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Abstract Background and Aims Preprocedural ultrasound (PPU) reduces the risk of technical failure in non‐obese patients and when technical difficulty is predicted. We conducted this review to determine if PPU improves first‐pass needle insertion success for neuraxial anesthesia in patients with obesity. Methods We conducted a systematic review without meta‐analysis, due to the small number of included studies. The study protocol was registered (PROSPERO: CRD42022368271). We conducted searches in MEDLINE, Embase, PubMed, and Cochrane Library from January 1, 1980 to October 1, 2022 for peer‐reviewed randomized controlled or observational studies comparing PPU versus landmark techniques in patients with body mass index >30 kg/m2. The quality of evidence was assessed using the revised Cochrane risk‐of‐bias tool for randomized trials and Grading of Recommendations Assessment, Development, and Evaluation approach. Results There were nine randomized controlled studies, comprising 866 patients having lumbo‐sacral neuraxial techniques. Three studies utilized a small handheld ultrasound device called Accuro™ and six utilized non‐handheld ultrasound devices. Certainty of evidence was low for improving the first‐pass success rate. There was evidence (moderate certainty) that PPU decreased number of passes, increased first insertion attempt success, and reduced number of insertion attempts. There was no evidence that PPU affected identifying time, needling time, or overall procedural time. There was no evidence that PPU influenced procedural failure rate (very low certainty evidence) and insufficient evidence to suggest that artificial intelligence‐supported handheld devices were superior to conventional ultrasound devices. Conclusions In patients with obesity, there is evidence of very‐low to moderate certainty that PPU improves markers of insertion success, with no indication of increased adverse effects. PPU should be used to reduce attempts. Further studies adhering to standardized outcome definitions are required for definitive recommendations. Registration The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022368271).

Abstract The release of sterilized insects to control pest populations has been used successfully during the past 6 decades, but application of the method in vertebrates has largely been overlooked or met with failure. Here, we demonstrate for the first time in fish, that a small population of sea lamprey (Petromyzon marinus; Class Agnatha), arguably one of the most impactful invasive fish in the world, can be controlled by the release of sterilized males. Specifically, the release of high numbers of sterile males (~ 1000's) into a geographically isolated population of adult sea lamprey resulted in the first multiyear delay in pesticide treatment since treatments began during 1966. Estimates of percent reduction in recruitment of age-1 sea lamprey due to sterile male release ranged from 7 to 99.9% with the precision of the estimate being low because of substantial year-to-year variability in larval density and distribution. Additional monitoring that accounts for recruitment variability in time and space would reduce uncertainty in the degree to which sterile male release reduces recruitment rates. The results are relevant to vertebrate pest control programs worldwide, especially as technical opportunities to sterilize vertebrates and manipulate sex ratios expand.

PurposeWe constructed a 13C/31P surface coil at 3 T for studying cancer metabolism and bioenergetics. In a single scan session, hyperpolarized 13C-pyruvate MRS and 31P MRS was carried out for a healthy rat brain.MethodsAll experiments were carried out at 3 Tesla. The multinuclear surface coil was designed as two coplanar loops each tuned to either the 13C or 31P operating frequency with an LCC trap on the 13C loop. A commercial volume proton coil was used for anatomical localization and B0 shimming. Single tuned coils operating at either the 13C or 31P frequency were built to evaluate the relative performance of the multinuclear coil. Coil performance metrics consisted of measuring Q factor ratio, calculating system input power using a single-pulse acquisition, and acquiring SNR and flip angle maps using 2D CSI sequences. To observe in vivo spectra, a bolus of hyperpolarized [1-13C] pyruvate was administered via tail vein. In vivo13C and endogenous 31P spectra were obtained in a single scan session using 1D slice selective acquisitions.ResultsWhen compared with single tuned surface coils, the multinuclear coil performance showed a decrease in Q factor ratio, SNR, and transmit efficiency. Flip angle maps showed adequate flip angles within the phantom when the transmit voltage was set using an external phantom. Results show good detection of 13C labeled lactate, alanine, and bicarbonate in addition to ATP from 31P MRS.ConclusionsThe coil enables obtaining complementary information within a scan session, thus reducing the number of trials and minimizing biological variability for studies of metabolism and bioenergetics.

