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1.
bioRxiv ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38260313

RESUMO

High spinal cord injury (SCI) leads to persistent and debilitating compromise in respiratory function. Cervical SCI not only causes the death of phrenic motor neurons (PhMNs) that innervate the diaphragm, but also damages descending respiratory pathways originating in the rostral ventral respiratory group (rVRG) located in the brainstem, resulting in denervation and consequent silencing of spared PhMNs located caudal to injury. It is imperative to determine whether interventions targeting rVRG axon growth and respiratory neural circuit reconnection are efficacious in chronic cervical contusion SCI, given that the vast majority of individuals are chronically-injured and most cases of SCI involve contusion-type damage to the cervical region. We therefore employed a clinically-relevant rat model of chronic cervical hemicontusion to test therapeutic manipulations aimed at reconstructing damaged rVRG-PhMN-diaphragm circuitry to achieve recovery of respiratory function. At a chronic time point post-injury, we systemically administered: an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential; an antagonist peptide directed against receptor-type protein tyrosine phosphatase sigma (PTPσ), another important negative regulator of axon growth capacity; or a combination of these two peptides. PTEN antagonist peptide (PAP4) promoted partial recovery of diaphragm motor activity out to nine months post-injury, while PTPσ peptide did not impact diaphragm function after cervical SCI. Furthermore, PAP4 promoted robust growth of descending bulbospinal rVRG axons caudal to the injury within the denervated portion of the PhMN pool, while PTPσ peptide did not affect rVRG axon growth at this location that is critical to control of diaphragmatic respiratory function. In conclusion, we find that, when PTEN inhibition is targeted at a chronic time point following cervical contusion that is most relevant to the SCI clinical population, our non-invasive PAP4 strategy can successfully promote significant regrowth of damaged respiratory neural circuitry and also partial recovery of diaphragm motor function. HIGHLIGHTS: PTEN antagonist peptide promotes partial diaphragm function recovery in chronic cervical contusion SCI.PTPσ inhibitory peptide does not impact diaphragm function recovery in chronic cervical contusion SCI.PTEN antagonist peptide promotes growth of bulbospinal rVRG axons in chronic cervical contusion SCI.PTPσ peptide does not affect rVRG axon growth in chronic cervical contusion SCI.

2.
Am J Dermatopathol ; 46(2): 111-113, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38055960

RESUMO

ABSTRACT: Coccidiomycosis is an infectious primary pulmonary disease caused by two highly virulent fungi, Coccidioides immitis and C. Posadasii. Coccidioides spp. are endemic to the southwestern USA, Central America, and South America with infection predominating in the summer and fall seasons. The disease commonly presents with flu-like symptoms. Cutaneous manifestations are rare and are a sign of a more serious infection with poorer outcomes. In this case, a 60-year-old female presented to the dermatology clinic with a 3-month history of a mild, non-pruritic, erythematous rash located on her proximal arms and legs. Two punch biopsies were obtained, and she was found to have a non-endemic case of disseminated coccidiomycosis.


Assuntos
Coccidioidomicose , Micoses , Humanos , Feminino , Pessoa de Meia-Idade , Coccidioidomicose/diagnóstico , Coccidioidomicose/tratamento farmacológico , Coccidioides , Pele , América do Sul/epidemiologia
3.
Foot Ankle Orthop ; 8(3): 24730114231193402, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37566696

RESUMO

Congenital dislocation of the fifth metatarsophalangeal (MTP) joint can cause significant limitations in a patient's ability to wear a closed shoe. Historic treatment has involved amputation of the digit or attempts at reconstruction. These techniques have had limited success with unreliable correction and/or unacceptable cosmesis. The authors present a detailed, methodical approach to reconstruction of this deformity with a stepwise algorithm that addresses both the bony and soft tissue components of the deformity. With this modern technique, reliable and satisfactory results can be expected.

