The Mediterranean diet and more specifically certain meats, fruits, vegetables, and olive oil found in certain parts of the Mediterranean region have been associated with a decreased cardiovascular ...and diabetes risk. More recently, several population based studies have observed with these lifestyle choices have reported an overall reduced risk for several cancers. One study in particular observed an inverse relationship between consumption of Mediterranean herbs such as rosemary, sage, parsley, and oregano with lung cancer. In light of these findings there is a need to explore and identify the anti-cancer properties of these medicinal herbs and to identify the phytochemicals therein. One agent in particular, carnosol, has been evaluated for anti-cancer property in prostate, breast, skin, leukemia, and colon cancer with promising results. These studies have provided evidence that carnosol targets multiple deregulated pathways associated with inflammation and cancer that include nuclear factor kappa B (NFκB), apoptotic related proteins, phosphatidylinositol-3-kinase (PI3 K)/Akt, androgen and estrogen receptors, as well as molecular targets. In addition, carnosol appears to be well tolerated in that it has a selective toxicity towards cancer cells versus non-tumorigenic cells and is well tolerated when administered to animals. This mini-review reports on the pre-clinical studies that have been performed to date with carnosol describing mechanistic, efficacy, and safety/tolerability studies as a cancer chemoprevention and anti-cancer agent.
Hearing and dementia: from ears to brain Johnson, Jeremy C S; Marshall, Charles R; Weil, Rimona S ...
Brain (London, England : 1878),
03/2021, Letnik:
144, Številka:
2
Journal Article
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Odprti dostop
The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the ...nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, based on structural and functional features of auditory brain organization that confer vulnerability to neurodegeneration, the extensive, reciprocal interplay between 'peripheral' and 'central' hearing dysfunction, and recently characterized auditory signatures of canonical neurodegenerative dementias (Alzheimer's disease, Lewy body disease and frontotemporal dementia). Moving beyond any simple dichotomy of ear and brain, we argue for a reappraisal of the role of auditory cognitive dysfunction and the critical coupling of brain to peripheral organs of hearing in the dementias. We call for a clinical assessment of real-world hearing in these diseases that moves beyond pure tone perception to the development of novel auditory 'cognitive stress tests' and proximity markers for the early diagnosis of dementia and management strategies that harness retained auditory plasticity.
High-field terahertz (THz) spectroscopy is enabling the ultrafast study and control of matter in new and exciting ways. However, when intense electromagnetic pulses are used in any kind of pump-probe ...spectroscopy, several nonlinear excitation pathways can result, leading to scenarios that required the development of multidimensional spectroscopies to illuminate the observed dynamics. Here we demonstrate a clear example where two-dimensional (2D) THz vibrational spectroscopy is needed to distinguish between nonlinear-excitation pathways in CdWO_{4}. We nonlinearly excite a set of Raman-active vibrational modes in CdWO_{4} with broadband THz pulses, and 2D spectroscopy allows us to determine the dominant excitation pathway. We provide a general framework for 2D THz and multi-THz nonlinear phonon spectroscopy in solid systems, which has important implications in contributing needed clarity to the nascent field of nonlinear phononics.
Office-based pulmonary function testing, also known as spirometry, is a powerful tool for primary care physicians to diagnose and manage respiratory problems. An obstructive defect is indicated by a ...low forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio, which is defined as less than 70% or below the fifth percentile based on data from the Third National Health and Nutrition Examination Survey (NHANES III) in adults, and less than 85% in patients five to 18 years of age. If an obstructive defect is present, the physician should determine if the disease is reversible based on the increase in FEV1 or FVC after bronchodilator treatment (i.e., increase of more than 12% in patients five to 18 years of age, or more than 12% and more than 200 mL in adults). Asthma is typically reversible, whereas chronic obstructive pulmonary disease is not. A restrictive pattern is indicated by an FVC below the fifth percentile based on NHANES III data in adults, or less than 80% in patients five to 18 years of age. If a restrictive pattern is present, full pulmonary function tests with diffusing capacity of the lung for carbon monoxide testing should be ordered to confirm restrictive lung disease and form a differential diagnosis. If both the FEV1/FVC ratio and the FVC are low, the patient has a mixed defect. The severity of the abnormality is determined by the FEV1 (percentage of predicted). If pulmonary function test results are normal, but the physician still suspects exercise- or allergen-induced asthma, bronchoprovocation (e.g., methacholine challenge, mannitol inhalation challenge, exercise testing) should be considered.
