Methamphetamine (meth) use disorder is part of an overarching use disorder that encompasses continued drug seeking and an increased risk of returning to drug use following periods of abstaining. Chronic meth use results in drug-induced cortical plasticity in the perirhinal cortex (PRC) that mediates responses to novelty. PRH projection targets are numerous and include the nucleus accumbens core (NAc).
View Article and Find Full Text PDFTreatment of giant cell arteritis (GCA) aims initially to prevent acute visual loss, and subsequently to optimise long-term quality of life. Initial prevention of acute visual loss in GCA is well-standardised with high-dose glucocorticoid therapy but in the longer term optimising quality of life requires tailoring of treatment to the individual. The licensing of the IL-6 receptor inhibitor tocilizumab combined with advances in vascular imaging have resulted in many changes to diagnostic and therapeutic practice.
View Article and Find Full Text PDFObjective: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST).
Methods: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications.
We report the direct and accurate spectroscopic quantification of the inverted singlet-triplet gap in 1,3,4,6,9b-pentaazaphenalene. This measurement is achieved by directly probing the lowest singlet and triplet states via high-resolution cryogenic anion photoelectron spectroscopy. The assignment of the first excited singlet state is confirmed by visible absorption spectroscopy in an argon matrix at 20 K.
View Article and Find Full Text PDFBackground: Developmental coordination disorder (DCD) affects movement coordination, but little is known about how the condition impacts the behaviours of car drivers and pedestrians.
Aims: This study examined the self-reported driving and pedestrian behaviours of adults with Developmental Coordination Disorder (DCD).
Methods And Procedures: One hundred and twenty-eight participants (62 adults with DCD vs.
Background: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 is an RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus.
Methods: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK.
Introduction: Empathic behaviors are driven by the ability to understand the emotional states of others along with the motivation to improve it. Evidence points towards forms of empathy, like targeted helping, in many species including rats. There are several variables that may modulate targeted helping, including sex, sensory modalities, and activity of multiple neural substrates.
View Article and Find Full Text PDFThe gas-phase rotational spectrum of 1-cyano-2-methylenecyclopropane (, CHN), an isomer of pyridine, is presented for the first time, covering the range from 235 to 500 GHz. Over 3600 -, -, and -type transitions for the ground vibrational state have been assigned, measured, and least-squares fit to partial-octic A- and S-reduced distorted-rotor Hamiltonians with low statistical uncertainty (σ = 42 kHz). Transitions for the two lowest-energy fundamental states (ν and ν) and the lowest-energy overtone (2ν) have been similarly measured, assigned, and least-squares fit to single-state Hamiltonians.
View Article and Find Full Text PDFBroad-band ultraviolet photolysis (λ > 200 nm) of (cyanomethylene)cyclopropane () in an argon matrix at 20 K generates 1-cyano-2-methylenecyclopropane (), a previously unknown compound. This product was initially identified by comparison of its infrared spectrum to that predicted by an anharmonic MP2/6-311+G(2d,p) calculation. This assignment was unambiguously confirmed by the synthesis of 1-cyano-2-methylenecyclopropane () and observation of its authentic infrared spectrum, which proved identical to that of the observed photoproduct.
View Article and Find Full Text PDFBackground: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5 -DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus.
Methods: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018-December 2022 in Yorkshire, UK.
We investigate the underlying assumptions and limits of applicability of several documented models for outbreaks of airborne disease inside buildings by showing how they may each be regarded as special cases of a system of equations which combines quanta conservation and compartmental epidemiological modelling. We investigate the behaviour of this system analytically, gaining insight to its behaviour at large time. We then investigate the characteristic timescales of an indoor outbreak, showing how the dilution rate of the space, and the quanta generation rate, incubation rate and removal rate associated with the illness may be used to predict the evolution of an outbreak over time, and may also be used to predict the relative performances of other indoor airborne outbreak models.
View Article and Find Full Text PDFJAMA Otolaryngol Head Neck Surg
December 2023
Choroid plexus insufficiency or glymphatic stasis are often classified as prequels to harmful accretion of toxic proteins in neurodegenerative disease. Cognitive decline and disordered neuronal signaling subsequently become cardinal features of Alzheimer's disease (AD), typically progressing with amyloid-ß and tau protein accumulation. For Parkinson's disease (PD), α-synuclein deposits and dopamine depletion are linked to impaired movement, resting tremor, and rigidity.
View Article and Find Full Text PDFReturn to methamphetamine (meth) use is part of an overarching addictive disorder hallmarked by cognitive sequela and cortical dysfunction in individuals who use meth chronically. In rats, long access meth self-administration produces object recognition memory deficits due to drug-induced plasticity within the perirhinal cortex (PRH). PRH projections are numerous and include the medial prefrontal cortex (mPFC).
