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Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a successful treatment option in Parkinson's disease (PD) for different motor and non-motor symptoms, but has been linked to postoperative cognitive impairment., Aim: Since both dopaminergic and norepinephrinergic neurotransmissions play important roles in symptom development, we analysed STN-DBS effects on dopamine and norepinephrine availability in different brain regions and morphological alterations of catecholaminergic neurons in the 6-hydroxydopamine PD rat model., Methods: We applied one week of continuous unilateral STN-DBS or sham stimulation, respectively, in groups of healthy and 6-hydroxydopamine-lesioned rats to quantify dopamine and norepinephrine contents in the striatum, olfactory bulb and dentate gyrus. In addition, we analysed dopaminergic cell counts in the substantia nigra pars compacta and area tegmentalis ventralis and norepinephrinergic neurons in the locus coeruleus after one and six weeks of STN-DBS., Results: In 6-hydroxydopamine-lesioned animals, one week of STN-DBS did not alter dopamine levels, while striatal norepinephrine levels were decreased. However, neither one nor six weeks of STN-DBS altered dopaminergic neuron numbers in the midbrain or norepinephrinergic neuron counts in the locus coeruleus. Dopaminergic fibre density in the dorsal and ventral striatum also remained unchanged after six weeks of STN-DBS. In healthy animals, one week of STN-DBS resulted in increased dopamine levels in the olfactory bulb and decreased contents in the dentate gyrus, but had no effects on norepinephrine availability., Conclusions: STN-DBS modulates striatal norepinephrinergic neurotransmission in a PD rat model. Additional behavioural studies are required to investigate the functional impact of this finding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bernal bilayer graphene has recently been discovered to exhibit a wide range of unique ordered phases resulting from interaction-driven effects and encompassing spin and valley magnetism, correlated insulators, correlated metals, and superconductivity. This Letter reports on a novel family of correlated phases characterized by spin and valley ordering, distinct from those reported previously. These phases emerge in electron-doped bilayer graphene where the energy bands are exceptionally flat, manifested through an intriguing nonlinear current-bias behavior that occurs at the onset of the phases and is accompanied by an insulating temperature dependence. These characteristics align with the presence of charge- or spin-density-wave states that open a gap on a portion of the Fermi surface or fully gapped Wigner crystals, resulting in an exceptionally intricate phase diagram.

Introduction: Despite the acknowledged impact of circadian rhythms on various aspects of life, behavioural tests with laboratory animals often overlook alignment with their natural activity patterns. This study aims to evaluate the influence of circadian variations on the results, validity, and reliability of different behavioural tests in rats., Methods: Three behavioural tests, the Light-Dark Box Test (LDB), assessing anxiety-related behaviour and locomotor activity; the Buried Pellet Test (BPT), revealing olfactory abilities and motivation issues; and the Sucrose Preference Test (SPT), studying the anhedonic response, were employed to encompass multiple daytime-dependent behavioural aspects in male Sprague-Dawley rats., Results: Our findings underscore distinct circadian effects on locomotor activity, exploratory behaviour, olfactory acuity, motivation, and hedonic response. Notably, anxious behaviour remained unaffected by daytime conditions. Furthermore, decreased data variance was found to be correlated with conducting behavioural tests during the subjects' active phase., Discussion: This study demonstrates extensive circadian influences on nearly all parameters investigated, coupled with a significant reduction in data variability during the active phase. Emphasising the importance of aligning experimental timing with rats' natural activity patterns, our results suggest that conducting tests during the active phase of the animals not only refines test sensitivity , reduces stress, and provides more representative data, but also contributes to ethical animal research (3 R) and improves test relevance. This, in turn, enhances the reliability and validity of experimental outcomes in behavioural research and promotes animal welfare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson's disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats., Methods: In our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation., Results: STN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches., Discussion: Our data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Fauser, Payonk, Weber, Statz, Winter, Hadar, Appali, van Rienen, Brandt and Storch.)

Bernal bilayer graphene (BLG) offers a highly flexible platform for tuning the band structure, featuring two distinct regimes. One is a tunable band gap induced by large displacement fields. Another is a gapless metallic band occurring at low fields, featuring rich fine structure consisting of four linearly dispersing Dirac cones and van Hove singularities. Even though BLG has been extensively studied experimentally, the evidence of this band structure is still elusive, likely due to insufficient energy resolution. Here, we use Landau levels as markers of the energy dispersion and analyze the Landau level spectrum in a regime where the cyclotron orbits of electrons or holes in momentum space are small enough to resolve the distinct mini Dirac cones. We identify the presence of four Dirac cones and map out topological transitions induced by displacement field. By clarifying the low-energy properties of BLG bands, these findings provide a valuable addition to the toolkit for graphene electronics., (© 2024. The Author(s).)