Abstract Background Hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, predisposing them to life‐threatening diseases. Varied responses to management strategies suggest the possibility of multiple subtypes. Hypothesis/Objective To identify and characterize HTG subtypes in Miniature Schnauzers through cluster analysis of lipoprotein profiles. We hypothesize that multiple phenotypes of primary HTG exist in this breed. Animals Twenty Miniature Schnauzers with normal serum triglyceride concentration (NTG), 25 with primary HTG, and 5 with secondary HTG. Methods Cross‐sectional study using archived samples. Lipoprotein profiles, generated using continuous lipoprotein density profiling, were clustered with hierarchical cluster analysis. Clinical data (age, sex, body condition score, and dietary fat content) was compared between clusters. Results Six clusters were identified. Dogs with primary HTG were dispersed among 4 clusters. One cluster showed the highest intensities for triglyceride‐rich lipoprotein (TRL) and low‐density lipoprotein (LDL) fractions and also included 4 dogs with secondary HTG. Two clusters had moderately high TRL fraction intensities and low‐to‐intermediate LDL intensities. The fourth cluster had high LDL but variable TRL fraction intensities with equal numbers of NTG and mild HTG dogs. The final 2 clusters comprised only NTG dogs with low TRL intensities and low‐to‐intermediate LDL intensities. The clusters did not appear to be driven by differences in the clinical data. Conclusions and Clinical Importance The results of this study support a spectrum of lipoprotein phenotypes within Miniature Schnauzers that cannot be predicted by triglyceride concentration alone. Lipoprotein profiling might be useful to determine if subtypes have different origins, clinical consequences, and response to treatment.

Abstract The characterization of the vibrations of the middle ear ossicles during sound transmission is a focal point in clinical research. However, the small size of the structures, their micrometer-scale movement, and the deep-seated position of the middle ear within the temporal bone make these types of measurements extremely challenging. In this work, dynamic synchrotron-based X-ray phase-contrast microtomography is used on acoustically stimulated intact human ears, allowing for the three-dimensional visualization of entire human eardrums and ossicular chains in motion. A post-gating algorithm is used to temporally resolve the fast micromotions at 128 Hz, coupled with a high-throughput pipeline to process the large tomographic datasets. Seven ex-vivo fresh-frozen human temporal bones in healthy conditions are studied, and the rigid body motions of the ossicles are quantitatively delineated. Clinically relevant regions of the ossicular chain are tracked in 3D, and the amplitudes of their displacement are computed for two acoustic stimuli.

Background: Cellulitis is a common infection in Emergency Departments (EDs), and unclear diagnostics may lead to unnecessary treatment with broad-spectrum antibiotics. The aim of this study was to characterize patients with cellulitis admitted to the ED, describe the type and route of antibiotic treatment and compare the prognosis for cellulitis to that for other infections. Methods: This multicenter, cross-sectional study prospectively included adult patients admitted to the ED suspected of having an infection. Data were collected from medical records, and an expert panel assigned a final diagnosis to each patient. Only patients diagnosed with an infection were included in this study. Results: A total of 777 patients were included, of which 77 were diagnosed with cellulitis. Diabetes, obesity and prior cellulitis were associated with cellulitis with an OR of 2.01 [95% CI: 1.17–3.46], OR 2.66 [95% CI: 1.54–4.59] and OR 14.88 [95% CI: 7.88–28.08], respectively. The majority of the patients were treated, according to the regional guidelines, with narrow-spectrum antibiotics. Broad-spectrum antibiotics were rarely used. The patients with cellulitis were hospitalized for a shorter time compared to those with other infections, but 26% were readmitted within 30 days. The 30-day mortality of the patients with cellulitis was 3.9% and did not differ significantly from other infections.

