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A wall-mounted far ultraviolet-C light device used for continuous air and surface decontamination in a dental office reduced aerosolized bacteriophage MS2 and methicillin-resistant Staphylococcus aureus on steel disks by >3 log10 in 2 hours in unshaded areas in a procedure room. Far ultraviolet-C delivery was substantially reduced in shaded areas.
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Dairy production is a key agricultural enterprise in the Upper Chesapeake Bay (UCB) basin, where phosphorous (P) and nitrogen (N) loading contribute to eutrophication. Import of forages and grains and application of mineral fertilizers contribute to nutrient imbalances in the basin. The UCB Long-Term Agroecosystem Research Cropland Common Experiment aims to evaluate diverse crop rotations that minimize the need for imported feed, maximize year-round living cover, and reduce nutrient losses. UCB's plot-scale experiment was established in 2018, incorporating an ongoing cropping system study that was established by the Pennsylvania State University in 2010. An alternative dairy cropping rotation (including silage and grain corn [Zea mayes L.], alfalfa [Medicago sativa L.]/orchardgrass [Dactylis glomerata L.] mix, winter rye silage [Secale cereale L.], and sorghum-sudangrass [Sorghum × drummondii (Steud.) Millsp. & Chas]) that employed manure injection, integrated pest management, and less frequent manure application was compared to a prevailing, conventionally managed silage corn-alfalfa rotation with higher manure application rates. A field-scale experiment was established in 2019 to monitor alternative production practices (manure injection and avoidance of neonicotinoid seed treatment) and prevailing practices in three fields on a commercial dairy farm. Findings suggest that crop rotation diversification, manure injection, and integrated pest management have the potential to increase the economic and environmental sustainability of dairy cropping systems, but long-term evaluation is needed for confirmation.
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BACKGROUND: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention. METHODS: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N=17,535) to receive 3 PF-06425090 or placebo doses (0,1,6-months). Primary endpoints were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary endpoints), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability/safety was assessed. RESULTS: The primary endpoint was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE)=31.0% (96.4%CI: -38.7%-66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE=28.6% (-28.4%-61.0%)]). Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P=0.02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE=100% [95%CI: 59.6%-100.0%]) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE=100% [54.8%-100.0%]). Local reactions were more frequent in PF-06425090 recipients and systemic events were generally similar between groups; most were mild-to-moderate. AE rates were similar between groups. CONCLUSIONS: Three PF-06425090 doses were safe and well-tolerated. Although the primary endpoint was not met, PF-06425090 reduced symptom duration, CDI requiring medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. NCT03090191.
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The Central Mississippi River Basin (CMRB) Common Experiment, with its marginal soils and southern Corn Belt climate, is an ideal location for evaluating progress toward environmental, productivity, and climatic adaptation goals. Sustainable production with conventional row-crop systems is more challenging than in the upper Corn Belt, making evaluation and adoption of alternative farming practices crucial. This Common Experiment has a hydrologically restrictive layer causing reduced plant available water capacity in the root zone. The CMRB site joined the Long-Term Agroecosystem Research Network in 2011 with the Cropland Common Experiment established in 2015. The Common Experiment contrasts prevailing and alternative practices at plot and field scale. Improvement of the soil ecosystem is key, as it underpins other objectives, including reduced nutrient losses, increased soil water holding capacity, and yield stability.
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Testing for dispersal of fluorescent gel from sink drains was sensitive for detection of sinks that dispersed gram-negative bacilli outside the bowl. Reducing the flow rate of sinks with rapid water inflow and/or elimination of obstruction leading to slow outflow was effective in preventing dispersal of fluorescence and gram-negative bacilli.
