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1.
Harm Reduct J ; 21(1): 74, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561753

RESUMO

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.


Assuntos
Estimulantes do Sistema Nervoso Central , Overdose de Drogas , Metanfetamina , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Humanos , Masculino , Estados Unidos/epidemiologia , Adulto , Feminino , Analgésicos Opioides/uso terapêutico , Motivação , Tolerância a Medicamentos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Overdose de Drogas/epidemiologia
2.
Soc Sci Med ; 346: 116660, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484417

RESUMO

BACKGROUND: In 2020, 2.8 million people required substance use disorder (SUD) treatment in nonmetropolitan or 'rural' areas in the U.S. Among this population, only 10% received SUD treatment from a specialty facility, and 1 in 500 received medication for opioid use disorder (MOUD). We explored the context surrounding barriers to SUD treatment in the rural United States. METHODS: We conducted semi-structured, in-depth interviews from 2018 to 2019 to assess barriers to SUD treatment among people who use drugs (PWUD) across seven rural U.S. study sites. Using the social-ecological model (SEM), we examined individual, interpersonal, organizational, community, and policy factors contributing to perceived barriers to SUD treatment. We employed deductive and inductive coding and analytical approaches to identify themes. We also calculated descriptive statistics for participant characteristics and salient themes. RESULTS: Among 304 participants (55% male, mean age 36 years), we identified barriers to SUD treatment in rural areas across SEM levels. At the individual/interpersonal level, relevant themes included: fear of withdrawal, the need to "get things in order" before entering treatment, close-knit communities and limited confidentiality, networks and settings that perpetuated drug use, and stigma. Organizational-level barriers included: strict facility rules, treatment programs managed like corrections facilities, lack of gender-specific treatment programs, and concerns about jeopardizing employment. Community-level barriers included: limited availability of treatment in local rural communities, long distances and limited transportation, waitlists, and a lack of information about treatment options. Policy-level themes included insurance challenges and system-imposed barriers such as arrest and incarceration. CONCLUSION: Our findings highlight multi-level barriers to SUD treatment in rural U.S. communities. Salient barriers included the need to travel long distances to treatment, challenges to confidentiality due to small, close-knit communities where people are highly familiar with one another, and high-threshold treatment program practices. Our findings point to the need to facilitate the elimination of treatment barriers at each level of the SEM in rural America.


Assuntos
Transtornos Relacionados ao Uso de Opioides , População Rural , Humanos , Estados Unidos , Masculino , Adulto , Feminino , Pesquisa Qualitativa , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Estigma Social
3.
bioRxiv ; 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38496683

RESUMO

Background: Cell migration and invasion are well-coordinated processes in development and disease but remain poorly understood. We previously showed that highly migratory neural crest (NC) cells share a 45-gene panel with other cell invasion phenomena, including cancer. To identify critical genes of the 45-gene panel, we performed a high-throughput siRNA screen and used statistical and deep learning methods to compare NC- versus non-NC-derived human cell lines. Results: We find 14 out of 45 genes significantly reduces c8161 melanoma cell migration; only 4 are shared with HT1080 fibrosarcoma cells (BMP4, ITGB1, KCNE3, RASGRP1). Deep learning attention network analysis identified distinct cell-cell interaction patterns and significant alterations after BMP4 or RASGRP1 knockdown in c8161 cells. Addition of recombinant proteins to the culture media identified 5 out of the 10 known secreted molecules stimulate c8161 cell migration, including BMP4. BMP4 siRNA knockdown inhibited c8161 cell invasion in vivo and in vitro ; however, its addition to the culture media rescued c8161 cell invasion. Conclusion: A high-throughput screen and deep learning rapidly distilled a 45-gene panel to a small subset of genes that appear critical to melanoma cell invasion and warrant deeper in vivo functional analysis for their role in driving the neural crest.

