Should All Patients With Stage IE Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Receive Antibiotic Eradication Therapy for Helicobacter pylori?

PURPOSE: H. pylori eradication therapy (HPE) can lead to tumor regression in H. pylori-positive (HPP) gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, some patients do not have detectable H. pylori (HP) infection (H. pylori-negative [HPN]) and the guidelines differ in their initial approach to HPN patients. The National Comprehensive Cancer Network (NCCN) recommends proceeding to radiation therapy, whereas European Society for Medical Oncology suggests HPE for every patient, even those who are HPN. To address this issue, we evaluated the effectiveness of HPE in limited-stage gastric MALT lymphoma. MATERIALS AND METHODS: We retrospectively reviewed patients newly diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. The primary outcome was the complete remission (CR) rate defined as no macroscopic findings of lymphoma and negative gastric biopsy at the follow-up gastric endoscopy. RESULTS: Fifty-two patients were reviewed, and HP infection was detected in 19 (36.5%) patients-14 by immunostaining, three by serology, and one each by stool antigen and urea breath test. All 19 HPP and eight of the 33 HPN patients received HPE treatment. The CR rate was 63% (12/19) in HPP patients and 13% (1/8) in HPN patients (P = .033). After a median follow-up of 89.7 months, only two of the 12 HPP patients achieving CR have relapsed; the one HPN patient who received HPE remains in CR at 12+ months. CONCLUSION: For limited-stage HPP gastric MALT lymphoma, HPE is an effective and durable first-line treatment and should be used. For HPN patients, the CR rate with HPE is very low in our experience and is thus in support of the NCCN guideline.

Testing of putative antiseizure medications in a preclinical Dravet syndrome zebrafish model.

Dravet syndrome is a severe genetic epilepsy primarily caused by de novo mutations in a voltage-activated sodium channel gene (SCN1A). Patients face life-threatening seizures that are largely resistant to available anti-seizure medications. Preclinical Dravet syndrome animal models are a valuable tool to identify candidate anti-seizure medications for these patients. Among these, scn1lab mutant zebrafish, exhibiting spontaneous seizure-like activity, are particularly amenable to large-scale drug screening. Thus far, we have screened more than 3000 drug candidates in scn1lab zebrafish mutants, identifying valproate, stiripentol, and fenfluramine e.g. Food and Drug Administration-approved drugs, with clinical application in the Dravet syndrome population. Successful phenotypic screening in scn1lab mutant zebrafish is rigorous and consists of two stages: (i) a locomotion-based assay measuring high-velocity convulsive swim behaviour and (ii) an electrophysiology-based assay, using in vivo local field potential recordings, to quantify electrographic seizure-like events. Historically, nearly 90% of drug candidates fail during translation from preclinical models to the clinic. With such a high failure rate, it becomes necessary to address issues of replication and false positive identification. Leveraging our scn1lab zebrafish assays is one approach to address these problems. Here, we curated a list of nine anti-seizure drug candidates recently identified by other groups using preclinical Dravet syndrome models: 1-Ethyl-2-benzimidazolinone, AA43279, chlorzoxazone, donepezil, lisuride, mifepristone, pargyline, soticlestat and vorinostat. First-stage locomotion-based assays in scn1lab mutant zebrafish identified only 1-Ethyl-2-benzimidazolinone, chlorzoxazone and lisuride. However, second-stage local field potential recording assays did not show significant suppression of spontaneous electrographic seizure activity for any of the nine anti-seizure drug candidates. Surprisingly, soticlestat induced frank electrographic seizure-like discharges in wild-type control zebrafish. Taken together, our results failed to replicate clear anti-seizure efficacy for these drug candidates highlighting a necessity for strict scientific standards in preclinical identification of anti-seizure medications.

Phytosensors: harnessing plants to understand the world around us.

Although plants are sessile, their ubiquitous distribution, ability to harness energy from the sun, and ability to sense above and belowground signals make them ideal candidates for biosensor development. Synthetic biology has allowed scientists to reimagine biosensors as engineered devices that are focused on accomplishing novel tasks. As such, a new wave of plant-based sensors, phytosensors, are being engineered as multi-component sense-and-report devices that can alert human operators to a variety of hazards. While phytosensors are intrinsically tied to agriculture, a new generation of phytosensors has been envisioned to function in the built environment and even in austere environments, such as space. In this review, we will explore the current state of the art with regard to phytosensor engineering.

Midpoint of sleep is associated with sleep quality in older adults with and without symptomatic Alzheimer's disease.

