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1.
Proc Natl Acad Sci U S A ; 121(22): e2316149121, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38768342

ABSTRACT

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals.


Subject(s)
Language , Parkinson Disease , Speech , Subthalamic Nucleus , Humans , Parkinson Disease/physiopathology , Parkinson Disease/drug therapy , Subthalamic Nucleus/physiopathology , Subthalamic Nucleus/drug effects , Male , Speech/physiology , Speech/drug effects , Female , Middle Aged , Aged , Magnetic Resonance Imaging , Dopamine/metabolism , Nerve Net/drug effects , Nerve Net/physiopathology , Cognition/drug effects , Dopamine Agents/pharmacology , Dopamine Agents/therapeutic use
2.
J Am Chem Soc ; 146(18): 12645-12655, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38651821

ABSTRACT

The increased production of plastics is leading to the accumulation of plastic waste and depletion of limited fossil fuel resources. In this context, we report a strategy to create polymers that can undergo controlled depolymerization by linking renewable feedstocks with siloxane bonds. α,ω-Diesters and α,ω-diols containing siloxane bonds were synthesized from an alkenoic ester derived from castor oil and then polymerized with varied monomers, including related biobased monomers. In addition, cyclic monomers derived from this alkenoic ester and hydrosiloxanes were prepared and cyclized to form a 26-membered macrolactone containing a siloxane unit. Sequential ring-opening polymerization of this macrolactone and lactide afforded an ABA triblock copolymer. This set of polymers containing siloxanes underwent programmed depolymerization into monomers in protic solvents or with hexamethyldisiloxane and an acid catalyst. Monomers afforded by the depolymerization of polyesters containing siloxane linkages were repolymerized to demonstrate circularity in select polymers. Evaluation of the environmental stability of these polymers toward enzymatic degradation showed that they undergo enzymatic hydrolysis by a fungal cutinase from Fusarium solani. Evaluation of soil microbial metabolism of monomers selectively labeled with 13C revealed differential metabolism of the main chain and side chain organic groups by soil microbes.


Subject(s)
Fusarium , Polymerization , Siloxanes , Siloxanes/chemistry , Plant Oils/chemistry , Polymers/chemistry , Molecular Structure , Carboxylic Ester Hydrolases
3.
Nat Commun ; 15(1): 3162, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605024

ABSTRACT

The organization of membrane proteins between and within membrane-bound compartments is critical to cellular function. Yet we lack approaches to regulate this organization in a range of membrane-based materials, such as engineered cells, exosomes, and liposomes. Uncovering and leveraging biophysical drivers of membrane protein organization to design membrane systems could greatly enhance the functionality of these materials. Towards this goal, we use de novo protein design, molecular dynamic simulations, and cell-free systems to explore how membrane-protein hydrophobic mismatch could be used to tune protein cotranslational integration and organization in synthetic lipid membranes. We find that membranes must deform to accommodate membrane-protein hydrophobic mismatch, which reduces the expression and co-translational insertion of membrane proteins into synthetic membranes. We use this principle to sort proteins both between and within membranes, thereby achieving one-pot assembly of vesicles with distinct functions and controlled split-protein assembly, respectively. Our results shed light on protein organization in biological membranes and provide a framework to design self-organizing membrane-based materials with applications such as artificial cells, biosensors, and therapeutic nanoparticles.


Subject(s)
Artificial Cells , Membrane Proteins , Cell Membrane/metabolism , Membranes/metabolism , Membrane Proteins/metabolism , Liposomes , Lipid Bilayers/chemistry
4.
ACS Sustain Chem Eng ; 12(16): 6281-6288, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38665800

ABSTRACT

The cross-linked nature of vulcanized rubbers as used in tire and many other applications prohibits an effective closed-loop mechanical or chemical recycling. Moreover, vulcanization significantly retards the material's biodegradation. Here, we report a recyclable and biodegradable rubber that is generated by the vulcanization of amorphous, unsaturated polyesters. The elastic material can be broken down via solvolysis into the underlying monomers. After removal of the vulcanized repeat units, the saturated monomers, constituting the major share of the material, can be recovered in overall recycling rates exceeding 90%. Respirometric biodegradation experiments by 13CO2 tracking under environmental conditions via the polyesters' diol monomer indicated depolymerization and partial mineralization of the vulcanized polyester rubbers.

