Clostridioides difficile infection (CDI) is the fifth leading cause of death from nonmalignant gastrointestinal disease in the United States. The contribution of resistance to C. difficile-active ...antibiotics to the outcomes of CDI is unclear. We evaluated the antimicrobial susceptibility of C. difficile isolates in a U.S. hospital and determined associations of clinical variables and binary toxin positivity with antibiotic resistance. C. difficile spores were cultured from fecal specimens of adult patients with CDI for genotyping and antimicrobial susceptibility assay (for clindamycin CLI, fidaxomicin FDX, metronidazole MTZ, moxifloxacin MXF, tigecycline TGC, and vancomycin VAN). Electronic medical records were reviewed for clinical data extraction. Ninety-seven of 130 (75%) fecal samples grew toxigenic C. difficile in culture. Most of the isolates were
(80.4%), and 18.6% and 1% were
and
, respectively. Susceptibility to VAN, MTZ, FDX, TGC, MXF, and CLI was 96%, 94%, 100%, 100%, 8%, and 79%, respectively. Six isolates, all
positive and belonging to the 027 ribotype, were resistant to VAN and/or MTZ. Higher MICs were found in isolates with a mutation in the VAN-related resistance gene
, but not
. In addition,
isolates exhibited higher MICs of VAN, MTZ, TGC, CLI, and MXF compared to
strains. Patients with greater intestinal inflammation or severe disease were more likely to be infected with
strains. Decreased susceptibility to antibiotics is not directly associated with either severe or recurrent CDI. However, antimicrobial susceptibility of C. difficile is decreased in strains positive for the binary toxin gene.
The Rocky Mountain Population (RMP) of greater sandhill cranes uses a key stopover area, the San Luis Valley (SLV) in Colorado. Parameters of migration phenology can differ between autumn and spring ...and are affected by weather and environmental factors. We hypothesized that sandhill cranes in the SLV would have a longer stopover duration in autumn than in spring, and that wind assistance, crosswinds, temperature change, barometric air pressure, and surface water area would influence persistence probability. We used data from sandhill cranes fitted with transmitters that spanned autumn and spring, 2015-2022. We used an open robust design mark-recapture model to estimate stopover duration, arrival probability, and persistence probability. We examined the effects of weather and surface water on the persistence probability for 106 sandhill cranes in the SLV. Stopover duration was longer in autumn than in spring and had higher variability across years. Arrival probability to the SLV peaked on 13 October in autumn and 21 February in spring. Persistence probability declined around mid-December in autumn and mid-March in spring. We found that several weather covariates influenced persistence in both seasons. In autumn, sandhill cranes departed the SLV with higher tailwinds, lower crosswinds, and higher surface water availability. In spring, sandhill cranes departed the SLV with lower crosswinds and higher barometric air pressure at the surface and higher wind speeds at altitudes of about 3,000 m. The effect of wind speed was stronger later in the spring. Given the lower variability of arrival and persistence probability and shorter stopover duration in spring compared to autumn, we suspect that RMP sandhill cranes are using a time-minimization strategy during spring. However, given the use of supportive winds and weather conditions ideal for soaring, RMP sandhill cranes appear to be using strategies that save energy in both seasons. Our study identifies the optimal timing of water management and surveys for RMP sandhill cranes and confirms that weather influences their persistence. Understanding differences in migration patterns between seasons and the factors that influence persistence at stopover sites will also be important for anticipating phenological impacts from climate change and land use alterations.
Patients enrolled in hospice and palliative care programs experience a vast array of symptoms requiring the expertise of a multidisciplinary team to address. Acupuncture can be an effective addition ...to a hospice team whose goal is maximum comfort and quality of life (QOL). The objective of this project was to examine the effectiveness of acupuncture to relieve symptoms commonly observed in patients in a hospice program.
All over 26 patients participated in the acupuncture trial, receiving a course of weekly treatments that ranged from 1 to 14 weeks. The average number of treatments was five. The Edmonton Symptom Assessment Scale (ESAS) was used to assess the severity of pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and dyspnea. A two-tailed, paired t test was applied to the data to compare symptom scores pre- versus post-acupuncture treatment.
Patients enrolled in All Care Hospice’s home care program were given the option to receive acupuncture to supplement usual care offered by the hospice team. Treatment was provided by licensed acupuncturists in the patient’s place of residence.