Introduction: Disrupted sleep is common in individuals with Alzheimer's disease (AD) and may be a marker for AD risk. The timing of sleep affects sleep-wake activity and is also associated with AD, but little is known about links between sleep architecture and the midpoint of sleep in older adults. In this study, we tested if the midpoint of sleep is associated with different measures of sleep architecture, AD biomarkers, and cognitive status among older adults with and without symptomatic AD. Methods: Participants (N = 243) with a mean age of 74 underwent standardized cognitive assessments, measurement of CSF AD biomarkers, and sleep monitoring via single-channel EEG, actigraphy, a home sleep apnea test, and self-reported sleep logs. The midpoint of sleep was defined by actigraphy. Results: A later midpoint of sleep was associated with African-American race and greater night-to-night variability in the sleep midpoint. After adjusting for multiple potential confounding factors, a later sleep midpoint was associated with longer rapid-eye movement (REM) onset latency, decreased REM sleep time, more actigraphic awakenings at night, and higher < 2 Hz non-REM slow-wave activity. Conclusions: Noninvasive in vivo markers of brain function, such as sleep, are needed to track both future risk of cognitive impairment and response to interventions in older adults at risk for AD. Sleep timing is associated with multiple other sleep measures and may affect their utility as markers of AD. The midpoint of sleep may be changed through behavioral intervention and should be taken into account when using sleep as a marker for AD risk.

The impact of heat-set milk protein gel textures modified by pH on circulating amino acid appearance and gastric function in healthy female adults: a randomised controlled trial.

Modification of dairy proteins during processing impacts structural assemblies, influencing textural and nutritional properties of dairy products, and release and availability of amino acids during digestion. By modifying only pH, acid heat-set bovine dairy gels with divergent textural properties were developed to alter protein digestion. In vitro assay confirmed faster digestion of protein from a firm gel (pH 5.65) versus a soft gel (pH 6.55). We hypothesised that firm gel (FIRM-G; pH 5.6) would result in greater indispensable amino acid (IAA) appearance in circulation over 5 h and corresponding differences in gastric myoelectrical activity relative to soft gel (SOFT-G; pH 6.2). In a randomised, single-blind cross-over trial, healthy females (n = 20) consumed 150 g of each gel; plasma amino acid appearance was assessed over 5 hours. Iso-nitrogenous, iso-caloric gels were prepared from identical mixtures of bovine milk and whey protein concentrates; providing 17.7 g (FIRM-G) and 18.9 g (SOFT-G) of protein per serving. Secondary outcomes included gastric myoelectrical activity measured by body surface gastric mapping, glycaemic, triglyceridaemic, and subjective appetite and digestive responses. Overall plasma IAA (area under the curve) did not differ between gels. However, plasma IAA concentrations were higher, and increased more rapidly over time after SOFT-G compared with FIRM-G (1455 ± 53 versus 1350 ± 62 µmol L-1 at 30 min, p = 0.024). Similarly, total, branched-chain and dispensable amino acids were higher at 30 min with SOFT-G than FIRM-G (total: 3939 ± 97 versus 3702 ± 127 µmol L-1, p = 0.014; branched-chain: 677 ± 30 versus 619 ± 34 µmol L-1, p = 0.047; dispensable: 2334 ± 53 versus 2210 ± 76 µmol L-1, p = 0.032). All other measured parameters were similar between gels. Peak postprandial aminoacidaemia was higher and faster following ingestion of SOFT-G. Customised plasma amino acid appearance from dairy is achievable by altering gel coagulum structure using pH during processing and may have minimal influence on related postprandial responses, with implications for targeting food design for optimal health. The Clinical Trial Registry number is ACTRN12622001418763 (https://www.anzctr.org.au) registered November 7, 2022.

Some, but not all, cochlear implant users prefer music stimuli with congruent haptic stimulation.

Cochlear implant (CI) users often report being unsatisfied by music listening through their hearing device. Vibrotactile stimulation could help alleviate those challenges. Previous research has shown that musical stimuli was given higher preference ratings by normal-hearing listeners when concurrent vibrotactile stimulation was congruent in intensity and timing with the corresponding auditory signal compared to incongruent. However, it is not known whether this is also the case for CI users. Therefore, in this experiment, we presented 18 CI users and 24 normal-hearing listeners with five melodies and five different audio-to-tactile maps. Each map varied the congruence between the audio and tactile signals related to intensity, fundamental frequency, and timing. Participants were asked to rate the maps from zero to 100, based on preference. It was shown that almost all normal-hearing listeners, as well as a subset of the CI users, preferred tactile stimulation, which was congruent with the audio in intensity and timing. However, many CI users had no difference in preference between timing aligned and timing unaligned stimuli. The results provide evidence that vibrotactile music enjoyment enhancement could be a solution for some CI users; however, more research is needed to understand which CI users can benefit from it most.

