The prevalence of gram-negative bacteria with difficult-to-treat resistance and utilization of novel ß-lactam antibiotics in the southeastern United States.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel ß-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design: Retrospective, multicenter, cohort. Setting: Ten hospitals in the southeastern United States. Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel ß-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel ß-lactams. Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel ß-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden. Conclusions: The overall prevalence of GNB with DTR and the use of novel ß-lactams remain low. However, the uptrend in the use of novel ß-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

Controlling the europium oxidation state in diopside through flux concentration.

This paper explores the connection between the H3BO3 flux concentration and the co-existence of Eu2+ and Eu3+ dopants within CaMgSi2O6 crystals (diopside). The samples were synthesised using a solid-state synthesis method under varying atmospheric conditions, including oxidative (air), neutral (N2), and reductive (H2/N2 mixture) environments. Additionally, some materials underwent chemical modification by partially substituting Si4+ with Al3+ ions acting as charge compensation defects stabilizing Eu3+ luminescence. Depending on the specific synthesis conditions, the materials predominantly displayed either the orange-red luminescence of Eu3+ (under oxidising conditions) or the blue luminescence of Eu2+; however, the comprehensive results confirmed the co-existence of Eu3+/Eu2+ luminescence in both cases. This work shows that varying flux concentrations added during synthesis significantly affect the relative strength of Eu2+ and Eu3+ emissions in a manner dependent on the synthesis atmosphere. The emission of Eu2+ increases with a higher flux concentration in materials synthesised under oxidative and neutral atmospheres independent of the chemical modification. In contrast, for materials obtained under a reductive atmosphere, the changes in the Eu3+ emission intensity depended on the presence or absence of Al3+ ions namely the increase of flux increased the Eu3+ intensity in the case of unmodified materials and decreased in the Al-modified ones. All observed effects were qualitatively explained considering the double role of the flux in the studied system, which besides facilitating the diffusion of chemical species during synthesis acts as a charge compensating agent by creating B'Si centres stabilizing Eu3+ emission.

Orbital-flop transition of superfluid 3He in anisotropic silica aerogel.

Superfluid 3He is a paradigm for odd-parity Cooper pairing, ranging from neutron stars to uranium-based superconducting compounds. Recently it has been shown that 3He, imbibed in anisotropic silica aerogel with either positive or negative strain, preferentially selects either the chiral A-phase or the time-reversal-symmetric B-phase. This control over basic order parameter symmetry provides a useful model for understanding imperfect unconventional superconductors. For both phases, the orbital quantization axis is fixed by the direction of strain. Unexpectedly, at a specific temperature Tx, the orbital axis flops by 90∘, but in reverse order for A and B-phases. Aided by diffusion limited cluster aggregation simulations of anisotropic aerogel and small angle X-ray measurements, we are able to classify these aerogels as either "planar" and "nematic" concluding that the orbital-flop is caused by competition between short and long range structures in these aerogels.

Validated assays for the quantification of C9orf72 human pathology.

A repeat expansion mutation in the C9orf72 gene is the leading known genetic cause of FTD and ALS. The C9orf72-ALS/FTD field has been plagued by a lack of reliable tools to monitor this genomic locus and its RNA and protein products. We have validated assays that quantify C9orf72 pathobiology at the DNA, RNA and protein levels using knock-out human iPSC lines as controls. Here we show that single-molecule sequencing can accurately measure the repeat expansion and faithfully report on changes to the C9orf72 locus in what has been a traditionally hard to sequence genomic region. This is of particular value to sizing and phasing the repeat expansion and determining changes to the gene locus after gene editing. We developed ddPCR assays to quantify two major C9orf72 transcript variants, which we validated by selective excision of their distinct transcriptional start sites. Using validated knock-out human iPSC lines, we validated 4 commercially available antibodies (of 9 tested) that were specific for C9orf72 protein quantification by Western blot, but none were specific for immunocytochemistry. We tested 15 combinations of antibodies against dipeptide repeat proteins (DPRs) across 66 concentrations using MSD immunoassay, and found two (against poly-GA and poly-GP) that yielded a 1.5-fold or greater signal increase in patient iPSC-motor neurons compared to knock-out control, and validated them in human postmortem and transgenic mouse brain tissue. Our validated DNA, RNA and protein assays are applicable to discovery research as well as clinical trials.

