Miracle-dz/UniFAR-FTUs huggingface dataset:
Perioperative Multimodal Anesthetic Care Incorporating Transversus Abdominis Plane Block Is Associated With Reduced Narcotic Use in Laparoscopic Sleeve Gastrectomy

Background Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric surgery performed in North America. As our knowledge of the importance in limiting narcotic use in postoperative patients increases, we sought to evaluate the effect of transversus abdominis plane (TAP) blocks on inpatient narcotic use in patients undergoing LSG. Methods A retrospective review of LSG performed at a single institution by 3 bariatric surgeons was performed. All cases over a 15-month period were included, and anesthesia records were reviewed to stratify patients that received a TAP block and those that did not. Demographic, as well as surgical, outcomes were collected for all patients. Narcotic utilization, as reported in morphine equivalents (ME), was evaluated between the 2 groups. Results 384 LSG patients were identified, of which 37 (9.6%) received a TAP block. There was no statistically significant difference in postoperative morbidity, length of stay, or readmission between groups. Median narcotic utilization in hospital days 1 and 2 in patients with TAP blocks was 49 ME (Interquartile Range (IQR) 14.5-84.5) to 82.5 ME (IQR 57.4-106) in the no-TAP group (P < .001). After controlling for multiple demographic- and patient-related cofactors, multiple linear regression analysis demonstrated TAP block patients utilized 22.48 ME less than the no-TAP group (P < .001) in the first 2 days of their hospitalization. Discussion Patients that received a TAP block as a part of their perioperative anesthetic care utilized less in-hospital narcotics than those patients that did not receive a TAP block. TAP blocks should be considered as part of a multimodal pain control strategy for patients undergoing LSG.
Lipid droplets and autophagy—links and regulations from yeast to humans

Recent advances in the yeast Saccharomyces cerevisiae and higher eukaryotes have been increasingly connecting lipid droplet (LD) dynamics to the regulation of autophagy. In this review we will discuss implications that connect LD de novo synthesis and LD mobilization to autophagy and how autophagy is regulated by these mechanisms. Elucidating these connections might pose a chance to further understand autophagy induction and membrane biogenesis for the growing autophagosome under different conditions. Increasing our understanding of these mechanisms might provide a chance to understand several conditions that might be related to LD dysregulation and, possibly, as a consequence of this, dysregulation of autophagy.
Individual Alpha Peak Frequency, an Important Biomarker for Live Z-Score Training Neurofeedback in Adolescents with Learning Disabilities

Learning disabilities (LDs) have an estimated prevalence between 5% and 9% in the pediatric population and are associated with difficulties in reading, arithmetic, and writing. Previous electroencephalography (EEG) research has reported a lag in alpha-band development in specific LD phenotypes, which seems to offer a possible explanation for differences in EEG maturation. In this study, 40 adolescents aged 10–15 years with LDs underwent 10 sessions of Live Z-Score Training Neurofeedback (LZT-NF) Training to improve their cognition and behavior. Based on the individual alpha peak frequency (i-APF) values from the spectrogram, a group with normal i-APF (ni-APF) and a group with low i-APF (li-APF) were compared in a pre-and-post-LZT-NF intervention. There were no statistical differences in age, gender, or the distribution of LDs between the groups. The li-APF group showed a higher theta absolute power in P4 (p = 0.016) at baseline and higher Hi-Beta absolute power in F3 (p = 0.007) post-treatment compared with the ni-APF group. In both groups, extreme waves (absolute Z-score of ≥1.5) were more likely to move toward the normative values, with better results in the ni-APF group. Conversely, the waves within the normal range at baseline were more likely to move out of the range after treatment in the li-APF group. Our results provide evidence of a viable biomarker for identifying optimal responders for the LZT-NF technique based on the i-APF metric reflecting the patient’s neurophysiological individuality.
Drought stress-induced physiological mechanisms, signaling pathways and molecular response of chloroplasts in common vegetable crops

