Barriers to reporting non-motor symptoms to health-care providers in people with Parkinson's

Background: Non-motor symptoms (NMS) are common in Parkinson's disease (PD) and cause significant distress. A high rate of non-declaration of NMS by patients to healthcare providers (HCP) means that many NMS remain untreated. Current understanding of the factors preventing disclosure of NMS to HCPs is limited. The present study aimed to i) further assess the prevalence of NMS and associated distress, ii) establish current rates of NMS reporting across a range of sources, and iii) explore overall and any symptom specific barriers to help-seeking for NMS. Methods: 358 PD patients completed a cross-sectional survey of NMS severity, reporting and barriers to help-seeking. A series of Generalised Estimating Equations were used to determine whether barriers were symptom specific. Results: A mean of 10.5 NMS were reported by each patient. Rates of non-reporting of NMS ranged from 15 to 72% of those experiencing distressing symptoms. The most commonly reported barriers to help-seeking were acceptance of symptoms; lack of awareness that a symptom was associated with PD, and belief that no effective treatments were available. Symptom specific barriers were found for sexual dysfunction (embarrassment), unexplained pain and urinary problems (belief about lack of treatment availability). Conclusion: A diverse range of barriers prevent PD patients reporting NMS to HCPs and these barriers differ between NMS. The study provides the foundations for developing interventions to increase reporting by targeting individual NMS. Increasing rates of help-seeking for NMS by patients to their Parkinson's healthcare providers will increase appropriate clinical care which may improve quality of life and well-being

Examining acute psychopharmacological effects of nicotine vaping versus heated tobacco products in a randomised crossover study of product naive adult smokers

Nicotine vaping products (NVPs) and heated tobacco products (HTPs) are designed to replicate the sensory and behavioural aspects of smoking cigarettes while avoiding combustion. The success of these products as harm reduction tools will partially depend on their ability to satisfy smokers and alleviate nicotine-related withdrawal symptoms. This study aims to compare short-term effects of NVPs (Juul and Aspire PockeX) versus HTPs (IQOS) on smoking-related withdrawal relief, product satisfaction, intention to switch to NVP/HTP, perceptions and attitudes in UK adult cigarette smokers naïve to these products. In a randomized cross-over study, 45 participants visited the lab twice, at each visit trying one of the two products (NVP/HTP) and completing a questionnaire. Responses were normalized on a 0-100% scale and mean differences (MD) between NVP and HTP scores computed, with positive and negative MD values indicating greater endorsement for NVP and HTP, respectively. Cigarette cravings were reduced similarly (~20.0%) by both products (MD=4.5%, 95%Confidence Interval (CI) -4.8, 13.8). Direct positive effects (MD=-3.5%, 95%CI -7.2, 0.2) and adverse side effects (MD=1.8%, 95%CI -0.3, 3.8) were comparable after each product use, though marginally favouring HTPs. HTPs were perceived as more satisfying overall (MD=-13.2%, 95%CI -20.3 -6.1) than NVPs but both were perceived as similarly addictive (MD=3.6%, 95%CI -4.6, 11.8), relative to cigarettes. Intention to switch to either product was comparable (MD=4.0%, 95%CI -5.7, 13.8). Comparison of acute use of NVP versus HTP in a sample of UK smokers naïve to these products suggests that HTPs are perceived as more satisfying than NVPs, though still less satisfying than cigarettes

Spitzer Space Telescope Spectroscopy of Ices toward Low-Mass Embedded Protostars

Sensitive 5-38 μm Spitzer Space Telescope and ground-based 3-5 μm spectra of the embedded low-mass protostars B5 IRS1 and HH 46 IRS show deep ice absorption bands superposed on steeply rising mid-infrared continua. The ices likely originate in the circumstellar envelopes. The CO_2 bending mode at 15 μm is a particularly powerful tracer of the ice composition and processing history. Toward these protostars, this band shows little evidence for thermal processing at temperatures above 50 K. Signatures of lower temperature processing are present in the CO and OCN^- bands, however. The observed CO2 profile indicates an intimate mixture with H_(2)O, but not necessarily with CH_(3)OH, in contrast to some high-mass protostars. This is consistent with the low CH_(3)OH abundance derived from the ground-based L-band spectra. The CO_2 : H_(2)O column density ratios are high in both B5 IRS1 and HH 46 IRS (~35%). Clearly, the Spitzer spectra are essential for studying ice evolution in low-mass protostellar environments and for eventually determining the relation between interstellar and solar system ices

Averaged Energy Conditions in 4D Evaporating Black Hole Backgrounds

Using Visser's semi-analytical model for the stress-energy tensor corresponding to the conformally coupled massless scalar field in the Unruh vacuum, we examine, by explicitly evaluating the relevant integrals over half-complete geodesics, the averaged weak (AWEC) and averaged null (ANEC) energy conditions along with Ford-Roman quantum inequality-type restrictions on negative energy in the context of four dimensional evaporating black hole backgrounds. We find that in all cases where the averaged energy conditions fail, there exist quantum inequality bounds on the magnitude and duration of negative energy densities.Comment: Revtex, 13 pages, to appear in Phy. Rev.

Restrictions on Negative Energy Density in Flat Spacetime

In a previous paper, a bound on the negative energy density seen by an arbitrary inertial observer was derived for the free massless, quantized scalar field in four-dimensional Minkowski spacetime. This constraint has the form of an uncertainty principle-type limitation on the magnitude and duration of the negative energy density. That result was obtained after a somewhat complicated analysis. The goal of the current paper is to present a much simpler method for obtaining such constraints. Similar ``quantum inequality'' bounds on negative energy density are derived for the electromagnetic field, and for the massive scalar field in both two and four-dimensional Minkowski spacetime.Comment: 17 pages, including two figures, uses epsf, minor revisions in the Introduction, conclusions unchange

Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model.