Laparoscopic versus robotic TAPP/TEP inguinal hernia repair: a multicenter, propensity score weighted study.

PURPOSE: The objective of this retrospective study was to assess safety and comparative clinical effectiveness of laparoscopic inguinal hernia repair (LIHR) and robot-assisted inguinal hernia repair (RIHR) from multi-institutional experience in Taiwan. METHODS: Medical records from a total of eight hospitals were retrospectively collected and analyzed. Patients primarily diagnosed of inguinal hernia, recurrent inguinal hernia or incarceration groin hernia patients who either underwent laparoscopic or robot-assisted inguinal hernia repair between January 2018 and December 2022 were included in the study. Baseline characteristics, intra-operative and post-operative results were analyzed. To compare two cohorts, overlap weighting was employed to balance the significant inter-group differences. We also conducted subgroup analyses by state of a hernia (primary or recurrent/incarceration) and laterality (unilateral or bilateral) that indicated complexity of surgery. RESULTS: A total of 1,080 patients who underwent minimally invasive inguinal hernia repair from 8 hospitals across Taiwan were collected. Following the application of inclusion criteria, there were 279 patients received RIHR and 763 patients received LIHR. In the baseline analysis, RIHR was more often performed in recurrent/incarceration (RIHR 18.6% vs LIHR 10.3%, p = 0.001) and bilateral cases (RIHR 81.4 vs LIHR 58.3, p < 0.001). Suturing was dominant mesh fixation method in RIHR (RIHR 81% vs LIHR 35.8%, p < 0.001). More overweight patients were treated with RIHR (RIHR 58.8% vs LIHR 48.9%, p = 0.006). After overlap weighting, there were no significant difference in intraoperative and post-operative complications between RIHR and LIHR. Reoperation and prescription rates of pain medication (opioid) were significantly lower in RIHR than LIHR in overall group comparison (reoperation: RIHR 0% vs. LIHR 2.9%, p = 0.016) (Opioid prescription: RIHR 3.34 mg vs LIHR 10.82 mg, p = 0.001) while operation time was significantly longer in RIHR (OR time: RIHR 155.27 min vs LIHR 95.30 min, p < 0.001). CONCLUSIONS: This real-world experience suggested that RIHR is a safe, and feasible option with comparable intra-operative and post-operative outcomes to LHIR. In our study, RIHR showed technical advantages in more complicated hernia cases with yielding to lower reoperation rates, and less opioid use.

Sarcopenia Screened with SARC-F and Subjective Memory Complaints Are Independently Associated with Increased Risk of Incident Dementia among Cognitively Unimpaired Older Adults.

OBJECTIVES: The main aim of this study was to examine the association of sarcopenia and subjective memory complaints with the incidence of dementia in a population-based cohort of cognitively unimpaired older adults. DESIGN: Three-year longitudinal study. SETTINGS AND PARTICIPANTS: A total of 2163 community-dwelling persons aged 65 years or older who participated in the National Health Interview Survey in Taiwan, 2017. MEASUREMENTS: Sarcopenia was determined based on SARC-F, a self-reported symptom-based questionnaire that includes five components: strength, assistance walking, rise from a chair, climb stairs, and falls. Two questions ("Do you have difficulties with your memory or attention?" and "Do you have difficulties with your memory only or attention only or both?") were used to screen for subjective memory complaints (SMCs). The incidence of dementia was determined by data linkage to the Taiwan National Health Insurance claims database from 2018 to 2020. RESULTS: Among the 2163 participants without dementia at baseline, 135 had incident dementia during the 3-year follow-up, giving a crude incidence rate of 6.2% (135/2163). Compared to participants free from sarcopenia and SMCs, the adjusted hazard ratio for incident dementia was 1.83 (95% confidence interval [CI]: 1.23-2.72) for SMCs alone, 2.40 (95% CI: 1.17-4.93) for sarcopenia alone, and 2.49 (95% CI: 1.21-5.11) for coexisting SMCs and sarcopenia. CONCLUSIONS: Our results indicate that sarcopenia screened with SARC-F and SMCs independently predict the cognitively unimpaired older adults at risk of incident dementia. Our findings highlight the importance of screening not only for cognitive but also muscle deficits to identify those at increased risk of incident dementia.