Utility of the occipital nerve block in the emergency department: A case series.

INTRODUCTION: Tension headaches, as well as various scalp pathologies including lacerations and abscesses are commonly treated in the emergency department (ED). The occipital nerve block (ONB), previously described in anesthesia and neurology literature, offers analgesia of the posterior scalp on the side ipsilateral to the injection while maintaining a low adverse effect profile. CASE REPORT: We report three cases in which ONB was utilized for tension headache, scalp laceration repair, and incision and drainage of scalp abscess. These patients all reported significant pain improvement without any reported complications. CONCLUSION: The ONB is a landmark based technique that offers an opportunity to provide analgesia in the ED that is simple, effective, and without known significant risks that are associated with other modalities of treatment.

Molecular epidemiology of Western equine encephalitis virus in Brazil, 2023-2024.

During the ongoing western equine encephalitis virus (WEEV) outbreak in South America, we described three fatal cases in horses from Rio Grande do Sul, Brazil. We sequenced WEEV strains and identified a novel lineage causing these cases. Continued surveillance and horse immunization are needed to mitigate the WEEV burden.

Systematic evaluation of methods for iron-impregnation of biochar and effects on arsenic in flooded soils.

There is a need for innovative strategies to decrease the mobility of metal(loids) including arsenic (As) and cadmium (Cd) in agricultural soils, including rice paddies, so as to minimize dietary exposure to these toxic elements. Iron (Fe)-modified biochars (FBCs) are used to immobilize As and Cd in soil-water systems, but there is a lack of clarity on optimal methods for preparing FBCs because there are only limited studies that directly compare BCs impregnated with Fe under different conditions. There is also a lack of information on the long-term performance of FBCs in flooded soil environments, where reductive dissolution of Fe (oxy)hydroxide phases loaded onto biochar surfaces may decrease the effectiveness of FBCs. This study uses material characterization methods including FTIR, SEM-EDX, BET, and adsorption isotherm experiments to investigate the effects of Fe-impregnation methods (pH, pyrolysis sequence, and sonication) on the morphology and mineralogy of Fe loaded onto the biochar surface, and to FBC adsorbent properties for arsenate (As(V)), arsenite (As(III)), and Cd. Acidic impregnation conditions favored the adsorption of As(III) onto amorphous Fe phases that were evenly distributed on the biochar surface, including within the biochar pore structure. The combination of sonication with acidic Fe-impregnation conditions led to the best adsorption capacities for As(V) and As(III) (4830 and 11,166 µg As g-1 biochar, respectively). Alkaline Fe-impregnation conditions led to the highest Cd adsorption capacity of 3054 µg Cd g-1 biochar, but had poor effectiveness as an As adsorbent. Amending soil with 5% (w/w) of an acid-impregnated and sonicated FBC was more effective than an alkaline-impregnated FBC or ferrihydrite in decreasing porewater As concentrations. The acid-impregnated FBC also had greater longevity, decreasing As by 54% and 56% in two flooded phases, probably due to the greater stability of Fe(III) within the biochar pore structure that may have a direct chemical bond to the biochar surface. This study demonstrates that FBCs can be designed with selectivity towards different As species or Cd and that they can maintain their effectiveness under anaerobic soil conditions. This is the first study to systematically test how impregnation conditions affect the stability of FBCs in soils under multiple drying-rewetting cycles.

Enhanced Recovery After Surgery (ERAS) Spine Pathways and the Role of Perioperative Checklists.

