Perioperative Cannabinoids Significantly Reduce Postoperative Opioid Requirements in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Background Opioids, commonly used to control pain associated with surgery, are known to prolong the duration of mechanical ventilation and length of hospital stay. A wide range of adjunctive strategies are currently utilized to reduce postoperative pain, such as local and regional nerve blocks, nerve cryoablation, and adjunctive medications. We hypothesized that dronabinol (a synthetic cannabinoid) in conjunction with standard opioid pain management will reduce opioid requirements to manage postoperative pain. Methods Sixty-eight patients who underwent isolated first-time coronary artery bypass graft surgery were randomized to either the control group, who received only standard opioid-based analgesia, or the dronabinol group, who received dronabinol (a synthetic cannabinoid) in addition to standard opioid-based analgesia. Dronabinol was given in the preoperative unit, before extubation in the ICU, and after extubation on the first postoperative day. Preoperative, intraoperative, and postoperative parameters were compared under an IRB-approved protocol. The primary endpoints were the postoperative opioid requirement, duration of mechanical ventilation, and ICU length of stay, and the secondary endpoints were the duration of inotropic support needed, left ventricular ejection fraction (LVEF), and the change in LVEF. This study was undertaken at Northwest Medical Center, Tucson, AZ, USA. Results Sixty-eight patients were randomized to either the control group (n = 37) or the dronabinol group (n = 31). Groups were similar in terms of demographic features and comorbidities. The total postoperative opioid requirement was significantly lower in the dronabinol group [39.62 vs 23.68 morphine milligram equivalents (MMEs), p = 0.0037], representing a 40% reduction. Duration of mechanical ventilation (7.03 vs 6.03h, p = 0.5004), ICU length of stay (71.43 vs 63.77h, p = 0.4227), and inotropic support requirement (0.6757 vs 0.6129 days, p = 0.7333) were similar in the control and the dronabinol groups. However, there was a trend towards lower durations in each endpoint in the dronabinol group. Interestingly, a significantly better preoperative to postoperative LVEF change was observed in the dronabinol group (3.51% vs 6.45%, p = 0.0451). Conclusions Our study found a 40% reduction in opioid use and a significantly greater improvement in LVEF in patients treated with adjunctive dronabinol. Mechanical ventilation duration, ICU length of stay, and inotropic support requirement tended to be lower in the dronabinol group, though did not reach statistical significance. The results of this study, although limited by sample size, are very encouraging and validate our ongoing investigation.

Development and application of artificial intelligence-based facial skin image diagnosis system: Changes in facial skin characteristics with ageing in Korean women.

OBJECTIVE: To develop and validate an artificial intelligence (AI)-based diagnostic system for analysing facial skin images using expert judgements and explore its feasibility for skin ageing research, specifically by evaluating facial skin changes in Korean women of various ages. METHODS: Our AI-based facial skin diagnosis system (Dr. AMORE®) uses facial images of Korean women to analyse wrinkles, pigmentation, skin pores, and other skin red spots. The system is trained using clinical expert evaluations and deep learning. We assessed the system's precision and sensitivity by analysing the correlation between the diagnoses by the AI system and those of the experts. We used 120 images of Korean women aged 10-60 years to evaluate the changes in various facial skin characteristics with ageing. RESULTS: The precision and sensitivity of the developed system were excellent (>0.9%), and the diagnosis scores using the detected area and intensity of each item were correlated significantly higher with the visual evaluation results of the clinical experts (>0.8, p < 0.001). We also analysed facial images of Korean women aged 10-60 years to quantify changes in the scores of wrinkles, pigmentation, and skin pores with age. We identified the age group with the most significant changes as 20s to 30s. Analysis of the detailed skin characteristics of each item showed that wrinkles and pigmentation changed significantly in the 20s-30s, and skin pores increased significantly in the 10s-20s. There was no significant correlation with age or change according to the age group for skin red spots. CONCLUSION: Developed AI-based facial skin diagnosis system can automatically diagnose skin conditions based on clinical expert judgement using only photographic images and analyse various items in detail, quantitatively, and visually. This AI system can provide new and useful approaches in research areas that require a lot of resources and different characterizations, such as the study of facial skin ageing.

