Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing oral absorption of poorly water-soluble herb (Kaempferia parviflora) extract using self-nanoemulsifying formulation

Abstract Kaempferia parviflora, a medicinal herb, treats hypertension and promotes longevity with good health and well-being. Its bioactive component is poorly soluble in water, resulting in poor absorption. This study aimed to enhance the bioavailability of K. parviflora dichloromethane (KPD) extract using a self-nanoemulsifying drug delivery system (SNEDDS). KPD was dissolved in diethylene glycol monoethyl, polyoxyl-35 castor oil and caprylic/capric glyceride, and clear yellow SNEDDS solution was obtained. The methoxyflavone markers were used for content and dissolution analysis. Solid SNEDDS was prepared by stepwise mixing of KPD using a mortar and pestle (1:1 ratio) with five solid carriers: Aerosil® 200, Florite® RE, Neusilin® US2 (NEUS), Fujicalin®, and Neusilin® UFL2. The USP apparatus II with simulated gastric fluid USP (SGF without pepsin, pH 1.2) was used in order to perform the in vitro dissolution. The methoxyflavones dissolution at 60 min from KPD, SEDDS, and SNEDDS/NEUS were approximately 16, 92, and 73%, respectively. The pharmacokinetic profiles of methoxyflavones for oral administration were studied using Wistar rats; the areas under the curve of SNEDDS/NEUS (1.77-fold) and SNEDDS (5.38-fold) were significantly higher than that of KPD. The developed formulations showed good stability after storage for 6 months under accelerated and normal conditions.
Return to Work Following Surgery for Incidental Diffuse Low-Grade Glioma: A Prospective Series With 74 Patients.

BACKGROUND Therapeutic strategy concerning incidental low-grade glioma (ILGG) is still debated. Early "prophylactic" surgery has been proposed in asymptomatic patients with favorable neurological and oncological outcomes. OBJECTIVE To assess postoperative ability to resume employment following awake surgery in asymptomatic ILGG patients. To assess extent of resection (EOR), timeline for adjuvant oncological treatment, and survival. METHODS A total of 74 patients with ILGG who underwent awake surgery with intraoperative mapping were prospectively included, with a minimum follow-up of 12 mo. All clinicoradiological data were collected, and statistical correlations with return to work (RTW) were performed. RESULTS A total of 66 patients (97.1%) among 68 patients with preoperative professional activities resumed their employment including 62 (91.2%) within 12 mo. Mean time before RTW was 6.8 mo (median: 6 mo, range: 1-36). Two patients experienced seizure-related legal issues impacting their RTW. Clinicoradiological features did not correlate with RTW apart from postoperative seizures (P = .02). Mean EOR was 95.7%. A total of 43 patients (58.1%) underwent supratotal/total resections. All patients recovered from transient deficits at 3 mo. No patients received consecutive adjuvant treatment. A total of 24 patients (32.4%) were reoperated, 24 patients received chemotherapy, and 7 patients (9.5%) received radiotherapy, on average 73.1 mo after surgery. Mean follow-up was 67 mo (range 12-240). Four patients (5.4%) died during the follow-up. CONCLUSION We observed a high rate of RTW (97.1%, including 91.2% within 12 mo) after awake surgery in ILGG patients. Delayed resumption of work was due to employer not clearing them for RTW, personal choice, and, in rare occasions, related to seizures.
Oral Anticoagulation in Asian Patients With Atrial Fibrillation and a History of Intracranial Hemorrhage