4.
Chemistry ; 30(3): e202302714, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37983723

RESUMO

Metal imine-thiolate complexes, M(NS)2 are known to undergo imine C-C bond formation to give M(N2 S2 ) complexes (M=Co, Ni) containing a redox-active ligand. Although these transfor-mations are not typically quantitative, we demonstrate here that the one-electron reduction of a related Ni bis(imine-thiolate) complex affords the corresponding paramagnetic [Ni(N2 S2 )]- anion (2⋅- ) exclusively; subsequent oxidation with [Cp2 Fe]BF4 then affords a high yield of neutral 2 (Cp=η5 -cyclopentadienyl). Moreover, electrochemical studies indicate that a second one-electron reduction affords the diamagnetic dianion. Both anionic products were isolated and characterized by SC-XRD and their electronic structures were investigated by UV-vis spectro-electrochemistry, EPR and NMR spectroscopy, and DFT studies. These studies show that reduction proceeds primarily on the ligand, with (N2 S2 )4- containing both thiolate and ring-delocalized anions.

5.
Dalton Trans ; 52(34): 11768-11772, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37584163

RESUMO

Two tetranuclear Cu(I) complexes bearing thiolate- and amido-SNS ligands were characterized by X-ray diffraction and mass spectrometry. Although the amido ligand undergoes irreversible N-protonation by the copper-bound alkyne, the thiolate complex demonstrates good activity in the copper-catalyzed azide-alkyne cycloaddition reaction with a variety of substrates. The base-free reactions are performed in water and afford excellent yields over 2 h at 70 °C. DFT calculations suggest a proton-shuttle role for the thiolate donor in formation of the initial dicopper σ,π-alkynyl intermediate.

6.
Int J Obstet Anesth ; 55: 103899, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37329691

RESUMO

BACKGROUND: Spinal anaesthesia, the most common form of anaesthesia for caesarean section, leads to sympathetic blockade and profound maternal hypotension resulting in adverse maternal and neonatal outcomes. Hypotension, nausea and vomiting remain common but until the publication of the National Institute of Health and Care Excellence (NICE) 2021 guidance, no national guideline existed on how best to manage maternal hypotension following spinal anaesthesia for caesarean section. A 2017 international consensus statement recommended prophylactic vasopressor administration to maintain a systolic blood pressure of >90% of an accurate pre-spinal value, and to avoid a drop to <80% of this value. This survey aimed to assess regional adherence to these recommendations, the presence of local guidelines for management of hypotension during caesarean section under spinal anaesthesia, and the individual clinician's treatment thresholds for maternal hypotension and tachycardia. METHODS: The West Midlands Trainee-led Research in Anaesthesia and Intensive Care Network co-ordinated surveys of obstetric anaesthetic departments and consultant obstetric anaesthetists across 11 National Health Service Trusts in the Midlands, England. RESULTS: One-hundred-and-two consultant obstetric anaesthetists returned the survey and 73% of sites had a policy for vasopressor use; 91% used phenylephrine as the first-line drug but a wide range of recommended delivery methods was noted and target blood pressure was only listed in 50% of policies. Significant variation existed in both vasopressor delivery methods and target blood pressures. CONCLUSIONS: Although NICE has since recommended prophylactic phenylephrine infusion and a target blood pressure, the previous international consensus statement was not adhered to routinely.


Assuntos
Anestesia Obstétrica , Raquianestesia , Cesárea , Hipotensão , Vasoconstritores , Humanos , Feminino , Gravidez , Adulto , Hipotensão/etiologia , Raquianestesia/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Reino Unido , Inquéritos e Questionários , Vasoconstritores/administração & dosagem , Vasoconstritores/efeitos adversos
7.
Acc Chem Res ; 56(7): 798-809, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-36921212