OBJECTIF: Développer et valider un système de diagnostic basé sur l'intelligence artificielle (IA) pour analyser les images de la peau du visage à l'aide de jugements d'experts et explorer sa faisabilité pour la recherche sur le vieillissement de la peau, en particulier en évaluant les changements de la peau du visage chez les femmes Coréennes de différents âges. MÉTHODES: Notre système de diagnostic de la peau du visage basé sur l'intelligence artificielle (Dr. AMORE®) utilise des images du visage de femmes Coréennes pour analyser les rides, la pigmentation, les pores de la peau et d'autres taches rouges de la peau. Le système est entraîné à l'aide d'évaluations d'experts cliniques et de l'apprentissage profond. Nous avons évalué la précision et la sensibilité du système en analysant la corrélation entre les diagnostics du système d'IA et ceux des experts. Nous avons utilisé 120 images de femmes coréennes âgées de 10 à 60 ans pour évaluer les changements de diverses caractéristiques de la peau du visage avec le vieillissement. RÉSULTATS: la précision et la sensibilité du système développé étaient excellentes (>0.9%), et les scores de diagnostic utilisant la zone détectée et l'intensité de chaque élément étaient corrélés de manière significativement plus élevée avec les résultats de l'évaluation visuelle des experts cliniques (>.8, p < 0.001). Nous avons également analysé des images du visage de femmes coréennes âgées de 10 à 60 ans afin de quantifier les changements dans les scores des rides, de la pigmentation et des pores de la peau avec l'âge. Nous avons identifié le groupe d'âge présentant les changements les plus significatifs comme étant celui des 20­30 ans. L'analyse des caractéristiques détaillées de la peau pour chaque élément a montré que les rides et la pigmentation changeaient de manière significative chez les 20­30 ans, et que les pores de la peau augmentaient de manière significative chez les 10­20 ans. Il n'y avait pas de corrélation significative avec l'âge ou de changement en fonction du groupe d'âge pour les taches rouges de la peau. CONCLUSION: Le système de diagnostic de la peau du visage basé sur l'IA peut diagnostiquer automatiquement les affections cutanées sur la base d'un jugement d'expert clinique en utilisant uniquement des images photographiques et analyser divers éléments en détail, quantitativement et visuellement. Ce système d'IA peut fournir des approches nouvelles et utiles dans des domaines de recherché qui nécessitent beaucoup de ressources et de caractérisations différentes, comme l'étude du vieillissement de la peau du visage.

Evaluation of Intravenous Push Piperacillin-Tazobactam on Time to Antibiotic Administration in Emergency Department Patients with Sepsis.

Purpose: The purpose of this study was to determine if intravenous push (IVP) administration of piperacillin-tazobactam reduced the time to antibiotic administration compared to intravenous piggyback (IVPB) in emergency department (ED) patients who present with sepsis. Methods: This was a retrospective cohort study of patients with sepsis who received piperacillin-tazobactam before and after implementation of an IVPB to IVP conversion protocol. Results: A total of 486 charts were reviewed and the final analysis included 127 patients in each group. The mean time to administration of piperacillin-tazobactam was 67 (± 48) minutes and 58 (± 36) minutes in the IVPB and IVP cohorts, respectively (P = NS). The time to administration of secondary antibiotics was reduced by 38 minutes in patients who received piperacillin-tazobactam by IVP (105 min ±69 vs 67 min ±37; P < .001). Nurse administration time was reduced by 11 min for piperacillin-tazobactam (54 min ±46 vs 43 min ±33; P = .034) and 40 min for secondary antibiotics (90 min ±67 vs 50 min ±32; P = < .001) in the IVP group. There was no difference in hypersensitivity reactions, hospital length of stay, or mortality. Conclusion: Conversion from piperacillin-tazobactam IVPB to IVP was associated with a reduction in time to piperacillin-tazobactam and secondary antibiotic administration in emergency department patients with sepsis. Further prospective research is needed to evaluate clinical outcomes associated with IVP administration.