Abstract Objective Scleroderma is a complex chronic progressive immune‐mediated disease that causes fibrosis of the skin and internal organs, and vasculopathy. Ear involvement has been poorly studied in patients with scleroderma. Vasculitic and autoimmune mechanisms are considered as possible etiologies on hearing impairment, however, this etiology still unclear. Herein, we reviewed three cases of scleroderma from a temporal bone repository. Methods The national temporal bone database was reviewed for cases with scleroderma. Clinical case review and correlative otopathologic analysis. Middle and inner ear otopathologic analysis was performed following hematoxylin and eosin staining under light microscopy. Findings were compared to three age‐matched controls. Results Two patients (three cases) with a history of serologically confirmed scleroderma were identified. Both individuals reported tinnitus and demonstrated bilateral moderate to severe down‐sloping sensorineural hearing loss on audiometry. Histologically, the incudomallear joint space was diminished and ossicles appeared demineralized. A loss of hyaline cartilage, and obliteration of the incudomallear and incudostapedial joint synovial spaces was observed. Decreased caliber and intimal hyperplasia of arteries adjacent to ossicles was also identified. Mild diffuse atrophy of stria vascularis in the middle and apical turns of cochlea were found. Hair cell populations were normal. Total spiral ganglion neurons were lower in cases of scleroderma (range 29%–51%) compared to age‐matched controls. Conclusion Fibrosis, inflammation, and vascular changes were observed in the middle and inner ear in patients with scleroderma. Findings have implications for understanding hearing and vestibular dysfunction in this patient population. Level of evidence Retrospective study.

Abstract Objectives Age‐related hearing loss (presbycusis) is a prevalent condition traditionally attributed to inner ear dysfunction. Little is known about age‐related changes in the ossicular joints or their contribution to presbycusis. Herein, we performed an otopathologic evaluation of the ossicular joints in cases of presbycusis without a clear sensorineural explanation. Methods Histopathologic analysis of the incudomallear (IM) and incudostapedial (IS) joints was performed in specimens from the National Temporal Bone Registry with audiometrically confirmed presbycusis but without histologically observed sensorineural, strial, or mixed features; deemed cases of “indeterminate” presbycusis. Specimens identified as “indeterminate” presbycusis (IP, n = 18) were compared to specimens with histologically confirmed sensorineural presbycusis (n = 16) and strial presbycusis (n = 11). Presbycutic specimens were also compared to age‐matched controls (n = 9) and young controls (n = 14). Results The synovial space at the center of the IM joint was wider in the IP group (194 ± 36.8 μm) compared to age‐matched controls (138 ± 36.5 μm), young controls (149 ± 32.2 μm), and ears with sensorineural presbycusis (148 ± 52.7 μm) (p

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-driven connective tissue disorder that results in fibrosis of the skin and internal organs such as the lung. Fibroblasts are known as the main effector cells involved in the progression of SSc through the induction of extracellular matrix (ECM) proteins and myofibroblast differentiation. Here, we demonstrate that 4'-(cyclopropylmethyl)-N2-4-pyridinyl-[4,5'-bipyrimidine]-2,2'-diamine (PIK-III), known as class III phosphatidylinositol 3-kinase (PIK3C3/VPS34) inhibitor, exerts potent antifibrotic effects in human dermal fibroblasts (HDFs) by attenuating transforming growth factor-beta 1 (TGF-β1)-induced ECM expression, cell contraction and myofibroblast differentiation. Unexpectedly, neither genetic silencing of PIK3C3 nor other PIK3C3 inhibitors (e.g., SAR405 and Autophinib) were able to mimic PIK-III-mediated antifibrotic effect in dermal fibroblasts, suggesting that PIK-III inhibits fibroblast activation through another signaling pathway. We identified that PIK-III effectively inhibits p38 activation in TGF-β1-stimulated dermal fibroblasts. Finally, PIK-III administration significantly attenuated dermal and lung fibrosis in bleomycin-injured mice.

Abstract Derangements of the blood-brain barrier (BBB) or blood-retinal barrier (BRB) occur in disorders ranging from stroke, cancer, diabetic retinopathy, and Alzheimer’s disease. The Norrin/FZD4/TSPAN12 pathway activates WNT/β-catenin signaling, which is essential for BBB and BRB function. However, systemic pharmacologic FZD4 stimulation is hindered by obligate palmitoylation and insolubility of native WNTs and suboptimal properties of the FZD4-selective ligand Norrin. Here, we develop L6-F4-2, a non-lipidated, FZD4-specific surrogate which significantly improves subpicomolar affinity versus native Norrin. In Norrin knockout (Ndp KO ) mice, L6-F4-2 not only potently reverses neonatal retinal angiogenesis deficits, but also restores BRB and BBB function. In adult C57Bl/6J mice, post-stroke systemic delivery of L6-F4-2 strongly reduces BBB permeability, infarction, and edema, while improving neurologic score and capillary pericyte coverage. Our findings reveal systemic efficacy of a bioengineered FZD4-selective WNT surrogate during ischemic BBB dysfunction, with potential applicability to adult CNS disorders characterized by an aberrant blood-brain barrier.