Supplemental Digital Content is available in the text. Background and Purpose— Warfarin is associated with a better net clinical benefit compared with no treatment in patients with nonvalvular atrial fibrillation (AF) and history of intracranial hemorrhage (ICH). There are limited data on nonvitamin K antagonist oral anticoagulants (NOACs) in these patients, especially in the Asian population. We aimed to compare the effectiveness and safety of NOACs to warfarin in a large-scale nationwide Asian population with AF and a history of ICH. Methods— Using the Korean Health Insurance Review and Assessment database from January 2010 to April 2018, we identified patients with oral anticoagulant naïve nonvalvular AF with a prior spontaneous ICH. For the comparisons, warfarin and NOAC groups were balanced using propensity score weighting. Ischemic stroke, ICH, composite outcome (ischemic stroke+ICH), fatal ischemic stroke, fatal ICH, death from composite outcome, and all-cause death were evaluated as clinical outcomes. Results— Among 5712 patients with AF with prior ICH, 2434 were treated with warfarin and 3278 were treated with NOAC. Baseline characteristics were well-balanced after propensity score weighting (mean age 72.5 years and CHA2DS2-VASc score 4.0). Compared with warfarin, NOAC was associated with lower risks of ischemic stroke (hazard ratio [HR], 0.77 [95% CI, 0.61–0.97]), ICH (HR, 0.66 [95% CI, 0.47–0.92]), and composite outcome (HR, 0.73 [95% CI, 0.60–0.88]). NOAC was associated with lower risks of fatal stroke (HR, 0.54 [95% CI, 0.32–0.89]), death from composite outcome (HR, 0.53 [95% CI, 0.34–0.81]), and all-cause death (HR, 0.83 [95% CI, 0.69–0.99]) than warfarin. NOAC showed nonsignificant trends toward to reduce fatal ICH compared with warfarin (HR, 0.47 [95% CI, 0.20–1.03]). Conclusions— NOAC was associated with a significant lower risk of ICH and ischemic stroke compared with warfarin. NOAC might be a more effective and safer treatment option for Asian patients with nonvalvular AF and a prior history of ICH.
Spinal sagittal alignment, spinal shrinkage and back pain changes in office workers during a workday

Purpose. Prolonged sitting is a risk factor for the appearance of lower back pain during work. The aim of this study was to observe changes in spinal sagittal alignment, height and the perception of back pain in office workers during a workday. Materials and methods. Forty-one office workers (20 women) were enrolled into a cross-sectional study. Height, sitting height and degrees of thoracic kyphosis and lumbar lordosis as well as perceived neck pain, lower back pain and upper back pain were determined, before and after an 8-h workday. Results. At the end of the day, workers had a significant decrease (p = 0.000) in height and sitting height, and upper back pain increased significantly (p = 0.023). In men, spinal shrinkage correlated with neck pain (r = 0.410, p = 0.027), and lumbar lordosis degrees in women correlated negatively with upper back pain at the end of the day (r = −0.440, p = 0.012). Conclusions. Spinal shrinkage equally affects men and women who perform the same work. There are no changes in spinal sagittal alignment throughout the workday in office workers. Office workers show significantly increased pain in the upper back at the end of the day.
Hormone Therapy as a Protective Factor for Age-Related Macular Degeneration

ABSTRACT Purpose: The purpose of this study was to determine if the use of menopausal hormone therapy (HT) is related to the development of neovascular (NV) age-related macular degeneration (AMD), geographic atrophy (GA) and/or early/intermediate AMD. Methods: A case–control study was conducted from patients prospectively recruited from July 2014 to June 2019. Cases were females with AMD recruited into a registry and controls were females with age-related cataract and no AMD. Age-related macular degeneration was categorized into NV-AMD, GA, and early/intermediate. Hormone therapy (historic and current) was self-reported by the patient and categorized as ever/never use. Adjusted odds ratios (ORs) from multinomial logistic regressions are presented for each AMD group. Results: Female AMD case patients (n = 409) and controls (n = 132) were included in the analytic database. Almost half (45.5%) of the female AMD patients had NV-AMD, 14.9% had GA, and 39.6% had early/intermediate AMD. Among all study participants, 285 (52.7%) reported historic and/or current use of HT. Controls were significantly more likely to have any HT use (71.2%), compared to 43.0% (p ≤ 0.001) of NV-AMD patients, 47.5% (p = .002) of GA patients, and 50.6% (p ≤ 0.001) of early/intermediate AMD patients. Adjusted for potential confounders of age and Caucasian race, cases were significantly more likely to have lower HT use compared to controls: NV-AMD, OR = 0.31 (95%CI: 0.18–0.54), GA, OR = 0.40 (95%CI: 0.20–0.80), and early/intermediate AMD, OR = 0.36 (95%CI: 0.22–0.61). Conclusion: Our case–control study found that the use of HT was associated with a lower odds of all AMD stages studied: NV-AMD, GA and early/intermediate.
Can Conjunctival Impression Cytology be the First Line Diagnostic Test for Evaluation of Dry Eye Syndrome