Carbon-Coated ZnS-FeS2 Heterostructure as an Anode Material for Lithium-Ion Battery Applications.

The construction of carbon-coated heterostructures of bimetallic sulfide is an effective technique to improve the electrochemical activity of anode materials in lithium-ion batteries. In this work, the carbon-coated heterostructured ZnS-FeS2 is prepared by a two-step hydrothermal method. The crystallinity and nature of carbon-coating are confirmed by the investigation of XRD and Raman spectroscopy techniques. The nanoparticle morphology of ZnS and plate-like morphology of FeS2 is established by TEM images. The chemical composition of heterostructure ZnS-FeS2@C is discovered by an XPS study. The CV results have disclosed the charge storage mechanism, which depends on the capacitive and diffusion process. The BET surface area (37.95 m2g-1) and lower Rct value (137 Ω) of ZnS-FeS2@C are beneficial to attain higher lithium-ion storage performance. It delivered a discharge capacity of 821 mAh g-1 in the 500th continuous cycle @ A g-1, with a coulombic efficiency of around 100%, which is higher than the ZnS-FeS2 heterostructure (512 mAh g-1). The proposed strategy can improve the electrochemical performance and stability of lithium-ion batteries, and can be helpful in finding highly effective anode materials for energy storage devices.

A Flower-like In2O3 Catalyst Derived via Metal-Organic Frameworks for Photocatalytic Applications.

The most pressing concerns in environmental remediation are the design and development of catalysts with benign, low-cost, and efficient photocatalytic activity. The present study effectively generated a flower-like indium oxide (In2O3-MF) catalyst employing a convenient MOF-based solvothermal self-assembly technique. The In2O3-MF photocatalyst exhibits a flower-like structure, according to morphology and structural analysis. The enhanced photocatalytic activity of the In2O3-MF catalyst for 4-nitrophenol (4-NP) and methylene blue (MB) is likely due to its unique 3D structure, which includes a large surface area (486.95 m2 g-1), a wide spectrum response, and the prevention of electron-hole recombination compared to In2O3-MR (indium oxide-micro rod) and In2O3-MD (indium oxide-micro disc). In the presence of NaBH4 and visible light, the catalytic performances of the In2O3-MF, In2O3-MR, and In2O3-MD catalysts for the reduction of 4-NP and MB degradation were investigated. Using In2O3-MF as a catalyst, we were able to achieve a 99.32 percent reduction of 4-NP in 20 min and 99.2 percent degradation of MB in 3 min. Interestingly, the conversion rates of catalytic 4-NP and MB were still larger than 95 and 96 percent after five consecutive cycles of catalytic tests, suggesting that the In2O3-MF catalyst has outstanding catalytic performance and a high reutilization rate.

Clinical outcomes of concomitant use of enteral and intravenous sedatives and analgesics in mechanically ventilated patients with COVID-19.

PURPOSE: To evaluate potential differences in days on mechanical ventilation for patients with coronavirus disease 2019 (COVID-19) based on route of administration of analgesic and sedative medications: intravenous (IV) alone vs IV + enteral (EN). SUMMARY: This institutional review board-approved study evaluated ventilation time and fentanyl or midazolam requirements with or without concurrent EN hydromorphone and lorazepam. Patients were included in the study if they were 18 to 89 years old and were admitted to the intensive care unit with a positive severe acute respiratory syndrome coronavirus 2 reverse transcription and polymerase chain reaction or antigen test and respiratory failure requiring invasive mechanical ventilation for more than 72 hours. In total, 100 patients were evaluated, 60 in the IV-only group and 40 in the IV + EN group. There was not a significant difference in ventilation time between the groups (mean [SD], 19.6 [12.8] days for IV + EN vs 15.6 [11.2] days for IV only; P = 0.104). However, fentanyl (2,064 [847] µg vs 2,443 [779] µg; P < 0.001) and midazolam (137 [72] mg vs 158 [70] mg; P = 0.004) requirements on day 3 were significantly higher in the IV-only group, and the increase in fentanyl requirements from day 1 to day 3 was greater in the IV-only group than in the IV + EN group (378 [625] µg vs 34 [971] µg; P = 0.033). CONCLUSION: Addition of EN analgesic and sedative medications to those administered by the IV route did not change the duration of mechanical ventilation in patients with COVID-19, but the combination may reduce IV opioid requirements, decreasing the impact of IV medication shortages.

