Latent membrane protein 1 and macrophage-derived TNFα synergistically activate and mobilize invadopodia to drive invasion of nasopharyngeal carcinoma.

Invadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they have been visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Changes in relative peripheral refraction in children who switched from single-vision lenses to Defocus Incorporated Multiple Segments lenses.

PURPOSE: To investigate changes in relative peripheral refraction (RPR) associated with myopia progression in children who wore single-vision (SV) lenses for 2 years and switched to Defocus Incorporated Multiple Segments (DIMS) lenses in the third year versus children who wore DIMS lenses for 3 years. METHODS: In the first 2 years, children were allocated randomly to wear either DIMS or SV lenses. In the third year, children in the DIMS group continued to wear these lenses, while those in the SV group were switched to DIMS lenses (Control-to-DIMS group). Central and peripheral refraction and axial length were monitored every 6 months. RESULTS: Over 3 years, the DIMS group (n = 65) showed good myopia control and maintained a relatively constant and symmetrical RPR profile without significant changes. In the first 2 years, children who wore SV lenses (n = 55) showed asymmetrical RPR changes, with significant increases in hyperopic RPR at 20° nasal (N) (mean difference: 0.88 ± 1.06 D, p < 0.0001) and 30N (mean difference: 1.07 ± 1.09 D, p < 0.0001). The Control-to-DIMS group showed significant myopia retardation after wearing DIMS lenses in the third year. When compared with the RPR changes in the first 2 years, significant reductions in hyperopic RPR were observed at 20N (mean difference: -1.14 ± 1.93 D, p < 0.0001) and 30N (mean difference: -1.07 ± 1.17 D, p < 0.0001) in the third year. However, no significant difference between the RPR changes found in the nasal retina and temporal retina (p > 0.05) was noted in the third year. CONCLUSION: Symmetrical changes in RPR were found in children switching from SV to DIMS lenses, and a symmetrical pattern of RPR was noted in children who wore DIMS for 3 years. Myopia control using myopic defocus in the mid-periphery influenced the RPR changes and retarded myopia progression by altering the eye's growth pattern.

Efficacy of physical therapy interventions on quality of life and upper quadrant pain severity in women with post-mastectomy pain syndrome: a systematic review and meta-analysis.

PURPOSE: To determine the efficacy of physical therapy interventions on quality of life (QoL) and pain severity in post-mastectomy pain syndrome (PMPS). METHODS: Multiple databases were searched from database inception to October 2020. Searches were limited to human studies published in either English or Chinese in peer-reviewed journals with full text available for randomized controlled trials conducted on females. Trials comparing the effectiveness of physical therapy interventions against control conditions on QoL and pain were included. RESULTS: Eighteen trials were included in the review. The pooled analysis of the four exercise trials revealed a significant effect of the intervention on general [standardized mean difference [SMD]: 0.87 (95%CI: 0.36, 1.37); p = 0.001], physical [SMD: 0.34 (95%CI: 0.01, 0.66); p = 0.044], and mental health components [SMD: 0.27 (95%CI: 0.03, 0.51); p = 0.027] of QoL compared with the control condition. Meta-analyses of six exercise trials, two myofascial release trials, and two acupuncture trials revealed a significant improvement in pain severity in the treatment group than in the control group. However, meta-analyses of two studies revealed a non-significant effect of compression therapy compared to control on pain severity. CONCLUSION: Our meta-analyses found that exercise is beneficial for improving the QoL and pain severity of women with PMPS. Future studies are needed to determine the optimal parameters for exercise interventions designed to improve QoL and pain severity in women with PMPS. The effect of acupuncture, myofascial release, and compression therapy remains inconclusive, and future research is required to validate the effect of these interventions on PMPS.

Assessment of droplet digital polymerase chain reaction for measuring BCR-ABL1 in chronic myeloid leukaemia in an international interlaboratory study.