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OBJECTIVE: The objective was to identify clinical and radiological factors associated with sleep-disordered breathing (SDB) in children with Chiari type I malformation (CIM) and to evaluate the efficacy of foramen magnum decompression (FMD) in resolving SDB. METHODS: A retrospective chart review was conducted for all children evaluated for CIM at a single institution from 2002 to 2022, identifying all children who had undergone nocturnal polysomnography (PSG). Apnea-hypopnea index (AHI) score, sleep apnea type (obstructive, central, mixed, and unspecified), clinical manifestations, and radiological measurements were recorded. SDB was considered present when officially diagnosed in the PSG report. Logistic regression was performed to identify factors correlating with the presence of SDB. For children with SDB who underwent FMD, the Wilcoxon signed-rank test was used to assess AHI improvement. RESULTS: Of the 997 children referred for CIM, 310 completed PSG. SDB was diagnosed in 147 patients (overall prevalence 14.7%, 95% CI 12.7%-17.1%; prevalence among children with PSG 47.4%, 95% CI 41.9%-53%). Specific SDB diagnosis consisted of 33% of patients with central sleep apnea, 27% with obstructive sleep apnea, 9% mixed, and 31% unspecified. Lower cranial nerve (CN) dysfunction (OR 3.891, p = 0.009), tonsillar position (OR 1.049, p = 0.017), Chiari type 1.5 malformation (OR 1.862, p = 0.044), and BMI (OR 1.039, p = 0.036) were significantly associated with presence of SDB. Of the 310 patients who underwent PSG, 47 were originally categorized as asymptomatic: 27 (57%) of these asymptomatic patients were diagnosed with SDB on PSG. Of children diagnosed with SDB, 34 completed PSG before and after FMD. Median AHI score decreased from 6.5 preoperatively to 1.8 postoperatively, with a median (IQR) difference of -2.3 (-11.9 to 0.1) (p = 0.001). Twelve (35%) had resolution of SDB. CONCLUSIONS: The authors' findings suggest that the prevalence of SDB in children with CIM is high (15%-47%). Furthermore, lower CN dysfunction, Chiari type 1.5, lower tonsillar position, and higher BMI may be risk factors. Notably, SDB can be present even in the absence of clinical symptoms. This study also demonstrates that surgical intervention has the potential to reduce the severity of SDB. These results could help clinicians identify CIM patients at risk for SDB and those who may benefit from surgical decompression.
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OBJECTIVE: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort. METHODS: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months. RESULTS: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013). CONCLUSIONS: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.
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INTRODUCTION: Myelomeningocele (MMC) is the most common neural tube defect, but rarely seen in premature infants. Most centers advocate for closure of MMC within 24 h of birth. However, this is not always possible in severely premature infants. Given the rarity of this patient population, we aimed to share our institutional experience and outcomes of severely premature infants with MMC. METHODS: We performed a retrospective, observational review of premature infants (≤ 32 weeks gestational age) identified through our multidisciplinary spina bifida clinic (1995-2021) and surgical logs. Descriptive statistics were compiled about this sample including timing of MMC closure and incidence of adverse events such as sepsis, CSF diversion, meningitis, and death. RESULTS: Eight patients were identified (50% male) with MMC who were born ≤ 32 weeks gestational age. Mean gestational age of the population was 27.3 weeks (SD 3.5). Median time to MMC closure was 1.5 days (IQR = 1-80.8). Five patients were taken for surgery within the recommended 48 h of birth; 2 patients underwent significantly delayed closure (107 and 139 days); and one patient's defect epithelized without surgical intervention. Six of eight patients required permanent cerebrospinal fluid (CSF) diversion (2 patients were treated with ventriculoperitoneal shunting (VPS), three were treated with endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) and 1 patient treated with ETV; mean of 3 years after birth, ranging from 1 day to 16 years). Two patients required more than one permanent CSF diversion procedure. Two patients developed sepsis (defined as meeting at least 2/4 SIRS criteria). In both cases of sepsis, patients developed signs and symptoms more than 72 h after birth. Notably, both instances of sepsis occurred unrelated to operative intervention as they occurred before permanent MMC closure. Two patients had intraventricular hemorrhage (both grade III). No patients developed meningitis (defined as positive CSF cultures) prior to MMC closure. Median follow up duration was 9.7 years. During this time epoch, 3 patients died: Two before 2 years of age of causes unrelated to surgical intervention. One of the two patients with grade III IVH died within 24 h of MMC closure. CONCLUSIONS: In our institutional experience with premature infants with MMC, some patients underwent delayed MMC closure. The overall rate of meningitis, sepsis, and mortality for preterm children with MMC was similar to MMC patients born at term.
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We report a large outbreak of severe acute respiratory syndrome coronavirus 2 in a residential living facility. Measurements of carbon dioxide levels, aerosol particle clearance, and airflow were used to identify and remediate areas with suboptimal ventilation. A simple intervention involving continuous operation of bathroom fans was effective in significantly improving ventilation in resident rooms.
