesh are at increased risk for adverse effects from the COVID-19 pandemic, as they have existing risk factors for isolation including language barriers and more recent immigration. This study examined measures of health and connectedness amongst 297 South Asian adults in New York City who were 60 years or older using a phone-based survey instrument. Surveys were conducted from August 2021 to April 2022. We found that immigrants from Bangladesh were more likely to report a higher effect of the COVID-19 pandemic on financial and food insecurity and faced significantly higher levels of loneliness than South Asian immigrants from other countries. Our findings suggest that older immigrants from Bangladesh disproportionally face social isolation compared to older immigrants from other South Asian countries and our study encourages further research and intervention for this immigrant subgroup.


Assuntos
COVID-19 , Emigrantes e Imigrantes , Adulto , Humanos , Estados Unidos , Avaliação das Necessidades , Pandemias , Cidade de Nova Iorque
9.
3 Biotech ; 13(6): 175, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37188291

RESUMO

Juvenile hormone (JH) plays pivotal roles in several critical developmental processes in insects, including metamorphosis and reproduction. JH-biosynthetic pathway enzymes are considered highly promising targets for discovering novel insecticides. The oxidation of farnesol to farnesal, catalysed by farnesol dehydrogenase (FDL), represents a rate-limiting step in JH biosynthesis. Here, we report farnesol dehydrogenase (HaFDL) from H. armigera as a promising insecticidal target. The inhibitory potential of natural substrate analogue geranylgeraniol (GGol) was tested in vitro, wherein it showed a high binding affinity (kd 595 µM) for HaFDL in isothermal titration calorimetry (ITC) and subsequently exhibited dose-dependent enzyme inhibition in GC-MS coupled qualitative enzyme inhibition assay. Moreover, the experimentally determined inhibitory activity of GGol was augmented by the in silico molecular docking simulation which showed that GGol formed a stable complex with HaFDL, occupied the active site pocket and interacted with key active site residues (Ser147 and Tyr162) as well as other residues that are crucial in determining the active site architecture. Further, the diet-incorporated oral feeding of GGol caused detrimental effects on larval growth and development, exhibiting a significantly reduced rate of larval weight gain (P < 0.01), aberrant pupal and adult morphogenesis, and a cumulative mortality of ~ 63%. To the best of our knowledge, the study presents the first report on evaluating GGol as a potential inhibitor for HaFDL. Overall, the findings revealed the suitability of HaFDL as a potential insecticidal target for the management H. armigera.

10.
Int J Biol Macromol ; 242(Pt 1): 124674, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37137348

RESUMO

N-acetylglucosamine kinase (NAGK), a major enzyme of sugar-kinase/Hsp70/actin superfamily, catalyses the conversion of N-acetylglucosamine to N-acetylglucosamine-6-phosphate, the first step leading to the salvage synthesis of uridine diphosphate N-acetylglucosamine. Here, we present the first report on identification, cloning, recombinant expression and functional characterisation of NAGK from Helicoverpa armigera (HaNAGK). The purified soluble HaNAGK exhibited a molecular mass of ∼39 kDa with monomeric conformation. It catalysed the sequential transformation of GlcNAc into UDP-GlcNAc, indicating its role as the initiator of UDP-GlcNAc salvage pathway. HaNAGK exhibited ubiquitous expressions across all the developmental stages and major tissues of H. armigera. The gene was significantly upregulated (80 %; p < 0.01) by the moulting hormone 20-hydroxyecdysone and significantly downregulated (89 %; p < 0.001) by the chitin synthesis inhibitor novaluron, indicating its involvement in ecdysis and chitin metabolism. Furthermore, RNAi of HaNAGK caused poor weight gain, deformed insect bodies, aberrant metamorphosis and pronounced wing abnormalities in >55 % of surviving adults, while recording 7.79 ± 1.52 % and 24.25 ± 7.21 % mortality during larval and pupal stages, respectively. Altogether, the present findings suggest that HaNAGK plays a crucial role in the growth and development of H. armigera and thus, could be considered as a compelling gene of interest while formulating novel pest management strategies.


