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2.
J Am Chem Soc ; 146(18): 12808-12818, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38668701

RESUMEN

The surface chemistry of colloidal semiconductor nanocrystals (QDs) profoundly influences their physical and chemical attributes. The insulating organic shell ensuring colloidal stability impedes charge transfer, thus limiting optoelectronic applications. Exchanging these ligands with shorter inorganic ones enhances charge mobility and stability, which is pivotal for using these materials as active layers for LEDs, photodetectors, and transistors. Among those, InP QDs also serve as a model for surface chemistry investigations. This study focuses on group III metal salts as inorganic ligands for InP QDs. We explored the ligand exchange mechanism when metal halide, nitrate, and perchlorate salts of group III (Al, In Ga), common Lewis acids, are used as ligands for the conductive inks. Moreover, we compared the exchange mechanism for two starting model systems: InP QDs capped with myristate and oleylamine as X- and L-type native organic ligands, respectively. We found that all metal halide, nitrate, and perchlorate salts dissolved in polar solvents (such as n-methylformamide, dimethylformamide, dimethyl sulfoxide, H2O) with various polarity formed metal-solvent complex cations [M(Solvent)6]3+ (e.g., [Al(MFA)6]3+, [Ga(MFA)6]3+, [In(MFA)6]3+), which passivated the surface of InP QDs after the removal of the initial organic ligand. All metal halide capped InP/[M(Solvent)6]3+ QDs show excellent colloidal stability in polar solvents with high dielectric constant even after 6 months in concentrations up to 74 mg/mL. Our findings demonstrate the dominance of dissociation-complexation mechanisms in polar solvents, ensuring colloidal stability. This comprehensive understanding of InP QD surface chemistry paves the way for exploring more complex QD systems such as InAs and InSb QDs.

3.
Med Phys ; 50(12): 7904-7920, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37418478

RESUMEN

BACKGROUND: Accuracy of electrode placement for deep brain stimulation (DBS) is critical to achieving desired surgical outcomes and impacts the efficacy of treating neurodegenerative diseases. Intraoperative brain shift degrades the accuracy of surgical navigation based on preoperative images. PURPOSE: We extended a model-based image updating scheme to address intraoperative brain shift in DBS surgery and improved its accuracy in deep brain. METHODS: We evaluated 10 patients, retrospectively, who underwent bilateral DBS surgery and classified them into groups of large and small deformation based on a 2 mm subsurface movement threshold and brain shift index of 5%. In each case, sparse brain deformation data were used to estimate whole brain displacements and deform preoperative CT (preCT) to generate updated CT (uCT). Accuracy of uCT was assessed using target registration errors (TREs) at the Anterior Commissure (AC), Posterior Commissure (PC), and four calcification points in the sub-ventricular area by comparing their locations in uCT with their ground truth counterparts in postoperative CT (postCT). RESULTS: In the large deformation group, TREs were reduced from 2.5 mm in preCT to 1.2 mm in uCT (53% compensation); in the small deformation group, errors were reduced from 1.25 to 0.74 mm (41%). Average reduction of TREs at AC, PC and pineal gland were significant, statistically (p ⩽ 0.01). CONCLUSIONS: With more rigorous validation of model results, this study confirms the feasibility of improving the accuracy of model-based image updating in compensating for intraoperative brain shift during DBS procedures by assimilating deep brain sparse data.


Asunto(s)
Estimulación Encefálica Profunda , Cirugía Asistida por Computador , Humanos , Estimulación Encefálica Profunda/métodos , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Electrodos Implantados
4.
Cancers (Basel) ; 15(13)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37444542

RESUMEN

Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential.

