Reducing Temperature of Fused Deposition Modelling 3D Printing for Linalool Fast Dissolving Oral Films by Increasing Printer Nozzle Diameter.

Oral thrush and throat infections can occur in a wide range of patients. Treatments are available; however, resistance to drugs is a major problem for treating oral and throat infections. Three-dimensional printing (3DP) of fast dissolving oral films (FDFs) of linalool oil may provide an alternative solution. Linalool oil FDFs were printed by fused deposition modelling across 1-18 % w/w linalool content range with nozzle diameters of 0.4 or 1 mm at the temperature range of 150 °C-185 °C. The FDFs were evaluated for physicochemical and mechanical properties. Increasing the printer nozzle diameter to 1 mm allowed reducing the printing temperature from 185 °C to 150 °C; consequently, more linalool was quantified in the films with improved content uniformity. The higher linalool content in the films increased the film disintegration time and mechanical strength. FDFs containing 10% w/w linalool showed clear antifungal activity against Candida albicans. Raman spectroscopy suggested linalool separation from excipients at higher temperature printing. Viscoelastic measurements indicated that to achieve printing; the elastic modulus of molten filament needed to be higher than the loss modulus at low angular frequencies. In conclusion, increasing the printing nozzle diameter may avoid loss of the active ingredient by reducing the temperature of the 3DP process.

Early-life caffeine exposure induces morphological changes and altered physiology in Caenorhabditiselegans.

Caffeine, a widely consumed stimulant, is known for its effects on alertness and fatigue reduction by blockade of adenosine receptors. While it holds therapeutic potential, its diverse impacts pose risks, particularly in early development. This study explores the developmental effects of caffeine exposure using Caenorhabditis elegans (C. elegans) as a model organism. We investigated morphological and behavioral changes induced by caffeine exposure at the L1 stage and assessed their impact at the L4 stage, which roughly corresponds to human infancy and adolescence, respectively. Caffeine-exposed worms displayed increased body length, body bends, and pharyngeal pumping rates compared to control worms. These findings indicate heightened food-seeking behavior and greater food intake, leading to the observed morphological changes. While caffeine did not affect other locomotor behaviors, its stimulatory effect on growth and development highlights its significance. This study provides insights into the potential impact of early-life caffeine exposure on long-term health and development, offering a foundation for future research in vertebrates to uncover its implications on metabolism and other metrics of health.

Characterization of Medication Discrepancies and Interventions Resulting From Pharmacy-Led Medication Reconciliation in the Critical Care Setting.

BACKGROUND: Medication reconciliation has been shown to reduce medication-related errors in hospitalized patients, but the impact of pharmacy-led medication reconciliation in the intensive care unit (ICU) has not been extensively studied. METHODS: This was a retrospective chart review of patients with a pharmacy-led medication reconciliation on admission to an ICU between January 1st and March 31st, 2018. Pharmacy-led medication reconciliations were completed by pharmacists, pharmacy residents, and pharmacy students. The objective of this study was to describe medication discrepancies identified by pharmacy-led medication reconciliation and to evaluate the interventions following. RESULTS: A total of 288 patients were screened and 247 met inclusion criteria. There were 1148 medication discrepancies identified resulting in an average of 4.65 discrepancies per patient. Medication addition (54.25%) and medication deletion (45.75%) were most common. Within 24 hours of medication reconciliation, 214 interventions were made to active orders. No differences were observed between discrepancies identified and type of pharmacy staff completing the medication reconciliation. CONCLUSIONS: This study identified a high rate of medication discrepancies on admission to the ICU. Furthermore, it describes the types of pharmacist interventions following pharmacy-led medication reconciliation. This process may be impactful to incorporate as a standard practice in ICUs and warrants further investigation into value, cost, and pharmacist workflow.

Evaluation of Dexmedetomidine Dosing in Obese Critically Ill Patients.