Enhanced recovery after surgery (ERAS) proposes a multimodal, evidence-based approach to perioperative care. ERAS pathways have been shown to help reduce complications, hospital length of stay (LOS), 30-day readmission rates, pain scores, and ultimately surgical costs, while improving patient satisfaction scores and outcomes in multiple surgical subspecialties [1-6]. Numerous specialties have implemented ERAS programs across the globe, providing a foundation for spine surgeons to begin the process themselves. Over the last few years, a significant number of papers have been addressing ERAS pathways for spinal surgery [7-19]. The majority have addressed the lumbar spine [9, 20-26]. The number of cervical ERAS pathways has been limited [27-29]. Many spine programs have begun the implementation of ERAS pathways, incorporating principles and interventions to various spine surgical procedures. Although differences in implementation across programs exist, there are a few common elements that promote a successful enhanced recovery approach [11, 16, 23, 25, 30-33]. All spinal ERAS pathways have three major elements, which are preoperative, perioperative, and postoperative phases. Within these phases some common elements include preoperative and intraoperative surgical checklists. Intraoperative checklist in addition to the "surgical time out" has been integrated into the workflow of most hospitals doing surgeries and have become a standard of care. The surgical checklist is designed to help reduce surgical errors and prevent wrong site/patient surgeries. Several surgical checklists have been developed throughout the years. Despite these safety protocols wrong site/level and other surgical errors continue to occur. Many cases of wrong level spine surgery (WLSS) still occur even when intraoperative imaging is performed [34, 35]. One survey reported that about 50% of spine surgeons have performed at least one WLSS during their career [36, 37]. Another survey reported that 36% of spine surgeons had performed at least one WLSS that was not recognized intraoperatively [38]. On a similar account, about 30% of spine surgery fellows have experienced wrong-site surgery [39]. From raw incidence rates, WLSS may seem rare, but these surveys show that the experience of WLSS is rather common among spine surgeons. WLSS is not yet a "never event." This may be due to poor quality of the intraoperative images, hindering subsequent level identification [34, 35, 38, 40]. Errors in interpretation of the imaging may also occur, including inconsistency in numbering vertebrae, inconsistency in landmark usage for level counting, and problems with numbering vertebrae due to lumbosacral transitional vertebrae (LSTV) and other anatomical variants [34, 38, 41-43]. This chapter will describe a framework for the development and implementation of ERAS pathway for patients undergoing spine surgery. In addition, we will propose preoperative imaging guidelines and a comprehensive spine surgical checklist to incorporate into the perioperative phase to help reduce further surgical errors and WLSS.

PyOKR: A Semi-Automated Method for Quantifying Optokinetic Reflex Tracking Ability.

The study of behavioral responses to visual stimuli is a key component of understanding visual system function. One notable response is the optokinetic reflex (OKR), a highly conserved innate behavior necessary for image stabilization on the retina. The OKR provides a robust readout of image tracking ability and has been extensively studied to understand visual system circuitry and function in animals from different genetic backgrounds. The OKR consists of two phases: a slow tracking phase as the eye follows a stimulus to the edge of the visual plane and a compensatory fast phase saccade that resets the position of the eye in the orbit. Previous methods of tracking gain quantification, although reliable, are labor intensive and can be subjective or arbitrarily derived. To obtain more rapid and reproducible quantification of eye tracking ability, we have developed a novel semi-automated analysis program, PyOKR, that allows for quantification of two-dimensional eye tracking motion in response to any directional stimulus, in addition to being adaptable to any type of video-oculography equipment. This method provides automated filtering, selection of slow tracking phases, modeling of vertical and horizontal eye vectors, quantification of eye movement gains relative to stimulus speed, and organization of resultant data into a usable spreadsheet for statistical and graphical comparisons. This quantitative and streamlined analysis pipeline, readily accessible via PyPI import, provides a fast and direct measurement of OKR responses, thereby facilitating the study of visual behavioral responses.

Human Saposin B Ligand Binding and Presentation to α-Galactosidase A.

Sphingolipid activator protein B (saposin B; SapB) is an essential activator of globotriaosylceramide (Gb3) catabolism by α-galactosidase A. However, the manner by which SapB stimulates α-galactosidase A activity remains unknown. To uncover the molecular mechanism of SapB presenting Gb3 to α-galactosidase A, we subjected the fluorescent substrate globotriaosylceramide-nitrobenzoxidazole (Gb3-NBD) to a series of biochemical and structural assays involving SapB. First, we showed that SapB stably binds Gb3-NBD using a fluorescence equilibrium binding assay, isolates Gb3-NBD from micelles, and facilitates α-galactosidase A cleavage of Gb3-NBD in vitro. Second, we crystallized SapB in the presence of Gb3-NBD and validated the ligand-bound assembly. Third, we captured transient interactions between SapB and α-galactosidase A by chemical cross-linking. Finally, we determined the crystal structure of SapB bound to α-galactosidase A. These findings establish general principles for molecular recognition in saposin:hydrolase complexes and highlight the utility of NBD reporter lipids in saposin biochemistry and structural biology.

Late fall synthetic acaricide application is effective at reducing host-seeking adult and nymphal Ixodes scapularis (Ixodida: Ixodidae) abundances the following spring.