Scale-Up Production of Type O and A Foot-and-Mouth Disease Bivalent Vaccine and Its Protective Efficacy in Pigs.

South Korea has experienced FMD outbreaks almost every year since 2014. Therefore, a novel local vaccine that can cover various topotypes of viruses is required. Two virus strains, O/Boeun/SKR/2017 and A/Yeoncheon/SKR/2017, were cultured up to the pilot scale based on the optimized conditions set up on the flask scale. FMDV particles (146S) of 2 µg/mL or more were obtained from the virus culture supernatant using a 100 L bioreactor. The viruses were fully inactivated using binary ethylenimine within 16 h through two inactivation cycles and mixed with an adjuvant into a bivalent vaccine (types O and A) consisting of 15 µg viruses per strain. The experimental bivalent vaccine showed a broad spectrum of high neutralizing antibody titers against heterologous viruses, including type O Cathay strain and type A Asia topotypes, except for GVII. The 50% protective dose was determined as 12.5 for O/Boeun/SKR/2017 and 15.6 for A/Yeoncheon/SKR/2017. Collectively, we expect that the bivalent vaccine could protect against FMDV types O and A circulating in South Korea and neighboring countries. To our knowledge, this is the first report demonstrating that the vaccine strains could be successfully scaled-up to a 100 L bioreactor, with the determination of its protective efficacy in pigs.

Measuring fatigue: a meta-review.

There is a lack of validated tools to measure fatigue in patients with inflammatory skin, neuropsychiatric, and medical disorders. The use of nonvalidated tools may compromise the quality of data. The purpose of this meta-review was to evaluate existing fatigue scales commonly used to assess fatigue in other inflammatory conditions and to identify if there are scales that have been validated in dermatologic conditions. The PubMed/MEDLINE and SCOPUS databases were systematically searched from inception through March 10, 2020, in accordance with the PRISMA statement. Validated tools were identified and assessed according to their main measurement properties. The literature search identified 403 references, and eight studies were eligible and assessed in this review. The unidimensional fatigue scales included were the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), Brief Fatigue Inventory, Fatigue Severity Scale, Numerical Rating Scale - Fatigue, and Visual Analog Scale - Fatigue. The multidimensional fatigue scales found were the Checklist Individual Strength, Chalder Fatigue Scale, Multidimensional Assessment of Fatigue, Multidimensional Fatigue Inventory Scale, and Piper Fatigue Scale. To measure fatigue, a brief scale with the ability to detect change is needed as there is a growing interest in evaluating this dimension of treatment response. In addition, a good content validity is also needed. From this systematic review, none of the selected scales have had content validation, even though the FACIT was validated in patients with psoriatic arthritis. Validation studies in specific disorders are urgently warranted.

Recombinant adiponectin protects the newborn rat lung from lipopolysaccharide-induced inflammatory injury.

Preterm infants are at high risk for developing bronchopulmonary dysplasia and pulmonary hypertension from inflammatory lung injury. In adult models, adiponectin (APN)-an adipocyte-derived hormone-protects the lung from inflammatory injury and pulmonary vascular remodeling. Cord blood APN levels in premature infants born < 26 weeks gestation are 5% of the level in infants born at term. We previously reported the expression profile of APN and its receptors in neonatal rat lung homogenates during the first 3 weeks of postnatal development. Here, we characterize the expression profile of APN and its receptors in specific lung cells and the effects of exogenous recombinant APN (rAPN) on lipopolysaccharide-(LPS)-induced cytokine and chemokine production in total lung homogenates and specific lung cells. In vitro, rAPN added to primary cultures of pulmonary artery smooth muscle cells attenuated the expression of LPS-induced pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines. In vivo, intraperitoneal rAPN (2 mg/kg), given 4 hr prior to intrapharyngeal administration of LPS (5 mg/kg) to newborn rats at postnatal day 4, significantly reduced gene and protein expression of the pro-inflammatory cytokine IL-1ß and reduced protein expression of the chemokines monocyte chemoattractant protein (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1α) in the lung. LPS-induced histopathological changes in the lung were also decreased. Moreover, rAPN given 20 hr after intrapharyngeal LPS had a similar effect on lung inflammation. These findings suggest a role for APN in protecting the lung from inflammation during early stages of lung development.

