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We conducted an analysis of a nationwide survey of US physician offices between 2016 and 2019 and calculated annualized prevalence rates of urinary tract infections (UTIs). During the 3-year study period, UTI was the most common infection in US physician offices, accounting for approximately 10 million annualized encounters.
The World Cancer Research Fund and the American Institute for Cancer Research recommend a plant-based diet to cancer survivors, which may reduce chronic inflammation and excess adiposity associated with worse survival. We investigated associations of plant-based dietary patterns with inflammation biomarkers and body composition in the Pathways Study, in which 3659 women with breast cancer provided validated food frequency questionnaires approximately 2 months after diagnosis. We derived three plant-based diet indices: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI). We assayed circulating inflammation biomarkers related to systemic inflammation (high-sensitivity C-reactive protein [hsCRP]), pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13). We estimated areas (cm2) of muscle and visceral and subcutaneous adipose tissue (VAT and SAT) from computed tomography scans. Using multivariable linear regression, we calculated the differences in inflammation biomarkers and body composition for each index. Per 10-point increase for each index: hsCRP was significantly lower by 6·9 % (95 % CI 1·6%, 11·8%) for PDI and 9·0 % (95 % CI 4·9%, 12·8%) for hPDI but significantly higher by 5·4 % (95 % CI 0·5%, 10·5%) for uPDI, and VAT was significantly lower by 7·8 cm2 (95 % CI 2·0 cm2, 13·6 cm2) for PDI and 8·6 cm2 (95 % CI 4·1 cm2, 13·2 cm2) for hPDI but significantly higher by 6·2 cm2 (95 % CI 1·3 cm2, 11·1 cm2) for uPDI. No significant associations were observed for other inflammation biomarkers, muscle, or SAT. A plant-based diet, especially a healthful plant-based diet, may be associated with reduced inflammation and visceral adiposity among breast cancer survivors.
Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.
Syphilis remains a serious public health problem in mainland China that requires attention, modelling to describe and predict its prevalence patterns can help the government to develop more scientific interventions. The seasonal autoregressive integrated moving average (SARIMA) model, long short-term memory network (LSTM) model, hybrid SARIMA-LSTM model, and hybrid SARIMA-nonlinear auto-regressive models with exogenous inputs (SARIMA-NARX) model were used to simulate the time series data of the syphilis incidence from January 2004 to November 2023 respectively. Compared to the SARIMA, LSTM, and SARIMA-LSTM models, the median absolute deviation (MAD) value of the SARIMA-NARX model decreases by 352.69%, 4.98%, and 3.73%, respectively. The mean absolute percentage error (MAPE) value decreases by 73.7%, 23.46%, and 13.06%, respectively. The root mean square error (RMSE) value decreases by 68.02%, 26.68%, and 23.78%, respectively. The mean absolute error (MAE) value decreases by 70.90%, 23.00%, and 21.80%, respectively. The hybrid SARIMA-NARX and SARIMA-LSTM methods predict syphilis cases more accurately than the basic SARIMA and LSTM methods, so that can be used for governments to develop long-term syphilis prevention and control programs. In addition, the predicted cases still maintain a fairly high level of incidence, so there is an urgent need to develop more comprehensive prevention strategies.
Polarized electron beam production via laser wakefield acceleration in pre-polarized plasma is investigated by particle-in-cell simulations. The evolution of the electron beam polarization is studied based on the Thomas–Bargmann–Michel–Telegdi equation for the transverse and longitudinal self-injection, and the depolarization process is found to be influenced by the injection schemes. In the case of transverse self-injection, as found typically in the bubble regime, the spin precession of the accelerated electrons is mainly influenced by the wakefield. However, in the case of longitudinal injection in the quasi-1D regime (for example, F. Y. Li et al., Phys. Rev. Lett. 110, 135002 (2013)), the direction of electron spin oscillates in the laser field. Since the electrons move around the laser axis, the net influence of the laser field is nearly zero and the contribution of the wakefield can be ignored. Finally, an ultra-short electron beam with polarization of $99\%$ can be obtained using longitudinal self-injection.