5.
Neonatal Netw ; 43(2): 92-104, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38599771

ABSTRACT

Cytomegalovirus (CMV), a beta-herpes virus, is the most common viral infection in infants. Transmission may occur congenitally (cCMV) or postnatally (pCMV). Early detection and intervention are crucial in reducing morbidities, notable developmental delays, and sensorineural hearing loss. However, more than 90% of infants are asymptomatic at birth. Treatment involves intravenous ganciclovir or the oral prodrug, valganciclovir, drugs usually reserved for use with symptomatic infants because of the toxicity profile. Research currently supports standardized antenatal CMV screening and treatment of affected pregnant patients with hyperimmune globulin as well as vaccination against CMV in unaffected pregnant patients, although widespread adoption is lacking. Standardized postnatal CMV screening is a proven, cost-effective way to detect and diagnose CMV and optimize outcomes across the lifespan. This article presents a case series of cCMV and pCMV and a review of the state of science of CMV as well as promising scientific advances that are on the horizon.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Female , Humans , Infant, Newborn , Pregnancy , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Ganciclovir/pharmacology , Ganciclovir/therapeutic use , Neonatal Screening , Valganciclovir/pharmacology , Valganciclovir/therapeutic use
6.
Cureus ; 16(1): e53220, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38425641

ABSTRACT

This report details the presentation of a 72-year-old female with left-sided continuous non-rhythmic involuntary movements persisting for two months. The movements affected the left side of her face, arm, and leg. The patient had a history of multiple hyperglycemic episodes and diabetic ketoacidosis. This report investigates the basal ganglia's involvement in hemiballismus, a movement disorder possibly linked to the patient's hyperglycemia. It discusses the complex management of hyperglycemia-induced hemiballismus and the need for more research to understand the underlying mechanism and optimal treatment strategies.

7.
ACS Synth Biol ; 13(4): 1273-1289, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38536408

ABSTRACT

As the use of engineered cell therapies expands from pioneering efforts in cancer immunotherapy to other applications, an attractive but less explored approach is the use of engineered red blood cells (RBCs). Compared to other cells, RBCs have a very long circulation time and reside in the blood compartment, so they could be ideally suited for applications as sentinel cells that enable in situ sensing and diagnostics. However, we largely lack tools for converting RBCs into biosensors. A unique challenge is that RBCs remodel their membranes during maturation, shedding many membrane components, suggesting that an RBC-specific approach may be needed. Toward addressing this need, here we develop a biosensing architecture built on RBC membrane proteins that are retained through erythropoiesis. This biosensor employs a mechanism in which extracellular ligand binding is transduced into intracellular reconstitution of a split output protein (including either a fluorophore or an enzyme). By comparatively evaluating a range of biosensor architectures, linker types, scaffold choices, and output signals, we identify biosensor designs and design features that confer substantial ligand-induced signal in vitro. Finally, we demonstrate that erythroid precursor cells engineered with our RBC-protein biosensors function in vivo. This study establishes a foundation for developing RBC-based biosensors that could ultimately address unmet needs including noninvasive monitoring of physiological signals for a range of diagnostic applications.


Subject(s)
Biosensing Techniques , Erythrocytes , Ligands , Erythrocytes/metabolism , Membrane Proteins/metabolism
8.
Chem Rev ; 124(5): 2327-2351, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38408312

ABSTRACT

Polyethylene deconstruction to reusable smaller molecules is hindered by the chemical inertness of its hydrocarbon chains. Pyrolysis and related approaches commonly require high temperatures, are energy-intensive, and yield mixtures of multiple classes of compounds. Selective cleavage reactions under mild conditions (