The impact of catheter ablation of atrial fibrillation on the left atrial volume and function: study using three-dimensional echocardiography.

PURPOSE: The exact correlation between the baseline left atrial (LA) volume (LAV) and atrial fibrillation (AF) radiofrequency catheter ablation (RFCA) outcomes and changes to the LA after AF RFCA has not yet been fully understood. We sought to evaluate the serial changes in the LAV and LA function after RFCA using 3D echocardiography. METHODS: Consecutive patients who received RFCA of paroxysmal (PAF) or persistent AF (PeAF) at our center between January 2013 and March 2016 were included. Real-time 3D apical full-volume images were acquired, and a 3D volumetric assessment was performed using an automated three-beat averaging method. The LAV index (LAVI) was calculated and the LA ejection fraction (LAEF) was calculated as [LAVmax - LAVmin]/LAVmax. RESULTS: Ninety-nine total patients were enrolled, and the mean age was 58.0 ± 8.2 years and 75 (74.7%) were male. There were 59 (59.6%) PAF patients and the remaining 40 (40.4%) had PeAF. AF recurred in 5 of 59 (8.5%) PAF and in 10 of 40 (25%) PeAF patients. The LAVImax increased on 1 day, decreased at 3 months, and then increased again at 1 year but was lower than that at baseline. The LAEF changes were similar to the volume changes but were more prominent in PeAF than PAF patients. The baseline 3D LAVImax was an independent predictor of AF recurrence after RFCA and the cut-off value was 44.13 ml/m2. CONCLUSION: In our study, even after 3 months of scar formation due to ablation, structural remodeling of the LA continued. The changes were more prominent in the non-recurrent, PeAF patients.

Chronic Intermittent Hypoxia in Premature Infants: The Link Between Low Fat Stores, Adiponectin Receptor Signaling and Lung Injury.

Premature infants have chronic intermittent hypoxia (CIH) that increases morbidity, and the youngest and the smallest premature infants are at the greatest risk. The combination of lung injury from inflammation/oxidative stress causing low functional residual capacity combined with frequent short apneas leads to CIH. Adiponectin (APN) is an adipose-derived adipokine that protects the lung from inflammation and oxidative stress. Premature and small for gestational age (SGA) infants have minimal body fat and low levels of circulating APN. To begin to understand the potential role of APN in lung protection during lung development, we characterized the developmental profile of APN and APN receptors (AdipoR1 and AdipoR2) protein and mRNA expression in the newborn rat lung at fetal day (FD) 19, and postnatal days (PD) 1, 4, 7, 10, 14, 21, and 28. Protein levels in lung homogenates were measured by western blot analyses; relative mRNA expression was detected by quantitative PCR (qPCR); and serum high molecular weight (HMW) APN was measured using enzyme-linked immunosorbent assay (ELISA). Results: APN protein and mRNA levels were lowest at FD19 and PD1, increased 2.2-fold at PD4, decreased at PD10, and then increased again at PD21. AdipoR1 protein and mRNA levels peaked at PD1, followed by a threefold drop by PD4, and remained low until PD21. AdipoR2 protein and mRNA levels also peaked at PD1, but remained high at PD4, followed by a 1.7-fold drop by PD10 that remained low by PD21. Serum APN levels detected by ELISA did not differ from PD4 to PD28. To date, this is the first report characterizing APN and APN receptor protein and mRNA expression in the rat lung during development. The developmental stage of the newborn rat lung models that of the premature human infant; both are in the saccular stage of lung development. In the newborn rat lung, alveolarization begins at PD4, peaks at PD10, and ends at PD21. Importantly, we found that AdipoR1 receptor protein and mRNA expression is lowest during lung alveolarization (PD4 to PD21). Thus, we speculate that low levels of AdipoR1 during lung alveolarization contributes to the increased susceptibility to developing acute lung edema and chronic lung injury such as bronchopulmonary dysplasia (BPD) in premature human infants.