The purple mangosteen (Garcinia mangostana) is a popular Southeast Asian fruit that has been used traditionally for its health promoting benefits for years. Unique to the mangosteen are a class of ...phytochemicals known as xanthones that have been reported to display significant anti-cancer and anti-tumor activities, specifically through the promotion of apoptosis, targeting of specific cancer-related proteins, or modulation of cell signaling pathways. α-Mangostin, the most abundant xanthone isolated from the mangosteen, has received substantial attention as it has proven to be a potent phytochemical, specifically as an anticancer agent, in numerous different cancer cell studies and cancer animal models. While the mechanisms for these anticancer effects have been reported in many studies, lesser xanthones, including gartanin, β-mangostin, γ-mangostin, garcinone C, and garcinone E, and mangosteen extracts from the pericarp, roots, rind, and stem show promise for their anticancer activity but their mechanisms of action are not as well developed and remain to be determined. Mangosteen products appear safe and have been well tolerated in human clinical trials where they show antioxidant activity, though their clinical anticancer activity has not yet been evaluated. This review summarizes the work that has been done to explore and explain the anticancer and antitumor activities of α-mangostin, lesser xanthones, and mangosteen extracts in vitro, in vivo, and in humans in various cancers.
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Highlights • Diterpenes from rosemary elicit a decrease of cell viability and proliferation. • Diterpenes are well absorbed and can achieve plasma concentrations that are physiologically relevant. • ...Rosemary extract is approved as a food preservative increasing the likelihood of human exposure to these phytochemicals.
The "textbook" phonon mean free path of heat carrying phonons in silicon at room temperature is ∼40 nm. However, a large contribution to the thermal conductivity comes from low-frequency phonons ...with much longer mean free paths. We present a simple experiment demonstrating that room-temperature thermal transport in Si significantly deviates from the diffusion model already at micron distances. Absorption of crossed laser pulses in a freestanding silicon membrane sets up a sinusoidal temperature profile that is monitored via diffraction of a probe laser beam. By changing the period of the thermal grating we vary the heat transport distance within the range ∼1-10 μm. At small distances, we observe a reduction in the effective thermal conductivity indicating a transition from the diffusive to the ballistic transport regime for the low-frequency part of the phonon spectrum.
Binary reversals (exemplified by 'yes'/'no' confusions) have been described in patients with primary progressive aphasia (PPA) but their diagnostic value and phenotypic correlates have not been ...defined.
We conducted a retrospective cohort study analysing demographic, clinical, neuropsychological, linguistic and behavioural data from patients representing all major PPA syndromes (non-fluent/agrammatic variant, nfvPPA; logopenic variant, lvPPA; semantic variant, svPPA) and behavioural variant frontotemporal dementia (bvFTD). The prevalence of binary reversals and behavioural abnormalities, illness duration, parkinsonian features and neuropsychological test scores were compared between neurodegenerative syndromes, and the diagnostic predictive value of binary reversals was assessed using logistic regression.
Data were obtained for 83 patients (21 nfvPPA, 13 lvPPA, 22 svPPA, 27 bvFTD). Binary reversals occurred in all patients with nfvPPA, but significantly less frequently and later in lvPPA (54%), svPPA (9%) and bvFTD (44%). Patients with bvFTD with binary reversals had significantly more severe language (but not general executive or behavioural) deficits than those without reversals. Controlling for potentially confounding variables, binary reversals strongly predicted a diagnosis of nfvPPA over other syndromes.
Binary reversals are a sensitive (though not specific) neurolinguistic feature of nfvPPA, and should suggest this diagnosis if present as a prominent early symptom.
Our aim was to describe a broad number of subthreshold psychiatric symptoms (SPS) in a nationally representative population and evaluate associations with substance use. SPS describe groups of ...symptoms with significant pathology, but that do not quite meet full psychiatric diagnostic criteria. They have been associated with significant impairment and cost.
The National Epidemiologic Survey on Alcohol and Related Conditions-III was a multistage, weighted, cross-sectional survey completed in the United States in 2013 comprising 36,309 noninstitutionalized adults. We report lifetime prevalence rates of 14 SPS related to mood, anxiety, trauma, eating, and personality disorders. We then evaluate associations with lifetime alcohol use disorders (AUD) and all substance use disorders (SUD) using logistic regression and adjusted odds ratios. SPS and psychiatric diagnoses were mutually exclusive (could not co-occur).