9.
J Int Neuropsychol Soc ; 30(3): 232-243, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37642015

ABSTRACT

OBJECTIVE: Preclinical Alzheimer disease (AD) has been associated with subtle changes in memory, attention, and spatial navigation abilities. The current study examined whether self- and informant-reported domain-specific cognitive changes are sensitive to AD-associated biomarkers. METHOD: Clinically normal adults aged 56-93 and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog). Reliability and validity of these subsections were examined using Cronbach's alpha and confirmatory factor analysis. Logistic regression was used to examine the ability of ECog subsections to predict AD-related biomarkers (cerebrospinal fluid (CSF) ptau181/Aß42 ratio (N = 371) or hippocampal volume (N = 313)). Hierarchical logistic regression was used to examine whether the self-reported subsections continued to predict biomarkers when controlling for depressive symptomatology if available (N = 197). Additionally, logistic regression was used to examine the ability of neuropsychological composites assessing the same or similar cognitive domains as the subsections (memory, executive function, and visuospatial abilities) to predict biomarkers to allow for comparison of the predictive ability of subjective and objective measures. RESULTS: All subsections demonstrated appropriate reliability and validity. Self-reported memory (with outliers removed) was the only significant predictor of AD biomarker positivity (i.e., CSF ptau181/Aß42 ratio; p = .018) but was not significant when examined in the subsample with depressive symptomatology available (p = .517). Self-reported memory (with outliers removed) was a significant predictor of CSF ptau181/Aß42 ratio biomarker positivity when the objective memory composite was included in the model. CONCLUSIONS: ECog subsections were not robust predictors of AD biomarker positivity.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Spatial Navigation , Humans , Alzheimer Disease/psychology , Reproducibility of Results , Amyloid beta-Peptides/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Neuropsychological Tests , Biomarkers/cerebrospinal fluid , Attention , Peptide Fragments/cerebrospinal fluid , Cognitive Dysfunction/psychology
10.
J Int Neuropsychol Soc ; 30(4): 313-327, 2024 May.
Article in English | MEDLINE | ID: mdl-38014546

ABSTRACT

OBJECTIVE: Subtle changes in memory, attention, and spatial navigation abilities have been associated with preclinical Alzheimer disease (AD). The current study examined whether baseline AD biomarkers are associated with self- and informant-reported decline in memory, attention, and spatial navigation. METHOD: Clinically normal (Clinical Dementia Rating Scale (CDR®) = 0) adults aged 56-93 (N = 320) and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog) annually for an average of 4 years. Biomarker data was collected within (±) 2 years of baseline (i.e., cerebrospinal fluid (CSF) p-tau181/Aß42 ratio and hippocampal volume). Clinical progression was defined as CDR > 0 at time of final available ECog. RESULTS: Self- and informant-reported memory, attention, and spatial navigation significantly declined over time (ps < .001). Baseline AD biomarkers were significantly associated with self- and informant-reported decline in cognitive ability (ps < .030), with the exception of p-tau181/Aß42 ratio and self-reported attention (p = .364). Clinical progression did not significantly moderate the relationship between AD biomarkers and decline in self- or informant-reported cognitive ability (ps > .062). Post-hoc analyses indicated that biomarker burden was also associated with self- and informant-reported decline in total ECog (ps < .002), and again clinical progression did not significantly moderate these relationships (ps > .299). CONCLUSIONS: AD biomarkers at baseline may indicate risk of decline in self- and informant-reported change in memory, attention, and spatial navigation ability. As such, subjectively reported decline in these domains may have clinical utility in tracking the subtle cognitive changes associated with the earliest stages of AD.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Spatial Navigation , Humans , Alzheimer Disease/psychology , Amyloid beta-Peptides/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Disease Progression , Attention , Cognitive Dysfunction/etiology , Cognitive Dysfunction/cerebrospinal fluid
11.
Cureus ; 15(10): e47718, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38021841

ABSTRACT

Gastric banding was one of the first operations to gain popularity within the field of bariatric surgery. This case details one patient's presentation and subsequent management of gastric band erosion with the hope of guiding other physicians and supporting the decreased use of gastric banding. The patient, a 61-year-old Caucasian female, presented to the bariatric clinic complaining of a multiyear history of epigastric pain and acid reflux, which was refractory to treatment with proton pump inhibitors. She had a history of laparoscopic adjustable gastric band (LAGB) placement in 2007. She was initially successful in achieving weight loss and maintained regular band adjustments but was lost to follow-up and regained a body mass index (BMI) of 41.59 kg/m2. Evaluation with upper gastrointestinal (GI) endoscopy was recommended and performed. This revealed a LAGB in its entirety with tubing within the gastric fundus. Removal with dual endoscopy and abdominal laparoscopy was recommended and scheduled. During attempts to remove the band using an endoscopic snare, significant difficulty was encountered. Ultimately, an endoscopic rat-tooth grasper was used to lyse the band and tubing into four sections for complete removal. The subcutaneous port of the band was successfully removed laparoscopically, and the patient was discharged from the operating room. She reported limited pain in the postoperative suite but was lost to follow-up regarding long-term symptom relief. This report describes the presentation and management of one patient's experience with a known complication of LAGB-band erosion. This complication necessitated two additional procedures with anesthesia and placed the patient at increased risk for esophageal perforation, complications related to sedation, and the development of abdominal adhesions. Her case aims to support the decreasing prevalence of LAGBs within bariatric surgery and hopes to guide other physicians challenged with the management of similar cases.