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In response to climate-driven water shortages, Duke University in 2014 constructed a water reuse reservoir and wetland complex (Pond) to capture urban stormwater and recycle water to provide campus cooling and reduce downstream loading of nutrients and sediment into Jordan Lake, a regional water supply. We postulated that even with significant water level changes due to withdrawals, the Pond would function to reduce downstream nutrients and sediment once wetland plants became established in the littoral zone. Throughout the project (2015-2021), baseflow nutrient concentrations downstream decreased, with Unfiltered Total Nitrogen (UTN) falling by 44 % and Unfiltered Total Phosphorus (UTP) by 50 %. Storm mean concentrations decreased by 31 % for UTN, 54 % for UTP, and 72 % for Total Suspended Solids (TSS). The annual reductions in mass fluxes (UTN, UTP, and TSS) were between 58 and 85 % across a range of storm intensities. Regardless of water level, temperature, pH, and oxygen concentrations downstream were not significantly changed. Between 2015 and 2020, a littoral survey of planted and naturally introduced species showed that wetter years resulted in a greater number of species across a gradient of three inundation zones (i.e., moist, wet, and aquatic). Conversely, dryer years resulted in fewer species across overlapping zones. The dominant plants that successfully colonized the Pond are all obligate wetland species despite the Pond's highly variable water depths and periods of inundation. The final plant populations were dominated by invasive native species supporting the self-design theory of plant succession as nearly half of the original planted species died. The reuse Pond design (pond-wetland complex) showed the capability of using stormwater runoff for campus cooling while improving water quality services and providing habitat for wetland plants. Thus, campuses with watershed runoff capture capability should consider a nature-based recycling approach as part of their water sustainability program.
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Qualidade da Água , Áreas Alagadas , Universidades , Abastecimento de Água , Jordânia , Fósforo/análise , Plantas , Monitoramento Ambiental , Nitrogênio/análise , ChuvaRESUMO
In a 12-year single-center quasi-experimental study, a switch from ciprofloxacin to ceftriaxone prophylaxis for transrectal ultrasound-guided prostate biopsy procedures was associated with a significant reduction in 30-day postprocedure urinary tract infection, urinary tract infection-related hospitalizations, antibiotic prescriptions, and isolation of fluoroquinolone-resistant organisms from urine or blood cultures.
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Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.
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Dicetopiperazinas , Penicillium , Penicillium/química , Dicetopiperazinas/farmacologia , Dicetopiperazinas/química , Estrutura Molecular , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Background: Community-associated Clostridioides difficile infection is a major public health hazard to adults and older children. Infants frequently excrete toxigenic C difficile asymptomatically in their stool, but their importance as a community reservoir of C difficile is uncertain. Methods: Families of healthy infants were recruited at the baby's 4-month well child visit and were followed longitudinally until the baby was approximately 9 months old. Babies and mothers submitted stool or rectal swabs every 2 weeks that were cultivated for C difficile; fathers' participation was encouraged but not required. Clostridioides difficile isolates were strain-typed by fluorescent polymerase chain reaction ribotyping and by core genome multilocus sequence typing, and the number of families in whom the same strain was cultivated from >1 family member ("strain sharing") was assessed. Results: Thirty families were enrolled, including 33 infants (3 sets of twins) and 30 mothers; 19 fathers also participated. Clostridioides difficile was identified in 28 of these 30 families over the course of the study, and strain sharing was identified in 17 of these 28. In 3 families, 2 separate strains were shared. The infant was involved in 17 of 20 instances of strain sharing, and in 13 of these, the baby was identified first, with or without a concomitantly excreting adult. Excretion of shared strains usually was persistent. Conclusions: Clostridioides difficile strain sharing was frequent in healthy families caring for an infant, increasing the likelihood that asymptomatically excreting babies and their families represent a reservoir of the organism in the community.