Measurement of BCR activator of RhoGEF and GTPase -ABL proto-oncogene 1, non-receptor tyrosine kinase (BCR-ABL1) mRNA levels by reverse transcription quantitative polymerase chain reaction (RTqPCR) has been critical to treatment protocols and clinical trials in chronic myeloid leukaemia; however, interlaboratory variation remains a significant issue. Reverse transcriptase droplet digital PCR (RTddPCR) has shown potential to improve testing but a large-scale interlaboratory study is required to definitively establish this. In the present study, 10 BCR-ABL1-positive samples with levels ranging from molecular response (MR)1·0 -MR5·0 were tested by 23 laboratories using RTddPCR with the QXDX BCR-ABL %IS kit. A subset of participants tested the samples using RTqPCR. All 23 participants using RTddPCR detected BCR-ABL1 in all samples to MR4·0 . Detection rates for deep-response samples were 95·7% at MR4·5 , 78·3% at MR4·7 and 87·0% at MR5·0 . Interlaboratory coefficient of variation was indirectly proportional to BCR-ABL1 level ranging from 29·3% to 69·0%. Linearity ranged from 0·9330 to 1·000 (average 0·9936). When results were compared for the 11 participants who performed both RTddPCR and RTqPCR, RTddPCR showed a similar limit of detection to RTqPCR with reduced interlaboratory variation and better assay linearity. The ability to detect deep responses with RTddPCR, matched with an improved linearity and reduced interlaboratory variation will allow improved patient management, and is of particular importance for future clinical trials focussed on achieving and maintaining treatment-free remission.

Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update.

BACKGROUND: While phosphodiesterase type-5 inhibitors (PDE5Is) are highly effective for the treatment of erectile dysfunction (ED) and well tolerated, updated data on prescription patterns have been limited in real-world settings. AIM: To describe men in the United States who are prescribed PDE5Is for ED treatment and to evaluate patterns of initiation, switching, and treatment overlap. METHODS: This retrospective claims study used MarketScan Commercial and Medicare Supplement Databases from January 1, 2010, to December 31, 2015, to identify initial PDE5I claims (index date) for sildenafil, tadalafil, and/or vardenafil. Adults aged ≥18 years with ED were identified between July 1, 2010, and December 31, 2014, allowing for a 6-month preindex and 12-month follow-up period from the index date. OUTCOMES: Outcomes included patient demographics and treatment-related patterns after treatment initiation. RESULTS: A total of 106,206 identified patients met all inclusion criteria. Of these, 51,694, 40,193, and 14,319 had initial claims for sildenafil, tadalafil, and vardenafil, respectively. Mean age was 50.35 years, and comorbidities included dyslipidemia (44.17%), hypertension (43.09%), diabetes (15.32%), and depression (10.61%). More patients (48.67%) initiated on sildenafil than tadalafil (37.85%) or vardenafil (13.48%). Rate of switching was lower in the 60 days after the end of day supply of the initial prescription in the sildenafil cohort (2.71%) compared with the tadalafil (2.81%) and vardenafil (3.88%) cohorts (P < .001 for sildenafil vs tadalafil or vardenafil). Treatment overlap was lower in the sildenafil cohort (0.35%) than in the tadalafil (0.75%) and vardenafil (0.62%) groups (P < .001 for sildenafil vs tadalafil or vardenafil). CLINICAL IMPLICATIONS: These findings provide insight into updated patterns of PDE5I prescriptions in the United States and may aid in clinical decision-making. STRENGTHS & LIMITATIONS: Strengths include the large sample size, long data coverage period, and the real-world nature of the study. Limitations include the retrospective study design, use of data collected with a primary focus of claims, and lack of further details regarding reasons that drive switching. Actual rates of ED and impact on prescription patterns may be underestimated because the claims database only captured patients electing to visit a health-care provider. CONCLUSION: Among men with ED in the United States, rates of switching and treatment overlap were low for all PDE5Is but were found to be the lowest for sildenafil compared with tadalafil and vardenafil. Mulhall JP, Chopra I, Patel D, et al. Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update. J Sex Med 2020;17:941-948.

Long-term stability of multilayer MoS2 transistors with mica gate dielectric.