BACKGROUND: Dexmedetomidine is a highly selective α2-adrenoreceptor agonist that produces dose-dependent sedation, anxiolysis, and analgesia without respiratory depression. Due to these ideal sedative properties, there has been increased interest in utilizing dexmedetomidine as a first-line sedative for critically ill patients requiring light sedation. OBJECTIVE: To evaluate the ability to achieve goal intensive care unit (ICU) sedation before and after an institutional change of dosing from actual (ABW) to adjusted (AdjBW) body weight in obese patients on dexmedetomidine. METHODS: This study included patients ≥ 18 years old, admitted to a surgical or medical ICU, required dexmedetomidine for at least 8 hours as a single continuous infusion sedative, and weighed ≥ 120% of ideal body weight. Percentage of RASS measurements within goal range (-1 to +1) during the first 48 hours after initiation of dexmedetomidine as the sole sedative agent or until discontinuation dosed on ABW compared to AdjBW was evaluated. RESULTS: 100 patients were included in the ABW cohort and 100 in the AdjBW cohort. The median dosing weight was significantly higher in the ABW group (95.9 [78.9-119.5] vs 82.2 [72.1-89.8] kg; p = 0.001). There was no statistical difference in percent of RASS measurements in goal range (61.5% vs 69.6%, p = 0.267) in patients that received dexmedetomidine dosed based on ABW versus AdjBW. CONCLUSION: Dosing dexmedetomidine using AdjBW in obese critically ill patients for ongoing ICU sedation resulted in no statistical difference in the percent of RASS measurements within goal when compared to ABW dosing. Further studies are warranted.

Evaluation of Dexmedetomidine's Effect on Temperature in Obese Critically Ill Patients.

INTRODUCTION: Previous literature showed an association between hyperthermia and dexmedetomidine (DEX) use for ongoing sedation in non-obese patients. The purpose of this study is to evaluate DEX's effect on temperature in obese critically ill patients. METHODS: This single center, retrospective, cohort study included patients ≥18 years, admitted to a surgical or medical ICU, received DEX for ≥8 hours as a single continuous infusion sedative, and weighed ≥120% of ideal body weight. Patients were excluded if they had a fever (≥38°C) and positive cultures within 48 hours of DEX initiation. The primary endpoint was a fever (Tmax of ≥38°C) within 48 hours of DEX initiation. RESULTS: A total of 186 patients were included for evaluation. Forty-two patients (22.5%) had a fever during the first 48 hours of DEX initiation. Median weight was not different between the febrile and afebrile groups (99.4 [90.6-122.4] vs 97.6 [81.6-114.2] kg, P = .6). Median change from baseline temperature for all patients within 48 hours was an increase of .5 (.1-.8) °C, P < .001. In multiple regression analysis, duration of DEX and baseline temperature were the only significant predictors of fever development with an adjusted odds ratio of 1.041 (95% CI 1.009-1.074, P = .012) and 7.058 (95% CI 3.307-15.064, P < .001), respectively. CONCLUSIONS: This study suggests that there is a significant increase in body temperature from baseline for obese patients on DEX. Duration of DEX and baseline temperature were found to be risk factors for fever development in this population. Further studies are warranted.

Nebulized Heparin for Adult Patients With Smoke Inhalation Injury: A Review of the Literature.

Objective: To review the clinical effects of nebulized heparin and N-acetylcysteine (NAC) in patients with smoke inhalation injury (IHI) and provide recommendations for use. Data Sources: A search of PubMed, MEDLINE, and Scopus databases was completed from database inception through April 15, 2020, using terms: heparin, acetylcysteine, smoke inhalation injury, and burn injury. Study Selection and Data Extraction: All studies pertaining to efficacy and safety of nebulized heparin and/or NAC for IHI in adult patients were evaluated. Reference lists were reviewed for additional publications. Nonhuman studies, non-English, and case report publications were excluded. Data Synthesis: Eight studies were included. Four demonstrated positive outcomes, 3 demonstrated no benefit or possible harm, and 1 assessed safety. Supporting trials treated patients within 48 hours of injury with 10 000 units of nebulized heparin with NAC for 7 days or until extubation. Two trials with negative findings treated patients within 72 hours, or unspecified, with 5000 units of nebulized heparin with NAC for 7 days, while the third used 25 000 units within 36 hours but was grossly underpowered for analysis. Clinical findings include reduced duration of mechanical ventilation and improved lung function with possible increase risk of pneumonia and no evidence of increased bleeding risk. Conclusions: Nebulized heparin may improve oxygenation and reduce duration of mechanical ventilation in IHI. If nebulized heparin is used, 10 000 units every 4 hours alternating with NAC and albuterol at 4-hour intervals is recommended. Sterile technique should be emphasized. Monitoring for bronchospasm or new-onset pneumonia should be considered.

Intrapleural Tissue Plasminogen Activator for Traumatic Retained Hemothorax.