Assuntos
Acetilglucosamina , Mariposas , Animais , Acetilglucosamina/metabolismo , Mariposas/metabolismo , Larva/metabolismo , Difosfato de Uridina/metabolismo , Quitina/metabolismo
11.
J Investig Med High Impact Case Rep ; 11: 23247096231165736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37052044

RESUMO

COVID-19 infection has been found to precipitate hypercoagulability and transiently increase antiphospholipid antibodies. However, it is yet to be determined how likely these transient changes contribute to thrombotic events and antiphospholipid syndrome. We present a case in which antiphospholipid antibodies were detected in the presence of significant thromboses. The patient was subsequently treated for suspected catastrophic antiphospholipid syndrome following COVID-19 infection.


Assuntos
Síndrome Antifosfolipídica , COVID-19 , Trombose , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , COVID-19/complicações , Anticorpos Antifosfolipídeos , Trombose/complicações
13.
J Am Acad Orthop Surg ; 31(4): 189-197, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36728328

RESUMO

Trunnion in total hip arthroplasty refers to the interface between the neck of a femoral stem and the femoral head. Clinical complications arising from damage to this junction, whether it be due to mechanical wear, corrosion, or a combination, are referred to as mechanically assisted crevice corrosion (MACC), also commonly known as trunnionosis. With the use of modular hip prostheses, which help customize offset and leg length to an individual patient's anatomy, the incidence of MACC and revision due to MACC has increased in recent years. Although the cause of MACC is multifactorial, with patient factors and technique factors contributing to this condition, taper design and geometry, metallurgical properties of implants, and size mismatch of the bearing couple are some of the implant factors that have also been implicated in this clinical phenomenon. Understanding the history of taper design and geometry, the track record of older implants, and the rationale behind the development of current prostheses can help surgeons choose the right implants for their patients and accurately assess the pros and cons of new implants being introduced to the market each year.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Falha de Prótese , Desenho de Prótese , Prótese de Quadril/efeitos adversos , Fêmur/cirurgia , Corrosão
14.
Ann Jt ; 8: 2, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38529229

RESUMO

Background: Periprosthetic joint infections (PJIs) remain challenging to eradicate even after surgical management, which in most cases involves either debridement, antibiotics and implant retention (DAIR) or single- or two-staged revision. The purpose of this study is to determine predictors of PJI recurrence after operative management for PJI, and to determine differences in recurrence-free survival between DAIR and staged revision. Methods: This is a retrospective analysis of prospectively collected data of revision hip and knee arthroplasty surgeries due to PJI between 2011 and 2018 at an academic hospital. Any patient undergoing revision surgery for PJI was included except if the index surgery information was unknown. The primary outcome was confirmed PJI recurrence. Multivariable logistic regression analysis was utilized to determine the relationship between the predictor variables and outcome variable. Log rank testing was used to compare recurrence-free survival between DAIR and staged revision. Results: A total of 89 patients (91 joints) underwent revision surgery due to PJI. Younger age and presence of a sinus tract were statistically significant for risk of PJI recurrence. A multivariable logistic regression model including both variables was significant for predicting recurrence of PJI (χ2=10.2, P=0.006). Survival was not significantly different between patients who underwent DAIR versus a staged revision. Conclusions: Younger patients and those with a chronic sinus tract are at significantly higher risk of recurrent PJI. This study also demonstrated that PJI can be successfully managed in the majority of cases with DAIR or staged revision.

15.
Arthroplast Today ; 24: 101246, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38205059

RESUMO

Background: There is limited literature evaluating patient satisfaction and outcomes after outpatient joint arthroplasty procedures in academic medical centers (AMCs). The aims of this study are to determine: (1) patients' desires to repeat their procedures and be discharged on the same day, (2) patient-reported outcome measures (PROMs), (3) time to discharge, (4) readmission rates, and (5) factors that predict PROMs in patients undergoing outpatient joint arthroplasty in AMCs. Methods: A prospective survey was completed by 66 total hip arthroplasty (THA), 35 total knee arthroplasty (TKA), and 180 unicondylar knee arthroplasty (UKA) outpatients who underwent surgery from May 2018 to December 2020 in 2 AMCs. The survey consisted of questions regarding hip or knee PROMs (Hip Disability and Osteoarthritis Outcome Score for Joint Replacement, and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement), satisfaction with outpatient procedures and discharges, and reasons for readmissions. Linear regression analysis was conducted with statistical significance set at P < .05. Results: 100% of THA, 93.8% of TKA, and 93.0% of UKA outpatients stated that they would re-elect to undergo their respective procedure. Furthermore, 94% of THA, 81% of TKA, and 95% of UKA patients stated they would like same-day discharge again. THA, TKA, and UKA patients reported respective mean PROM scores of 94.7, 89.9, and 86.1. Readmission rates were 1.5%, 0.0%, and 0.5%, for THA, TKA, and UKA, respectively. Conclusions: Patients who underwent outpatient joint arthroplasty procedures at 2 AMCs experienced minimal readmissions and reported a high desire to repeat their outpatient procedures.