Abstract Drought stress is one of the most adverse abiotic stresses that hinder plants’ growth and productivity, threatening sustainable crop production. It impairs normal growth, disturbs water relations and reduces water-use efficiency in plants. However, plants have evolved many physiological and biochemical responses at the cellular and organism levels, in order to cope with drought stress. Photosynthesis, which is considered one of the most crucial biological processes for survival of plants, is greatly affected by drought stress. A gradual decrease in CO2 assimilation rates, reduced leaf size, stem extension and root proliferation under drought stress, disturbs plant water relations, reducing water-use efficiency, disrupts photosynthetic pigments and reduces the gas exchange affecting the plants adversely. In such conditions, the chloroplast, organelle responsible for photosynthesis, is found to counteract the ill effects of drought stress by its critical involvement as a sensor of changes occurring in the environment, as the first process that drought stress affects is photosynthesis. Beside photosynthesis, chloroplasts carry out primary metabolic functions such as the biosynthesis of starch, amino acids, lipids, and tetrapyroles, and play a central role in the assimilation of nitrogen and sulfur. Because the chloroplasts are central organelles where the photosynthetic reactions take place, modifications in their physiology and protein pools are expected in response to the drought stress-induced variations in leaf gas exchanges and the accumulation of ROS. Higher expression levels of various transcription factors and other proteins including heat shock-related protein, LEA proteins seem to be regulating the heat tolerance mechanisms. However, several aspects of plastid alterations, following a water deficit environment are still poorly characterized. Since plants adapt to various stress tolerance mechanisms to respond to drought stress, understanding mechanisms of drought stress tolerance in plants will lead toward the development of drought tolerance in crop plants. This review throws light on major droughts stress-induced molecular/physiological mechanisms in response to severe and prolonged drought stress and addresses the molecular response of chloroplasts in common vegetable crops. It further highlights research gaps, identifying unexplored domains and suggesting recommendations for future investigations.
Carbon Source-Dependent Reprogramming of Anaerobic Metabolism in Staphylococcus aureus

Under infection conditions, S. aureus needs to ensure survival when energy production via oxidative phosphorylation is not possible, e.g., either due to the lack of terminal electron acceptors or by the inactivation of components of the respiratory chain. Under these conditions, S. aureus can switch to mixed-acid fermentation to sustain ATP production by substrate-level phosphorylation. ABSTRACT To be a successful pathogen, Staphylococcus aureus has to adapt its metabolism to the typically oxygen- and glucose-limited environment of the host. Under fermenting conditions and in the presence of glucose, S. aureus uses glycolysis to generate ATP via substrate-level phosphorylation and mainly lactic acid fermentation to maintain the redox balance by reoxidation of NADH equivalents. However, it is less clear how S. aureus proceeds under anoxic conditions and glucose limitation, likely representing the bona fide situation in the host. Using a combination of proteomic, transcriptional, and metabolomic analyses, we show that in the absence of an abundant glycolysis substrate, the available carbon source pyruvate is converted to acetyl coenzyme A (AcCoA) in a pyruvate formate-lyase (PflB)-dependent reaction to produce ATP and acetate. This process critically depends on derepression of the catabolite control protein A (CcpA), leading to upregulation of pflB transcription. Under these conditions, ethanol production is repressed to prevent wasteful consumption of AcCoA. In addition, our global and quantitative characterization of the metabolic switch prioritizing acetate over lactate fermentation when glucose is absent illustrates examples of carbon source-dependent control of colonization and pathogenicity factors. IMPORTANCE Under infection conditions, S. aureus needs to ensure survival when energy production via oxidative phosphorylation is not possible, e.g., either due to the lack of terminal electron acceptors or by the inactivation of components of the respiratory chain. Under these conditions, S. aureus can switch to mixed-acid fermentation to sustain ATP production by substrate level phosphorylation. The drop in the cellular NAD+/NADH ratio is sensed by the repressor Rex, resulting in derepression of fermentation genes. Here, we show that expression of fermentation pathways is further controlled by CcpA in response to the availability of glucose to ensure optimal resource utilization under growth-limiting conditions. We provide evidence for carbon source-dependent control of colonization and virulence factors. These findings add another level to the regulatory network controlling mixed-acid fermentation in S. aureus and provide additional evidence for the lifestyle-modulating effect of carbon sources available to S. aureus.
Effect of Cilastatin on Cisplatin-Induced Nephrotoxicity in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control (n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group (n = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.
Management of inflammatory bowel disease in the COVID-19 era