RESUMO

ConspectusHomogeneous catalysis is at the forefront of global efforts to innovate the synthesis of fine chemicals and achieve carbon-neutrality in energy applications. For decades, the push toward sustainable catalysis has focused on the development of first-row transition metal catalysts to supplant widespread use of precious metals. Metal-ligand cooperativity is an effective strategy to yield high-performing first-row metal molecular catalysts. Despite remarkable progress, state of the art catalysts often employ phosphorus-based ligands which are air-sensitive, potentially toxic, and on occasion offset the cost-savings of the metal. Thus, the development of simple and economical ligands composed of biomimetic donors should be a key focus that cannot be overlooked in the pursuit of sustainable catalyst candidates. This is an Account of our group's efforts to develop first-row transition metal complexes which use [SNS]-pincer ligands for bifunctional catalysis. We have synthesized two potentially tridentate ligands, one bearing an amido and two thioether donors [(SMeNSMe), L1] and one which includes thiolate, imine, and thioether donors [(SNSMe), L2], and used them as platforms upon which to explore the reaction pathways of first-row metals. The [SNS] ligand, L1, leads to formation of high-spin paramagnetic metal complexes of the type M(L1)2 in which the 6-membered ring thioether donor is hemilabile (M = Mn, Fe, Co). This allows Mn(L1)2 to function as a carbonyl hydroboration catalyst that operates by a novel hydride-free, inner-sphere reaction pathway. Exploring the reactivity of L2 with Fe and Ni revealed unique coordination chemistry and a variety of mono-, di-, tri-, and tetranuclear complexes enabled by bridging thiolates. Further studies showed L2 undergoes selective Caryl-S bond cleavage upon coordination to a metal with electron-rich phosphine donors, yielding a new (CNS)2- pincer ligand. The analogous reaction with L1 afforded a new (CNSMe)- pincer ligand via both Caryl-S and benzylic C-H bond cleavage. In an attempt to prepare Fe(L2)2, we obtained instead an Fe(N2S3) complex in which imine C-C bond formation affords a potentially hexadentate redox-active ligand. The Fe(N2S3) complex is a selective catalyst for hydroboration of aldehydes and appears to operate through a complicated mechanism. In contrast, a mechanistic study of Mn(L2)(CO)3-photocatalyzed dihydroboration of nitriles indicated that both the flexibility of the κ3-SNSMe ligand (fac- vs mer-coordination) and ability of Mn to undergo a spin-state change are required to access low energy barriers for this transformation. To effectively compare the reactivity of the thiolate vs amido donor, we prepared two Cu complexes, Cu(L1)(IPr) and Cu(L2)(IPr) [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene], showing that, while both served as carbonyl hydroboration catalysts, only the amido complex was an effective catalyst for carbonyl hydrosilylation. In addition, complexes of the type Zn(L1)2, Zn(L2)2, and Zn(L1)(L2), were also effective for catalytic carbonyl hydroboration. While Zn(L1)(L2) was most active, catalyst speciation studies showed that each undergoes bifunctional catalyst activation to form a Zn bis(alkoxide) catalyst. Overall, our observations using [SNS] ligands with first-row transition metals show how the absence of traditional phosphine donors leads to different fundamental reactivity. Furthermore, this Account demonstrates the gap of knowledge which exists in understanding the reactivity of sulfur-based ligands to promote more widespread adoption of sustainable ligands.

8.
Chem Commun (Camb) ; 59(27): 4044-4046, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36928477

RESUMO

Three new IPr-Ag- and -Au-SNS amido and thiolate complexes were synthesized and compared to their previously reported Cu analogues as carbonyl hydroboration catalysts (IPr = bis(2,6-diisopropylphenyl)imidazol-2-ylidene). Although these complexes showed no catalytic activity, treatment of the IPr-Ag-SNS amido complex with pinacolborane released the N-borylated ligand, SMeNBpinSMe, (L1-Bpin). This finding led us to reinvestigate the IPr-Cu-SNS amido precatalyst, revealing that immediate loss of L1-Bpin converts our catalyst system to [CuH(IPr)]2.

10.
Inorg Chem ; 61(49): 19998-20007, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36455067

RESUMO

One of the key steps in many metal complex-catalyzed hydroboration reactions is B-H bond activation, which results in metal hydride formation. Anionic ligands that include multiple lone pairs of electrons, in cooperation with a metal center, have notable potential in redox-neutral B-H bond activation through metal-ligand cooperation. Herein, using an easily prepared NpyridineNimineNpyrrolide ligand (L2)-, a series of divalent NiIIX(NNN) complexes were synthesized, with X = bromide (2), phenoxide (3), thiophenoxide (4), 2,5-dimethylpyrrolide (5), diphenylphosphide (6), and phenyl (7). The complexes were characterized using 1H and 13C NMR spectroscopy, mass spectrometry, and X-ray crystallography and employed as precatalysts for nitrile dihydroboration. Superior activity of the phenoxy derivative (3) [vs thiophenoxy (4) or phenyl (7)] suggests that B-H bond activation occurs at the Ni-X (vs ligand Ni-Npyrrolide) bond. Furthermore, stoichiometric treatment of 2-7 with a nitrile showed no reaction, whereas stoichiometric reactions of 2-7 with pinacolborane (HBpin) gave the same Ni-H complex for 2, 3, and 5. Considering that only 2, 3, and 5 successfully catalyzed nitrile dihydroboration, we suggest that the catalytic cycle involves a conventional inner sphere pathway initiated by substrate insertion into Ni-H.