Objective Energy poverty contributes to the general well-being of households; however, there is representational paucity on its role in household nutrition across sub-Saharan Africa (SSA). This study examined the influence of different domains of energy poverty and a Multidimensional Energy Poverty Index (MEPI) on household burden of malnutrition in SSA.Setting Secondary data from the most recent Demographic and Health Survey conducted in 18 SSA countries were analysed.Design A cross-sectional design was used to examine the relationship between household energy poverty and household burden of malnutrition.Methods Different dimensions of household energy poverty and an MEPI were computed from the sources of energy used for cooking, lighting, entertainment and accessing information by households. Household burden of malnutrition was coded as a binary categorical dependent variable using indicators of undernutrition, overnutrition and anaemia among women of reproductive age (15–49 years) and children under five years in the household.Results More than nine in ten households were energy poor in terms of cooking fuel and about three in four were energy poor in terms of lighting. Considering the various domains of energy poverty, lack of electricity for lighting, using biofuels, not owning a refrigerator/freezer, not owning a television/radio and not owning a mobile phone were associated with increased odds of a household experiencing undernutrition. Similarly, deprivation in these domains was associated with a lower likelihood of households experiencing overnutrition, the only exception being using biofuels. Overall, households that were most energy poor on the MEPI were more likely to be undernourished and double and triple burden malnutrition households but less likely to suffer from overnutrition.Conclusion These results highlight the complex and multifaceted nature of the relationship between energy poverty and household burden of malnutrition and provides guidance for appropriate interventions to address energy poverty and malnutrition in SSA.

Due to global climate change resulting in extreme temperature fluctuations, it becomes increasingly necessary to explore the natural genetic variation in model crops such as rice to facilitate the breeding of climate-resilient cultivars. To uncover genomic regions in rice involved in managing cold stress tolerance responses and to identify associated cold tolerance genes, two inbred line populations developed from crosses between cold-tolerant and cold-sensitive parents were used for quantitative trait locus (QTL) mapping of two traits: degree of membrane damage after 1 week of cold exposure quantified as percent electrolyte leakage (EL) and percent low-temperature seedling survivability (LTSS) after 1 week of recovery growth. This revealed four EL QTL and 12 LTSS QTL, all overlapping with larger QTL regions previously uncovered by genome-wide association study (GWAS) mapping approaches. Within the QTL regions, 25 cold-tolerant candidate genes were identified based on genomic differences between the cold-tolerant and cold-sensitive parents. Of those genes, 20% coded for receptor-like kinases potentially involved in signal transduction of cold tolerance responses; 16% coded for transcription factors or factors potentially involved in regulating cold tolerance response effector genes; and 64% coded for protein chaperons or enzymes potentially serving as cold tolerance effector proteins. Most of the 25 genes were cold temperature regulated and had deleterious nucleotide variants in the cold-sensitive parent, which might contribute to its cold-sensitive phenotype.

Summary: Circadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific intestinal microbial circadian rhythms in host metabolism using germ-free and conventionalized mice and manipulation of dietary-derived fat, fiber, and microbiota-accessible carbohydrates. Our findings demonstrate that sex differences in circadian rhythms of genes involved in immunity and metabolism depend on oscillations in microbiota, microbial metabolic functions, and microbial metabolites. Further, we show that consuming an obesogenic, high-fat, low-fiber diet produced sex-specific changes in circadian rhythms in microbiota, metabolites, and host gene expression, which were linked to sex differences in the severity of metabolic dysfunction. Our results reveal that microbial circadian rhythms contribute to sex differences in immunity and metabolism and that dietary factors can entrain new circadian rhythms and modify the magnitude of sex differences in host-microbe circadian dynamics.