5.
Artículo en Inglés | MEDLINE | ID: mdl-37009434

RESUMEN

Iatrogenic nerve injury is a common complication across all surgical specialties. Better nerve visualization and identification during surgery will improve outcomes and reduce nerve injuries. The Gibbs Laboratory at Oregon Health and Science University has developed a library of near-infrared, nerve-specific fluorophores to highlight nerves intraoperatively and aid surgeons in nerve identification and visualization; the current lead agent is LGW16-03. Prior to this study, testing of LGW16-03 was restricted to animal models; therefore, it was unknown how LGW16-03 performs in human tissue. To advance LGW16-03 to clinic, we sought to test this current lead agent in ex vivo human tissues from a cohort of patients and determine if the route of administration affects LGW16-03 fluorescence contrast between nerves and adjacent background tissues (muscle and adipose). LGW16-03 was applied to ex vivo human tissue from lower limb amputations via two strategies: (1) systemic administration of the fluorophore using our first-in-kind model for fluorophore testing, and (2) topical application of the fluorophore. Results showed no statistical difference between topical and systemic administration. However, in vivo human validation of these findings is required.

6.
Cureus ; 15(2): e34679, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36909033

RESUMEN

INTRODUCTION:  In the United States (U.S.), African Americans and other minority groups have longer wait times for kidney transplantation than Caucasians. To date, many studies analyzing time spent on the waitlist for each race/ethnicity have been done. However, there are few to no studies examining waitlist time after the 2019 policy changes to the geographic distribution of donated kidneys. METHODS: Data collected from the National Organ Procurement and Transplantation Network database were used to analyze associations between race and time spent on the waitlist for a kidney transplant in the U.S. Additional sub-categorical data were analyzed to determine further associations and potential covariates, such as gender, age, citizenship, primary source of payment, region of transplant center, BMI, Kidney Donor Profile Index (KDPI), renal diagnosis, and presence/type of diabetes. Data were analyzed using odds ratios and validated by Bonferroni-Holm's corrected chi-square tests at confidence intervals of 95% to determine if there are statistically significant differences between transplant time spent on the waitlist and ethnicity, as well as age, diagnosis category, region of transplant center, and KDPI. RESULTS: Statistically significant increased odds of remaining on the transplant list at two years existed for all non-white races/ethnicities, except those identifying as multiracial. Asian American candidates had the greatest odds of remaining on the waitlist greater than two years in comparison to white candidates: 1.51 times that of a patient categorized as white (odds ratio [OR] 1.51, confidence interval [CI] 1.44-1.57). African American/Black, (OR 1.38, CI 1.34-1.43) Pacific Islander (OR 1.38, CI 1.17-1.63), Hispanic candidates (OR 1.37, CI 1.32-1.41), and American Indian or Native Alaskan candidates (OR 1.23, CI 1.12-1.46) also had increased odds of remaining on the transplant waitlist greater than two years compared to white candidates. DISCUSSION: In this study, ethnic disparities persisted as a barrier for non-white individuals receiving treatment for end-stage kidney disease, specifically in the context of time spent on the waitlist for a kidney transplant. Further research is needed regarding the causes of these disparities in time spent on the waitlist, such as cultural restrictions in organ donation, racial differences in parameters for organ match, and institutionalized racism in health care practitioners.

7.
Neurosurgery ; 92(1): 186-194, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36255216

RESUMEN

BACKGROUND: Direct cortical stimulation of the mesial frontal premotor cortex, including the supplementary motor area (SMA), is challenging in humans. Limited access to these brain regions impedes understanding of human premotor cortex functional organization and somatotopy. OBJECTIVE: To test whether seizure onset within the SMA was associated with functional remapping of mesial frontal premotor areas in a cohort of patients with epilepsy who underwent awake brain mapping after implantation of interhemispheric subdural electrodes. METHODS: Stimulation trials from 646 interhemispheric subdural electrodes were analyzed and compared between patients who had seizure onset in the SMA (n = 13) vs patients who had seizure onset outside of the SMA (n = 12). 1:1 matching with replacement between SMA and non-SMA data sets was used to ensure similar spatial distribution of electrodes. Centroids and 95% confidence regions were computed for clustered head, trunk, upper extremity, lower extremity, and vision responses. A generalized linear mixed-effects model was used to test for significant differences in the resulting functional maps. Clinical, radiographic, and histopathologic data were reviewed. RESULTS: After analyzing direct cortical stimulation trials from interhemispheric electrodes, we found significant displacement of the head and trunk responses in SMA compared with non-SMA patients ( P < .01 for both). These differences remained significant after accounting for structural lesions, preexisting motor deficits, and seizure outcome. CONCLUSION: The somatotopy of the mesial frontal premotor regions is significantly altered in patients who have SMA-onset seizures compared with patients who have seizure onset outside of the SMA, suggesting that functional remapping can occur in these brain regions.