To avoid surface damage of a MoS2 channel, a mica flake with high permittivity and atomically flat surface was dry transferred onto a multilayer MoS2 flake to prepare top-gated transistors. For the first time, the interface properties of mica/MoS2 and the long-term stability of devices were investigated when the transistors were exposed to ambient air. Results show that the electrical performance of the transistors is degraded significantly when the devices are exposed to ambient moisture for a long time, due to the strong hydrophilism of mica. The transfer curves of the transistors cannot be recovered to their initial states even after annealing. The adsorbed moisture can become trapped at the interface between the MoS2 channel and mica dielectric or on the MoS2 surface, resulting in enhanced carrier scattering and degraded device performance. However, the top-gated MoS2 transistor with Al2O3 encapsulation exhibits enhanced stability even after annealing or exposure to atmosphere for 200 days. The excellent stability should be attributed to the effective insulation of moisture from the ambient air by Al2O3 encapsulation. Therefore, a dense and hydrophobic encapsulation layer is indispensable for stable and high-performance top-gated MoS2 transistors with mica gate dielectric.

Optimizing Al-doped ZrO2 as the gate dielectric for MoS2 field-effect transistors.

In this work, we investigate the effects on the electrical properties of few-layered MoS2 field-effect transistors (FETs) following Al incorporation into ZrO2 as the gate dielectrics of the devices. A large improvement in device performance is achieved with the Al-doped ZrO2 gate dielectric when Zr:Al = 1:1. The relevant MoS2 transistor exhibits the best electrical characteristics: high carrier mobility of 40.6 cm2 V-1 s-1 (41% higher than that of the control sample, and an intrinsic mobility of 68.0 cm2 V-1 s-1), a small subthreshold swing of 143 mV dec-1, high on/off current ratio of 6 × 106 and small threshold voltage of 0.71 V. These are attributed to the facts that (i) Al incorporation into ZrO2 can decrease its oxygen vacancies; densify the dielectric film; and smooth the gate dielectric surface, thus reducing the traps at/near the Zr0.5Al0.5O y /MoS2 interface and the gate leakage current; (ii) adjusting the dielectric constant of the gate dielectric to an appropriate value, which achieves a reasonable trade-off between the gate screening effect on the Coulomb-impurity scattering and the surface optical phonon scattering. These results demonstrate that optimized Zr0.5Al0.5Oy is a potential gate dielectric material for MoS2 FET applications.

Next-generation sequencing with a 54-gene panel identified unique mutational profile and prognostic markers in Chinese patients with myelofibrosis.

Current prognostication in myelofibrosis (MF) is based on clinicopathological features and mutations in a limited number of driver genes. The impact of other genetic mutations remains unclear. We evaluated for mutations in a myeloid panel of 54 genes using next-generation sequencing. Multivariate Cox regression analysis was used to determine prognostic factors for overall survival (OS) and leukaemia-free survival (LFS), based on mutations of these genes and relevant clinical and haematological features. One hundred and one patients (primary MF, N = 70; secondary MF, N = 31) with a median follow-up of 49 (1-256) months were studied. For the entire cohort, inferior OS was associated with male gender (P = 0.04), age > 65 years (P = 0.04), haemoglobin < 10 g/dL (P = 0.001), CUX1 mutation (P = 0.003) and TP53 mutation (P = 0.049); and inferior LFS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.04) and SRSF2 mutations (P = 0.008). In primary MF, inferior OS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.002), platelet count < 100 × 109/L (P = 0.02), TET2 mutation (P = 0.01) and CUX1 mutation (P = 0.01); and inferior LFS was associated with haemoglobin < 10 g/dL (P = 0.02), platelet count < 100 × 109/L (P = 0.02), TET2 mutations (P = 0.01) and CUX1 mutations (P = 0.04). These results showed that clinical and haematological features and genetic mutations should be considered in MF prognostication.

Damage-free mica/MoS2 interface for high-performance multilayer MoS2 field-effect transistors.

For top-gated MoS2 field-effect transistors, damaging the MoS2 surface to the MoS2 channel are inevitable due to chemical bonding and/or high-energy metal atoms during the vacuum deposition of gate dielectric, thus leading to degradations of field-effect mobility (µ FE) and subthreshold swing (SS). A top-gated MoS2 transistor is fabricated by directly transferring a 9 nm mica flake (as gate dielectric) onto the MoS2 surface without any chemical bonding, and exhibits excellent electrical properties with an on-off ratio of ∼108, a low threshold voltage of ∼0.2 V, a record µ FE of 134 cm2 V-1 s-1, a small SS of 72 mV dec-1 and a low interface-state density of 8.8 × 1011 cm-2 eV-1, without relying on electrode-contact engineered and/or phase-engineered MoS2. Although the equivalent oxide thickness of the mica dielectric is in the sub-5 nm regime, enhanced stability characterized by normalized threshold voltage shift (1.2 × 10-2 V MV-1 cm-1) has also been demonstrated for the transistor after a gate-bias stressing at 4.4 MV cm-1 for 103 s. All these improvements should be ascribed to a damage-free MoS2 channel achieved by a dry transfer of gate dielectric and a clean and smooth surface of the mica flake, which greatly decreases the charged-impurity and interface-roughness scatterings. The proposed transistor with low threshold voltage and high stability is highly desirable for low-power electronic applications.