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BACKGROUND: Adult congenital heart disease (ACHD) can negatively impact quality of life (QOL). Strengthening resilience may improve this and other psychosocial outcomes important for living a meaningful life. OBJECTIVES: The purpose of this study was to describe resilience and key psychosocial health outcomes in ACHD and evaluate the associations between resilience and these outcomes. METHODS: We conducted a prospective cohort study of outpatients with moderate or complex ACHD between May 2021 and June 2022. Participants completed surveys at baseline and 3 months, evaluating resilience (Connor-Davidson Resilience Scale-10), health-related QOL (EQ5D-3L, linear analog scale), health status (Euroqol visual analog scale), self-competence (Perceived Competence Scale), and psychological symptom burden (Hospital Anxiety and Depression Scale) and distress (Kessler-6). RESULTS: The mean participant age (N = 138) was 41 ± 14 years, 51% were female, and 83% self-identified as non-Hispanic White. ACHD was moderate for 75%; 57% were physiologic class B. Mean baseline resilience score (Connor-Davidson Resilience Scale-10) was 29.20 ± 7.54. Participants had relatively good health-related QOL, health status, and self-competence, and low psychological symptom burden and distress. Higher baseline resilience was associated with better values of all outcomes at 3 months (eg, 1 point higher resilience was associated with 0.92 higher linear analog scale; 95% CI: 0.52-1.32) with or without adjustment for demographics. After further adjusting for the baseline psychosocial measure, only the association between resilience and QOL measures at 3 months remained statistically significant. CONCLUSIONS: Resilience is positively associated with health-related QOL for outpatients with moderate or complex ACHD, though relationships are small in magnitude. Study findings can guide the application of resilience-building interventions to the ACHD population.
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Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A 42-year-old man with treatment-resistant major depressive disorder took 1 g of Psilocybe cubensis mushrooms, while prescribed tranylcypromine, extended-release dextroamphetamine-amphetamine, and other medications. Approximately half an hour later, he developed severe hypertension with chest pain, palpitations, and headache. Upon hospital presentation, the electrocardiogram demonstrated ST-elevation. The patient was diagnosed with a myocardial infarction and treated with lorazepam, nitroglycerin, and aspirin. He subsequently underwent emergency cardiac catheterization, which revealed no significant cardiac abnormalities. Following overnight hospitalization, he was discharged home with no lasting physical sequelae. Though data are few, past studies suggest that classic serotonergic psychedelics (5HT-2A receptor agonists) such as dimethyltryptamine (DMT), lysergic acid (LSD), and synthetic psilocybin should not produce hypertensive emergency when combined with MAOIs. We suspect phenylethylamine, found in Psilocybe cubensis and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine.
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INTRODUCTION: A subset of children with Chiari 1 malformation (CM-1) have a 4th ventricle arachnoid veil-a thin membrane covering the outlet of the 4th ventricle. Studies suggest that failure to disrupt this veil during posterior fossa decompression can reduce the likelihood of syringomyelia resolution. However, there is no reliable method for predicting the presence of the veil without direct surgical exploration. This study aims to evaluate the association between pre-operative symptoms, radiographic measurements, and the arachnoid veil. METHODS: A retrospective review of an institutional database of children evaluated for CM-I was conducted. For patients treated with surgery, operative notes were reviewed to determine if an arachnoid veil was present. Logistic regression was used to test for relationship of clinical variables and radiographic measurements with the presence of an arachnoid veil. RESULTS: Out of 997 children with CM-1, 226 surgical patients were included in the analysis after excluding those with inadequate documentation. An arachnoid veil was found in 23 patients (10.2%). Larger syrinx, spinal canal, and thecal sac diameters were significantly associated with the presence of a veil, with odds ratios of 1.23 (95% CI 1.2-1.48; p = 0.03), 1.27 (95% CI 1.02-1.59; p = 0.03), and 1.35 (95% CI 1.03-1.77; p = 0.03), respectively. No significant associations were found with any signs or symptoms. CONCLUSIONS: Arachnoid veil was present in 10% of cases. Radiographic measurements indicating larger syrinx size were the only variables found to be significantly associated with an arachnoid veil. Exploration of the 4th ventricular outlet is recommended for CM-I decompression in the setting of expansile syringomyelia.