During the coronavirus disease 2019 (COVID-19) pandemic, many unpredictable changes have occurred in the medical field. Risk of COVID-19 does not seem to increase in patients with inflammatory bowel disease (IBD) considering based on current reports. Current medications for IBD do not increase this risk; on the contrary, some of these might be used as therapeutics against COVID-19 and are under clinical trial. Unless the patients have confirmed COVID-19 and severe pneumonia or a high oxygen demand, medical treatment should be continued during the pandemic, except for the use of high-dose corticosteroids. Adherence to general recommendations such as social distancing, wearing facial masks, and vaccination, especially for pneumococcal infections and influenza, is also required. Patients with COVID-19 need to be withhold immunomodulators or biologics for at least 2 weeks and treated based on both IBD and COVID-19 severity. Prevention of IBD relapse caused by sudden medication interruption is important because negative outcomes associated with disease flare up, such as corticosteroid use or hospitalization, are much riskier than medications. The outpatient clinic and infusion center for biologics need to be reserved safe spaces, and endoscopy or surgery should be considered in urgent cases only.
Investigating the energetic and entropic components of effective potentials across a glass transition

By eliminating unnecessary details, coarse-grained (CG) models provide the necessary efficiency for simulating scales that are inaccessible to higher resolution models. However, because they average over atomic details, the effective potentials governing CG degrees of freedom necessarily incorporate significant entropic contributions, which limit their transferability and complicate the treatment of thermodynamic properties. This work employs a dual-potential approach to consider the energetic and entropic contributions to effective interaction potentials for CG models. Specifically, we consider one- and three-site CG models for ortho-terphenyl (OTP) both above and below its glass transition. We employ the multiscale coarse-graining (MS-CG) variational principle to determine interaction potentials that accurately reproduce the structural properties of an all-atom (AA) model for OTP at each state point. We employ an energy-matching variational principle to determine an energy operator that accurately reproduces the intra- and inter-molecular energy of the AA model. While the MS-CG pair potentials are almost purely repulsive, the corresponding pair energy functions feature a pronounced minima that corresponds to contacting benzene rings. These energetic functions then determine an estimate for the entropic component of the MS-CG interaction potentials. These entropic functions accurately predict the MS-CG pair potentials across a wide range of liquid state points at constant density. Moreover, the entropic functions also predict pair potentials that quite accurately model the AA pair structure below the glass transition. Thus, the dual-potential approach appears a promising approach for modeling AA energetics, as well as for predicting the temperature-dependence of CG effective potentials.
Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.

BACKGROUND Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown. METHODS In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months. RESULTS Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups. CONCLUSIONS Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).
Urinary fluoride and micronutrients intake in children from San Luis Potosi, Mexico

ABSTRACT To assess the relationship between urinary fluoride and micronutrients intake we recruited 121 schoolchildren from San Luis Potosí. We evaluated fluoride concentrations in drinking water and urine with the ion-selective electrode method and estimated calcium, magnesium, and phosphorus intakes with a validated consumption frequency questionnaire. About 72% of the population used tap water for drinking and cooking. Fluoride concentrations were 2.36 ± 0.02 mg/L in tap water, 0.14 ± 0.04 mg/L in bottled water and 2.05 ± 0.62 mg/L in urine. Urinary fluoride was higher in children with a consumption <50% of the Recommended Daily Intake (RDI) of calcium (2.20 v/s 1.96 mg/L; p < 0.05), <50% RDI of magnesium (2.58 v/s 1.96 and 1.90 mg/L; p < 0.05) and >150% RDI of phosphorus (2.43 v/s 1.82 mg/L; p < 0.05). These data indicated that fluoride concentration in tap water is higher than bottled water and estimated micronutrients intake is related to urinary fluoride.
Cubogel as potential platform for glaucoma management