National Health and Wellness Survey exploratory cluster analysis of males 40-70 years old focused on erectile dysfunction and associated risk factors across the USA, Italy, Brazil and China.

OBJECTIVES: Prior studies of erectile dysfunction (ED) tend to narrowly focus on relationships with specific comorbidities, rather than evaluating a more comprehensive array of risk factors and assessing naturalistic patterns among them. This study identifies natural clusters of male characteristics from a general population sample per country, quantifies ED dynamics in these profiles and compares profiles across the US, Italy, Brazil and China samples. METHODS: National Health and Wellness Survey 2015 and 2016 patient-reported data on men aged 40-70 years (USA n = 15,652; Italy n = 2,521; Brazil n = 2,822; China n = 5,553) were analysed. Hierarchical agglomerative clustering identified clusters where predictors included demographics, health characteristics/behaviours, ED risk factors and provider visits in the past 6 months. Multinomial logistic regression assessed the independent utility of variables in predicting cluster membership, compared with the healthiest control cluster per country. RESULTS: Different natural clusters were found across countries, with four clusters for the USA, Italy and China and three clusters for Brazil. Age, income, employment, health behaviours and ED risk factors predicted different cluster membership across countries. In the USA, Italy and Brazil, younger clusters were predicted by ED, unhealthy behaviours and ED risk factors. Unique cluster profiles were identified in China, with ED and ED risk factors (aside from hypertension) not predicting cluster membership, while socio-demographics and health behaviours were strongly predictive. CONCLUSIONS: Natural cluster profiles revealed notable ED rates among adult males of age 40-70 in four different countries. Clusters were mainly predicted by unhealthy behaviours, ED risk factors and ED, regardless of level or presence of positive health characteristics and behaviours. This analysis identified meaningful subgroups of men with heightened ED risk factors, which can help healthcare providers to better recognise specific populations with the greatest need for intervention.

The association of erectile dysfunction with productivity and absenteeism in eight countries globally.

AIM: To evaluate the association of erectile dysfunction (ED) with work productivity loss, activity impairment and health-related quality of life (HRQoL) across Brazil, China, France, Germany, Italy, Spain, the UK and the US. METHODS: This cross-sectional observational study used data from adult men (40-70 years old; N = 52 697) from the 2015 and 2016 National Health and Wellness Surveys. ED assessment was based on self-reported difficulty in achieving or maintaining an erection in the past 6 months. Impairment to work and non-work activities and HRQoL were assessed for each country and compared against the US. Multivariable models tested interactions between ED status and country for each outcome. RESULTS: Overall ED prevalence was reported as 49.7%, with Italy reporting the highest rate (54.7%). Men with ED reported significantly higher absenteeism (7.1% vs 3.2%), presenteeism (22.5% vs 10.1%), overall work productivity impairment (24.8% vs 11.2%), activity impairment (28.6% vs 14.5%) and significantly lower Mental Component Summary scores (MCS; 46.7 vs 51.2), Physical Component Summary scores (PCS; 48.3 vs 53.0), and health state utilities (SF-6D: 0.693 vs 0.778; all, P < 0.001) than men with no ED. After adjusting for covariates, compared with the US, the association of ED status with overall work productivity impairment was greatest in the UK (26% higher; P < 0.05), and with MCS, PCS and SF-6D scores was greatest in China (-2.67, -1.58, and -0.043 points, respectively; all, P < 0.001). Greater ED severity was significantly associated with higher impairment to work and non-work activities and lower HRQoL, with China reporting the highest burden, compared with the US (most P < 0.05). CONCLUSION: ED poses a significant burden with respect to work productivity and HRQoL, with greater severity associated with worse outcomes. Better management and earlier detection may help reduce this burden, especially in countries reporting a strong association between ED and poor economic and health outcomes.