Regulation of ethanol-sensitive EAAT2 expression through adenosine A1 receptor in astrocytes.

Adenosine-regulated glutamate signaling in astrocytes is implicated in many neurological and neuropsychiatric disorders. In this study, we examined whether adenosine A1 receptor regulates EAAT2 expression in astrocytes using pharmacological agents and siRNAs. We found that adenosine A1 receptor-specific antagonist DPCPX or PSB36 decreased EAAT2 expression in a dose-dependent manner. Consistently, knockdown of A1 receptor in astrocytes decreased EAAT2 mRNA expression while overexpression of A1 receptor upregulated EAAT2 expression and function. Since A1 receptor activation is mainly coupled to inhibitory G-proteins and inhibits the activity of adenylate cyclase, we investigated the effect of forskolin, which activates adenylate cyclase activity, on EAAT2 mRNA levels. Interestingly, we found that forskolin reduced EAAT2 expression in dose- and time-dependent manners. In contrast, adenylate cyclase inhibitor SQ22536 increased EAAT2 expression in dose- and time-dependent manners. In addition, forskolin blocked ethanol-induced EAAT2 upregulation. Taken together, these results suggest that A1 receptor-mediated signaling regulates EAAT2 expression in astrocytes.

Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability.

Accumulating evidence reveals that sole mutations in hENT3 cause a spectrum of human genetic disorders. Among these include H syndrome, characterized by scleroderma, hyperpigmentation, hypertrichosis, hepatomegaly, cardiac abnormalities and musculoskeletal deformities, pigmented hypertrichotic dermatosis with insulin-dependent diabetes syndrome, characterized by autoantibody-negative diabetes mellitus and skin deformities, familial Rosai-Dorfman disease, characterized by short stature, familial histiocytosis and sinus histiocytosis with massive lymphadenopathy (SHML), characterized by severe tissue infiltration of immune cells and swollen lymph nodes. hENT3 spectrum disorders share a common mutation and share overlapping clinical manifestations that display many intriguing resemblances to mitochondrial and lysosomal disorders. Although earlier studies identify hENT3 as a mitochondrial and a lysosomal nucleoside transporter, the precise connections between hENT3 and the pathophysiology of these disorders remain unresolved. In this study, we performed functional and biochemical characterization of these mutations in hENT3. We report severe reductions/losses of hENT3 nucleoside transport functions of hENT3 syndrome mutants. In addition to transport alterations, we provide evidence for possible loss of hENT3 functions in all H and pigmented hypertrichotic dermatosis with insulin-dependent diabetes syndromes due to either mistrafficking or altered stability of mutant hENT3 proteins.

Construction of an amylolytic industrial strain of Saccharomyces cerevisiae containing the Schwanniomyces occidentalis alpha-amylase gene.

The gene encoding Schwanniomyces occidentalis alpha-amylase (AMY) was introduced into the chromosomal delta sequences of an industrial strain of Saccharomyces cerevisiae. To obtain a strain suitable for commercial use, an delta-integrative cassette devoid of bacterial DNA sequences was constructed that contains the AMY gene and aureobasidin A resistance gene (AUR1-C) as the selection marker. The AMY gene was expressed under the control of the alcohol dehydrogenase gene promoter (ADC1p). The alpha-amylase activity of Sacc. cerevisiae transformed with this integrative cassette was 6 times higher than that of Sch. occidentalis. The transformants (integrants) were mitotically stable after 100 generations in nonselective medium.