Lifetime prevalence of having at least one of 14 SPS was 57% compared with 37% for the related psychiatric disorders. This was similar for males and females, in contrast to psychiatric disorders in which prevalence was 42% in females and 31% in males. Otherwise, overall SPS and disorders had similar prevalence patterns across sociodemographic characteristics. Subthreshold personality symptoms had the highest prevalence rates (schizotypal 21.3%, antisocial 18.3%, and borderline 17.6%), followed by posttraumatic stress (13.1%). Subthreshold bipolar and depression had lifetime prevalence rates of 2.7 and 8.5%, respectively. Prevalence rates of subthreshold anxiety symptoms ranged from 2.2% (agoraphobia) to 9.8% (specific phobia). Subthreshold eating disorder related symptoms had the lowest prevalence rates (anorexia 1.5% and bulimia 1.7%). Half (seven) of the SPS had significantly increased odds of lifetime AUD. This number increased to 12 for all SUD. Subthreshold antisocial personality symptoms had the highest odds of AUD (2.2; 95% CI 2.00-2.37) and SUD (3.5; 95% CI 3.22-3.81).
We found high lifetime SPS prevalence rates and significant associations with AUD and SUD. To our knowledge, this is the first published study evaluating a broad number of SPS. This indicates possible opportunities for early intervention and prevention but requires additional research and development of infrastructure and guidelines to better understand and manage patients who experience SPS.
Despite being characterized as a disorder of language production, nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) is frequently associated with auditory symptoms. However, to our ...knowledge, peripheral auditory function has not been defined in this condition.
To assess peripheral hearing function in individuals with nfvPPA compared with healthy older individuals and patients with Alzheimer disease (AD).
This cross-sectional single-center study was conducted at the Dementia Research Centre of University College London between August 2015 and July 2018. A consecutive cohort of patients with nfvPPA and patients with AD were compared with healthy control participants. No participant had substantial otological or cerebrovascular disease; all eligible patients fulfilling diagnostic criteria and able to comply with audiometry were included.
We measured mean threshold sound levels required to detect pure tones at frequencies of 500, 1000, 2000, 4000, and 6000 Hz in the left and right ears separately; these were used to generate better-ear mean and worse-ear mean composite hearing threshold scores and interaural difference scores for each participant. All analyses were adjusted for participant age.
We studied 19 patients with nfvPPA (9 female; mean SD age, 70.3 9.0 years), 20 patients with AD (9 female; mean SD age, 69.4 8.1 years) and 34 control participants (15 female; mean SD age, 66.7 6.3 years). The patients with nfvPPA had significantly higher scores than control participants on better-ear mean scores (patients with nfvPPA: mean SD, 36.3 9.4 decibels dB; control participants: 28.9 7.3 dB; age-adjusted difference, 5.7 95% CI, 1.4-10.0 dB; P = .01) and worse-ear mean scores (patients with nfvPPA: 42.2 11.5 dB; control participants: 31.7 8.1 dB; age-adjusted difference, 8.5 95% CI, 3.6-13.4 dB; P = .001). The patients with nfvPPA also had significantly higher better-ear mean scores than patients with AD (patients with AD: mean SD 31.1 7.5 dB; age-adjusted difference, 4.8 95% CI, 0.0-9.6 dB; P = .048) and worse-ear mean scores (patients with AD: mean SD, 33.8 8.2 dB; age-adjusted difference, 7.8 95% CI, 2.4-13.2 dB; P = .005). The difference scores (worse-ear mean minus better-ear mean) were significantly higher in the patients with nfvPPA (mean SD, 5.9 5.2 dB) than control participants (mean SD, 2.8 2.2 dB; age-adjusted difference, 2.8 95% CI, 0.9-4.7 dB; P = .004) and patients with AD (mean SD, 2.8 2.1 dB; age-adjusted difference, 3.0 95% CI, 0.9-5.1 dB; P = .005).
In this study, patients with nfvPPA performed worse on pure-tone audiometry than healthy older individuals or patients with AD, and the difference was not attributable to age or general disease factors. Cases of nfvPPA were additionally associated with increased functional interaural audiometric asymmetry. These findings suggest conjoint peripheral afferent and more central regulatory auditory dysfunction in individuals with nfvPPA.
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