Abstract The aim of this work is to survey the potential of cubogel as an ocular dosage form to boost the corneal permeability of Dorzolamide Hydrochloride DZ; an antiglaucomal drug. DZ-loaded cubosomal dispersions were prepared according to Box-Behnken design, where the effect of independent variables; Monoolein MO concentration (2.5, 5 and 7.5%w/w), Pluronic® F127 concentration (0.25, 0.5 and 0.75%w/w) and magnetic stirrer speed of (400, 800 and 1200 rpm) was studied on PS (nm), Zp (−mV) and Q 2 h (%) respectively. The prepared formulae were characterized via drug content DC (%), particle size PS (nm), polydispersity index PDI, zeta potential Zp (−mV), in-vitro drug release (Q 2 h%) and finally TEM. The optimized formulation composed of: 6.13% w/w of MO, 0.75% w/w of F127 and prepared at 1200 rpm stirring speed was chosen based on the criteria of minimum PS (nm), maximum Zp (−mV) and minimum Q 2 h (%). Results revealed that the optimum formula showed PS of 153.3 ± 8.4 n, Zp of 32 ± 3 −mV and 37.78 ± 1.3% released after 2 h. Carbopol 934 (1% w/v) as gelling agent was used to prepare the optimum cubogel, which was further evaluated by DSC, ex-vivo permeation and stability studies at 4 °C for three months. Moreover, in vivo studies of the optimized cubogel include; draize test, histological examination, confocal laser scanning microscopy (CLSM) and intraocular pressure (IOP) measurement. Results revealed that the optimized cubogel was considerably safe, stable and competent to corneal delivery as assured by draize and histological examination. CLSM showed a deeper penetration of more than 2.5-fold. A higher bioavailability (288.24 mg. h/ml) was attained from cubogel compared to the market product Trusopt® eye drops (115.40 mg. h/ml) following IOP measurement. Therefore, DZ-loaded cubogel could be considered as promising delivery system to boost the transcorneal permeation hence corneal bioavailability of DZ as antiglaucomal drug.
Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles.

BACKGROUND Removal of cytokines, chemokines, and microvesicles from the supernatant of allogeneic erythrocytes may help mitigate adverse transfusion reactions. Blood bank-based washing procedures present logistical difficulties; therefore, we tested the hypothesis that on-demand bedside washing of allogeneic erythrocyte units is capable of removing soluble factors and is feasible in a clinical setting. METHODS There were in vitro and prospective, observation cohort components to this a priori planned substudy evaluating bedside allogeneic erythrocyte washing, with a cell saver, during cardiac surgery. Laboratory data were collected from the first 75 washed units given to a subset of patients nested in the intervention arm of a parent clinical trial. Paired pre- and postwash samples from the blood unit bags were centrifuged. The supernatant was aspirated and frozen at -70°C, then batch-tested for cell-derived microvesicles, soluble CD40 ligand, chemokine ligand 5, and neutral lipids (all previously associated with transfusion reactions) and cell-free hemoglobin (possibly increased by washing). From the entire cohort randomized to the intervention arm of the trial, bedside washing was defined as feasible if at least 75% of prescribed units were washed per protocol. RESULTS Paired data were available for 74 units. Washing reduced soluble CD40 ligand (median [interquartile range]; from 143 [1 to 338] ng/ml to zero), chemokine ligand 5 (from 1,314 [715 to 2,551] to 305 [179 to 488] ng/ml), and microvesicle numbers (from 6.90 [4.10 to 20.0] to 0.83 [0.33 to 2.80] × 106), while cell-free hemoglobin concentration increased from 72.6 (53.6 to 171.6) mg/dl to 210.5 (126.6 to 479.6) mg/dl (P < 0.0001 for each). There was no effect on neutral lipids. Bedside washing was determined as feasible for 80 of 81 patients (99%); overall, 293 of 314 (93%) units were washed per protocol. CONCLUSIONS Bedside erythrocyte washing was clinically feasible and greatly reduced concentrations of soluble factors thought to be associated with transfusion-related adverse reactions, increasing concentrations of cell-free hemoglobin while maintaining acceptable (less than 0.8%) hemolysis. EDITOR’S PERSPECTIVE
Mitochondria-Targeted Antioxidants MitoQ and MitoTEMPO Do Not Influence BRAF-Driven Malignant Melanoma and KRAS-Driven Lung Cancer Progression in Mice

Cancer cells produce high levels of mitochondria-associated reactive oxygen species (ROS) that can damage macromolecules, but also promote cell signaling and proliferation. Therefore, mitochondria-targeted antioxidants have been suggested to be useful in anti-cancer therapy, but no studies have convincingly addressed this question. Here, we administered the mitochondria-targeted antioxidants MitoQ and MitoTEMPO to mice with BRAF-induced malignant melanoma and KRAS-induced lung cancer, and found that these compounds had no impact on the number of primary tumors and metastases; and did not influence mitochondrial and nuclear DNA damage levels. Moreover, MitoQ and MitoTEMPO did not influence proliferation of human melanoma and lung cancer cell lines. MitoQ and its control substance dTPP, but not MitoTEMPO, increased glycolytic rates and reduced respiration in melanoma cells; whereas only dTPP produced this effect in lung cancer cells. Our results do not support the use of mitochondria-targeted antioxidants for anti-cancer monotherapy, at least not in malignant melanoma and lung cancer.