Purpose To determine how Conjunctival Impression Cytology (CIC), Schirmer test, Tear Film Break up Time (TBUT) and Rose Bengal Stain (RBS) correlate with dry eye symptoms. To calculate the sensitivity, specificity and likelihood ratio (LR) of these tests for diagnosis of dry eye. Methods A case control study was done at two referral eye centers in northern part of the Indian subcontinent. Symptomatic patients with dry eye were recruited based on their response to a questionnaire of dry eye related symptoms (Table 1). Age and sex matched healthy subjects served as controls. Sensitivity and specificity, as estimated by the area under receiver operating characteristic (ROC) curve were primary outcome measures and the correlation between dry eye symptoms (DESS) and ocular surface tests, were secondary outcome measures. Results Eyes of 320 symptomatic patients were compared to 350 eyes of age and sex matched healthy controls. The mean symptom score in cases and controls was 8±2.6 and 1.2±2, respectively (P TBUT (AUC=0.793)>Schirmer (AUC= 0.765)>RBS (AUC=0.723). There was a stronger correlation between symptoms, CIC (Pearson's coefficient, Adjusted R
Treatment strategies for mixed aortic valve disease in nonelderly patients

ABSTRACT Introduction: Mixed aortic valve disease (MAVD) is defined by simultaneous occurrence of aortic stenosis (AS) and aortic regurgitation (AR). In our review, we focus on treatment options for nonelderly MAVD patients (age<55 years), who suffer from congenital aortic valve disease (unicuspid/bicuspid aortic valves). Areas covered: A systematic literature search was performed on PubMed and Embase databases using the following terms: mixed aortic valve disease, aortic stenosis/regurgitation, bicuspid/unicuspid aortic valve, mechanical/bioprosthetic aortic valve replacement, TAVR, Ross procedure. After preselection of title and abstracts, two authors (M.S. and E.G.) assessed the methodological quality of the full-text articles prior to final inclusion in the manuscript. Expert opinion: Currently, no ideal valvular substitutes are available in the treatment of nonelderly MAVD patients. Mechanical valves are associated with a reduced life expectancy due to a combination of prothesis-associated factors, mainly thrombotic and bleeding complications. Bioprostheses degenerate in the second decade and re-operations are inevitable, which also limit life expectancy. Long-term outcomes and durability of transcatheter aortic valve replacement are currently unknown. Finally, only Ross procedure is a therapeutic option with excellent long-term outcomes comparable to the healthy population. However, the Ross procedure has some important drawbacks and should therefore be only performed in expert centers and in well-selected patients.
Dominant symbiotic bacteria associated with wild medfly populations reveal a bacteriocin-like killing phenotype: a ‘cold-case’ study

Abstract The gut of the agricultural pest Ceratitis capitata hosts a varied community of bacteria, mainly Enterobacteriaceae, that were implicated in several processes that increase the fitness of the insect. In this study, we investigated the antagonistic activity in vitro of Klebsiella oxytoca strains isolated in the 1990s from the alimentary tract of wild medflies collected from different varieties of fruit trees at diverse localities. Assays were carried out against reference strains (representative of Gram-negative and -positive bacterial species) of the American Type Culture Collection (ATCC). Eight Klebsiella, out of 11, expressed a killing activity against Escherichia coli ATCC 23739, and Enterobacter cloacae ATCC 13047; among the eight strains, at least one showed activity against Salmonella typhimurium ATCC 23853. Genomic DNA derived from all Klebsiella strains was then subjected to PCR amplification using specific primer pairs designed from each of the four bacteriocin (KlebB, C, D, CCL) sequences found so far in Klebsiella. KlebD primer pairs were the only to produce a single product for all strains expressing the killing phenotype in vitro. One of the amplicons was cloned and sequenced; the DNA sequence shows 93% identity with a plasmid-carried colicin-D gene of a strain of Klebsiella michiganensis, and 86% identity with the sequence encoding for the klebicin D activity protein in K. oxytoca. Our work provides the first evidence that dominant symbiotic bacteria associated with wild medfly populations express a killing phenotype that may mediate inter and intraspecies competition among bacterial populations in the insect gut in vivo.
Touch-stimulation increases host-seeking behavior in Steinernema Carpocapsae