12.
Angew Chem Int Ed Engl ; 62(43): e202310729, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37675615

ABSTRACT

Monomers sourced from waste or biomass are often mixtures of different chain lengths; e.g. catalytic oxidation of polyethylene waste yields mixtures of dicarboxylic acids (DCAs). Yet, polyesters synthesized from such monomer mixtures have rarely been studied. We report polyesters based on multiple linear aliphatic DCAs, present in chain length distributions that vary in their centers and ranges. We demonstrate that these materials can adopt high-density polyethylene-like solid state structures, and are ductile (e.g. Et 610 MPa), allowing for injection molding, or film and fiber extrusion. Melting and crystallization points of the polyesters show no odd-even effects as dipoles cannot favorably align in the crystal, similar to traditional odd carbon numbered, long-chain DCA polyesters. Biodegradation studies of 13 C-labelled polyesters in soil reveal rapid mineralization, and depolymerization by methanolysis indicates suitability for closed-loop recycling.

13.
Cancer ; 129(19): 2946-2965, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37489837

ABSTRACT

BACKGROUND: Social isolation and connectedness are social determinants of health that have demonstrated effects on cancer-related outcomes. These constructs have been systematically evaluated among pediatric and older adult cancer populations. In this review, the authors evaluated the prevalence, correlates, and psychosocial implications of social isolation and connectedness among young adult (YA) cancer survivors aged 18-39 years. METHODS: Peer-reviewed articles published in English before June 2021 were identified from database searches and included articles' reference lists according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included articles described studies that assessed social isolation and/or connectedness among YA cancer survivors. RESULTS: In total, 5094 unique records were identified; 4143 were excluded after title/abstract screening, and 907 were excluded after full-text review. Forty-four articles were included. Few studies used validated measures or directly assessed social isolation or connectedness. Social isolation was similarly prevalent among YAs and older cancer survivors and noncancer populations. Demographic, clinical, and behavioral risk and protective factors for social isolation were identified. Social isolation was related to worse psychological well-being, whereas social connectedness was often, but not always, related to better psychological well-being. CONCLUSIONS: This growing literature underscores the relevance of social isolation and connectedness as important health determinants among YA cancer survivors. The identified risk and protective factors can identify YAs who especially may benefit from screening for social isolation. Future studies are needed that directly, reliably, and validly evaluate social isolation and connectedness to inform the development of interventions to decrease isolation and increase connectedness.


Subject(s)
Cancer Survivors , Neoplasms , Humans , Young Adult , Child , Aged , Social Isolation/psychology , Neoplasms/psychology
14.
Article in English | MEDLINE | ID: mdl-37453387

ABSTRACT

The extracellular cellular matrix (ECM) maintains tissue structure and regulates signaling functions by continuous degradation and remodeling. Inflammation or other disease conditions activate proteases including matrix metalloproteinases (MMPs) that degrade ECM proteins and in particular generate fragments of collagen and elastin, some of which are biologically active ECM peptides or matrikines. Stepwise degradation of collagen by MMP 8, 9 and prolyl endopeptidase release the matrikine proline-glycine-proline (PGP) and its product acetyl-PGP (AcPGP). These peptides are considered as potential biomarkers and therapeutic targets for many disease conditions such as chronic lung disease, heart disease, and cancer. However, there is no published, validated method for the measurement of PGP and AcPGP in plasma and therefore, we developed a sensitive, selective and reliable, isotope dilution LC-multiple reaction monitoring MS method for their determination in human plasma. The chromatographic separation of PGP and AcPGP was achieved in 3 min using Jupiter column with a gradient consisting of acidified acetonitrile and water at a flow rate of 0.5 ml/min. The limit of detection (LOD) for PGP and AcPGP was 0.01 ng/ml and the limit of quantification (LOQ) was 0.05 ng/ml and 0.1 ng/ml, respectively. Precision and accuracy values for all analytes were within 20 % except for the lowest QC of 0.01 ng/ml. The mean extraction recoveries of these analytes were > 90 % using a Phenomenex Phree cartridge and the matrix effect was < 15 % for all the QCs for PGP and AcPGP except the lowest QC. The stability of PGP and AcPGP was > 90 % in several tested conditions including autosampler use, storage at -80 °C, and after 6 times freeze-thaw cycles. Using this method, we successfully extracted and determined PGP levels in human plasma from healthy and COPD subjects. Therefore, this method is suitable for quantification of these peptides in the clinical setting.