16.
Pestic Biochem Physiol ; 188: 105273, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464378

RESUMO

The chitin metabolic pathway is one of the most lucrative targets for designing pest management regimes. Inhibition of the chitin synthesis pathway causes detrimental effects on the normal growth and development of insects. Phospho-N-acetylglucosamine mutase (AGM) and UDP-N-acetylglucosamine pyrophosphorylase (UAP) are two key chitin biosynthesis enzymes in insects including Helicoverpa armigera, a pest of global significance. In the present study, we have identified, cloned and recombinantly expressed AGM and UAP from H. armigera (HaAGM and HaUAP). Biochemical characterization of recombinant HaAGM and HaUAP exhibited high affinities for their natural substrates N-acetyl glucosamine-6-phosphate (Km 38.72 ± 2.41) and N-acetyl glucosamine-1-phosphate (Km 3.66 ± 0.13), respectively. In the coupled enzyme-catalytic assay, HaAGM and HaUAP yielded the end-products, inorganic pyrophosphate and UDP-GlcNAc, confirming their active participation in the chitin synthesis pathway of H. armigera. Gene expression profiling revealed that HaAGM and HaUAP genes were expressed in all developmental stages and key tissues. These genes also showed substantial responses towards the moulting hormone 20-hydroxyecdysone and chitin biosynthesis inhibitor, novaluron. Remarkably, the RNAi-mediated knockdown of either HaAGM or HaUAP led to severe developmental deformities and significant mortality ranging from 65.61 to 72.54%. Overall findings suggest that HaAGM and HaUAP play crucial roles in the ecdysis and survival of H. armigera. Further, these genes could serve as potential targets for designing pest management strategies for H. armigera.


Assuntos
Muda , Mariposas , Animais , Muda/genética , Quitina , Ecdisterona/farmacologia , Glucosamina , Mariposas/genética
17.
Cell Rep ; 41(11): 111822, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36516777

RESUMO

Argonaute proteins are at the core of the microRNA-mediated gene silencing pathway essential for animals. In C. elegans, the microRNA-specific Argonautes ALG-1 and ALG-2 regulate multiple processes required for proper animal developmental timing and viability. Here we identified a phosphorylation site on ALG-1 that modulates microRNA association. Mutating ALG-1 serine 642 into a phospho-mimicking residue impairs microRNA binding and causes embryonic lethality and post-embryonic phenotypes that are consistent with alteration of microRNA functions. Monitoring microRNA levels in alg-1 phosphorylation mutant animals shows that microRNA passenger strands increase in abundance but are not preferentially loaded into ALG-1, indicating that the miRNA binding defects could lead to microRNA duplex accumulation. Our genetic and biochemical experiments support protein kinase A (PKA) KIN-1 as the putative kinase that phosphorylates ALG-1 serine 642. Our data indicate that PKA triggers ALG-1 phosphorylation to regulate its microRNA association during C. elegans development.


Assuntos
Proteínas de Caenorhabditis elegans , MicroRNAs , Animais , Caenorhabditis elegans/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fosforilação , Proteínas de Ligação a RNA/metabolismo , Serina/metabolismo
18.
JAMA Netw Open ; 5(10): e2237783, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36282505