4.
bioRxiv ; 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37034676

RESUMO

Development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. Current strategies for developing pan-coronavirus countermeasures have largely focused on the receptor binding domain (RBD) and S2 regions of the coronavirus Spike protein; it has been unclear whether the N-terminal domain (NTD) is a viable target for universal vaccines and broadly neutralizing antibodies (Abs). Additionally, many RBD-targeting Abs have proven susceptible to viral escape. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees using multiplexed panels of uniquely barcoded antigens in a high-throughput single cell workflow to isolate over 9,000 SARS-CoV-2-specific monoclonal Abs (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. We observed many instances of clonal coalescence between individuals, suggesting that Ab responses frequently converge independently on similar genetic solutions. Among the recovered antibodies was TXG-0078, a public neutralizing mAb that binds the NTD supersite region of the coronavirus Spike protein and recognizes a diverse collection of alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy chain-dominant binding pattern seen in other NTD supersite-specific neutralizing Abs with much narrower specificity. We also report the discovery of CC24.2, a pan-sarbecovirus neutralizing mAb that targets a novel RBD epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 provides protection against in vivo challenge with SARS-CoV-2, suggesting potential future use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.

5.
Microorganisms ; 11(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36838305

RESUMO

Rodents and bats are the most diverse mammal group that host Bartonella species. In the Americas, they were described as harboring Bartonella species; however, they were mostly characterized to the genotypic level. We describe here Bartonella isolates obtained from blood samples of one rodent (Peromyscus yucatanicus from San José Pibtuch, Yucatan) and two bat species (Desmodus rotundus from Progreso, and Pteronotus parnellii from Chamela-Cuitzmala) from Mexico. We sequenced and described the genomic features of three Bartonella strains and performed phylogenomic and pangenome analyses to decipher their phylogenetic relationships. The mouse-associated genome was closely related to Bartonella vinsonii. The two bat-associated genomes clustered into a single distinct clade in between lineages 3 and 4, suggesting to be an ancestor of the rodent-associated Bartonella clade (lineage 4). These three genomes showed <95% OrthoANI values compared to any other Bartonella genome, and therefore should be considered as novel species. In addition, our analyses suggest that the B. vinsonii complex should be revised, and all B. vinsonii subspecies need to be renamed and considered as full species. The phylogenomic clustering of the bat-associated Bartonella strains and their virulence factor profile (lack of the Vbh/TraG conjugation system remains of the T4SS) suggest that it should be considered as a new lineage clade (L5) within the Bartonella genus.

6.
PLoS Biol ; 21(1): e3001958, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36603052

RESUMO

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.


Assuntos
Gânglios Espinais , Nociceptividade , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Gânglios Espinais/fisiologia , Sistema Nervoso Central , Dor , Ácido gama-Aminobutírico
7.
Nature ; 611(7935): 352-357, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36289331

RESUMO

The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies that bind particular antigens1. In most mammals, antibodies are composed of heavy and light chains that are generated sequentially by recombination of V, D (for heavy chains), J and C gene segments. Each chain contains three complementarity-determining regions (CDR1-CDR3), which contribute to antigen specificity. Certain heavy and light chains are preferred for particular antigens2-22. Here we consider pairs of B cells that share the same heavy chain V gene and CDRH3 amino acid sequence and were isolated from different donors, also known as public clonotypes23,24. We show that for naive antibodies (those not yet adapted to antigens), the probability that they use the same light chain V gene is around 10%, whereas for memory (functional) antibodies, it is around 80%, even if only one cell per clonotype is used. This property of functional antibodies is a phenomenon that we call light chain coherence. We also observe this phenomenon when similar heavy chains recur within a donor. Thus, although naive antibodies seem to recur by chance, the recurrence of functional antibodies reveals surprising constraint and determinism in the processes of V(D)J recombination and immune selection. For most functional antibodies, the heavy chain determines the light chain.


Assuntos
Anticorpos , Seleção Clonal Mediada por Antígeno , Cadeias Pesadas de Imunoglobulinas , Cadeias Leves de Imunoglobulina , Animais , Sequência de Aminoácidos , Anticorpos/química , Anticorpos/genética , Anticorpos/imunologia , Antígenos/química , Antígenos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/imunologia , Cadeias Pesadas de Imunoglobulinas/química , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Mamíferos , Cadeias Leves de Imunoglobulina/química , Cadeias Leves de Imunoglobulina/genética , Cadeias Leves de Imunoglobulina/imunologia , Memória Imunológica , Recombinação V(D)J , Seleção Clonal Mediada por Antígeno/genética , Seleção Clonal Mediada por Antígeno/imunologia
8.
Pediatrics ; 150(4)2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36097858

RESUMO

It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis. OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results. METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results. RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL. CONCLUSIONS: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making.