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been a highly effective treatment option for mid-to-late-stage Parkinson's disease (PD) for decades. Besides direct effects on brain networks, neuroprotective effects of STN-DBS - potentially via alterations of growth factor expression levels - have been proposed as additional mechanisms of action., Objective: In the context of clarifying DBS mechanisms, we analyzed brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels in the basal ganglia, motor and parietal cortices, and dentate gyrus in an animal model of stable, severe dopaminergic deficiency., Methods: We applied one week of continuous unilateral STN-DBS in a group of stable 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats (6-OHDA STIM ) in comparison to a 6-OHDA control group (6-OHDA SHAM ) as well as healthy controls (CTRL STIM and CTRL SHAM ). BDNF and GDNF levels were determined via ELISAs., Results: The 6-OHDA lesion did not result in a persistent alteration in either BDNF or GDNF levels in a model of severe dopaminergic deficiency after completion of the dopaminergic degeneration. STN-DBS modestly increased BDNF levels in the entopeduncular nucleus, but even impaired BDNF and GDNF expression in cortical areas., Conclusions: STN-DBS does not increase growth factor expression when applied to a model of completed, severe dopaminergic deficiency in contrast to other studies in models of modest and ongoing dopaminergic degeneration. In healthy controls, STN-DBS does not influence BDNF or GDNF expression. We consider these findings relevant for clinical purposes since DBS in PD is usually applied late in the course of the disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Molecular doping-the use of redox-active small molecules as dopants for organic semiconductors-has seen a surge in research interest driven by emerging applications in sensing, bioelectronics, and thermoelectrics. However, molecular doping carries with it several intrinsic problems stemming directly from the redox-active character of these materials. A recent breakthrough was a doping technique based on ion-exchange, which separates the redox and charge compensation steps of the doping process. Here, the equilibrium and kinetics of ion exchange doping in a model system, poly(2,5-bis(3-alkylthiophen-2-yl)thieno(3,2-b)thiophene) (PBTTT) doped with FeCl 3 and an ionic liquid, is studied, reaching conductivities in excess of 1000 S cm -1 and ion exchange efficiencies above 99%. Several factors that enable such high performance, including the choice of acetonitrile as the doping solvent, which largely eliminates electrolyte association effects and dramatically increases the doping strength of FeCl 3 , are demonstrated. In this high ion exchange efficiency regime, a simple connection between electrochemical doping and ion exchange is illustrated, and it is shown that the performance and stability of highly doped PBTTT is ultimately limited by intrinsically poor stability at high redox potential., (© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Doped organic semiconductors are critical to emerging device applications, including thermoelectrics, bioelectronics, and neuromorphic computing devices. It is commonly assumed that low conductivities in these materials result primarily from charge trapping by the Coulomb potentials of the dopant counterions. Here, we present a combined experimental and theoretical study rebutting this belief. Using a newly developed doping technique based on ion exchange, we prepare highly doped films with several counterions of varying size and shape and characterize their carrier density, electrical conductivity, and paracrystalline disorder. In this uniquely large data set composed of several classes of high-mobility conjugated polymers, each doped with at least five different ions, we find electrical conductivity to be strongly correlated with paracrystalline disorder but poorly correlated with ionic size, suggesting that Coulomb traps do not limit transport. A general model for interacting electrons in highly doped polymers is proposed and carefully parametrized against atomistic calculations, enabling the calculation of electrical conductivity within the framework of transient localization theory. Theoretical calculations are in excellent agreement with experimental data, providing insights into the disorder-limited nature of charge transport and suggesting new strategies to further improve conductivities.

Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E 2 (PGE 2 ) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE 2 to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE 2 synthesis. PGE 2 in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE 2 in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.

This study describes the primary and secondary partnerships of aging gay men participating in the Understanding Patterns of Healthy Aging Among Men Who Have Sex with Men substudy of the Multicenter AIDS Cohort Study and examines differences in the prevalence of these relationship structures by HIV status while adjusting for age, education, and race/ethnicity. Relationships were compared within the following structural categories: "only a primary partnership", "only a secondary partnership", "both a primary and secondary relationship", or "neither a primary nor secondary relationship". There were 1,054 participants (51.9% HIV negative/48.1% HIV positive) included in the study. Participants had a median age of 62.0 years (interquartile range: 56.0-67.0) and most reported being non-Hispanic white (74.6%) and college educated (88.0%). Of the 1,004 participants with available partnership status data, 384 (38.2%) reported no primary or secondary partnerships, 108 (10.8%) reported secondary-only partnership, 385 (38.3%) reported primary-only partnership, and 127 (12.6%) reported both primary and secondary partnerships. Of participants who reported primary partnerships only, the prevalence rates (PRs) were lower among those 62 years and older, HIV positive, black non-Hispanic and Hispanics. Of participants who reported only having a secondary partnership, the PRs were higher among those 62 years and older and HIV positive. Of participants who did not report having either a primary or secondary partnership, the PRs were higher among those 62 years and older, HIV positive, and black non-Hispanic compared with their respective referent groups. There was no significant difference in PRs of having both primary and secondary partnerships by age category, HIV status, race/ethnicity, and education. This study aimed to fill a knowledge gap in the literature regarding both primary and secondary supportive partnerships among aging HIV-positive and HIV-negative gay men., Competing Interests: The authors have declared that no competing interests exist.