Assuntos
Metais , Nitrilas , Ligantes , Modelos Moleculares , Cristalografia por Raios X , Catálise
11.
J Am Chem Soc ; 144(49): 22713-22721, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36469940

RESUMO

Hydrofluoroolefins (HFOs) constitute the newest generation of fluorocarbon refrigerants and foam-blowing agents due to their reduced global warming potential vs their saturated analogues. To identify new synthetic routes to HFOs, we show that reactions of bulky Ni(0) phosphine and -NHC complexes with vinylidene difluoride (VF2) afford µ-fluoro-1,1,3-trifluorobut-3-enyl Ni complexes. Moreover, addition of triisopropylsilane allows for reductive elimination of the reduced product─2,4,4-trifluoro-1-butene─demonstrating the Ni-catalyzed hydrodefluorodimerization of VF2. Accompanying DFT calculations identify the T-shaped nickelacyclopentane intermediate that spontaneously undergoes selective intramolecular ß-F (vs ß-H) elimination.


Assuntos
Níquel , Catálise
12.
Chem Sci ; 13(42): 12550-12559, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36382284

RESUMO

The role of S-donors in ligand-assisted catalysis using first-row metals has not been broadly investigated. Herein is described a combined experimental and computational mechanistic study of the dihydroboration of nitriles with pinacolborane (HBpin) catalyzed by the Mn(i) complex, Mn(κ3-SMeNS)(CO)3, that features thioether, imine, and thiolate donors. Mechanistic studies revealed that catalysis requires the presence of UV light to enter and remain in the catalytic cycle and evidence is presented for loss of two CO ligands. Stoichiometric reactions showed that HBpin reduces the imine N[double bond, length as m-dash]C of the ligand backbone in the absence of nitrile, forming an inactive off-cycle by-product. DFT calculations showed that the bifunctional thiolate donor, coordinative flexibility of the SMeNS ligand, and access to an open-shell intermediate are all crucuial to accessing low-energy intermediates during catalysis.

13.
Chem Commun (Camb) ; 58(59): 8266-8269, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35788228

RESUMO

N-donors are the most commonly employed Lewis bases in ligand-assisted catalysis. A dimeric zinc complex (Zn-1) employing a tetradentate pyridine-thioether-anilido-aryloxide NSNO ligand (L) effects the quantitative conversion of nitriles to the corresponding double hydroborated products at 1 mol% catalyst loading. Variable Time Normalization Analysis kinetic studies showed a first-order dependence with respect to the nitrile, pinacolborane and zinc and clear evidence for catalyst deactivation. A plausible ligand-assisted reaction pathway involves B-H bond activation by the aryloxide (vs. anilido) donor.