Assuntos
Bacteriemia , Infecções Bacterianas , Meningites Bacterianas , Infecções Urinárias , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Infecções Bacterianas/complicações , Criança , Febre/complicações , Febre/diagnóstico , Febre/epidemiologia , Humanos , Lactente , Meningites Bacterianas/complicações , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/epidemiologia , Pró-Calcitonina , Urinálise , Infecções Urinárias/epidemiologia
9.
Foot Ankle Surg ; 28(8): 1345-1349, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35810126

RESUMO

BACKGROUND: Proximal interphalangeal (PIP) joint fusion with Kirschner (K) -wire fixation remains a popular strategy for hammertoe correction. This study was performed to evaluate the effect of length of wire fixation on clinical outcomes. METHODS: A retrospective review of all hammertoe reconstructions by a single surgeon was performed. Wire length was chosen at the surgeon's discretion. Outcomes were assessed with metatarsophalangeal (MTP) congruency, pin complications, and PIP union. RESULTS: 157 toes underwent reconstruction. Seventy had wires that spanned the MTP and 87 that did not. Wire breaks were significantly more common with longer wire fixation (P = .024). MTP incongruency was significantly more common in the MTP group (P = .014). CONCLUSION: Pin breakage was rare and only occurred in the MTP group. MTP incongruence was significantly more common in the MTP group but may not reflect surgical technique. PIP union was more common with longer wire fixation but is not clinically significant. LEVEL OF EVIDENCE: III.


Assuntos
Síndrome do Dedo do Pé em Martelo , Humanos , Síndrome do Dedo do Pé em Martelo/cirurgia , Fios Ortopédicos , Artrodese/métodos , Estudos Retrospectivos
10.
J Vis Exp ; (184)2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35758711

RESUMO

Mitochondria play an important role in cellular ATP production, reactive oxygen species regulation, and Ca2+ concentration control. Mitochondrial dysfunction has been implicated in the pathogenesis of multiple neurodegenerative diseases, including Parkinson's disease (PD), Huntington's disease, and Alzheimer's disease. To study the role of mitochondria in models of these diseases, we can measure mitochondrial respiration via oxygen consumption rate (OCR) as a proxy for mitochondrial function. OCR has already been successfully measured in cell cultures, as well as isolated mitochondria. However, these techniques are less physiologically relevant than measuring OCR in acute brain slices. To overcome this limitation, the authors developed a new method using a Seahorse XF analyzer to directly measure the OCR in acute striatal slices from adult mice. The technique is optimized with a focus on the striatum, a brain area involved in PD and Huntington's disease. The analyzer performs a live cell assay using a 24-well plate, which allows the simultaneous kinetic measurement of 24 samples. The method uses circular-punched pieces of striatal brain slices as samples. We demonstrate the effectiveness of this technique by identifying a lower basal OCR in striatal slices of a mouse model of PD. This method will be of broad interest to researchers working in the field of PD and Huntington's disease.


Assuntos
Doença de Huntington , Animais , Corpo Estriado/metabolismo , Doença de Huntington/metabolismo , Camundongos , Mitocôndrias/metabolismo , Consumo de Oxigênio/fisiologia , Espécies Reativas de Oxigênio/metabolismo
11.
Cells ; 11(4)2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35203371