Understanding the charge transport mechanisms in chirality-selected single-walled carbon nanotube (SWCNT) networks and the influence of network parameters is essential for further advances of their optoelectronic and thermoelectric applications. Here, we report on charge density and temperature-dependent field-effect mobility and on-chip field-effect-modulated Seebeck coefficient measurements of polymer-sorted monochiral small-diameter (6,5) (0.76 nm) and mixed large-diameter SWCNT (1.17-1.55 nm) networks (plasma torch nanotubes, RN) with different network densities and length distributions. All untreated networks display balanced ambipolar transport and electron-hole symmetric Seebeck coefficients. We show that charge and thermoelectric transport in SWCNT networks can be modeled by the Boltzmann transport formalism, incorporating transport in heterogeneous media and fluctuation-induced tunneling. Considering the diameter-dependent one-dimensional density of states (DoS) of the SWCNTs composing the network, we can simulate the charge density and temperature-dependent Seebeck coefficients. Our simulations suggest that scattering in these networks cannot be described as simple one-dimensional acoustic and optical phonon scattering as for single SWCNTs. Instead the relaxation time is inversely proportional to energy (τ ∝ ( E - E C ) s , s = -1, E C being the energy of the first van Hove singularity), presumably pointing toward the more two-dimensional character of scattering events and the necessity to include scattering at the SWCNT junctions. Finally, our observation of higher power factors in trap-free, 1,2,4,5-tetrakis(tetramethylguanidino)benzene-treated (6,5) networks than in the RN networks emphasizes the importance of chirality selection to tune the width of the DoS. To benefit from both higher intrinsic mobilities and a large thermally accessible DoS, we propose trap-free, narrow DoS distribution, large-diameter SWCNT networks for both electronic and thermoelectric applications.

The crystallization and aggregation behaviors of semiconducting polymers play a critical role in determining the ultimate performance of optoelectronic devices based on these materials. Due to the soft nature of polymers, crystallite imperfection exists ubiquitously. To this aspect, crystallinity is often used to represent the degree of crystallite imperfection in a reciprocal relation. Despite of the importance, the discussion on crystallinity is still on the phenomenological level and ambiguous in many cases. As two major contributors to crystallite imperfection, crystallite size and paracrystallinity are highly intertwined and hardly separated, hindering more accurate and trustworthy structural analysis. Herein, with the aid of synchrotron-based X-ray diffraction, combined with environmentally controlled heating capability, the evolution of crystallite size and paracrystallinity of two prototypical polythiophene-based thin films have been successfully measured. Strikingly, the paracrystallinity of poly(3-hexylthiophene-2,5-diyl) (P3HT) crystallites remains unchanged with annealing, while the paracrystallinity of poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2- b ]thiophene] (PBTTT) becomes diminished with crystallite growth. This work delivers a promising gesture to semiconducting polymers community, confirming that it is possible to experimentally separate crystallite size and paracrystallinity, both of which are highly intertwined. With this progress, investigation on the correlation between further detailed microstructural parameters and device performance can be achieved.

We introduce "rural legal deserts," or rural areas experiencing attorney shortages, as a meaningful health determinant. We demonstrate that the absence of rural attorneys has significant impacts on public health-impacts that are rapidly exacerbated by COVID-19.Our work builds on recent scholarship that underscores the public health relevance of attorneys in civil and criminal contexts. It recognizes attorneys as crucial to interprofessional health care teams and to establishing equitable health-related laws and policies. Attorney interventions transform institutional practices and help facilitate the stability necessary for health maintenance and recovery. Yet, critically, many rural residents cannot access legal supports.As more individuals experience unemployment, eviction, and insecure benefits amid the COVID-19 pandemic, there is a need for attorneys to address these social determinants of health as legal needs. Accordingly, the growing absence of attorneys in the rural United States proves particularly consequential-because of this pandemic context but also because of rural health disparities. We argue that unless a collaborative understanding of these interrelated phenomena is adopted, justice gaps will continue to compound rural health inequities.

