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1.
Microbiology (Reading) ; 170(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38787390

RESUMO

Archaeal cell biology is an emerging field expected to identify fundamental cellular processes, help resolve the deep evolutionary history of cellular life, and contribute new components and functions in biotechnology and synthetic biology. To facilitate these, we have developed plasmid vectors that allow convenient cloning and production of proteins and fusion proteins with flexible, rigid, or semi-rigid linkers in the model archaeon Haloferax volcanii. For protein subcellular localization studies using fluorescent protein (FP) tags, we created vectors incorporating a range of codon-optimized fluorescent proteins for N- or C-terminal tagging, including GFP, mNeonGreen, mCherry, YPet, mTurquoise2 and mScarlet-I. Obtaining functional fusion proteins can be challenging with proteins involved in multiple interactions, mainly due to steric interference. We demonstrated the use of the new vector system to screen for improved function in cytoskeletal protein FP fusions, and identified FtsZ1-FPs that are functional in cell division and CetZ1-FPs that are functional in motility and rod cell development. Both the type of linker and the type of FP influenced the functionality of the resulting fusions. The vector design also facilitates convenient cloning and tandem expression of two genes or fusion genes, controlled by a modified tryptophan-inducible promoter, and we demonstrated its use for dual-colour imaging of tagged proteins in H. volcanii cells. These tools should promote further development and applications of archaeal molecular and cellular biology and biotechnology.


Assuntos
Proteínas Arqueais , Clonagem Molecular , Vetores Genéticos , Haloferax volcanii , Proteínas Luminescentes , Plasmídeos , Haloferax volcanii/genética , Haloferax volcanii/metabolismo , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas Arqueais/genética , Proteínas Arqueais/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo
2.
Proc Natl Acad Sci U S A ; 121(23): e2318843121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38805277

RESUMO

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Mutação , Glioma/genética , Glioma/cirurgia , Glioma/patologia , Isocitrato Desidrogenase/genética , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Espectrometria de Massas em Tandem/métodos , Glutaratos/metabolismo , Espectrometria de Massas/métodos , Ácido Glutâmico/metabolismo , Ácido Glutâmico/genética
3.
bioRxiv ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38798418

RESUMO

Organisms must sense temperature and modify their physiology to ensure survival during environmental stress. Elevated temperature leads to reduced fertility in most sexually reproducing organisms. Maternally supplied mRNAs are required for embryogenesis. They encode proteins that govern early events in embryonic patterning. RNA-binding proteins (RBPs) are major effectors of maternal mRNA regulation. MEX-3 is a conserved RBP essential for anterior patterning of Caenorhabditis elegans embryos. We previously demonstrated that the mex-3 3' untranslated region (3'UTR) represses MEX-3 abundance in the germline yet is dispensable for fertility. Here, we show that the 3'UTR becomes essential during thermal stress. Deletion of the 3'UTR causes a highly penetrant temperature sensitive embryonic lethality phenotype distinct from a mex-3 null. Loss of the 3'UTR decreases MEX-3 abundance specifically in maturing oocytes and early embryos experiencing temperature stress, suggesting a mechanism that regulates MEX-3 abundance at the oocyte-to-embryo transition is sensitive to temperature. We propose that a primary role of the mex-3 3'UTR is to buffer MEX-3 expression to ensure viability during fluctuating temperature. We hypothesize that a major role of maternally supplied mRNAs is to ensure robust expression of key cell fate determinants in uncertain conditions.