RESUMO

There is growing appreciation for astrocyte heterogeneity both across and within central nervous system (CNS) regions, as well as between intact and diseased states. Recent work identified multiple astrocyte subpopulations in mature brain. Interestingly, one subpopulation (Population C) was shown to possess significantly enhanced synaptogenic properties in vitro, as compared with other astrocyte subpopulations of adult cortex and spinal cord. Following spinal cord injury (SCI), damaged neurons lose synaptic connections with neuronal partners, resulting in persistent functional loss. We determined whether SCI induces an enhanced synaptomodulatory astrocyte phenotype by shifting toward a greater proportion of Population C cells and/or increasing expression of relevant synapse formation-associated genes within one or more astrocyte subpopulations. Using flow cytometry and RNAscope in situ hybridization, we found that astrocyte subpopulation distribution in the spinal cord did not change to a selectively synaptogenic phenotype following mouse cervical hemisection-type SCI. We also found that spinal cord astrocytes expressed synapse formation-associated genes to a similar degree across subpopulations, as well as in an unchanged manner between uninjured and SCI conditions. Finally, we confirmed these astrocyte subpopulations are also present in the human spinal cord in a similar distribution as mouse, suggesting possible conservation of spinal cord astrocyte heterogeneity across species.


Assuntos
Astrócitos , Traumatismos da Medula Espinal , Animais , Astrócitos/metabolismo , Camundongos , Neurogênese , Neurônios/metabolismo , Traumatismos da Medula Espinal/metabolismo
12.
J Orthop ; 25: 88-92, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994704

RESUMO

For septic arthritis of the knee, we attempted to determine: the preferred surgical technique in the United-States (US), the believed "gold-standard" treatment among others. This was performed by an electronic-survey distributed to all academic orthopaedic faculty throughout the US. The preferred method was arthroscopy (69.8%). Arthroscopy is believed to be the gold-standard in 27.0%, arthrotomy in 29.4%, while 43.5% believe no gold-standard exists. In conclusion the majority of surgeons prefer arthroscopy when managing a native, septic knee in an adult patient. However, there is no national consensus on a gold-standard treatment or the role of synovectomy.

13.
Foot Ankle Int ; 42(5): 527-535, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33554643

RESUMO

BACKGROUND: Total ankle arthroplasty (TAA) is advocated over ankle arthrodesis to preserve ankle motion (ROM). Clinical and gait analysis studies have shown significant improvement after TAA. The role and outcomes of TAA in stiff ankles, which have little motion to be preserved, has been the subject of limited investigation. This investigation evaluated the mid- to long-term functional outcomes of TAA in stiff ankles. METHODS: A retrospective study of prospectively collected functional gait data in 33 TAA patients at a mean of 7.6 (5-13) years postoperatively used 1-way analysis of variance and multivariate regression analysis to compare among preoperative and postoperative demographic data (age, gender, body mass index, years postsurgery, and diagnosis) and gait parameters according to quartiles of preoperative sagittal ROM. RESULTS: The stiffest ankles had a mean ROM of 7.8 degrees, compared to 14.3 degrees for the middle 2 quartiles, and 21.0 degrees for the most flexible ankles. Patients in the lowest quartile (Q1) also had statistically significantly lower step length, speed, max plantarflexion, and power preoperatively. Postoperatively, they increased step length, speed, max plantarflexion, and ankle power to levels comparable to patients with more flexible ankles preoperatively (Q2, Q3, and Q4). They had the greatest absolute and relative increases in these parameters of any group, but the final total ROM was still statistically significantly the lowest. CONCLUSION: Preoperative ROM was predictive of overall postoperative gait function at an average of 7.6 (range 5-13) years. Although greater preoperative sagittal ROM predicted greater postoperative ROM, the stiffest ankles showed the greatest percentage increase in ROM. Patients with the stiffest ankles had the greatest absolute and relative improvements in objective function after TAA, as measured by multiple gait parameters. At intermediate- to long-term follow-up, patients with stiff ankles maintained significant functional improvements after TAA. LEVEL OF EVIDENCE: Level III, comparative study.