14.
J Integr Plant Biol ; 64(8): 1531-1542, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35652263

RESUMO

Arabidopsis MITOGEN-ACTIVATED PROTEIN KINASE3 (MAPK3 or MPK3) and MPK6 play important signaling roles in plant immunity and growth/development. MAPK KINASE4 (MKK4) and MKK5 function redundantly upstream of MPK3 and MPK6 in these processes. YODA (YDA), also known as MAPK KINASE KINASE4 (MAPKKK4), is upstream of MKK4/MKK5 and forms a complete MAPK cascade (YDA-MKK4/MKK5-MPK3/MPK6) in regulating plant growth and development. In plant immunity, MAPKKK3 and MAPKKK5 function redundantly upstream of the same MKK4/MKK5-MPK3/MPK6 module. However, the residual activation of MPK3/MPK6 in the mapkkk3 mapkkk5 double mutant in response to flg22 pathogen-associated molecular pattern (PAMP) treatment suggests the presence of additional MAPKKK(s) in this MAPK cascade in signaling plant immunity. To investigate whether YDA is also involved in plant immunity, we attempted to generate mapkkk3 mapkkk5 yda triple mutants. However, it was not possible to recover one of the double mutant combinations (mapkkk5 yda) or the triple mutant (mapkkk3 mapkkk5 yda) due to a failure of embryogenesis. Using the clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 (Cas9) approach, we generated weak, N-terminal deletion alleles of YDA, yda-del, in a mapkkk3 mapkkk5 background. PAMP-triggered MPK3/MPK6 activation was further reduced in the mapkkk3 mapkkk5 yda-del mutant, and the triple mutant was more susceptible to pathogen infection, suggesting YDA also plays an important role in plant immune signaling. In addition, MAPKKK5 and, to a lesser extent, MAPKKK3 were found to contribute to gamete function and embryogenesis, together with YDA. While the double homozygous mapkkk3 yda mutant showed the same growth and development defects as the yda single mutant, mapkkk5 yda double mutant and mapkkk3 mapkkk5 yda triple mutants were embryo lethal, similar to the mpk3 mpk6 double mutants. These results demonstrate that YDA, MAPKKK3, and MAPKKK5 have overlapping functions upstream of the MKK4/MKK5-MPK3/MPK6 module in both plant immunity and growth/development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , MAP Quinase Quinase Quinase 5/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Moléculas com Motivos Associados a Patógenos/metabolismo , Desenvolvimento Vegetal , Imunidade Vegetal/genética
15.
Biotech Histochem ; 97(8): 604-615, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35394397

RESUMO

Anti-beta-2 glycoprotein 1 (anti-ß2GP1) is an antiphospholipid antibody found in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Its presence commonly is associated with thrombosis; however, the mechanisms of interaction of anti-ß2GP1 antibodies and platelets remain unclear. We investigated the effects of APS and SLE patient-derived IgG fractions on collagen-mediated platelet aggregation and examined the binding of patient-derived IgG to platelets before and after activation by collagen. IgG fractions, 150, 200, 300 or 350 µg/ml, isolated from 11 patients with APS and SLE were incubated with two sets of platelet-rich plasma (PRP) in the incubation wells of an aggregometer. The first set was activated by collagen and the other set was incubated for an additional 10 min. All platelets were collected by centrifugation and fixed in cell blocks. We assessed binding of IgG to platelets using immunocytochemistry (ICC). Patient-derived IgG fractions did not affect collagen-induced platelet aggregation. ICC staining using anti-human IgG antibodies demonstrated that patient-derived IgG fractions had greater affinity for non-activated platelets than those activated by 0.75 µg/ml collagen. Patient-derived IgG fractions bound to the surface of platelets and potentially could be internalized by platelets. IgG fractions from APS and SLE patients may sensitize non-activated platelets, which could increase platelet reactivity and thrombotic risk in patients. We did not detect secondary effects of patient-derived IgG fractions.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , beta 2-Glicoproteína I , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Anticorpos Antifosfolipídeos , Ativação Plaquetária , Imunoglobulina G , Colágeno/farmacologia
16.
Chem Commun (Camb) ; 58(23): 3795-3798, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35234221

RESUMO

Ligands that include Lewis acid/base functionality have extensive applications in bifunctional catalysis using first row metals. In this work, zinc bis(amido), bis(thiolate) and amido-thiolate SNS complexes were prepared and compared as precatalysts for carbonyl hydroboration using pinacolborane. Mechanistic studies revealed two different ligand-assisted precatalyst activation pathways, both leading to an active and robust zinc alkoxide catalyst. This work furthers our understanding of metal-ligand cooperation in first-row metal catalysis.