4.
Plast Reconstr Surg Glob Open ; 12(5): e5763, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38784831

RESUMO

A 13-year-old girl with a painful left neck mass was referred to our institution due to suspicions of malignancy. The patient reported pain that accompanied her frequent neck spasms. Computed tomography revealed a large, soft-tissue mass in the left neck, deep to the sternocleidomastoid. The lesion anteriorly displaced the internal carotid artery and both displaced and crushed the internal left jugular vein. Uniquely, a three-dimensional virtual reality model combining magnetic resonance imaging and computed tomography data was used to determine the lesion's resectability and visualize which structures would be encountered or require protection while ensuring total resection. During operation, we confirmed that the mass also laterally displaced the brachial plexus, cranial nerves X and XI, and spinal nerves C3-C5 (including the phrenic) of the cervical plexus. Postsurgical pathological analysis confirmed a diagnosis of desmoid tumor, also known as aggressive fibromatosis, whereas DNA sequencing revealed a CTNNB1 mutation, a somatic genetic marker found in approximately 90% of desmoid tumor cases. When possible, the most widely used method for the treatment of desmoid tumors has been gross resection. Chemotherapy, radiotherapy, and local excision are also used in the treatment of fibromatoses when complete resection is judged infeasible. In this case, a complete surgical resection with tumor-free surgical margins was performed. A standard cervical approach with a modified posterolateral incision site was implemented to avoid a conspicuous anterior neck scar. No flap, nerve repair, or reconstruction was warranted. At 1 year of postsurgical follow-up, the patient showed minimal scarring and no signs of recurrence.

5.
J Telemed Telecare ; : 1357633X241251522, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38751377

RESUMO

BACKGROUND: Telemedicine has gained traction in surgical subspecialties, particularly since the COVID-19 pandemic. This study aims to identify whether telemedicine can be appropriately integrated within surgical oncology practice. METHODS: This retrospective study evaluated patients who received either telemedicine or office follow-up after undergoing surgical oncology operations between 2016 and 2021. The telemedicine group (TG) and office group (OG) received a 15-question survey regarding their satisfaction with their care. Patient outcomes and responses were analyzed utilizing propensity-score matching in 1:1 fashion. RESULTS: Telemedicine group and OG each had 21 patients. Length of stay, complication frequency, follow-up frequency, and readmissions frequency within 90-days were comparable between groups. Telemedicine group expressed comparable satisfaction with postoperative care relative to OG (95.2% vs. 85.7%, p = 0.61). All telemedicine patients said they would utilize telemedicine again in the future and would recommend its use to others. CONCLUSION: Patient satisfaction with postoperative telemedicine follow-up is comparable to those with in-person follow-up.

6.
Schizophr Res ; 267: 301-307, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38603838

RESUMO

BACKGROUND: Individuals with a schizophrenia spectrum disorder were at heightened risk for interruptions in psychiatric care during the coronavirus-19 (COVID 19) pandemic. There is limited work exploring the pandemic's impact on emergency department (ED) visit volume, use of restraint and parenteral medications, inpatient psychiatric (IP) hospitalization, and ED length of stay (LOS) among this population. METHODS: We retrospectively examined 2134 ED visits with a billing code for psychosis between March 1, 2019-February 28, 2021. We used Poisson regression analysis to compare ED visit volume between the pandemic and pre-pandemic periods. Restraint use, parenteral antipsychotic or benzodiazepine use, IP hospitalization, and ED LOS were compared between the two periods using chi-square tests and independent samples t-tests. RESULTS: Overall volume of psychosis-related ED visits during the pandemic did not differ significantly from the prior year. Rates of restraint use (16.2 % vs 11.6 %, p < .01), parenteral antipsychotic (22.6 % vs 14.9, p < .001), and parenteral benzodiazepine (22.3 % vs 16.3 %, p < .001) use were significantly higher during the pandemic. Fewer patients had an IP hospital disposition during the pandemic than the year prior (57.8 % vs. 61.9 %, p < .05). ED LOS was longer during the pandemic compared to pre-pandemic (28.37 h vs 20.26 h, p < .001). CONCLUSIONS: Although the volume of psychosis-related ED visits remained constant, restraint and parenteral medication use rates were significantly higher during the pandemic. ED LOS increased but fewer ED visits resulted in IP hospitalization. These findings underscore the importance of planning for increased acuity of psychosis ED presentations during public health emergencies.


Assuntos
Antipsicóticos , COVID-19 , Serviço Hospitalar de Emergência , Hospitalização , Tempo de Internação , Transtornos Psicóticos , Restrição Física , Humanos , COVID-19/epidemiologia , Masculino , Feminino , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adulto , Tempo de Internação/estatística & dados numéricos , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/terapia , Estudos Retrospectivos , Restrição Física/estatística & dados numéricos , Pessoa de Meia-Idade , Antipsicóticos/uso terapêutico , Hospitalização/estatística & dados numéricos , Adulto Jovem , Esquizofrenia/epidemiologia , Esquizofrenia/terapia , Esquizofrenia/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Visitas ao Pronto Socorro
7.
Sex Transm Dis ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38647241