Effects of HfO2 encapsulation on electrical performances of few-layered MoS2 transistor with ALD HfO2 as back-gate dielectric.

The carrier mobility of MoS2 transistors can be greatly improved by the screening role of high-k gate dielectric. In this work, atomic-layer deposited (ALD) HfO2 annealed in NH3 is used to replace SiO2 as the gate dielectric to fabricate back-gated few-layered MoS2 transistors, and good electrical properties are achieved with field-effect mobility (µ) of 19.1 cm2 V-1 s-1, subthreshold swing (SS) of 123.6 mV dec-1 and on/off ratio of 3.76 × 105. Furthermore, enhanced device performance is obtained when the surface of the MoS2 channel is coated by an ALD HfO2 layer with different thicknesses (10, 15 and 20 nm), where the transistor with a 15 nm HfO2 encapsulation layer exhibits the best overall electrical properties: µ = 42.1 cm2 V-1 s-1, SS = 87.9 mV dec-1 and on/off ratio of 2.72 × 106. These improvements should be associated with the enhanced screening effect on charged-impurity scattering and protection from absorption of environmental gas molecules by the high-k encapsulation. The capacitance equivalent thickness of the back-gate dielectric (HfO2) is only 6.58 nm, which is conducive to scaling of the MoS2 transistors.

Resilience and well-being of university nursing students in Hong Kong: a cross-sectional study.

BACKGROUND: University nursing students experience higher levels of academic stress than those of other disciplines. Academic stress leads to psychological distress and has detrimental effects on well-being. The ability to overcome such adversity and learn to be stronger from the experience is regarded as resilience. Resilience is found to have an impact on learning experience, academic performance, course completion and, in the longer term, professional practice. Resilience and positive coping strategies can resist stress and improve personal well-being. However, the relationship between resilience and well-being remains unexplored in nursing students, which are significant attributes to their academic success and future career persistence. METHODS: The study was a cross-sectional descriptive correlational design. Inclusion criteria for recruitment was students studying pre-registration nursing programmes at both undergraduate and postgraduate levels. The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) and World Health Organisation-5 Well-Being Index (WHO-5) were used to measure resilience and psychological well-being respectively. RESULTS: A convenience sample of 678 university nursing students was recruited from a university. The mean score of CD-RISC-10 was 24.0. When comparing the resilience levels of undergraduate and postgraduate students, the total scores were found to be 23.8 and 24.9 respectively. There was a statistically significant difference between the groups (p = .020). With regard to perceived well-being, the mean score of WHO-5 was 15.5. There was no significant difference between undergraduates and postgraduates (p = .131). Bivariate analysis showed that self-reported resilience had a medium, positive correlation with perceived well-being (r = .378, p = .000), and senior students had significantly higher level of perceived well-being than junior students (16.0 vs 15.1, p = .003). Multivariable regression analysis on perceived well-being indicated that self-reported resilience emerged as a significant predictor of perceived well-being (regression coefficient B = 0.259; p < .001). CONCLUSIONS: The results demonstrate that nursing students with a high level of resilience have better perceived well-being, and the level of resilience of postgraduates was significantly higher than that of undergraduates. Therefore, educational strategies should be developed in the nursing curriculum and a supportive learning environment should be created to foster resilience in the students.

Aqueous manganese dioxide ink for paper-based capacitive energy storage devices.

We report a simple approach based on a chemical reduction method to synthesize aqueous inorganic ink comprised of hexagonal MnO2 nanosheets. The MnO2 ink exhibits long-term stability and continuous thin films can be formed on various substrates without using any binder. To obtain a flexible electrode for capacitive energy storage, the MnO2 ink was printed onto commercially available A4 paper pretreated with multiwalled carbon nanotubes. The electrode exhibited a maximum specific capacitance of 1035 F g(-1) (91.7 mF cm(-2)). Paper-based symmetric and asymmetric capacitors were assembled, which gave a maximum specific energy density of 25.3 Wh kg(-1) and a power density of 81 kW kg(-1). The device could maintain a 98.9% capacitance retention over 10 000 cycles at 4 A g(-1). The MnO2 ink could be a versatile candidate for large-scale production of flexible and printable electronic devices for energy storage and conversion.