Asunto(s)
Epilepsia , Corteza Motora , Humanos , Convulsiones/cirugía , Mapeo Encefálico/métodos , Encéfalo
8.
J Neurosurg ; 138(1): 261-269, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35523259

RESUMEN

The New England Neurosurgical Society (NENS) was founded in 1951 under the leadership of its first President (Dr. William Beecher Scoville) and Secretary-Treasurer (Dr. Henry Thomas Ballantine). The purpose of creating the NENS was to unite local neurosurgeons in the New England area; it was one of the first regional neurosurgical societies in America. Although regional neurosurgical societies are important supplements to national organizations, they have often been overshadowed in the available literature. Now in its 70th year, the NENS continues to serve as a platform to represent the needs of New England neurosurgeons, foster connections and networks with colleagues, and provide research and educational opportunities for trainees. Additionally, regional societies enable discussion of issues uniquely relevant to the region, improve referral patterns, and allow for easier attendance with geographic proximity. In this paper, the authors describe the history of the NENS and provide a roadmap for its future. The first section portrays the founders who led the first meetings and establishment of the NENS. The second section describes the early years of the NENS and profiles key leaders. The third section discusses subsequent neurosurgeons who steered the NENS and partnerships with other societies. In the fourth section, the modern era of the NENS and its current activities are highlighted.


Asunto(s)
Neurocirugia , Sociedades Médicas , Humanos , Liderazgo , Neurocirujanos , Neurocirugia/historia , New England , Derivación y Consulta , Sociedades Médicas/historia , Sociedades Médicas/organización & administración , Historia del Siglo XX , Historia del Siglo XXI
9.
J Gen Intern Med ; 38(1): 30-35, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35556213

RESUMEN

BACKGROUND: Security emergency responses (SERs) are utilized by hospitals to ensure the safety of patients and staff but can cause unintended morbidity. The presence of racial and ethnic inequities in SER utilization has not been clearly elucidated. OBJECTIVE: To determine whether Black and Hispanic patients experience higher rates of SER and physical restraints in a non-psychiatric inpatient setting. DESIGN: Retrospective cohort study. PARTICIPANTS: All patients discharged from September 2018 through December 2019. EXPOSURE: Race and ethnicity, as reported by patients at time of registration. MAIN OUTCOMES: The primary outcome was whether a SER was called on a patient. The secondary outcome was the incidence of physical restraints among patients who experienced a SER. KEY RESULTS: Among 24,212 patients, 18,755 (77.5%) patients identified as white, 2,346 (9.7%) as Black, and 2,425 (10.0%) identified with another race. Among all patients, 1,827 (7.6%) identified as Hispanic and 21,554 (89.0%) as non-Hispanic. Sixty-six (2.8%) Black patients had a SER activated during their first admission, compared to 295 (1.6%) white patients. In a Firth logit multivariable model, Black patients had higher adjusted odds of a SER than white patients (adjusted odds ratio (aOR) 1.37 [95% confidence interval: 1.02, 1.81], p = 0.037). Hispanic patients did not have higher odds of having a SER called than non-Hispanic patients. In a Poisson multivariable model among patients who had a SER called, race and ethnicity were not found to be significant predictors of restraint. CONCLUSION: Black patients had higher odds of a SER compared to white patients. No significant differences were found between Hispanic and non-Hispanic patients. Future efforts should focus on assessing the generalizability of these findings, the underlying mechanisms driving these inequities, and effective interventions to address them.