RESUMO

BACKGROUND: In response to the 2022 mpox outbreak in the United States, people with higher potential for exposure to mpox were recommended to receive two doses of the JYNNEOS vaccine. Vaccine safety was monitored using two complementary systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that accepts reports of adverse events following vaccination. VAERS is capable of rapidly identifying rare adverse events and unusual reporting patterns. Medical records were requested and reviewed for adverse events of special interest, including myocarditis. Adverse event reporting rates were calculated as the number of verified adverse event cases divided by the number of JYNNEOS doses administered. V-safe for mpox was a voluntary smartphone-based vaccine safety surveillance system that sent enrolled persons text messages linked to health surveys asking about reactions and health impact events occurring after vaccination. RESULTS: There were 1,207,056 JYNNEOS doses administered in the United States. VAERS received 1,927 reports for JYNNEOS. The myocarditis reporting rate per million doses was 2.69 after dose 1 and 8.64 after dose 2. V-safe had 213 participants complete at least one health survey. Rates of injection site and systemic reactions were similar in the first week following dose 1 and dose 2. CONCLUSIONS: JYNNEOS vaccine safety surveillance findings from VAERS and v-safe did not identify any unexpected safety concerns. The VAERS reporting rate for myocarditis was similar to previously published population background rates.

8.
Neuropharmacology ; 253: 109963, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657945

RESUMO

Valproic acid (VPA) is an effective and commonly prescribed drug for epilepsy and bipolar disorder. However, children born from mothers treated with VPA during pregnancy exhibit an increased incidence of autism spectrum disorder (ASD). Although VPA may impair brain development at the cellular level, the mechanism of VPA-induced ASD has not been completely addressed. A previous study has found that VPA treatment strongly reduces δ-catenin mRNA levels in cultured human neurons. δ-catenin is important for the control of glutamatergic synapses and is strongly associated with ASD. VPA inhibits dendritic morphogenesis in developing neurons, an effect that is also found in neurons lacking δ-catenin expression. We thus hypothesize that prenatal exposure to VPA significantly reduces δ-catenin levels in the brain, which impairs glutamatergic synapses to cause ASD. Here, we found that prenatal exposure to VPA markedly reduced δ-catenin levels in the brain of mouse pups. VPA treatment also impaired dendritic branching in developing mouse cortical neurons, which was partially reversed by elevating δ-catenin expression. Prenatal VPA exposure significantly reduced synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor levels and postsynaptic density 95 (PSD95) in the brain of mouse pups, indicating dysfunctions in glutamatergic synaptic transmission. VPA exposure also significantly altered ultrasonic vocalization (USV) in newly born pups when they were isolated from their nest. Moreover, VPA-exposed pups show impaired hypothalamic response to isolation, which is required to produce animals' USVs following isolation from the nest. Therefore, these results suggest that VPA-induced ASD pathology can be mediated by the loss of δ-catenin functions.


Assuntos
Animais Recém-Nascidos , Efeitos Tardios da Exposição Pré-Natal , Ácido Valproico , Vocalização Animal , Animais , Ácido Valproico/farmacologia , Ácido Valproico/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Feminino , Vocalização Animal/efeitos dos fármacos , Vocalização Animal/fisiologia , Camundongos , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Cateninas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Receptores de AMPA/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/metabolismo
9.
PLoS One ; 19(3): e0298929, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547141

RESUMO

'Bushmeat' markets are often portrayed as chaotic spaces where exotic wild animals are sold. They are hypothesized to be important sites for zoonotic disease transmission, given the prolonged and intense nature of the cross-species encounters that occur within them. Whilst such markets have received some attention from researchers, rich qualitative descriptions of everyday practices in these markets are rare. Depictions of wild animal markets as sites for potential viral amplification often rely on exoticizing assumptions and narratives rather than actual evidence, and in some cases are based more on ideology than on science. We provide an in-depth ethnographic account of two bushmeat markets in Bo, Sierra Leone. Our analysis goes beyond common assumptions that zoonotic risk is located solely in the knowledge and behaviours of traders. Our account sheds light on the modes of touch, closeness and contact that shape this hypothesised zoonotic interface, outlining the possible risks to different people who use and spend time in the market. We found that inadequate infrastructure and sanitation facilities created risks of zoonotic disease transmission for diverse actors including traders, customers, children, and the wider public. Butchering and trading practices frequently resulted in people directly and indirectly encountering animal fluids. We also discuss how public health management of these markets focused on individual behaviours rather than on improving conditions. Urgent sanitary reform and infrastructure upgrades in these sites that support the economic needs of traders could encourage voluntary compliance with biosafety measures amongst traders seeking to balance responsibilities to family and public health. Our study reveals the value of moving beyond exoticized narratives about bushmeat markets to yield situated insights for reducing risk at this interface.