Objective: To describe the efficacy, safety, dosing regimen, and administration technique of intrapleural alteplase for the treatment of retained hemothorax. Data Sources: A PubMed, EMBASE, and Google Scholar search (January 2000 to February 2019) was conducted with the search terms intrapleural, fibrinolytic, fibrinolysis, alteplase, tissue plasminogen activator, and hemothorax. Study Selection and Data Extraction: Articles were included if they described the use of intrapleural alteplase in adult patients with a retained hemothorax; single patient case reports and abstracts were excluded. Data Synthesis: A total of 6 retrospective reviews and 1 meta-analysis were identified for inclusion. A variety of dosing strategies have been defined for the administration of intrapleural alteplase ranging from 6 to 100 mg, volume of fluid from 50 to 120 mL of normal saline, and the number of total doses has ranged from 1 to 8 over the treatment course. A majority of studies showed a greater than 80% success rate and less than 7% bleeding rate. Relevance to Patient Care and Clinical Practice: Because of the paucity of data for use of alteplase in retained hemothorax and administration of a high-risk medication, this review provides dosing and administration recommendations based on reported safety and efficacy. Conclusion: Administration of intrapleural alteplase should be considered in patients with retained hemothorax as an alternative to surgical intervention. In contrast to intrapleural alteplase administration for other indications such as empyema, higher doses and volumes of alteplase are recommended for retained hemothorax.

Evaluation of Rectal Vancomycin Irrigation for Treatment of Clostridioides difficile Infection in Patients Post-Colectomy for Toxic Colitis.

Background: Clostridioides difficile infection (CDI) accounts for as many as 25% of episodes of antibiotic-associated diarrhea and is the most common cause of healthcare-associated diarrhea. Rectal vancomycin irrigation is a therapy option; however, evidence is limited for its value post-colectomy. The objective of this study was to describe outcomes of patients who underwent total colectomy for fulminant C. difficile colitis and received rectal vancomycin post-operatively. Methods: This was a single-center retrospective chart review of adult patients who underwent total colectomy for fulminant CDI. Efficacy outcomes were all-cause in-hospital death, intensive care unit (ICU) and hospital length of stay, ventilator-free days at day 28 post-procedure, development of proctitis or pseudomembranes, need for re-initiation of CDI therapy, and normalization of infectious signs and symptoms at completion of CDI therapy. The primary safety outcome was the incidence of rectal stump blowout. Results: Of the 50 patients included, 38 (76%) received treatment with rectal vancomycin at the discretion of the surgeon. The Sequential Organ Failure Assessment score on the day of the procedure was higher in the rectal vancomycin group; however, this difference did not reach statistical significance. No difference was observed between the groups in the primary outcome of all-cause death. There was no significant difference between the groups for hospital length of stay, but there was a trend toward longer ICU length of stay for patients who received rectal vancomycin (9.5 days vs. 2.5 days; p = 0.05). No differences in the remaining secondary efficacy outcomes were observed. No episodes of rectal stump blowout were observed in either group. Conclusions: This study aimed to add to the limited data on the use of rectal vancomycin irrigation post-colectomy for toxic C. difficile colitis. Although our results do not support routine use of rectal vancomycin irrigation, they suggest that this therapy is not harmful if providers are considering its use for severe infections refractory to alternative treatment.

Agricultural land use creates evolutionary traps for nesting turtles and is exacerbated by mercury pollution.

The rate of anthropogenic habitat conversion often exceeds the rate of natural ecological and evolutionary processes, which sometimes creates mismatches between environmental cues and adaptive behaviors. In numerous species of aquatic turtles, nest site selection is primarily based on cues related to high solar exposure, which leads females to select sites where humans have disturbed habitat. These disturbed sites are often contaminated by pollutants, such as mercury. Despite the fact that anthropogenic disturbances often co-occur, few studies have examined the interactive influence of major global changes on animal development. Using Chelydra serpentina, we investigated the individual and interactive effects of crop agriculture and mercury pollution on hatch success and offspring phenotype. We hypothesized that following nesting, rapid crop growth would shade and cool nests in agricultural fields and subsequently negatively impact embryonic development. Agricultural and control nests were similar in temperature at the time of oviposition, but temperatures diverged as crops grew: agricultural nests averaged 2.5°C cooler than control nests over the course of incubation. In laboratory and field experiments, we found that turtles incubated under agricultural thermal regimens took longer to hatch, hatched at smaller body sizes, lost more mass, and had lower posthatching growth rates. Additionally, thermal conditions associated with agricultural land use interacted with mercury contamination to decrease hatching success. To our knowledge, this is the first documentation of negative interactive effects of mercury pollution and habitat quality on early vertebrate development and highlights the importance of examining the combined influence of anthropogenic global changes on organisms.

Repeatability and sources of variation of the bacteria-killing assay in the common snapping turtle.