Subject(s)
Glycine , Proline , Humans , Chromatography, Liquid , Tandem Mass Spectrometry , Peptides , Collagen
15.
J Cell Biol ; 222(8)2023 08 07.
Article in English | MEDLINE | ID: mdl-37326602

ABSTRACT

Intracellular Zn2+ concentrations increase via depolarization-mediated influx or intracellular release, but the immediate effects of Zn2+ signals on neuron function are not fully understood. By simultaneous recording of cytosolic Zn2+ and organelle motility, we find that elevated Zn2+ (IC50 ≈ 5-10 nM) reduces both lysosomal and mitochondrial motility in primary rat hippocampal neurons and HeLa cells. Using live-cell confocal microscopy and in vitro single-molecule TIRF imaging, we reveal that Zn2+ inhibits activity of motor proteins (kinesin and dynein) without disrupting their microtubule binding. Instead, Zn2+ directly binds to microtubules and selectively promotes detachment of tau, DCX, and MAP2C, but not MAP1B, MAP4, MAP7, MAP9, or p150glued. Bioinformatic predictions and structural modeling show that the Zn2+ binding sites on microtubules partially overlap with the microtubule binding sites of tau, DCX, dynein, and kinesin. Our results reveal that intraneuronal Zn2+ regulates axonal transport and microtubule-based processes by interacting with microtubules.


Subject(s)
Doublecortin Domain Proteins , Dyneins , Kinesins , Microtubule-Associated Proteins , Zinc , tau Proteins , Animals , Humans , Rats , Axonal Transport , Doublecortin Domain Proteins/metabolism , Dyneins/metabolism , HeLa Cells , Kinesins/metabolism , Microtubule-Associated Proteins/metabolism , Microtubules/metabolism , tau Proteins/metabolism , Zinc/metabolism
16.
Anal Chem ; 95(22): 8560-8568, 2023 Jun 06.
Article in English | MEDLINE | ID: mdl-37226811

ABSTRACT

Molecular weight (MW) is a key control of plastic polymer properties and their fate in the environment. However, the primary tool used to determine plastic MW, gel permeation chromatography (GPC), has major limitations, such as low precision and accuracy, requirements for dedicated instrumentation, production of high volumes of hazardous waste, and large sample sizes. In this study, we describe, validate, and apply a diffusion-ordered spectroscopy (DOSY) method for polymer MW determinations, with a focus on applications for consumer plastics. Several experimental conditions were systematically optimized and tested to validate the DOSY method, including the selection of pulse sequences, the effect of sample concentration, cross-validation with multiple sets of external standards, and long-term instrumental stability. Validation was performed for a wide range of polymers, solvents, and temperatures, highlighting its potential for broad applicability. A preliminary screening of polystyrene and polyethylene terephthalate consumer products revealed widely varying MWs (up to two-fold) for products made of the same polymer type. A preliminary experiment was also conducted to track the decrease in polystyrene MW via photochemical chain scission reactions, finding a 20% reduction in MW after less than 1 week of irradiation. Collectively, our results demonstrate the potential for DOSY to provide high-throughput, accurate, and precise measures of polymer MW, as well as the evolution of polymer MW during environmental weathering processes, such as photochemical degradation. We conclude with a discussion of (i) the many advantages of DOSY compared to GPC, (ii) future developments to enhance the depth of information obtained from DOSY, and (iii) approaches to broaden the accessibility of this promising analytical method to the research community.

17.
Brain Struct Funct ; 228(3-4): 845-858, 2023 May.
Article in English | MEDLINE | ID: mdl-37069296

ABSTRACT

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms.


Subject(s)
HIV Infections , Memory, Episodic , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , HIV Infections/complications , Memory Disorders/diagnostic imaging , Memory Disorders/etiology , Mental Recall , Neuropsychological Tests
18.
Small Methods ; 7(12): e2201718, 2023 12.
Article in English | MEDLINE | ID: mdl-37116099

ABSTRACT

The surface modification of membrane-based nanoparticles, such as liposomes, polymersomes, and lipid nanoparticles, with targeting molecules, such as binding proteins, is an important step in the design of therapeutic materials. However, this modification can be costly and time-consuming, requiring cellular hosts for protein expression and lengthy purification and conjugation steps to attach proteins to the surface of nanocarriers, which ultimately limits the development of effective protein-conjugated nanocarriers. Here, the use of cell-free protein synthesis systems to rapidly create protein-conjugated membrane-based nanocarriers is demonstrated. Using this approach, multiple types of functional binding proteins, including affibodies, computationally designed proteins, and scFvs, can be cell-free expressed and conjugated to liposomes in one-pot. The technique can be expanded further to other nanoparticles, including polymersomes and lipid nanoparticles, and is amenable to multiple conjugation strategies, including surface attachment to and integration into nanoparticle membranes. Leveraging these methods, rapid design of bispecific artificial antigen presenting cells and enhanced delivery of lipid nanoparticle cargo in vitro is demonstrated. It is envisioned that this workflow will enable the rapid generation of membrane-based delivery systems and bolster our ability to create cell-mimetic therapeutics.