View Article and Find Full Text PDFNo major breakthroughs have entered mainstream clinical fertility practice since egg donation and intracytoplasmic sperm injection decades ago, and oocyte deficits secondary to advanced age continue as the main manifestation of diminished ovarian reserve. In the meantime, several unproven IVF 'accessories' have emerged including so-called ovarian rejuvenation which entails placing fresh autologous platelet-rich plasma (PRP) directly into ovarian tissue. Among cellular responses attributed to this intervention are reduced oxidative stress, slowed apoptosis and improved metabolism.
View Article and Find Full Text PDFPlatelet-rich plasma (PRP) is an 'orthobiologic' with recognized roles in plastic surgery, musculoskeletal disorders, dentistry, dermatology, and more recently, 'ovarian rejuvenation'. Intraovarian PRP involves a complex secretome discharged after platelet activation, comprising multiple cytokine mediators delivered surgically to older or inactive ovarian tissue. Loss of oocyte meiotic fidelity and impaired fertilization accompanying advanced maternal age are already managed by IVF, but only with eggs provided by younger donors.
View Article and Find Full Text PDFNeuroendocrine tumors (NETs) of duodenal origin are an unusual subset among all NETs, comprising only about 3% of this neoplasm class. In general, NETs are characterized by overexpression of somatostatin receptors and carry an excellent prognosis with early diagnosis and intervention. Chromogranin A (CgA), a protein originating in secretory vesicles of neurons and endocrine cells, has gained wide usage in NET diagnosis and surveillance.
View Article and Find Full Text PDFThe millimeter-wave rotational spectrum of ketene (H2C=C=O) has been collected and analyzed from 130 to 750 GHz, providing highly precise spectroscopic constants from a sextic, S-reduced Hamiltonian in the Ir representation. The chemical synthesis of deuteriated samples allowed spectroscopic measurements of five previously unstudied ketene isotopologues. Combined with previous work, these data provide a new, highly precise, and accurate semi-experimental (reSE) structure for ketene from 32 independent moments of inertia.
View Article and Find Full Text PDFBackground: Recurrent in-frame insertions within exon 20 causing duplication of amino acids Tyrosine-Valine-Methionine-Alanine (YVMA) represent 80% of all alterations in non-small cell lung cancer (NSCLC). HER2 tyrosine kinase inhibitors (TKI), anti-HER2 monoclonal antibodies and HER2 directed antibody-drug conjugates have been evaluated in patients with mutated NSCLC. Limited data are available regarding the activity of these agents in exon 19 alterations.
View Article and Find Full Text PDFRelapse to drug seeking involves transient synaptic remodelling that occurs in response to drug-associated cues. This remodelling includes activation of matrix metalloproteinases (MMPs) to initiate catalytic signalling in the extracellular matrix in the nucleus accumbens core (NAcore). We hypothesized that MMP activity would be increased in the NAcore during cue-induced methamphetamine (meth) seeking in a rat model of meth use and relapse.
View Article and Find Full Text PDFIntroduction: There are numerous pharmacologic treatments for opioid use disorder (OUD), but none that directly target the underlying addictive effects of opioids. Oxytocin, a peptide hormone produced in the paraventricular nucleus (PVN) of the hypothalamus, has been investigated as a potential therapeutic for OUD. Promising preclinical and clinical results have been reported, but the brain region(s) and mechanism(s) by which oxytocin impacts reward processes remain undetermined.
View Article and Find Full Text PDFThis study covers the 5-year interval prior to COVID-19 admission for an otherwise healthy 46,XX adolescent expanding the developmental characterization of an unusual convergence of amenorrhea and genetic mutations. The patient experienced rapid collapse of endogenous estradiol output followed by secondary amenorrhea at 13 years of age. Euploid, diffusely hypocellular bone marrow was present on biopsy, although anemia or reduced total immunoglobulin production was not identified.
View Article and Find Full Text PDFWe present here a new example of chemical reactivity governed by quantum tunneling, which also highlights the limitations of the classical theories. The and conformers of a triplet 2-formylphenylnitrene, generated in a nitrogen matrix, were found to spontaneously rearrange to the corresponding 2,1-benzisoxazole and imino-ketene, respectively. The kinetics of both transformations were measured at 10 and 20 K and found to be temperature-independent, providing clear evidence of concomitant tunneling reactions (heavy-atom and H-atom).
View Article and Find Full Text PDFReprod Fertil
October 2022
Ovarian platelet-rich plasma (PRP) is claimed to restore the fertility potential by improving reserve, an effect perhaps mediated epigenetically by platelet-discharged regulatory elements rather than gonadotropin-activated G-protein coupled receptors, as with stimulated in vitro fertilization (IVF). The finding that fresh activated platelet releasate includes factors able to promote developmental signaling networks necessary to enable cell pluripotency tends to support this theory. The mechanistic uncertainty of intraovarian PRP notwithstanding, at least two other major challenges confront this controversial intervention.
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