How representative is the 'Representative Value' of refraction provided by the Shin-Nippon NVision-K 5001 autorefractor?

PURPOSE: The aim of the study was to evaluate the level of agreement between the 'Representative Value' (RV) of refraction obtained from the Shin-Nippon NVision-K 5001 instrument with values calculated from individual measurement readings using standard algebraic methods. METHODS: Cycloplegic autorefraction readings for 101 myopic children aged 8-13 years (10.9 ± 1.42 years) were obtained using the Shin-Nippon NVision-K 5001. Ten autorefractor measurements were taken for each eye. The spherical equivalent (SE), sphere (Sph) and cylindrical component (Cyl) power of each eye were calculated, firstly, by averaging the 10 repeated measurements (Mean SE, Mean Sph and Mean Cyl), and secondly, by the vector representation method (Vector SE, Vector Sph and Vector Cyl). These calculated values were then compared with those of RV (RV SE, RV Sph and RV Cyl) provided by the proprietary software of the NVision-K 5001 using one-way analysis of variance (anova). The agreement between the methods was also assessed. RESULTS: The SE of the subjects ranged from -5.37 to -0.62 D (mean ± SD, = -2.89 ± 1.01 D). The Mean SE was in exact agreement with the Vector SE. There were no significant differences between the RV readings and those calculated using non-vectorial or vectorial methods for any of the refractive powers (SE, p = 0.99; Sph, p = 0.93; Cyl, p = 0.24). The (mean ± SD) differences were: RV SE vs Mean SE (and also RV SE vs Vector SE) -0.01 ± 0.06 D; RV Sph vs Mean Sph, -0.01 ± 0.05 D; RV Sph vs Vector Sph, -0.04 ± 0.06 D; RV Cyl vs Mean Cyl, 0.01 ± 0.07 D; RV Cyl vs Vector Cyl, 0.06 ± 0.09 D. Ninety-eight percent of RV reading differed from their non-vectorial or vectorial counterparts by less than 0.25 D. CONCLUSION: The RV values showed good agreement to the results calculated using conventional methods. Although the formula used to calculate RV by the NVision-K 5001 autorefractor is proprietary, our results provide validation for the use of RV measurements in clinical practice and vision science research.

The inter-rater reliability test of the modified Morse Fall Scale among patients ≥ 55 years old in an acute care hospital in Singapore.

A prospective, descriptive study was conducted in an acute care hospital in Singapore to determine the inter-rater reliability of the modified Morse Fall Scale by evaluating the degrees of agreement on the ratings of the individual items and overall score between the 'gold standard' assessor and the facility assessors. One hundred and forty-two subjects were recruited during the 1.5 month data collection period. The simple and weighted κ-values were all > 0.8 except for the item 'effects of medications' (κ and κw = 0.63), and the correlation coefficient (rs = 0.89) was significantly high at a significance level of < 0.001. The modified Morse Fall Scale was shown to be a reliable fall risk assessment tool having a relative high inter-rater reliability level for the overall score and individual items. This study provides evidence-based psychometric support for the clinical application of this tool.

Masked Reactivity of Hydrated Clusters of Monovalent Manganese Ions: Water Insertion versus Nitrous Oxide Activation-A Density Functional Theory Investigation.

Previous mass spectrometric (MS) studies demonstrated that singly charged hydration clusters of manganese ions [Mn(H2O)n]+ were, on one hand, highly reactive toward intracluster water insertion but, on the other hand, inert toward nitrous oxide activation. This contrast in reactivity has been rationalized by our present theoretical investigation for the interconversion between the pristine Mn(I) monovalent form as a monatomic ion in [MnI(H2O)n]+ and the oxidized Mn(III) trivalent form as a hydride-hydroxide in [HMnIIIOH(H2O)n-1], as well as their reactivity toward nitrous oxide activation. Our theoretical interpretations are supported with quantum chemical calculations based on density functional theory (DFT), performed systematically for the cluster-size range of n = 1 - 12. Our DFT results show that water insertion is kinetically and thermodynamically favorable for n ≥ 8, suggesting [HMnIIIOH(H2O)n-1]+ is the predominant form, as observed in previous MS experiments. While [MnI(H2O)n]+ is capable of N2O reduction, the process of which is highly exothermic, similar reactions are unfavorable with [HMnIIIOH(H2O)n-1]+, which can only form weakly bound adducts with N2O. This work demonstrates the masking effect of water molecules over the high reactivity of the hydrated Mn(I) center and sheds light on the potential roles of water in transition metal systems.