Subject(s)
Liposomes , Nanoparticles , Drug Delivery Systems/methods , Nanoparticles/chemistry
19.
Anim Biotelemetry ; 11(1): 9, 2023.
Article in English | MEDLINE | ID: mdl-36937100

ABSTRACT

Background: Little is known about the transformer stage of the parasitic lampreys, a brief but critical period that encompasses juvenile out-migration from rivers to lakes or oceans to begin parasitic feeding. Information about this life stage could have significant conservation implications for both imperiled and invasive lampreys. We investigated tag retention, survival, wound healing, and swim performance of newly transformed sea lamprey (Petromyzon marinus) implanted with a new micro-acoustic transmitter, the eel-lamprey acoustic transmitter (ELAT), in a controlled laboratory environment. Results: The 61-day survival of our tagged subjects was 71%, within the range reported in similar studies of juvenile lampreys. However, survival was significantly lower in the tagged animals (vs control), with no effect statistically attributable to measures of animal length, mass, condition, or population of origin (Great Lakes vs. Atlantic drainage). Mortality in tagged fish was concentrated in the first four days post-surgery, suggesting injury from the surgical process. An unusually long recovery time from anesthesia may have contributed to the increased mortality. In a simple burst swim assay, tagged animals swam significantly slower (- 22.5%) than untagged animals, but were not significantly different in endurance swim tests. A composite wound healing score at day four was a significant predictor of maximum burst swim speed at day 20, and wound condition was related to animal mass, but not length, at the time of tagging. Conclusions: Impairments to survival and swim performance of juvenile sea lamprey implanted with the ELAT transmitter were within currently reported ranges for telemetry studies with small, difficult to observe fishes. Our results could be improved with more refined anesthesia and surgical techniques. The ability to track migratory movements of imperiled and pest populations of parasitic lampreys will improve our ability to estimate vital rates that underlie recruitment to the adult population (growth, survival) and to investigate the environmental factors that regulate the timing and rates of movement, in wild populations.

20.
Am J Otolaryngol ; 44(1): 103684, 2023.
Article in English | MEDLINE | ID: mdl-36343506

ABSTRACT

OBJECTIVE: There is hesitation to offer pediatric patients rhinoplasty due to concerns about postoperative effect on midface growth. A cross-sectional survey of members of the American Academy of Facial Plastic and Reconstructive Surgery was conducted regarding practice information and attitudes towards pediatric septorhinoplasty. The goal of the study is to describe the current attitudes on pediatric septorhinoplasty. STUDY DESIGN: Cross-sectional survey. SETTING: Community members of the American Academy of Facial Plastic and Reconstructive Surgery society. METHODS: A 19-question survey was distributed to surgeons surveying background information and current attitudes towards pediatric septorhinoplasty practices. Fisher's exact tests were implemented using Monte Carlo methods. RESULTS: There were 94 total respondents. A majority believed septorhinoplasty is safe in patients <16 years of age (n = 68, 72.34 %) with most choosing either 16 years (n = 30, 31.91 %) or 14 years (n = 29, 30.85 %) as the minimum age to consider the procedure. A majority of respondents would not perform any nasal procedures in patients ≤12 years (n = 40, 43.48 %). CONCLUSION: Trends in pediatric rhinoplasty practices have evolved overtime. Despite prior beliefs and studies cautioning against performing septorhinoplasty in pediatric patients (<16 years of age), a majority of practicing facial plastic surgeons believe that pediatric septorhinoplasty can be performed in patients >14 years old. LEVEL OF EVIDENCE: IV.


Subject(s)
Plastic Surgery Procedures , Rhinoplasty , Surgeons , Surgery, Plastic , Humans , United States , Child , Adolescent , Rhinoplasty/methods , Cross-Sectional Studies , Surveys and Questionnaires , Face/surgery , Surgery, Plastic/methods
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