Policy attention to growing rural "health care deserts" tends to identify rural distance as a primary spatial barrier to accessing care. This paper brings together geography, health policy, and ethnographic methods to instead theorize distance as an expansive and illuminating concept that highlights place-based expertise. It specifically engages rural women's interpretations of rural distance as a multifaceted dimension of accessing health care, which includes but is not limited to women's health services and maternity care. Presenting qualitative research with 51 women in a rural region of the U.S., thematic findings reveal an interpretation of barriers to rural health care as moral failings rather than as purely spatial or operational challenges, along with wide communication of negative health care experiences owing to spatially-disparate but trusted social networks. Amid or owing to the rural crisis context, medical mistrust here emerges as a meaningful but largely unrecognized barrier to rural women's ability-and willingness-to obtain health care. This underscores how a novel interpretation of distance may inform policy efforts to address rural medical deserts., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Precise control of the microstructure in organic semiconductors (OSCs) is essential for developing high-performance organic electronic devices. Here, a comprehensive charge transport characterization of two recently reported rigid-rod conjugated polymers that do not contain single bonds in the main chain is reported. It is demonstrated that the molecular design of the polymer makes it possible to achieve an extended linear backbone structure, which can be directly visualized by high-resolution scanning tunneling microscopy (STM). The rigid structure of the polymers allows the formation of thin films with uniaxially aligned polymer chains by using a simple one-step solution-shear/bar coating technique. These aligned films show a high optical anisotropy with a dichroic ratio of up to a factor of 6. Transport measurements performed using top-gate bottom-contact field-effect transistors exhibit a high saturation electron mobility of 0.2 cm 2 V -1 s -1 along the alignment direction, which is more than six times higher than the value reported in the previous work. This work demonstrates that this new class of polymers is able to achieve mobility values comparable to state-of-the-art n-type polymers and identifies an effective processing strategy for this class of rigid-rod polymer system to optimize their charge transport properties., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Patients with end-stage renal failure have increased oxidative stress and show elevated cardiovascular mortality. Whether increased cardiovascular events can be prevented by the administration of antioxidants is unknown., Methods and Results: We evaluated the effects of acetylcysteine, a thiol-containing antioxidant, on cardiovascular events in patients undergoing hemodialysis. A prospective, randomized, placebo-controlled trial was conducted between October 1, 1999, and September 30, 2001, in 134 patients (76 male and 58 female) with a mean age of 62+/-16 years (mean+/-SD) who had been undergoing maintenance hemodialysis for a minimum of 3 months 3 times weekly in an ambulatory center. Median (range) follow-up was 14.5 (1 to 24) months. Patients were randomly assigned either to receive acetylcysteine (600 mg BID) or placebo. The primary end point was a composite variable consisting of cardiac events including fatal and nonfatal myocardial infarction, cardiovascular disease death, need for coronary angioplasty or coronary bypass surgery, ischemic stroke, peripheral vascular disease with amputation, or need for angioplasty. Secondary end points included each of the component outcomes, total mortality, and cardiovascular mortality. A total of 18 (28%) of the 64 hemodialysis patients assigned to acetylcysteine group and 33 (47%) of the 70 hemodialysis patients assigned to control group had a primary end point (relative risk, 0.60 [95% CI, 0.38 to 0.95], P=0.03). No significant differences in secondary end points or total mortality were detected., Conclusions: In hemodialysis patients, treatment with acetylcysteine (600 mg BID) reduces composite cardiovascular end points.

The creation of a drainage orifice in the pericardium for the release of an accumulated effusion has been proven to be an effective means to eliminate the physiologic effects of a cardiac tamponade. Numerous surgical approaches have been used to create an opening in the pericardium for this purpose. Thoracic and thoracoscopic approaches have been found to produce a fair amount of morbidity by further compromising an already compromised cardiopulmonary system by necessitating an invasion into the hemithorax and the requirement of a thoracostomy tube. This report identifies a laparoscopic technique for the creation of a pericardial window with low morbidity that has been successfully used in 14 patients who presented to the Department of Surgery of the Rapid City Medical Center with clinical evidence of pericardial effusion and tamponade.

A follow-up of 41 patients 1-10 years after patellectomy was performed. A discrepancy between subjective satisfaction of the patient and objective functional results could be observed. Best results can be expected after patellectomy due to traumatic comminution of the patella. Patellectomy due to degenerative destruction of the patella results in decreasing pain but exercises only low influence on the functional result. Instability after patellectomy can be explained by loss of the major patellar function (sesamy bone in the patella and quadriceps tendon). The intact patella is of great importance. However, patellectomy of destroyed patellas is considered very helpful. Competent concomitant and after treatment as well as an accurate diagnosis at the right time are prerequisites for good results.