Assuntos
Tornozelo , Artroplastia de Substituição do Tornozelo , Articulação do Tornozelo/cirurgia , Humanos , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
14.
Pediatr Emerg Care ; 37(5): e221-e226, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32701869

RESUMO

OBJECTIVE: Few prospective studies have assessed the occurrence of radiographic pneumonia in young febrile infants. We analyzed factors associated with radiographic pneumonias in febrile infants 60 days or younger evaluated in pediatric emergency departments. STUDY DESIGN: We conducted a planned secondary analysis of a prospective cohort study within 26 emergency departments in a pediatric research network from 2008 to 2013. Febrile (≥38°C) infants 60 days or younger who received chest radiographs were included. Chest radiograph reports were categorized as "no," "possible," or "definite" pneumonia. We compared demographics, Yale Observation Scale scores (>10 implying ill appearance), laboratory markers, blood cultures, and viral testing among groups. RESULTS: Of 4778 infants, 1724 (36.1%) had chest radiographs performed; 2.7% (n = 46) had definite pneumonias, and 3.9% (n = 67) had possible pneumonias. Patients with definite (13/46 [28.3%]) or possible (15/67 [22.7%]) pneumonias more frequently had Yale Observation Scale score >10 compared with those without pneumonias (210/1611 [13.2%], P = 0.002) in univariable and multivariable analyses. Median white blood cell count (WBC), absolute neutrophil count (ANC), and procalcitonin (PCT) were higher in the definite (WBC, 11.5 [interquartile range, 9.8-15.5]; ANC, 5.0 [3.2-7.6]; PCT, 0.4 [0.2-2.1]) versus no pneumonia (WBC, 10.0 [7.6-13.3]; ANC, 3.4 [2.1-5.4]; PCT, 0.2 [0.2-0.3]; WBC, P = 0.006; ANC, P = 0.002; PCT, P = 0.046) groups, but of unclear clinical significance. There were no cases of bacteremia in the definite pneumonia group. Viral infections were more frequent in groups with definite (25/38 [65.8%]) and possible (28/55 [50.9%]) pneumonias than no pneumonias (534/1185 [45.1%], P = 0.02). CONCLUSIONS: Radiographic pneumonias were uncommon, often had viruses detected, and were associated with ill appearance, but few other predictors, in febrile infants 60 days or younger.


Assuntos
Bacteriemia , Pneumonia , Biomarcadores , Febre/etiologia , Humanos , Lactente , Contagem de Leucócitos , Pneumonia/diagnóstico por imagem , Estudos Prospectivos
15.
Cell ; 183(7): 1986-2002.e26, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33333022

RESUMO

Serotonin plays a central role in cognition and is the target of most pharmaceuticals for psychiatric disorders. Existing drugs have limited efficacy; creation of improved versions will require better understanding of serotonergic circuitry, which has been hampered by our inability to monitor serotonin release and transport with high spatial and temporal resolution. We developed and applied a binding-pocket redesign strategy, guided by machine learning, to create a high-performance, soluble, fluorescent serotonin sensor (iSeroSnFR), enabling optical detection of millisecond-scale serotonin transients. We demonstrate that iSeroSnFR can be used to detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep/wake transitions. We also developed a robust assay of serotonin transporter function and modulation by drugs. We expect that both machine-learning-guided binding-pocket redesign and iSeroSnFR will have broad utility for the development of other sensors and in vitro and in vivo serotonin detection, respectively.


Assuntos
Evolução Molecular Direcionada , Aprendizado de Máquina , Serotonina/metabolismo , Algoritmos , Sequência de Aminoácidos , Tonsila do Cerebelo/fisiologia , Animais , Comportamento Animal , Sítios de Ligação , Encéfalo/metabolismo , Células HEK293 , Humanos , Cinética , Modelos Lineares , Camundongos , Camundongos Endogâmicos C57BL , Fótons , Ligação Proteica , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Sono/fisiologia , Vigília/fisiologia
16.
Pediatr Emerg Care ; 36(12): e671-e676, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33181793