Asunto(s)
Etnicidad , Hispánicos o Latinos , Humanos , Estudios Retrospectivos , Hospitales , Población Negra
10.
J Vis Exp ; (187)2022 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-36190235

RESUMEN

Diffusely infiltrating gliomas are associated with high morbidity and mortality due to the infiltrative nature of tumor spread. They are morphologically complex tumors, with a high degree of proteomic variability across both the tumor itself and its heterogenous microenvironment. The malignant potential of these tumors is enhanced by the dysregulation of proteins involved in several key pathways, including processes that maintain cellular stability and preserve the structural integrity of the microenvironment. Although there have been numerous bulk and single-cell glioma analyses, there is a relative paucity of spatial stratification of these proteomic data. Understanding differences in spatial distribution of tumorigenic factors and immune cell populations between the intrinsic tumor, invasive edge, and microenvironment offers valuable insight into the mechanisms underlying tumor proliferation and propagation. Digital spatial profiling (DSP) represents a powerful technology that can form the foundation for these important multilayer analyses. DSP is a method that efficiently quantifies protein expression within user-specified spatial regions in a tissue specimen. DSP is ideal for studying the differential expression of multiple proteins within and across regions of distinction, enabling multiple levels of quantitative and qualitative analysis. The DSP protocol is systematic and user-friendly, allowing for customized spatial analysis of proteomic data. In this experiment, tissue microarrays are constructed from archived glioblastoma core biopsies. Next, a panel of antibodies is selected, targeting proteins of interest within the sample. The antibodies, which are preconjugated to UV-photocleavable DNA oligonucleotides, are then incubated with the tissue sample overnight. Under fluorescence microscopy visualization of the antibodies, regions of interest (ROIs) within which to quantify protein expression are defined with the samples. UV light is then directed at each ROI, cleaving the DNA oligonucleotides. The oligonucleotides are microaspirated and counted within each ROI, quantifying the corresponding protein on a spatial basis.


Asunto(s)
Glioblastoma , Glioma , Adulto , Glioma/patología , Humanos , Oligonucleótidos , Proteómica , Microambiente Tumoral
11.
Expert Opin Emerg Drugs ; 27(3): 263-275, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36039863

RESUMEN

INTRODUCTION: Major depressive disorder (MDD) continues to be one of the highest contributors to disease burden and years lived with disability in the world. Current existing treatments have been associated with intolerable side effects, long onset of action and suboptimal remission rates. Newer agents are being developed that will be reviewed here, such as glutamate and gamma-aminobutyric acid (GABA) and the reinvigorated testing of psychedelic drugs. This review will summarize the target mechanisms of the newer ADTs currently in development and available on the market. AREAS COVERED: It briefly covers the existing agents for MDD and treatment-resistant depression (TRD) and the need for new agents with higher efficacy. Therapeutic agents currently in Phase II or later clinical trials are listed and discussed, based on a thorough review of the US National Institutes of Health clinicaltrials.gov index and a search of the Informa Pharmaprojects database. Compounds of interest are grouped into scientific rationale and include atypical antipsychotics, GABA positive allosteric modulators, glutamatergic agents, opioids, orexin 2 receptor antagonists, and psychedelics. EXPERT OPINION: New therapeutic agents currently in development are promising, with a more rapid onset of action and the ability to augment and treat TRD.