Based on increases in reported cases of tick-borne illnesses, expanding ranges of native ticks, and repeated documentation of arrivals of nonnative tick species, there is a clear need for their effective management in the United States. Synthetic acaricides have proven efficacious in tick management, but real/perceived negative impacts to the environment and nontarget, beneficial insects must be addressed. We sought to determine whether late fall synthetic acaricide application, when most susceptible beneficial insects are presumably dormant or have migrated, could effectively manage host-seeking spring Ixodes scapularis Say abundances as compared to traditional spring application. We compared results of delivery of Demand CS (lambda-cyhalothrin) via truck-mounted high-pressure spray and powered backpack blower as well as delivery of granular Demand G to experimental control (water) in peridomestic habitats in fall 2021, spring 2022, and combined fall 2021/spring 2022. High-pressure fall delivery of Demand CS and backpack delivery of Demand G significantly reduced host-seeking adult I. scapularis abundances within-season and the following spring combined by 100% and 94%, respectively. No host-seeking nymphal I. scapularis were documented in spring after fall only, spring only, or fall and spring combined delivery of Demand CS via high-pressure or powered backpack blower. No adult I. scapularis were documented at any time posttreatment on locations that received high-pressure delivery of Demand CS. We conclude that high-pressure delivery of Demand CS in late fall successfully eliminated multiple stages of host-seeking I. scapularis through the following spring while likely limiting exposure of beneficial insects to synthetic pyrethroids.

A domain-swapped CaMKII conformation facilitates linker-mediated allosteric regulation.

Ca2+ signaling plays a key role in physiological processes such as memory formation and cardiac function. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is the primary kinase that responds to Ca2+ inputs in these cells. There are four CaMKII paralogs in mammals which are alternatively spliced in the variable linker region to create upwards of 70 different variants. In this study, we systematically studied different linker regions and determined that the position of charged residues within the linker region modulates the Ca2+/CaM sensitivity of the holoenzyme. We present an X-ray crystal structure of full-length CaMKIIδ that shows a domain-swapped conformation of the subunits within the dodecameric holoenzyme. In this structure, the kinase domain of one subunit is docked onto the hub domain of a different subunit, providing an additional interface within the holoenzyme. Mutations at the equatorial and lateral interfaces revealed that the kinase-hub interaction dissociates as the hub-hub interfaces are disturbed, which led alterations in the stoichiometry of CaMKII holoenzyme and Ca2+/CaM sensitivity. Molecular dynamics simulations of linker-containing domain-swapped and non-domain-swapped CaMKIIs reveal that the domain-swapped configuration facilitates an interaction between the calmodulin binding domain and the variable linker region, such that dynamic electrostatic forces between charges on these segments can modulate the equilibrium between the compact and extended conformational states of the holoenzyme. Small angle X-ray scattering data confirms that a negatively charged linker CaMKII holoenzyme adopts a more compact conformation compared to a positively charged linker. These data support a model where patches of charged linker residues interact with the calmodulin binding domain to allosterically regulate sensitivity to Ca2+/CaM. Our findings provide a new framework for understanding CaMKII structure and allosteric regulation by the variable linker region in Ca2+-sensitive cells.

Biosecurity indemnification and attitudes of United States swine producers towards the prevention of an african swine fever outbreak.

Animal disease outbreaks, such as the recent outbreak of African Swine Fever in 2018, are a major concern for stakeholders across the food supply chain due to their potential to disrupt global food security, cause economic losses, and threaten animal welfare. As a result of their transboundary nature, discussions have shifted to preventive measures aimed at protecting livestock while ensuring food security and safety. Emergency assistance has been a critical response option during pandemics. However, this may not be sustainable in the long run because the expectation of government bailout may encourage risk taking behaviours. Our hypothesis is that an indemnity policy that is conditioned on showing biosecurity practices would increase compliance and reduce government expenditure during disease outbreaks. We developed and launched a survey from March to July 2022 targeted at swine producers across the US. From the survey, we examined livestock farmers' attitudes and intentions regarding biosecurity investment and assessed their attitudes towards the purchase of livestock insurance and reporting suspected infected livestock on their farm. We used a partial proportion odds model analysis to examine the model. Our analysis revealed that intention to call a veterinarian, trust in government agencies and risk perception of farmers were instrumental in the willingness to self-invest in biosecurity, purchase livestock insurance, and promptly report infected livestock on their farms. This provides evidence that biosecurity compliance would increase if indemnification was tied to a demonstration of effort to adopt biosecurity practices. We also show that individuals who have been in the industry for a longer period may become complacent and less likely to report outbreaks. Farmers with a higher share of income from their production operations bear a greater risk from their operational income and are more willing to report any suspected infections on their farms. The data suggest that motivating the willingness of farmers to invest in biosecurity while overcoming cost concerns is achievable.