17.
Nat Plants ; 8(2): 171-180, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35194203

RESUMO

Phloem transport of photoassimilates from leaves to non-photosynthetic organs, such as the root and shoot apices and reproductive organs, is crucial to plant growth and yield. For nearly 90 years, evidence has been generally consistent with the theory of a pressure-flow mechanism of phloem transport. Central to this hypothesis is the loading of osmolytes, principally sugars, into the phloem to generate the osmotic pressure that propels bulk flow. Here we used genetic and light manipulations to test whether sugar import into the phloem is required as the driving force for phloem sap flow. Using carbon-11 radiotracer, we show that a maize sucrose transporter1 (sut1) loss-of-function mutant has severely reduced export of carbon from photosynthetic leaves (only ~4% of the wild type level). Yet, the mutant remarkably maintains phloem pressure at ~100% and sap flow speeds at ~50-75% of those of wild type. Potassium (K+) abundance in the phloem was elevated in sut1 mutant leaves. Fluid dynamic modelling supports the conclusion that increased K+ loading compensated for decreased sucrose loading to maintain phloem pressure, and thereby maintained phloem transport via the pressure-flow mechanism. Furthermore, these results suggest that sap flow and transport of other phloem-mobile nutrients and signalling molecules could be regulated independently of sugar loading into the phloem, potentially influencing carbon-nutrient homoeostasis and the distribution of signalling molecules in plants encountering different environmental conditions.


Assuntos
Floema , Zea mays , Folhas de Planta/genética , Plantas , Açúcares , Zea mays/genética
18.
Eur J Surg Oncol ; 48(11): 2250-2257, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34922810

RESUMO

The pre-operative phase in planning a pelvic exenteration or extended resections is critical to optimising patient outcomes. This review summarises the key components of preoperative assessment and planning in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LLRC) being considered for potential curative resection. The preoperative period can be considered in 5 key phases: 1) Multidisciplinary meeting (MDT) review and recommendation for neoadjuvant therapy and surgery, 2) Anaesthetic preoperative assessment of fitness for surgery and quantification of risk, 3) Shared decision making with the patient and the process of informed consent, 4) Prehabilitation and physiological optimisation 5) Technical aspects of surgical planning. This review will focus on patients who have been recommended for surgery by the MDT and have completed neoadjuvant therapy. Other important considerations beyond the scope of this review are the various neoadjuvant strategies employed which in this patient group include Total Neo-adjuvant Therapy and reirradiation. Critical to improving perioperative outcomes is the dual aim of achieving a negative resection margin in a patient fit enough for extended surgery. Advanced, realistic communication is required pre-operatively and should be maintained throughout recovery. Optimising patient's physiological and psychological reserve with a preoperative prehabilitation programme is important, with physiotherapy, psychological and nutritional input. From a surgical perspective, image based technical preoperative planning is important to identify risk points and ensure correct surgical strategy. Careful attention to the entire patient journey through these 5 preoperative phases can optimise outcomes with the accumulation of marginal gains at multiple timepoints.


Assuntos
Segunda Neoplasia Primária , Exenteração Pélvica , Neoplasias Retais , Humanos , Exenteração Pélvica/métodos , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Neoplasias Retais/cirurgia , Terapia Neoadjuvante , Margens de Excisão , Segunda Neoplasia Primária/cirurgia , Resultado do Tratamento
19.
Dalton Trans ; 50(41): 14542-14546, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34661593

RESUMO

The bifunctional reactivity of three metal SNS (bis)amido complexes was computationally assessed by comparing the nucleophilicity of the M-Namido donor (Mn, Fe, Co). Hirshfeld charges identified the Mn-Namido donor as most nucleophilic and Fe as most electrophilic metal. Reaction energy profiles of a model bifunctional H2 activation showed Mn with the lowest reaction barrier (17 kcal mol-1), followed by Fe and Co (21 and 29 kcal mol-1).

20.
Rev Sci Instrum ; 92(8): 084710, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470408

RESUMO

An insulated-gate bipolar transistor (IGBT) pulse generator for repetitive transcranial magnetic stimulation used for in vivo laboratory experiments on small animals, such as mice, is reported. The pulse generator is based upon an IGBT that can switch 700 A of current for 1 ms and that has a DC breakdown voltage of 1200 V. The duration of the design's output pulse is controlled by, and follows, an input trigger pulse. The voltage amplitude of the output pulses is determined by an external high-voltage power supply and the energy stored in a 330 µF capacitor bank. The approach enables the amplitude of the voltage applied across the coil, the length of time the voltage is applied, and the number of times the voltage pulses are applied all to be controlled and adjusted to facilitate a wide range of experimental options. This paper provides a detailed schematic of the design, design discussions, and some representative experimental results. Additionally, the reported design can be scaled to higher currents by using an IGBT with a higher current rating.


Assuntos
Laboratórios , Estimulação Magnética Transcraniana , Animais , Fontes de Energia Elétrica , Camundongos , Fenômenos Físicos
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