Asunto(s)
Antipsicóticos , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico
12.
J Neurosci ; 42(10): 1945-1957, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35101965

RESUMEN

Phosphatase and tensin homolog (PTEN) is a major negative regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway. Loss-of-function mutations in PTEN have been found in a subset of patients with macrocephaly and autism spectrum disorder (ASD). PTEN loss in neurons leads to somal hypertrophy, aberrant migration, dendritic overgrowth, increased spine density, and hyperactivity of neuronal circuits. These neuronal overgrowth phenotypes are present on Pten knock-out (KO) and reconstitution with autism-associated point mutations. The mechanism underlying dendritic overgrowth in Pten deficient neurons is unclear. In this study, we examined how Pten loss impacts microtubule (MT) dynamics in both sexes using retroviral infection and transfection strategies to manipulate PTEN expression and tag the plus-end MT binding protein, end-binding protein 3 (EB3). We found Pten KO neurons sprout more new processes over time compared with wild-type (WT) neurons. We also found an increase in MT polymerization rate in Pten KO dendritic growth cones. Reducing MT polymerization rate to the WT level was sufficient to reduce dendritic overgrowth in Pten KO neurons in vitro and in vivo Finally, we found that rescue of dendritic overgrowth via inhibition of MT polymerization was sufficient to improve the performance of Pten KO mice in a spatial memory task. Taken together, our data suggests that one factor underlying PTEN loss dependent dendritic overgrowth is increased MT polymerization. This opens the possibility for an intersectional approach targeting MT polymerization and mTOR with low doses of inhibitors to achieve therapeutic gains with minimal side effects in pathologies associated with loss of neuronal PTEN function.SIGNIFICANCE STATEMENT Loss of Pten function because of genetic deletion or expression of mutations associated with autism spectrum disorder (ASD), results in overgrowth of neurons including increased total dendritic length and branching. We have discovered that this overgrowth is accompanied by increased rate of microtubule (MT) polymerization. The increased polymerization rate is insensitive to acute inhibition of mechanistic target of rapamycin (mTOR)C1 or protein synthesis. Direct pharmacological inhibition of MT polymerization can slow the polymerization rate in Pten knock-out (KO) neurons to rates seen in wild-type (WT) neurons. Correction of the MT polymerization rate rescues increased total dendritic arborization and spatial memory. Our studies suggest that phosphatase and tensin homolog (PTEN) inhibits dendritic growth through parallel regulation of protein synthesis and cytoskeletal polymerization.


Asunto(s)
Trastorno del Espectro Autista , Encéfalo , Microtúbulos , Fosfohidrolasa PTEN , Animales , Trastorno del Espectro Autista/enzimología , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/patología , Encéfalo/citología , Encéfalo/enzimología , Encéfalo/metabolismo , Femenino , Humanos , Masculino , Ratones , Microtúbulos/metabolismo , Plasticidad Neuronal/fisiología , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Polimerizacion , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo
13.
Molecules ; 27(3)2022 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-35164002

RESUMEN

Carboxylic acid is a commonly utilized functional group for covalent surface conjugation of carbon nanoparticles that is typically generated by acid oxidation. However, acid oxidation generates additional oxygen containing groups, including epoxides, ketones, aldehydes, lactones, and alcohols. We present a method to specifically enrich the carboxylic acid content on fluorescent nanodiamond (FND) surfaces. Lithium aluminum hydride is used to reduce oxygen containing surface groups to alcohols. The alcohols are then converted to carboxylic acids through a rhodium (II) acetate catalyzed carbene insertion reaction with tert-butyl diazoacetate and subsequent ester cleavage with trifluoroacetic acid. This carboxylic acid enrichment process significantly enhanced nanodiamond homogeneity and improved the efficiency of functionalizing the FND surface. Biotin functionalized fluorescent nanodiamonds were demonstrated to be robust and stable single-molecule fluorescence and optical trapping probes.