Assuntos
Animais Selvagens , Zoonoses , Animais , Criança , Humanos , Serra Leoa , Zoonoses/epidemiologia , Saúde Pública , Saneamento
11.
Drug Saf ; 47(5): 487-493, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38411838

RESUMO

INTRODUCTION: Bivalent mRNA coronavirus disease 2019 (COVID-19) vaccines may be simultaneously administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. OBJECTIVE: The aim was to describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. METHODS: We searched the VAERS database for reports of adverse events (AEs) following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines during the period of September 1, 2022-March 31, 2023. We assessed the characteristics of these reports and described the most frequently reported AEs. Clinicians reviewed available medical records for reports of serious AEs and adverse events of special interest (AESI). RESULTS: During the period of 1 September 2022 through 31 March 2023, VAERS received 3689 reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. The median age of vaccinees was 59 years (interquartile range 39, 70 years); 342 reports (9.3%) were classified as serious. The most common AEs among non-serious reports were severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2) infection (785, 23.5%), cough (592, 17.7%), and fatigue (568, 17.0%). The most common AEs among serious reports were Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (88, 25.7%), dyspnea (81, 23.7%), and condition aggravated (55, 16.1%). DISCUSSION: Reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19) was expected due to Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) reporting requirements. CDC and FDA will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines.


Assuntos
COVID-19 , Vacinas contra Influenza , Humanos , Sistemas de Notificação de Reações Adversas a Medicamentos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra Influenza/efeitos adversos , RNA Mensageiro , SARS-CoV-2 , Estados Unidos , Adulto , Pessoa de Meia-Idade , Idoso
12.
Suicide Life Threat Behav ; 54(3): 479-488, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38375945

RESUMO

BACKGROUND: Most research investigating the effect of suicide on loss survivors has been limited to first-degree family members. Few studies examine the impact of suicide on others outside the immediate family and the influence of relationship type and closeness on mental health. METHODS: This study used data from a sample obtained through random digit dialing (n = 805) to assess exposure to suicide loss, relationship types, perceived closeness, and mental health symptoms (prolonged grief, depression, anxiety, and posttraumatic stress disorder). RESULTS: Familial status, friend status, and higher perceived closeness were associated with prolonged grief, depression, and posttraumatic stress disorder, with the strongest adjusted associations observed for posttraumatic stress disorder and prolonged grief. In general, the magnitude of adjusted standardized associations for closeness and mental health symptoms was stronger than those observed for familial status and mental health symptoms and friend status and mental health symptoms. CONCLUSION: Closeness, familial status, and friend status are associated with mental health symptoms experienced after suicide loss, but the magnitude of associations was strongest for closeness. Future studies should examine perceived closeness in addition to other factors related to relationship type and dynamics to assess the complexities of suicide bereavement reactions.


Assuntos
Pesar , Transtornos de Estresse Pós-Traumáticos , Suicídio , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/psicologia , Suicídio/psicologia , Saúde Mental , Depressão/psicologia , Luto , Família/psicologia , Relações Interpessoais , Idoso , Ansiedade/psicologia , Adolescente , Adulto Jovem , Amigos/psicologia
13.
J Anal Toxicol ; 48(2): 99-103, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952088

RESUMO

Current guidelines recommend universal screening for substance use disorders in obstetric patients, and neonatal drug testing is also frequently performed. Meconium is often the preferred specimen type to detect neonatal drug exposure due to a longer window of detection compared to urine, but most laboratories send out meconium testing to specialized reference laboratories, which can delay results for several days or more. Here, we evaluate a rapid and definitive liquid chromatography-tandem mass spectrometry method for neonatal urine drug testing and compare results obtained using this method to paired meconium drug testing in 1,424 neonates for amphetamines, cocaine, cannabinoids, opiates, oxycodone and phencyclidine. Urine testing showed equivalent sensitivity to current meconium methods for detecting in utero exposure to amphetamines and cocaine.