Bentonites are readily available clays used in the livestock industry as feed additives to reduce aflatoxin (AF) exposure; their potential interaction with nutrients is the main concern limiting their use, however. The objective of the present study was to determine the safety of a dietary sodium-bentonite (Na-bentonite) supplement as a potential AF adsorbent, using juvenile Sprague Dawley (SD) rats as a research model. Animals were fed either a control diet or a diet containing Na-bentonite at 0.25% and 2% (w/w) inclusion rate. Growth, serum, and blood biochemical parameters, including selected serum vitamins (A and E) and elements such as calcium (Ca), potassium (K), iron (Fe), and zinc (Zn) were measured. The mineral characteristics and the aflatoxin B1 sorption capacity of Na-bentonite were also determined. By the end of the study, males gained more weight than females in control and Na-bentonite groups (p ≤ 0.0001); the interaction between treatment and sex was not significant (p = 0.6780), however. Some significant differences between the control group and bentonite treatments were observed in serum biochemistry and vitamin and minerals measurements; however, parameters fell within reference clinical values reported for SD rats and no evidence of dose-dependency was found. Serum Na and Na/K ratios were increased, while K levels were decreased in males and females from Na-bentonite groups. Serum Zn levels were decreased only in males from Na-bentonite treatments. Overall, results showed that inclusion of Na-bentonite at 0.25% and 2% did not cause any observable toxicity in a 3-month rodent study.
The adsorption of two dinitrophenol herbicides, 4,6-dinitro-o-cresol (DNOC) and 4,6-dinitro-o-sec-butyl phenol (dinoseb), by two reference smectite clays (SWy-2 and SAz-1) was evaluated using a combination of sorption isotherms, Fourier transformation infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and molecular dynamic simulations. Clays were subject to saturation with various cations, and charge reduction. The DNOC adsorption decreased with increasing pH indicating that DNOC was primarily adsorbed as the neutral species. The FTIR spectra of DNOC-clay films showed that DNOC molecules are oriented parallel to the clay surface. Interlayer cations have a strong effect on adsorption depending largely on their hydration energies. Weakly hydrated cations, e.g. K+ and Cs+, resulted in greater sorption compared to more strongly hydrated cations such as Na+ or Ca2+. Lower hydration favors direct interactions of exchangeable cations with -NO2 groups of DNOC and manifests optimal interlayer spacings for adsorption. In the presence of sorbed DNOC, an interlayer spacing for K-SWy-2 of between 12 and 12.5 Å was maintained regardless of the presence of water. This d-spacing allowed DNOC molecules to interact simultaneously with the opposing clay layers thus minimizing contact of DNOC with water. The charge density of clays also affected sorption by controlling the size of adsorption domains. Accordingly, DNOC adsorption by low-charge clay (K-SWy-2) was much higher than by high-charge clay (K-SAz-1) and Li-charge reduction greatly enhanced dinoseb adsorption by K-SAz-1. Steric constraints were also evident from the observation that adsorption of DNOC, which contains a methyl substituent, was much greater than dinoseb, which contains a bulkier isobutyl group. Adsorption of DNOC by K-SAz-1 was not affected in the presence of dinoseb, whereas dinoseb adsorption was greatly reduced in the presence of DNOC.
Episodic memory functioning is distributed across two brain circuits, one of which courses through the dorsal anterior cingulate cortex (dACC). Thus, delivering non-invasive neuromodulation technology to the dACC may improve episodic memory functioning in patients with memory problems such as in amnestic mild cognitive impairment (aMCI). This preliminary study is a randomized, double-blinded, sham-controlled clinical trial to examine if high definition transcranial direct current stimulation (HD-tDCS) can be a viable treatment in aMCI.
Participants and Methods:
Eleven aMCI participants, of whom 9 had multidomain deficits, were randomized to receive 1 mA HD-tDCS (N=7) or sham (N=4) stimulation. HD-tDCS was applied over ten 20-minute sessions targeting the dACC. Neuropsychological measures of episodic memory, verbal fluency, and executive function were completed at baseline and after the last HD-tDCS session. Changes in composite scores for memory and language/executive function tests were compared between groups (one-tailed t-tests with a = 0.10 for significance). Clinically significant change, defined as > 1 SD improvement on at least one test in the memory and non-memory domains, was compared between active and sham stimulation based on the frequency of participants in each.
Results:
No statistical or clinically significant change (N-1 X2; p = 0.62) was seen in episodic memory for the active HD-tDCS (MDiff = 4.4; SD = 17.1) or sham groups (MDiff = -0.5; SD = 9.7). However, the language and executive function composite showed statistically significant improvement (p = 0.04; MDiff = -15.3; SD = 18.4) for the active HD-tDCS group only (Sham MDiff = -5.8; SD = 10.7). Multiple participants (N=4) in the active group had clinically significant enhancement in language and executive functioning tests, while nobody in the sham group did (p = 0.04).
Conclusions:
HD-tDCS targeting the dACC had no direct benefit for episodic memory deficits in aMCI based on preliminary findings for this ongoing clinical trial. However, significant improvement in language and executive function skills occurred in response to HD-tDCS, suggesting HD-tDCS in this configuration has promising potential as an intervention for language and executive function deficits in MCI.