14.
Spine J ; 22(6): 921-926, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35017053

RESUMEN

BACKGROUND CONTEXT: Spinal epidural abscess (SEA) is an uncommon yet serious infection, associated with significant morbidity and mortality. Patients diagnosed with SEA often require surgical interventions or critical care services that are not available at community hospitals and are therefore transferred to tertiary care centers. Little is known about the effects of interhospital transfer on acute outcomes for patients with SEA. PURPOSE: To study the effects of interhospital transfer on acute outcomes for patients with SEA. STUDY DESIGN: Cross sectional analysis using the 2009 to 2017 National Inpatient Sample (NIS). PATIENT SAMPLE: Using the 2009 to 2017 NIS, we identified cases of SEA using ICD, Ninth, or Tenth Revision diagnosis codes 324.1 & G06.1. OUTCOME MEASURES: Our primary endpoint was in hospital mortality. METHODS: The association between interhospital transfer and inpatient mortality was assessed using multivariable logistic regression to adjust for potential covariates. Patient and hospital factors associated with interhospital transfer were assessed in a secondary analysis. RESULTS: A total of 21.5% of patient with SEA were treated after transfer from another hospital. After adjusting for covariates, those who presented after transfer had higher odds of death during hospitalization (OR: 1.51, 95% CI 1.27-1.78, p<.001). Transferred patients were significantly more likely to live in rural communities (11.4 % vs. 5.3 % for nontransferred patients). CONCLUSIONS: Interhospital transfer, which occurred more frequently in patients from rural hospitals, was associated with death even after controlling for disease severity. Addressing healthcare delivery disparities across the US, including across the rural-urban spectrum, will require better understanding of the observed increased mortality of interhospital transfer as a preventable source of in-hospital mortality for SEA.


Asunto(s)
Absceso Epidural , Estudios Transversales , Mortalidad Hospitalaria , Hospitalización , Humanos , Transferencia de Pacientes , Estudios Retrospectivos
15.
Clin Neurol Neurosurg ; 213: 107101, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34959106

RESUMEN

OBJECTIVE: Excessive interfacility transfer to a tertiary care facility of minimally injured patients for subspecialty evaluation leads to overuse of resources and is referred to as secondary overtriage (SO). Little is known regarding the epidemiology of SO in rural settings, particularly for patients with a mild head injury who may be safely managed without admission to level I trauma centers. METHODS: In order to determine the rate of SO for neurosurgical patients with Glasgow Coma Scale (GCS) of 13-15 referred to a rural level 1 trauma center, we conducted a retrospective chart review of 224 patients evaluated for potential transfer to Dartmouth-Hitchcock Medical Center from January 1, 2014 through December 31, 2014. SO was defined as any admission where a patient was transferred from an outside facility, had a length of stay shorter than 48 h, did not require neurosurgical intervention, and was alive at the time of discharge. RESULTS: Of the 224 patients evaluated, 163 patients were transferred. Of the 163 patients included in this study, 43 (26.4%) met criteria for SO, 59 (36.2%) patients met criteria for intervention, and 61 (37.2%) patients met criteria for observation. CONCLUSIONS: Approximately a quarter of the total patients who are transferred to a rural level I trauma center for neurosurgical evaluation are minimally injured, do not require neurosurgical intervention, and are discharged within 48 h of presentation. Management at their referring facility with remote neurosurgical consultation is likely safe in this population. Understanding the rate of SO in neurosurgical patients and risk factors present in this group can better guide future transfer policies at rural medical centers.


Asunto(s)
Traumatismos Craneocerebrales , Centros Traumatológicos , Escala de Coma de Glasgow , Humanos , Transferencia de Pacientes , Estudios Retrospectivos , Atención Terciaria de Salud
17.
Curr Oncol ; 28(6): 5067-5072, 2021 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-34940065

RESUMEN

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. Herein we report a case of CD30-positive T-cell PTLD that was successfully treated with BV-CHP, suggesting the added value of the addition of BV to chemotherapy, contributing to our patient's long and ongoing progression-free survival. To our knowledge, this is the first documented case of successful treatment using BV-CHP for a CD30-positive, EBV-negative, late T-cell PTLD.