Clindamycin Plus Vancomycin Versus Linezolid for Treatment of Necrotizing Soft Tissue Infection.

Background: Necrotizing soft tissue infections (NSTIs) are life-threatening infections. The aim of this study is to evaluate the safety of clindamycin plus vancomycin versus linezolid as empiric treatment of NSTIs. Methods: This was a retrospective, single-center, quasi-experimental study of patients admitted from 1 June 2018 to 30 June 2019 (preintervention) and 1 May 2020 to 15 October 2021 (postintervention). Patients who received surgical management within 24 hours of NSTI diagnosis and at least 1 dose of linezolid or clindamycin were included. The primary endpoint was death at 30 days. The secondary outcomes included rates of acute kidney injury (AKI) and Clostridioides difficile infection (CDI). Results: A total of 274 patients were identified by admission diagnosis code for NSTI or Fournier gangrene; 164 patients met the inclusion criteria. Sixty-two matched pairs were evaluated. There was no difference in rates of 30-day mortality (8.06% vs 6.45%; hazard ratio [HR], 1.67 [95% confidence interval {CI}, .32-10.73]; P = .65). There was no difference in CDI (6.45% vs 1.61%; HR, Infinite [Inf], [95% CI, .66-Inf]; P = .07) but more AKI in the preintervention group (9.68% vs 1.61%; HR, 6 [95% CI, .73-276]; P = .05). Conclusions: In this small, retrospective, single-center, quasi-experimental study, there was no difference in 30-day mortality in patients receiving treatment with clindamycin plus vancomycin versus linezolid in combination with standard gram-negative and anaerobic therapy and surgical debridement for the treatment of NSTIs. A composite outcome of death, AKI, or CDI within 30 days was more common in the clindamycin plus vancomycin group.

INTERIM ANALYSIS OF PRIMARY HEALTHCARE SPECIALISTS TRAINING IN THE UNIVERSALLY PROGRESSIVE MODEL OF HOME-BASED SERVICES: ANTICIPATED PROSPECTS IN THE SOCIAL AREA.

This is an overview of the Interim analysis of primary healthcare specialists training in a universally progressive model of home-based services in the city of Astana, Akmola, and North Kazakhstan regions. A total of 482 persons were trained. Questionnaires filled in by trainees were analyzed.

Development and verification of the coaxial heterogeneous hyperspectral imaging system.

A hyperspectral imaging system (HIS) is a helpful tool that acquires spatial and spectral information from a target. This study developed a coaxial heterogeneous HIS (CHHIS) to collect spectral images with wavelengths ranging from 400 to 1700 nm. In this system, a visible (VIS) spectrometer and a short-wave infrared (SWIR) spectrometer are combined with a coaxial optical path to share the same field of view. This structure reduces the complexity of spatial registration and maintains the scanning duration of two spectrometers as that of a single spectrometer. The spectrometers are also replaceable for extending the detecting spectral range of the system. The calibration methodologies, including spatial correction, spectral calibration, and reflectance calibration, were developed for this system. The signal-to-noise ratio of VIS and SWIR spectrometers in the CHHIS was up to 40 and 60 dB when the exposure time of the VIS and SWIR imaging sensors was 1000 and 10 ms, respectively. When the target distance was at 600 mm, the spatial error of VIS and SWIR images in the scanning direction was less than 1 pixel; these results proved that the system was stable.

Supplementation with heat-inactivated Lacticaseibacillus paracasei K47 ameliorates allergic asthma in mice by regulating the Th1/Th2 balance.