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Malformação de Arnold-Chiari , Quarto Ventrículo , Humanos , Malformação de Arnold-Chiari/cirurgia , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/diagnóstico por imagem , Feminino , Masculino , Estudos Retrospectivos , Criança , Pré-Escolar , Adolescente , Quarto Ventrículo/diagnóstico por imagem , Quarto Ventrículo/cirurgia , Siringomielia/cirurgia , Siringomielia/diagnóstico por imagem , Siringomielia/complicações , Lactente , Descompressão Cirúrgica/métodos , Aracnoide-Máter/cirurgia , Aracnoide-Máter/diagnóstico por imagemRESUMO
Corn (Zea mays) crops harvested as grain in autumn do not provide opportunity for cover crop establishment, which may be remedied by interseeding cover crops into growing corn. Grazing cover crops after corn grain harvest could provide added revenues and increase nutrient cycling in the system while providing additional ecosystem services. However, tradeoffs between cash crop productivity and cover crop inclusion, and use as grazed forage, are not fully understood. This 4-year Long-Term Agroecosystem Research Integrated Common Experiment project evaluated the effect of interseeding cereal rye (Secale cereale) into corn for grazing after corn grain harvest on corn grain yield and late-season grazing. Cereal rye was interseeded into corn in early June. After corn grain harvest, six paddocks at each location were randomly allotted to grazed (GRAZ) or not grazed (NG). The GRAZ paddocks were grazed with beef cattle in late autumn and again in early spring if regrowth allowed. Paddocks were flown with an unmanned aerial system (UAS) to characterize spatial forage yield and quality. Cereal rye provided an additional 20-30 grazing days in the autumn for 24 beef cows on 4.8 ha. Early spring growth shows potential to provide even greater forage yields than autumn, but growth is less dependable. Corn grain yields did not decrease except in 2019 (dry year) when yields were 40% lower. There were no significant differences in soil health indicators between GRAZ and NG paddocks. The UAS shows promise as a tool for monitoring forage yield and quality and optimizing grazing management.
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BACKGROUND AND AIMS: Emerging data suggest neoadjuvant chemotherapy (NAC) for resectable pancreatic ductal adenocarcinoma (PDAC) is associated with improved survival. However, less than 40% of patients demonstrate a meaningful radiographic response to NAC. EUS-guided radiofrequency ablation (EUS-RFA) has emerged as a new modality to treat PDAC. We hypothesize that NAC plus EUS-RFA can be used in the management of resectable PDAC. METHODS: This was a prospective review of PDAC patients meeting the criteria of resectable tumor anatomy who underwent NAC chemotherapy plus EUS-RFA followed by pancreatic resection. Radiographic imaging and perioperative and short-term outcomes were recorded. Surgical pathology specimens were analyzed for treatment response. RESULTS: Three eligible patients with resectable PDAC received 4 months of NAC plus EUS-RFA. One month after completing NAC and EUS-RFA, all 3 patients underwent standard pancreaticoduodenectomy without adverse events. After a 6-week recovery, all patients completed 2 months of postoperative adjuvant chemotherapy. CONCLUSIONS: In our institutional experience, this treatment protocol appears to be safe as patients tolerated the combination of chemotherapy and ablation. Patients underwent pancreatic resection with uneventful recovery. This novel neoadjuvant approach may provide a more effective alternative to chemotherapy alone.
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BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to â¼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.
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Background: Technologies that provides safe and eï¬ective decontamination of surfaces and equipment between episodes of manual cleaning could be an important advance in eï¬orts to prevent transmission of the emerging fungal pathogen Candida auris. Methods: We tested the efficacy of a novel wall-mounted far ultraviolet-C (UV-C) light technology that delivers far UV-C, when people are not detected within the field of illumination, against C. auris isolates from clades I, II, III, and IV using a quantitative disk carrier test method. In an equipment room, we examined the efficacy of the technology in reducing an isolate of C. auris from clade IV inoculated on multiple sites on portable devices. Results: The far UV-C technology reduced isolates from all 4 clades of C. auris by >3 log10 colony-forming units (CFU) aï¬ er an 8-hour exposure on steel disks. For the clade IV isolate, similar reductions were achieved on glass and plastic carriers. In the equipment room, the technology reduced C. auris inoculated on multiple sites on portable equipment by >2 log10 CFU in 4 hours. Conclusions: The far UV-C technology could be useful for decontamination of surfaces and equipment between episodes of manual cleaning. Additional studies are needed to evaluate the use of the technology in clinical settings.