Asunto(s)
Linfoma de Células T Periférico , Trastornos Linfoproliferativos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Antígeno Ki-1/uso terapéutico , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/etiología , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/etiología , Prednisona/uso terapéutico
18.
Cell ; 184(22): 5608-5621.e18, 2021 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-34637701

RESUMEN

Mammals use glabrous (hairless) skin of their hands and feet to navigate and manipulate their environment. Cortical maps of the body surface across species contain disproportionately large numbers of neurons dedicated to glabrous skin sensation, in part reflecting a higher density of mechanoreceptors that innervate these skin regions. Here, we find that disproportionate representation of glabrous skin emerges over postnatal development at the first synapse between peripheral mechanoreceptors and their central targets in the brainstem. Mechanoreceptor synapses undergo developmental refinement that depends on proximity of their terminals to glabrous skin, such that those innervating glabrous skin make synaptic connections that expand their central representation. In mice incapable of sensing gentle touch, mechanoreceptors innervating glabrous skin still make more powerful synapses in the brainstem. We propose that the skin region a mechanoreceptor innervates controls the developmental refinement of its central synapses to shape the representation of touch in the brain.


Asunto(s)
Tronco Encefálico/metabolismo , Mecanorreceptores/metabolismo , Sinapsis/metabolismo , Percepción del Tacto/fisiología , Potenciales de Acción/fisiología , Animales , Animales Recién Nacidos , Axones/metabolismo , Canales Iónicos/metabolismo , Ratones Noqueados , Neuronas/metabolismo , Imagen Óptica , Optogenética , Piel/inervación
19.
World Neurosurg ; 153: e213-e219, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34182176

RESUMEN

BACKGROUND: Contralateral C7 (CC7) nerve transfer has successfully restored hand function in patients with spastic hemiplegia from chronic central nervous system injuries. However, little is known about the morphology and anatomy of the donor C7 nerve root in patients undergoing this procedure. This study quantified intraoperative measurements of donor C7 nerve roots during CC7 transfer surgery for spastic hemiplegia in patients treated at a high-volume center to describe observed anatomical variations for successful direct anastomosis. METHODS: A database of images from 21 patients (2 females, 19 males) undergoing CC7 surgery was searched for photographic data that contained a standard ruler measuring donor C7 nerve root length after surgical sectioning and before transfer. Two independent observers analyzed these images and recorded C7 nerve root diameter, length, and branch lengths. RESULTS: Mean (SD) values of donor C7 nerve measurements were length, 53.5 (8.0) mm; diameter, 5.1 (0.9) mm; branch length following surgical sectioning, 18.3 (6.3) mm. Right-sided donor C7 nerve roots yielded significantly longer branches compared with left-sided donor C7 nerve roots (P = 0.01). Other patient factors such as age, sex, or laterality of brain injury did not influence intraoperative anatomy. CONCLUSIONS: We report detailed intraoperative measurements of the donor C7 root during CC7 nerve transfer for spastic hemiplegia. These findings describe existing variation in surgical C7 nerve root anatomy in patients undergoing this procedure and may serve as a general reference for the expected donor C7 length in successful direct anastomosis.


Asunto(s)
Hemiplejía/cirugía , Transferencia de Nervios/métodos , Raíces Nerviosas Espinales/anatomía & histología , Nervios Espinales/trasplante , Adulto , Anciano , Lesiones Traumáticas del Encéfalo/complicaciones , Hemorragia Cerebral/complicaciones , Infarto Cerebral/complicaciones , Parálisis Cerebral/complicaciones , Vértebras Cervicales , Niño , Femenino , Hemiplejía/etiología , Hemiplejía/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Espasticidad Muscular/etiología , Espasticidad Muscular/fisiopatología , Espasticidad Muscular/cirugía , Tamaño de los Órganos , Nervios Espinales/anatomía & histología , Adulto Joven
20.
Biol Sex Differ ; 12(1): 33, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33933156

RESUMEN

BACKGROUND: The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes. METHODS: Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction. RESULTS: Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI. CONCLUSIONS: In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Adulto , Femenino , Humanos , Enfermedades Renales , Masculino , Persona de Mediana Edad , Receptores de Superficie Celular , Renina , Caracteres Sexuales , Receptor de Prorenina
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