Research on reptile ecoimmunology lags behind that on other vertebrates, despite the importance of such studies for conservation and evolution. Because the innate immune system is highly conserved across vertebrate lineages, assessments of its performance may be particularly useful in reptiles. The bacteria-killing assay requires a single, small blood sample and quantifies an individual's ability to kill microorganisms. The assay's construct validity and interpretability make it an attractive measure of innate immunity, but it requires proper optimization and sample storage. We optimized this assay for the common snapping turtle (Chelydra serpentina) to assess the repeatability of the assay and the effects of freezing and thawing on bactericidal capacity. We determined whether age (adult female and hatchlings) or incubation temperature influenced bactericidal capacity. We found that the assay was repeatable and that freezing plasma samples for 6 weeks at -80°C did not decrease bactericidal capacity nor did a single 30-min thaw and subsequent refreezing. However, we detected subtle interassay variation and results from one assay were 5-6% greater than those from the other two. Adult females had significantly greater bactericidal ability than hatchlings and we found no relationship between incubation temperature and bactericidal capacity. This assay is a useful tool in snapping turtles and may have applicability in other reptiles. However, species-specific optimization is required to ensure that variation among individuals exceeds interassay variation. Consideration should be given to optimization conditions that facilitate comparisons between or within groups, particularly groups that differ considerably in bactericidal capacity.

Effect of Subcutaneous Unfractionated Heparin Prophylaxis on Activated Partial Thromboplastin Time: A Retrospective Evaluation.

STUDY OBJECTIVE: Characterize the incidence of elevated aPTT results in patients treated with prophylactic, subcutaneous unfractionated heparin (UFH). DESIGN: Retrospective, cohort analysis. SETTING: Single-center, university hospital. MEASUREMENTS: Evaluation of 257 patients with activated partial thromboplastin time (aPTT) testing both prior to and following subcutaneous (SC) unfractionated heparin (UFH) therapy. MAIN RESULTS: Evaluated patients received UFH 5000 units every 8 hours. Baseline aPTT values were within the normal range (mean±SD, 32.0±8.5 seconds). After initiation of UFH, aPTT values increased (mean±SD, 37.6±15.2 seconds). After 24 hours of SC UFH, mean aPTT values (mean±SD, 38.6±15.5) exceeded the normal laboratory range (23.3-35.7 seconds). An elevated aPTT result after UFH was associated with baseline aPTT, length of therapy, and weight-based UFH dose. A significant association was not identified between aPTT elevation and age, race, sex, history of liver disease, type of admission, or transfusion of blood products. CONCLUSIONS: Treatment with UFH resulted in a small, but significant, increase in aPTT.

Pathologic processing of the total mesorectal excision.

Total mesorectal excision (TME) is the current optimal surgical treatment for patients with rectal carcinoma. A complete TME is related to lower local recurrence rates and increased patient survival. Many confounding factors in the patient's anatomy and prior therapy can make it difficult to obtain a perfect plane, and thus a complete TME. The resection specimen can be thoroughly evaluated, grossly and microscopically, to identify substandard surgical outcomes and increased risk of local recurrence. Complete and accurate data reporting is critical for patient care and helps surgeons improve their technique.

Malignant rhabdoid tumor of the kidney arising in an adult patient.

Malignant rhabdoid tumors (MRT) of the kidney are rare in children and even less common in adults, with only six previously reported adult cases. We present the case of a 60-year-old man with an MRT arising in the left kidney with extensive pulmonary micrometastases and thromboembolism resulting in thrombotic pulmonary microangiopathy (pulmonary tumor embolism syndrome). MRT is an extremely aggressive neoplasm with a short survival time.

Clinical and morphologic findings in disseminated Scedosporium apiospermum infections in immunocompromised patients.

Scedosporium apiospermum is a ubiquitous, saprophytic, filamentous mold that may cause localized, subcutaneous infections in immunocompetent hosts, but disseminated infection in severely immunocompromised patients. This mold is often highly resistant to multiple commonly used antifungal drugs. Even with treatment, there is a high mortality rate. We present two patients with fatal disseminated S. apiospermum infections after bone marrow and lung transplantation. This infection can be rapidly fatal, and survival may be improved by early recognition.

Altered Auditory Input and Language Webs to Improve Language Processing Skills.

A method of altering auditory input and a structured set of listening tasks are described. The parameters of rate, prosody, and pattern of pausing are modified in the Altered Auditory Input (AAI) technique to make language input easier for the child with language delays to process. This technique is used during play activities, reading to the child, language activities, faceto-face conversation, and structured listening tasks called Language Webs. The Language Webs are a set of highly redundant, hierarchical picture identification listening tasks. The goal of these approaches is to improve language processing in children with language difficulties so that they can both access their current language knowledge and learn new language.