Assuntos
Líquidos Corporais , Cocaína , Metanfetamina , Recém-Nascido , Feminino , Gravidez , Humanos , Mecônio , Detecção do Abuso de Substâncias
14.
Child Abuse Negl ; 147: 106567, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016390

RESUMO

BACKGROUND: Increases in child welfare investigations involving children's exposure to intimate partner violence (IPV) in Ontario are likely the result of three factors: 1) changes to legislation, policy, and assessment instruments; 2) increased awareness of the risks of exposure to IPV for children, and 3) referrals from professionals (e.g., police). OBJECTIVES: Using data from 6 cycles of the Ontario Incidence Study of Reported Child Abuse and Neglect (OIS) (1993, 1998, 2003, 2008, 2013, and 2018), this paper will examine the changes of the incidence rates of IPV exposure, providing important context for a type of investigation that is not well understood in Ontario. METHODS: The incidence of investigations where the primary concern of the investigating worker is IPV was derived and compared across OIS cycles. Investigation were compared across cycles using incidence counts. RESULTS: After the nearly 2-fold increase of investigations for all maltreatment types in Ontario between 1998 and 2003, IPV investigations are the only type that continue to increase. There is a growing gap between these investigations and substantiating child maltreatment. Rates of placement have not changed over time, remaining low. Rates of transfers and referrals have increased but not significantly. CONCLUSIONS: The continued growth in the rate of child welfare investigations involving exposure to IPV as well as the overwhelming endorsement of substantiated exposure to IPV, while maintaining the same proportion of transfers to ongoing child welfare services and low placement rates, is a significant concern for Ontario.


Assuntos
Maus-Tratos Infantis , Exposição à Violência , Violência por Parceiro Íntimo , Criança , Humanos , Ontário/epidemiologia , Proteção da Criança , Políticas
16.
Artigo em Inglês | MEDLINE | ID: mdl-37792287

RESUMO

BACKGROUND: Biologics are effective for chronic rhinosinusitis with nasal polyposis (CRSwNP) by reducing type 2 inflammation. Nonresponders often require functional endoscopic sinus surgery (FESS) and represent a challenging population potentially due to non-type 2 pathophysiology. This study characterizes the histopathologic features of biologic nonresponders. METHODS: A retrospective review of 257 CRSwNP patients undergoing FESS was conducted. The biologic nonresponder group included patients with prior biologic therapy who exhibited persistent symptoms and polyp burden. Those with CRSwNP not prescribed biologic therapy were selected as controls. Demographics, comorbidities, and structured histopathology consisting of 13 variables were collected. RESULTS: Of 257 CRSwNP patients, 20 were on biologics prior to FESS. Fourteen patients (70.0%) received dupilumab, one (5.0%) received mepolizumab, one (5.0%) received omalizumab, and four (20.0%) tried multiple biologics. The mean age for the biologic nonresponder group was 45.8 years compared to 50.4 years for the controls. Nonresponders had a significantly increased incidence of reduced tissue eosinophilia, defined as <5 per high power field (55% vs. 31.2%, p = 0.044) and increased basement membrane thickening (100% vs. 78.1%, p = 0.019). The remaining 11 variables did not reach statistical significance. CONCLUSION: Histopathologic analysis of biologic nonresponders demonstrates decreased eosinophilia and thickened basement membranes. These findings, particularly low tissue eosinophils, are consistent with a non-type 2 CRSwNP that may be recalcitrant to biologic therapies. Histopathologic analysis done in conjunction with FESS may aid clinicians in understanding response to biologic therapies in patients with CRSwNP who have persistent symptom burden necessitating FESS.