RESUMO

STUDY OBJECTIVE: To estimate the minimum dose and total sedation time of rapidly infused ketamine that achieves 3 to 5 minutes of effective sedation in children undergoing abscess incision and drainage in the emergency department. METHODS: The Up-Down method was used to estimate the dose of intravenous ketamine infused over 5 seconds or less that provided effective sedation in 50% (ED50) and 95% (ED95) for healthy children aged 2 to 5 years and 6 to 11 years undergoing abscess incision and drainage. None were pretreated with opioids. Three investigators blinded to ketamine dose independently graded sedation effectiveness by viewing a video recording of the first 5 minutes of sedation. Recovery was determined when patients reached a Modified Aldrete score of 10. RESULTS: We enrolled 20 children in each age group. The estimated ED50 was 0.9 and 0.6 mg/kg for the 2 to 5 years and 6 to 11 years' groups and the estimated ED95 was 1.1 mg/kg for both groups. The median time to full recovery for the 2 groups was 20.5 and 17.5 minutes when only 1 dose of ketamine was administered and 27.5 and 35 minutes when additional doses of ketamine were administered. No participants experienced serious adverse events. CONCLUSIONS: We estimated ED50 and ED95 for rapidly infused ketamine for 2 age groups undergoing abscess incision and drainage. Further studies are needed to get a more precise estimate of ED95. The total sedation time with this technique in the abscess group was shorter than most previous studies and is consistent with our previous observations in patients undergoing fracture reduction.


Assuntos
Abscesso/cirurgia , Anestésicos Dissociativos , Drenagem , Ketamina , Anestésicos Dissociativos/administração & dosagem , Criança , Pré-Escolar , Sedação Consciente , Humanos , Ketamina/administração & dosagem
17.
Exp Neurol ; 334: 113468, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32966805

RESUMO

A major portion of individuals affected by traumatic spinal cord injury (SCI) experience one or more types of chronic neuropathic pain (NP), which is often intractable to currently available treatments. The availability of reliable behavioral assays in pre-clinical models of SCI-induced NP is therefore critical to assess the efficacy of new potential therapies. Commonly used assays to evaluate NP-related behavior in rodents, such as Hargreaves thermal and von Frey mechanical testing, rely on the withdrawal response to an evoked stimulus. However, other assays that test spontaneous/non-evoked NP-related behavior or supraspinal aspects of NP would be highly useful for a more comprehensive assessment of NP following SCI. The Mouse Grimace Scale (MGS) is a tool to assess spontaneous, supraspinal pain-like behaviors in mice; however, the assay has not been characterized in a mouse model of SCI-induced chronic NP, despite the critical importance of mouse genetics as an experimental tool. We found that beginning 2 weeks after cervical contusion, SCI mice exhibited increased facial grimace features compared to laminectomy-only control mice, and this grimace phenotype persisted to the chronic time point of 5 weeks post-injury. We also found a significant relationship between facial grimace score and the evoked forepaw withdrawal response in both the Hargreaves and von Frey tests at 5 weeks post-injury when both laminectomy-only and SCI mice were included in the analysis. However, within only the SCI group, there was no correlation between grimace score and Hargreaves or von Frey responses. These results indicate both that facial grimace analysis can be used as an assay of spontaneous NP-related behavior in the mouse model of SCI and that the information provided by the MGS may be different than that provided by evoked tests of sensory function.


Assuntos
Expressão Facial , Neuralgia/psicologia , Medição da Dor/métodos , Medição da Dor/psicologia , Traumatismos da Medula Espinal/psicologia , Animais , Vértebras Cervicais/lesões , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/etiologia , Neuralgia/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia
18.
Dis Esophagus ; 33(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32448896

RESUMO

Given their malignant potential, resection of esophageal granular cell tumors (GCTs) is often undertaken, yet the optimal technique is unknown. We present a large series of dedicated endoscopic resection using band ligation (EMR-B) of esophageal GCTs. Patients diagnosed with esophageal GCTs between 2002 and 2019 were identified using a prospectively collected pathology database. Endoscopic reports were reviewed, and patients who underwent dedicated EMR-B of esophageal GCTs were included. Medical records were queried for demographics, findings, adverse events, and follow-up. We identified 21 patients who underwent dedicated EMR-B for previously identified esophageal GCT. Median age was 39 years; 16 (76%) were female. Eight (38%) had preceding signs or symptoms, potentially attributable to the GCT. Upon endoscopic evaluation, 12 (57%) were found in the distal esophagus. Endoscopic ultrasound was used in 15 cases (71%). Median lesion size was 7 mm, interquartile range 4 mm-8 mm. The largest lesion was 12 mm. A total of 20 (95%) had en bloc resection confirmed with pathologic examination. The only patient with tumor extending to the resection margin underwent surveillance endoscopy that showed no residual tumor. No patients experienced bleeding, perforation, or stricturing in our series. No patients have had known recurrence of their esophageal GCT. EMR-B of esophageal GCT achieves complete histopathologic resection with minimal adverse events. EMR-B is safe and effective and seems prudent compared with observation for what could be an aggressive and malignant tumor. EMR-B should be considered first-line therapy when resecting esophageal GCT up to 12 mm in diameter.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Tumor de Células Granulares , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Esofágicas/cirurgia , Feminino , Tumor de Células Granulares/diagnóstico por imagem , Tumor de Células Granulares/cirurgia , Humanos , Recém-Nascido , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
19.
Acad Emerg Med ; 27(9): 866-875, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32159909