Juglone as a Natural Quorum Sensing Inhibitor against Pseudomonas aeruginosa pqs-Mediated Virulence and Biofilms.

Pseudomonas aeruginosa is a notorious opportunistic pathogen associated with chronic biofilm-related infections, posing a significant challenge to effective treatment strategies. Quorum sensing (QS) and biofilm formation are critical virulence factors employed by P. aeruginosa, contributing to its pathogenicity and antibiotic resistance. Other than the homoserine-based QS systems, P. aeruginosa also possesses the quinolone-based Pseudomonas quinolone signal (PQS) QS signaling. Synthesis of the PQS signaling molecule is achieved by the pqsABCDEH operon, whereas the PQS signaling response was mediated by the PqsR receptor. In this study, we report the discovery of a novel natural compound, Juglone, with potent inhibitory effects on pqs QS and biofilm formation in P. aeruginosa. Through an extensive screening of natural compounds from diverse sources, we identified Juglone, a natural compound from walnut, as a promising candidate. We showed that Juglone could inhibit PqsR and the molecular docking results revealed that Juglone could potentially bind to the PqsR active site. Furthermore, Juglone could inhibit pqs-regulated virulence factors, such as pyocyanin and the PQS QS signaling molecule. Juglone could also significantly reduce both the quantity and quality of P. aeruginosa biofilms. Notably, this compound exhibited minimal cytotoxicity toward mammalian cells, suggesting its potential safety for therapeutic applications. To explore the clinical relevance of Juglone, we investigated its combinatorial effects with colistin, a commonly used antibiotic against P. aeruginosa infections. The Juglone-colistin combinatorial treatment could eliminate biofilms formed by wild-type P. aeruginosa PAO1 and its clinical isolates collected from cystic fibrosis patients. The Juglone-colistin combinatorial therapy dramatically improved colistin efficacy and reduced inflammation in a wound infection model, indicating its potential for clinical utility. In conclusion, the discovery of Juglone provides insights into the development of innovative antivirulence therapeutic strategies to combat P. aeruginosa biofilm-associated infections.

Impact of diet change on the gut microbiome of common marmosets (Callithrix jacchus).

Gastrointestinal diseases are the most frequently reported clinical problems in captive common marmosets (Callithrix jacchus), often affecting the health and welfare of the animal and ultimately their use as a research subject. The microbiome has been shown to be intimately connected to diet and gastrointestinal health. Here, we use shotgun metagenomics and untargeted metabolomics in fecal samples of common marmosets collected before, during, and after a dietary transition from a biscuit to a gel diet. The overall health of marmosets, measured as weight recovery and reproductive outcome, improved after the diet transition. Moreover, each marmoset pair had significant shifts in the microbiome and metabolome after the diet transition. In general, we saw a decrease in Escherichia coli and Prevotella species and an increase in Bifidobacterium species. Untargeted metabolic profiles indicated that polyamine levels, specifically cadaverine and putrescine, were high after diet transition, suggesting either an increase in excretion or a decrease in intestinal reabsorption at the intestinal level. In conclusion, our data suggest that Bifidobacterium species could potentially be useful as probiotic supplements to the laboratory marmoset diet. Future studies with a larger sample size will be beneficial to show that this is consistent with the diet change. IMPORTANCE: Appropriate diet and health of the common marmoset in captivity are essential both for the welfare of the animal and to improve experimental outcomes. Our study shows that a gel diet compared to a biscuit diet improves the health of a marmoset colony, is linked to increases in Bifidobacterium species, and increases the removal of molecules associated with disease. The diet transition had an influence on the molecular changes at both the pair and time point group levels, but only at the pair level for the microbial changes. It appears to be more important which genes and functions present changed rather than specific microbes. Further studies are needed to identify specific components that should be considered when choosing an appropriate diet and additional supplementary foods, as well as to validate the benefits of providing probiotics. Probiotics containing Bifidobacterium species appear to be useful as probiotic supplements to the laboratory marmoset diet, but additional work is needed to validate these findings.