17.
Sci Total Environ ; 905: 167799, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37838047

RESUMO

Limited data exist on how surface charge and morphology impact the effectiveness of nanoscale copper oxide (CuO) as an agricultural amendment under field conditions. This study investigated the impact of these factors on tomatoes and watermelons following foliar treatment with CuO nanosheets (NS-) or nanospikes (NP+ and NP-) exhibiting positive or negative surface charge. Results showed plant species-dependent benefits. Notably, tomatoes infected with Fusarium oxysporum had significantly reduced disease progression when treated with NS-. Watermelons benefited similarly from NP+. Although disease suppression was significant and trends indicated increased yield, the yield effects weren't statistically significant. However, several nanoscale treatments significantly enhanced the fruit's nutritional value, and this nano-enabled biofortification was a function of particle charge and morphology. Negatively charged nanospikes significantly increased the Fe content of healthy watermelon and tomato (20-28 %) and Ca in healthy tomato (66 %), compared to their positively charged counterpart. Negatively charged nanospikes also outperformed negatively charged nanosheets, leading to significant increases in the content of S and Mg in infected watermelon (37-38 %), Fe in healthy watermelon (58 %), and Ca (42 %) in healthy tomato. These findings highlight the potential of tuning nanoscale CuO chemistry for disease suppression and enhanced food quality under field conditions.


Assuntos
Citrullus , Fusarium , Solanum lycopersicum , Biofortificação , Doenças das Plantas/prevenção & controle
18.
J Appl Lab Med ; 8(6): 1092-1100, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37702018

RESUMO

BACKGROUND: Specimens contaminated with intravenous (IV) fluids are common in clinical laboratories. Current methods for detecting contamination rely on insensitive and workflow-disrupting delta checks or manual technologist review. Herein, we assessed the utility of large language models for detecting contamination by IV crystalloids and compared its performance to multiple, but variably trained healthcare personnel (HCP). METHODS: Contamination of basic metabolic panels was simulated using 0.9% normal saline (NS), with (n = 30) and without (n = 30) 5% dextrose (D5NS), at mixture ratios of 0.10 and 0.25. A multimodal language model (GPT-4) and a diverse panel of 8 HCP were asked to adjudicate between real and contaminated results. Classification performance, mixture quantification, and confidence was compared by Wilcoxon rank sum. RESULTS: The 95% CIs for accuracy were 0.57-0.71 vs 0.73-0.80 for GPT-4 and HCP, respectively, on the NS set and 0.57-0.57 vs 0.73-0.80 on the D5NS set. HCP overestimated severity of contamination in the 0.10 mixture group (95% CI of estimate error, 0.05-0.20) for both fluids, while GPT-4 markedly overestimated the D5NS mixture at both ratios (0.16-0.33 for NS, 0.11-0.35 for D5NS). There was no correlation between reported confidence and likelihood of a correct classification. CONCLUSIONS: GPT-4 is less accurate than trained HCP for detecting IV fluid contamination of basic metabolic panel results. However, trained individuals were imperfect at identifying contaminated specimens implying the need for novel, automated tools for its detection.


Assuntos
Glucose , Humanos
19.
Cell ; 186(20): 4365-4385.e27, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37774677

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology.


Assuntos
Doença de Alzheimer , Encéfalo , Idoso , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Cognição , Disfunção Cognitiva/metabolismo , Neurônios/metabolismo
20.
J Evid Based Soc Work (2019) ; 20(6): 840-850, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37394955

RESUMO

PURPOSE: Although spirituality seems to protect against suicidality and substance misuse, in 2022 81% of United States residents believe in God and yet prevalence of these global health issues are increasing. 12-Step programs are inherently spiritual in their approach to recovery. METHOD: We used a clinically mined dataset built from everyday clinical data that a substance use day treatment program in a midwestern state of the USA originally collected for their treatment purposes. Data included information from 444 client files from three day treatment sites within the same agency. Using logistic regression, we analyzed the relationships between suicidality, spirituality, and treatment discharge. RESULTS: Suicidality and spirituality, including 12-Step involvement prior to treatment, did not have a statistically significant effect on substance use day treatment discharge. However, treatment length and age were associated with completed treatment. DISCUSSION AND CONCLUSION: While spirituality and suicidality are important concepts with relevance to recovery, they did not affect whether clients completed substance use day treatment. However, because recovery is not just about abstinence or risk reduction, suicidality and spiritually likely have relevance for the overall recovery process.


Assuntos
Terapias Espirituais , Transtornos Relacionados ao Uso de Substâncias , Suicídio , Humanos , Estados Unidos , Espiritualidade , Alta do Paciente , Transtornos Relacionados ao Uso de Substâncias/terapia
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