Asthma is a chronic inflammatory disease related to the immune response of type 2 T helper cells (Th2), which affects all age groups. The incidence of asthma is increasing worldwide, and it has become a significant public health problem. This study aimed to investigate the immunomodulatory effects of Lacticaseibacillus (formerly Lactobacillus) paracasei K47 on mice with ovalbumin (OVA)-induced allergy. The consequences of orally administered heat-inactivated K47 in OVA-sensitised/challenged BALB/c mice were evaluated by assessing the serum levels of immunoglobulins (Igs), airway hyperresponsiveness (AHR), and bronchoalveolar lavage fluid (BALF) cytokine. In addition, the effect of K47 on type 1 T helper cells (Th1)/Th2 cytokine production in splenocytes from OVA-sensitised mice was evaluated. The results revealed that supplementation with K47 remarkably reduced serum levels of total IgE, OVA-specific IgE, and OVA-specific IgG1 in OVA-sensitised/challenged mice. In addition, K47 intervention ameliorated AHR and suppressed the accumulation of inflammatory cells in the BALF of OVA-sensitised/challenged mice. Furthermore, the immunomodulatory ability of K47 was mediated by regulation of the cytokine profile toward the Th1 response in the BALF, and splenocytes of OVA-sensitised mice. Taken together, these results suggested that K47 can modulate the host immune response to ameliorate AHR and inflammation in allergic asthma.

Associations between body composition and vertebral fracture risk in postmenopausal women.

INTRODUCTION: Osteoporosis is a metabolic bone disease with low bone mineral density (BMD) and high incidence of vertebral fractures (VFs). Postmenopausal women with osteoporosis have decreased total fat and lean mass. This study aimed to investigate the associations between body composition and VF risk and explore the potential predictor of VF risk in postmenopausal women. METHODS: Enrolled 731 postmenopausal women were referred by various departments and outpatient clinics to assess vertebral status between October 2016 and November 2017. The main measures were total body lean mass, fat mass, and BMD. Patients were divided into osteopenia, osteoporosis, and normal groups based on T-scores. Logistic regression analyses were performed to evaluate associations between body composition parameters and VF. RESULTS: VF was significantly associated with increased age, lower height, and lighter weight in all participants, and higher BMI was observed in VF participants. Participants in the osteoporosis group were older and had lower height, weight, and BMD than those in normal and osteopenia groups. Femoral and total hip T-scores as well as T-scores for lumbar spine were significantly lower in participants with VF than in non-VF participants. Percentage of bone mass was also significantly lower in VF participants compared to that of non-VF participants. Women with increased BMD and lower bone mass had reduced odds for VF occurrence. Bone mass was significantly able to identify VF occurrence. CONCLUSIONS: Body composition analysis discerns differences in the bone status of postmenopausal women with and without VF. The cutoff value of the bone mass might be used effectively as an indicator of risk for VF occurrence.

Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

Effects of Exercise Alone or in Combination with High-Protein Diet on Muscle Function, Aerobic Capacity, and Physical Function in Middle-Aged Obese Adults: A Randomized Controlled Trial.

BACKGROUND: Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults. MATERIALS AND METHODS: Sixty-nine middle-aged (50-64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a high-protein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention. RESULTS: After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test). CONCLUSIONS: For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.

Quantitative examination of early diabetes by light-emitting diodes light-induced pupillary light reflex.

This study investigated the abnormal pupillary light reflex in patients with early diabetes mellitus (DM) without retinopathy by using a custom-made noninvasive portable pupilometer. The pupilometer recorded and analyzed the pupillary light reflex. Two light intensities, 0.2 cd and 1.2 cd, and four wavelengths of stimulus light-white (400 nm-800 nm), red (640 ± 5 nm), green (534 ± 5 nm), and blue (470 ± 5 nm)-were used to stimulate the pupil for 10 ms. The pupillary response was recorded for 15 s. A total of 40 healthy people and 40 people with DM without retinopathy participated in the experiment at the National Taiwan University Hospital. The mean and standard deviation of DM duration were 4.5 years and 3.9 years. Of the 16 indices, the duration that pupil restores from its minimum size to half of its resting size (DRP), maximum pupil restoration velocity (MRV), and average restoration velocity (ARV) exhibited the most significant differences between the healthy people and those with DM. Compared with healthy participants, DRP was 16.33% higher, and MRV and ARV were 17.45% and 4.58% lower, respectively, in those with DM. This might be attributable to the sympathetic nervous system (SNS) controlling the dilator muscle during the dark-adapted period and relaxing the pupil; the SNS had few degenerated nerve endings in people with DM. The three aforementioned indices might be used to evaluate the severity of autonomic neuropathy in early DM.

New opportunities at the next-generation neutrino experiments I: BSM neutrino physics and dark matter.

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.