Seven out of nine symptoms were significantly (P < .001) improved with acupuncture, the exceptions being drowsiness and appetite. Although the ESAS scale demonstrated a reduction in symptom severity post-treatment for both drowsiness and appetite, this reduction was not found to be significant.
Acupuncture was found to be effective for the reduction and relief of symptoms that commonly affect patient QOL. Acupuncture effectively reduced symptoms of pain, tiredness, nausea, depression, anxiety, and shortness of breath, and enhanced feelings of well-being. More research is required to assess the long-term benefits and symptom reduction of acupuncture in a palliative care setting.
Patterns of animal movement associated with foraging lie at the heart of many ecological studies and often animals face decisions of staying in an environment they know versus relocating to new ...sites.
The lack of knowledge of new foraging sites means there is risk associated with a decision to relocate (e.g. poor foraging) as well as a potential benefit (e.g. improved foraging).
Using a unique long‐term satellite tracking dataset for several sea turtle species, combined with capture–mark–recapture data extending over 50 years, we show how, across species, individuals generally maintain tight fidelity to specific foraging sites after extended (up to almost 10,000 km) migration to and from distant breeding sites as well as across many decades.
Migrating individuals often travelled through suitable foraging areas en route to their ‘home’ site and so extended their journeys to maintain foraging site fidelity.
We explore the likely mechanistic underpinnings of this trait, which is also seen in some migrating birds, and suggest that individuals will forgo areas of suitable forage encountered en route during migration when they have poor knowledge of the long‐term suitability of those sites, making relocation to those sites risky.
Using satellite tracking in the western Indian Ocean and northern Australia, the authors show that adult green turtles have fidelity to small foraging areas that may be 1,000s of km from their nesting beach. Individuals often forgo suitable foraging areas encountered during migration, probably because relocation to those sites is risky.
•A minimum stimulation current of 2–4 mA is needed to elicit cortico-cortical evoked potentials (CCEPs) in responsive sites.•Several metrics quantifying CCEP amplitude, distribution, and morphology ...all show stimulation current-dependent relationships.•6–7 mA is an asymptotic threshold for maximizing CCEP amplitude and spatial distribution and stabilizing waveform morphology.
The aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks.
We studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5–10 mA, median 6 mA).
We found that with a biphasic 0.15 ms/phase pulse at least 2–4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6–7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology.
We determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate.
This titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans.
Here, we report a novel “CyClick” strategy for the macrocyclization of peptides that works in an exclusively intramolecular fashion thereby precluding the formation of dimers and oligomers via ...intermolecular reactions. The CyClick chemistry is highly chemoselective for the N‐terminus of the peptide with a C‐terminal aldehyde. In this protocol, the peptide conformation internally directs activation of the backbone amide bond and thereby facilitates formation of a stable 4‐imidazolidinone‐fused cyclic peptide with high diastereoselectivity (>99 %). This method is tolerant to a variety of peptide aldehydes and has been applied for the synthesis of 12‐ to 23‐membered rings with varying amino acid compositions in one pot under mild reaction conditions. The reaction generated peptide macrocycles featuring a 4‐imidazolidinone in their scaffolds, which acts as an endocyclic control element that promotes intramolecular hydrogen bonding and leads to macrocycles with conformationally rigid turn structures.
Exclusively intramolecular: The conformationally induced activation of the amide bond, the idea behind the “CyClick” strategy, is exploited for the macrocyclization of peptides and precludes the formation of dimers or oligomers via intermolecular reactions. This method is tolerant to a variety of peptide aldehydes and has been applied for the synthesis of 12‐ to 23‐membered rings.
The PROMIS-Preference (PROPr) score is a recently developed summary score for the Patient-Reported Outcomes Measurement Information System (PROMIS). PROPr is a preference-based scoring system for ...seven PROMIS domains created using multiplicative multi-attribute utility theory. It serves as a generic, societal, preference-based summary scoring system of health-related quality of life. This manuscript evaluates construct validity of PROPr in two large samples from the US general population.
We utilized 2 online panel surveys, the PROPr Estimation Survey and the Profiles-Health Utilities Index (HUI) Survey. Both included the PROPr measure, patient demographic information, self-reported chronic conditions, and other preference-based summary scores: the EuroQol-5D (EQ-5D-5L) and HUI in the PROPr Estimation Survey and the HUI in the Profiles-HUI Survey. The HUI was scored as both the Mark 2 and the Mark 3. Known-groups validity was evaluated using age- and gender-stratified mean scores and health condition impact estimates. Condition impact estimates were created using ordinary least squares regression in which a summary score was regressed on age, gender, and a single health condition. The coefficient for the health condition is the estimated effect on the preference score of having a condition vs. not having it. Convergent validity was evaluated using Pearson correlations between PROPr and other summary scores.