RESUMO

Importance: For patients discharged from the emergency department (ED), timely outpatient in-person follow-up is associated with improved mortality, but the effectiveness of telehealth as follow-up modality is unknown. Objective: To evaluate whether the rates of ED return visits and hospitalization differ between patients who obtain in-person vs telehealth encounters for post-ED follow-up care. Design, Setting, and Participants: This retrospective cohort study included adult patients who presented to either of 2 in-system EDs of a single integrated urban academic health system from April 1, 2020, to September 30, 2021; were discharged home; and obtained a follow-up appointment with a primary care physician within 14 days of their index ED visit (15 total days). Exposures: In-person vs telehealth post-ED discharge follow-up within 14 days. Main Outcomes and Measures: Multivariable logistic regression was used to estimate the odds of ED return visits (primary outcome) or hospitalization (secondary outcome) within 30 days of an ED visit based on the modality of post-ED discharge follow-up. Models were adjusted for age, sex, primary language, race, ethnicity, Social Vulnerability Index, insurance type, distance to the ED, ambulatory billing codes for the index visit, and the time from ED discharge to follow-up. Results: Overall, 12 848 patients with 16 987 ED encounters (mean [SD] age, 53 [20] years; 9714 [57%] women; 2009 [12%] Black or African American; 3806 [22%] Hispanic or Latinx; and 9858 [58%] White) were included; 11 818 (70%) obtained in-person follow-up, and 5169 (30%) obtained telehealth follow-up. Overall, 2802 initial ED encounters (17%) led to returns to the ED, and 676 (4%) led to subsequent hospitalization. In adjusted analyses, telehealth vs in-person follow-up visits were associated with increased rates of ED returns (28.3 [95% CI, 11.3-45.3] more ED returns per 1000 encounters) and hospitalizations (10.6 [95% CI, 2.9-18.3] more hospitalizations per 1000 encounters). Conclusions and Relevance: In this cohort study of patients in an urban integrated health care system, those with telehealth follow-up visits after an ED encounter were more likely to return to the ED and be hospitalized than patients with in-person follow-up. The use of telehealth warrants further evaluation to examine its effectiveness as a modality for continuing care after an initial ED presentation for acute illness.


Assuntos
Serviço Hospitalar de Emergência , Telemedicina , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Estudos de Coortes , Seguimentos , Hospitais
19.
Insects ; 13(9)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36135510

RESUMO

Exudation of mucilage from pinhead-sized boreholes in cocoa pods was recorded in Karnataka, India, during 2021. Further investigations showed the association of scolytine beetles with infested pods. The identity of the pest, Xylosandrus crassiusculus, was confirmed through morphological characterization and sequencing of the mitochondrial COI gene. We studied the predisposing factors for its infestation, visible and concealed damaging symptoms, and fungal symbionts. In addition to its well-known symbiotic fungus, Ambrosiella roeperi, a new association of yeast, Ambrosiozyma monospora, was discovered. We also traced the possible role of the mirid bug, Helopeltis theivora, in host selection by X. crassiusculus. Overall results indicated that a 'mirid bug-ambrosia beetle-pathogen complex' is responsible for the severe damage to cocoa pods in South India.

20.
Pathogens ; 11(9)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36145390

RESUMO

Background: High-titer convalescent plasma given early for COVID-19 may decrease progression into a severe infection. Here, we reported a study of serial antibody measurements in patients who received CP at our center and performed a systematic review of randomized trials on CP. Methods: Our center participated in the Mayo Clinic Expanded Access Program for COVID-19 Convalescent Plasma. Patients diagnosed with COVID-19 by nasopharyngeal polymerase chain reaction at our center between April and August 2020 were included in the study if staffing was available for specimen collection. Through a colloidal gold immunochromatography assay, these patients' IgM and IgG antibody responses were measured at baseline (Day 0) and after transfusion (Day 1, 2, etc.). Donor CP antibody levels were measured as well. Results: 110 serum specimens were obtained from 21 COVID-19 patients, 16 of whom received CP. The median time from developing symptoms to receiving CP was 11 days (range 4−21). In 9 of 14 (64%) cases where both recipient and donor CP antibody levels were tested, donor COVID-19 IgG was lower than that of the recipient. Higher donor antibody levels compared with the recipient (R = 0.71, p < 0.01) and low patient IgG before CP transfusion (p = 0.0108) correlated with increasing patient IgG levels from baseline to Day 1. Among all patients, an increased COVID-19 IgG in the short-term and longitudinally was positively correlated with improved clinical outcomes (ρ = 0.69, p = 0.003 and ρ = 0.58, p < 0.006, respectively). Conclusions: In a real-world setting where donor CP was not screened for the presence of antibodies, CP in donors might have less COVID-19 IgG than in recipients. An increase in patient antibody levels in the short term and longitudinally was associated with improved clinical outcomes.

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