The matrix metalloproteinase inhibitor batimastat was administered to a human colorectal cancer ascites model, which was initiated by injection of C170HM2 cells into the peritoneal cavity of SCID mice and resulted in solid tumour deposits and ascites formation. The cell line expressed both the 72 and 92 kDa forms of gelatinase by zymography. Batimastat administered from day 0 (40 mg kg-1) reduced the volume of ascites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly reduced to 77% of vehicle control when batimastat was administered from day 0 (P < 0.01) and 69% of control when administered from day 10 (P < 0.05). Thus, batimastat has the ability to reduce the volume of ascites forming in SCID mice injected intraperitoneally with the human colorectal cell line, C170HM2, when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in both treatment groups, highlighting the therapeutic potential of batimastat in this clinical condition

Cutibacterium acnes biofilm forming clinical isolates modify the formation and structure of Staphylococcus aureus biofilms, increasing their susceptibility to antibiotics

Cutibacterium acnes (formally Propionibacterium acnes) is frequently identified within surgical device related infections. It is often co-isolated from infection sites with other opportunistic pathogens. Recent studies have demonstrated that C. acnes is able to form biofilms and when co-cultured with Staphylococcus spp. both inhibitory and stimulatory effects have been reported across several studies. Here, we investigated the biofilm-forming ability of 100 clinical C. acnes isolates from various infection sites in human patients, both deep tissue and superficial, followed by an investigation of how the supernatants of C. acnes cultures influenced the attachment and maturation of S. aureus NCTC 6571 biofilms. All of the C. acnes isolates were able to form biofilms in vitro, although biofilm biomass varied between isolates. Nineteen isolates were weakly adherent, 33 were moderately adherent and the majority (48) showed strong adherence. The presence of C. acnes sterile supernatants reduced the biomass of S. aureus cultures, with a > 90% reduction observed in the presence of several of the C. acnes isolates. We observed that this decrease was not due to C. acnes affecting S. aureus viability, nor due to the presence of propionic acid. Biofilm maturation was however delayed over a 24-hour period as was biofilm surface structure, although initial (up to 8 h) surface attachment was not affected. We hypothesis that this defective biofilm maturation is the cause of the observed biomass decrease. In turn, these altered biofilms showed a greater susceptibility to antibiotic treatments. In contrast the presence of C. acnes supernatant in planktonic (defined as a free moving, non-surface attached population within the liquid column) S. aureus cultures increased antibiotic tolerance, via a currently undefined mechanism. This study suggests that complex interactions between C. acnes and other opportunistic pathogens are likely to exist during colonisation and infection events. Further investigation of these interactions may lead to increased treatment options and a better prognosis for patients

Structural and Functional Analysis of a Multimodular Hyperthermostable Xylanase-Glucuronoyl Esterase from Caldicellulosiruptor kristjansonii

The hyperthermophilic bacterium Caldicellulosiruptor kristjansonii encodes an unusual enzyme, CkXyn10C-GE15A, which incorporates two catalytic domains, a xylanase and a glucuronoyl esterase, and five carbohydrate-binding modules (CBMs) from families 9 and 22. The xylanase and glucuronoyl esterase catalytic domains were recently biochemically characterized, as was the ability of the individual CBMs to bind insoluble polysaccharides. Here, we further probed the abilities of the different CBMs from CkXyn10C-GE15A to bind to soluble poly- and oligosaccharides using affinity gel electrophoresis, isothermal titration calorimetry, and differential scanning fluorimetry. The results revealed additional binding properties of the proteins compared to the former studies on insoluble polysaccharides. Collectively, the results show that all five CBMs have their own distinct binding preferences and appear to complement each other and the catalytic domains in targeting complex cell wall polysaccharides. Additionally, through renewed efforts, we have achieved partial structural characterization of this complex multidomain protein. We have determined the structures of the third CBM9 domain (CBM9.3) and the glucuronoyl esterase (GE15A) by X-ray crystallography. CBM9.3 is the second CBM9 structure determined to date and was shown to bind oligosaccharide ligands at the same site but in a different binding mode compared to that of the previously determined CBM9 structure from Thermotoga maritima. GE15A represents a unique intermediate between reported fungal and bacterial glucuronoyl esterase structures as it lacks two inserted loop regions typical of bacterial enzymes and a third loop has an atypical structure. We also report small-angle X-ray scattering measurements of the N-terminal CBM22.1-CBM22.2-Xyn10C construct, indicating a compact arrangement at room temperature

The Quantum Interest Conjecture

Although quantum field theory allows local negative energy densities and fluxes, it also places severe restrictions upon the magnitude and extent of the negative energy. The restrictions take the form of quantum inequalities. These inequalities imply that a pulse of negative energy must not only be followed by a compensating pulse of positive energy, but that the temporal separation between the pulses is inversely proportional to their amplitude. In an earlier paper we conjectured that there is a further constraint upon a negative and positive energy delta-function pulse pair. This conjecture (the quantum interest conjecture) states that a positive energy pulse must overcompensate the negative energy pulse by an amount which is a monotonically increasing function of the pulse separation. In the present paper we prove the conjecture for massless quantized scalar fields in two and four-dimensional flat spacetime, and show that it is implied by the quantum inequalities.Comment: 17 pages, Latex, 3 figures, uses eps