The sample consisted of 983 respondents from the PROPr Estimation Survey and 3,000 from the Profiles-HUI survey. Age- and gender-stratified mean PROPr scores were lower than EQ-5D and HUI scores, with fewer subjects having scores corresponding to perfect health on the PROPr. In the PROPr Estimation survey, all 11 condition impact estimates were statistically significant using PROPr, 8 were statistically significant by the EQ-5D, 7 were statistically significant by HUI Mark 2, and 9 were statistically significant by HUI Mark 3. In the Profiles-HUI survey, all 21 condition impact estimates were statistically significant using summary scores from all three scoring systems. In these samples, the correlations between PROPr and the other summary measures ranged from 0.67 to 0.70.
These results provide evidence of construct validity for PROPr using samples from the US general population.
Successful outcomes in epilepsy surgery rely on the accurate localization of the seizure onset zone. Localizing the seizure onset zone is often a costly and time-consuming process wherein a patient ...undergoes intracranial EEG monitoring, and a team of clinicians wait for seizures to occur. Clinicians then analyse the intracranial EEG before each seizure onset to identify the seizure onset zone and localization accuracy increases when more seizures are captured. In this study, we develop a new approach to guide clinicians to actively elicit seizures with electrical stimulation. We propose that a brain region belongs to the seizure onset zone if a periodic stimulation at a particular frequency produces large amplitude oscillations in the intracranial EEG network that propagate seizure activity. Such responses occur when there is 'resonance' in the intracranial EEG network, and the resonant frequency can be detected by observing a sharp peak in the magnitude versus frequency response curve, called a Bode plot. To test our hypothesis, we analysed single-pulse electrical stimulation response data in 32 epilepsy patients undergoing intracranial EEG monitoring. For each patient and each stimulated brain region, we constructed a Bode plot by estimating a transfer function model from the intracranial EEG 'impulse' or single-pulse electrical stimulation response. The Bode plots were then analysed for evidence of resonance. First, we showed that when Bode plot features were used as a marker of the seizure onset zone, it distinguished successful from failed surgical outcomes with an area under the curve of 0.83, an accuracy that surpassed current methods of analysis with cortico-cortical evoked potential amplitude and cortico-cortical spectral responses. Then, we retrospectively showed that three out of five native seizures accidentally triggered in four patients during routine periodic stimulation at a given frequency corresponded to a resonant peak in the Bode plot. Last, we prospectively stimulated peak resonant frequencies gleaned from the Bode plots to elicit seizures in six patients, and this resulted in an induction of three seizures and three auras in these patients. These findings suggest neural resonance as a new biomarker of the seizure onset zone that can guide clinicians in eliciting native seizures to more quickly and accurately localize the seizure onset zone.
•Cortico-cortical evoked potential amplitude increases with current intensity with a greater effect in the seizure onset zone (SOZ).•SOZ response distributions are maximized at lower currents, while ...those outside the SOZ gradually increase with current intensity.•Responses to a range of current intensities provide better classification of the SOZ than responses to only one maximal intensity.
As single pulse electrical stimulation (SPES) is increasingly utilized to help localize the seizure onset zone (SOZ), it is important to understand how stimulation intensity can affect the ability to use cortico-cortical evoked potentials (CCEPs) to delineate epileptogenic regions.
We studied 15 drug-resistant epilepsy patients undergoing intracranial EEG monitoring and SPES with titrations of stimulation intensity. The N1 amplitude and distribution of CCEPs elicited in the SOZ and non-seizure onset zone (nSOZ) were quantified at each intensity. The separability of the SOZ and nSOZ using N1 amplitudes was compared between models using responses to titrations, responses to one maximal intensity, or both.
At 2 mA and above, the increase in N1 amplitude with current intensity was greater for responses within the SOZ, and SOZ response distribution was maximized by 4–6 mA. Models incorporating titrations achieved better separability of SOZ and nSOZ compared to those using one maximal intensity.
We demonstrated that differences in CCEP amplitude over a range of current intensities can improve discriminability of SOZ regions.
This study provides insight into the underlying excitability of the SOZ and how differences in current-dependent amplitudes of CCEPs may be used to help localize epileptogenic sites.
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