RESUMO

OBJECTIVES: Computed tomography (CT), the reference standard for diagnosis of intraabdominal injury (IAI), carries risk including ionizing radiation. CT-sparing clinical decision rules for children have relied heavily on physical examination, but they did not include focused assessment with sonography for trauma (FAST), which has emerged into widespread use during the past decade. We sought to determine the independent associations of physical examination, laboratory studies, and FAST with identification of IAI in children and to compare the test characteristics of these diagnostic variables. We hypothesized that FAST may add incremental utility to a physical examination alone to more accurately identify children who could forgo CT scan. METHODS: We reviewed a large trauma database of all children with blunt torso trauma presenting to a freestanding pediatric emergency department during a 20-month period. We used logistic regression to evaluate the association of FAST, physical examination, and selected laboratory data with IAI in children, and we compared the test characteristics of these variables. RESULTS: Among 354 children, 50 (14%) had IAI. Positive FAST (odds ratio [OR] = 14.8, 95% confidence interval [CI] = 7.5 to 30.8) and positive physical examination (OR = 15.2, 95% CI = 7.7 to 31.7) were identified as independent predictors for IAI. Physical examination and FAST each had sensitivities of 74% (95% CI = 60% to 85%). Combining FAST and physical examination as FAST-enhanced physical examination (exFAST) improved sensitivity and negative predictive value (NPV) over either test alone (sensitivity = 88%, 95% CI = 76% to 96%) and NPV of 97.3% (95% CI = 94.5% to 98.7%). CONCLUSIONS: In children, FAST and physical examinations each predicted the identification of IAI. However, the combination of the two (exFAST) had greater sensitivity and NPV than either physical examination or FAST alone. This supports the use of exFAST in refining clinical predication rules in children with blunt torso trauma.


Assuntos
Traumatismos Abdominais , Avaliação Sonográfica Focada no Trauma , Ferimentos não Penetrantes , Traumatismos Abdominais/diagnóstico por imagem , Criança , Humanos , Exame Físico , Estudos Retrospectivos , Sensibilidade e Especificidade , Tronco , Ferimentos não Penetrantes/diagnóstico por imagem
20.
Acta Trop ; 205: 105277, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32035056

RESUMO

Dogs can be infected by a wide range of Bartonella spp., but studies regarding the prevalence of Bartonella infection in dogs in the Philippines have not been conducted. This study aimed at determining the prevalence of Bartonella infection in pets dogs from two veterinary clinics in Metro Manila, The Philippines, using both serology and polymerase chain reaction (PCR). Blood samples from 116 dogs from two different groups, one of 60 mainly "healthy dogs" and the other one of 56 dogs enrolled in a tick-borne disease suspect group, were tested for presence of B. henselae antibodies and to detect Bartonella DNA using primers specific for the citrate synthase gene. Seroprevalence for B. henselae was very low (2.6%), as the only three (5%) seropositive dogs (titer 1:64) where among the healthy pet dog group. Following subsequent sequencing, 13 samples, all from the tick-borne disease group, were determined positive for B. henselae (11.2%). This is the first study to report dog infection with B. henselae in the Philippines.


Assuntos
Infecções por Bartonella/veterinária , Doenças do Cão/epidemiologia , Animais de Estimação/microbiologia , Animais , Infecções por Bartonella/epidemiologia , Cães , Feminino , Masculino , Filipinas/epidemiologia , Prevalência , Estudos Soroepidemiológicos , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/veterinária
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