Antimicrobial stewardship programs (ASPs) exist to optimize antibiotic use, reduce selection for antimicrobial-resistant microorganisms, and improve patient outcomes. Rapid and accurate diagnosis is essential to optimal antibiotic use. Because diagnostic testing plays a significant role in diagnosing patients, it has one of the strongest influences on clinician antibiotic prescribing behaviors. Diagnostic stewardship, consequently, has emerged to improve clinician diagnostic testing and test result interpretation. Antimicrobial stewardship and diagnostic stewardship share common goals and are synergistic when used together. Although ASP requires a relationship with clinicians and focuses on person-to-person communication, diagnostic stewardship centers on a relationship with the laboratory and hardwiring testing changes into laboratory processes and the electronic health record. Here, we discuss how diagnostic stewardship can optimize the “Four Moments of Antibiotic Decision Making” created by the Agency for Healthcare Research and Quality and work synergistically with ASPs.
As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.
Without rapid international action to curb greenhouse gas emissions, climate scientists have predicted catastrophic sea-level rise by 2100. Globally, archaeologists are documenting the effects of sea-level rise on coastal cultural heritage. Here, the authors model the impact of 1m, 2m and 5m sea-level rise on China's coastal archaeological sites using data from the Atlas of Chinese Cultural Relics and Shanghai City's Third National Survey of Cultural Relics. Although the resulting number of endangered sites is large, the authors argue that these represent only a fraction of those actually at risk, and they issue a call to mitigate the direct and indirect effects of rising sea levels.
When vaccination depends on injection, it is plausible that the blood-injection-injury cluster of fears may contribute to hesitancy. Our primary aim was to estimate in the UK adult population the proportion of COVID-19 vaccine hesitancy explained by blood-injection-injury fears.
Methods
In total, 15 014 UK adults, quota sampled to match the population for age, gender, ethnicity, income and region, took part (19 January–5 February 2021) in a non-probability online survey. The Oxford COVID-19 Vaccine Hesitancy Scale assessed intent to be vaccinated. Two scales (Specific Phobia Scale-blood-injection-injury phobia and Medical Fear Survey–injections and blood subscale) assessed blood-injection-injury fears. Four items from these scales were used to create a factor score specifically for injection fears.
Results
In total, 3927 (26.2%) screened positive for blood-injection-injury phobia. Individuals screening positive (22.0%) were more likely to report COVID-19 vaccine hesitancy compared to individuals screening negative (11.5%), odds ratio = 2.18, 95% confidence interval (CI) 1.97–2.40, p < 0.001. The population attributable fraction (PAF) indicated that if blood-injection-injury phobia were absent then this may prevent 11.5% of all instances of vaccine hesitancy, AF = 0.11; 95% CI 0.09–0.14, p < 0.001. COVID-19 vaccine hesitancy was associated with higher scores on the Specific Phobia Scale, r = 0.22, p < 0.001, Medical Fear Survey, r = 0.23, p = <0.001 and injection fears, r = 0.25, p < 0.001. Injection fears were higher in youth and in Black and Asian ethnic groups, and explained a small degree of why vaccine hesitancy is higher in these groups.
Conclusions
Across the adult population, blood-injection-injury fears may explain approximately 10% of cases of COVID-19 vaccine hesitancy. Addressing such fears will likely improve the effectiveness of vaccination programmes.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
Radiofrequency ablation (RFA) is a non-invasive image-guided procedure where tumors are heated in the body with electrical current. RFA procedures are commonly indicated for patients with limited local disease or who are not surgical candidates. Current methods of RFA use multiple cords and wires that ergonomically complicate the procedure and present the risk of cutting or shorting the circuit if they are damaged. A wireless RFA technique based on electromagnetic induction is presented in this paper. The transmitting and receiving coils were coupled to resonate at the same frequency to ensure the highest power output. The receiving coil was connected to two insulated electrodes on a catheter, which allowed the current to flow to the targeted tissue. The prototype system was tested with ex-vivo bovine tissue, which has similar thermal and electrical properties to human tissue. The setup can monitor the received power, efficiency, temperature, and ablation zone during ablation procedures. The maximum received power was 15 W, and the average maximum efficiency was 63.27%. The novel system was also able to ablate up to a 2 cm ablation zone in non-perfused tissue. This proof of concept for performing RFA wirelessly with electromagnetic induction may merit further optimization.
Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and β-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.
There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.
Excavations at Shichengzi, the probable location of ancient Shule, have revealed diverse burial practices suggesting a population with varied cultural backgrounds. Together with archaeobotanical evidence, this indicates a community of agro-pastoralists and Han Dynasty migrants using diverse cropping patterns to attain self-sufficiency. The project raises interesting questions about the impact of migrations on the identities of inhabitants.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Methods
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Results
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
Conclusion
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.