Abstract Previous research demonstrated that Steinernema carpocapsae infective juveniles (IJs) exposed to a host cuticle were more attracted toward certain host-associated volatile odors. We wanted to test the specificity of attraction that results from exposure to host cuticle. Host recognition behavior was analyzed after stimulating IJs by allowing them to physically interact with Galleria mellonella cuticles. The subsequent behavioral response and the proportion of the population participating in chemotaxis to multiple host odors were measured. We found that exposure to host cuticles resulted in a significantly higher percentage of the population participating in host-seeking behavior, with threefold more nematodes participating in chemotaxis. We tested whether exposure to live or dead host cuticle resulted in a different response and found that a higher percentage of IJs exposed to a live host cuticle participated in chemotaxis than IJs exposed to a dead host cuticle, but that IJs exposed to a dead host demonstrated significantly higher participation than was observed for non-stimulated IJs. To test whether the increase in IJ participation in host-seeking behaviors after exposure to a live host cuticle was specific, we exposed stimulated IJs to a known repulsive odor, a neutral odor, and two predicted attractants. We found that stimulation of IJs through physical contact with a host cuticle induces a specific enhancement of host-seeking behavior to host-specific odors rather than a general increased chemotactic response to all volatile stimuli. However, the nematodes displayed an enhanced response to multiple host-specific odors. Future work should focus on the mechanism through which contact with live host cuticle stimulates increased behavioral response.
Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis

Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability‐based approach, we evaluated the ability of different continuous infusion strategies to provide steady‐state concentrations (Css) within an analgesic concentration range (1‐3 ng/mL). Fifty‐three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2‐19 years) and 52 kg (16‐164 kg), respectively. The majority of children (94%) were obese. A 2‐compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving Css within target; however, the risk of achieving Css > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model‐based infusion strategy maintained consistent probabilities across the examined weight range for achieving Css within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model‐derived continuous infusion strategy maximized the probability of achieving target Css in children of varying weights.
Emerging roles of N- and C-terminally truncated Aβ species in Alzheimer’s disease

ABSTRACT Introduction: Alzheimer’s disease (AD) is characterized by a cerebral accumulation and aggregation of amyloid-β (Aβ) peptides, which mainly accumulate in the form of extracellular deposits. In addition to the well-described full-length peptides Aβ1-40 and Aβ1-42, a variety of amino- and carboxy-terminally truncated Aβ variants have been identified in brain samples from sporadic and familial AD cases. Areas covered: This review gives an overview on the role of truncated Aβ species in human AD, as well as in transgenic AD mouse models. We outline the relevance of the most abundant N- and C-truncated Aβ species, highlight potential mechanisms with regard to their generation and discuss their suitability as targets for pharmacological interventions. Expert opinion: A variety of recent clinical trials aiming either at a reduced Aβ production by the use of secretase inhibitors or at increased Aβ clearance by the use of immunotherapy were terminated unsuccessfully. Truncated or post-translationally modified Aβ peptides are becoming increasingly recognized as important players in the etiology of AD and a more thorough comprehension of their cellular origin and biochemical peculiarities might break new ground for therapeutic strategies.
Weight Regain Following Roux-en-Y Gastric Bypass: Etiology and Surgical Treatment.

BACKGROUND The Roux-en-Y gastric bypass (RYGB) surgery helps patients achieve excellent excess weight loss, with subsequent improvement or resolution of co-morbidities. However, up to 20% of all RYGB patients, and 40% of the super morbidly obese, experience significant weight regain. The etiology of weight regain is multifactorial; hence, multidisciplinary management is mandatory. Revision options for failed conservative and medical management include resizing the restrictive component of the bypass or intensifying malabsorption. While improvement of restriction generally has limited efficacy, intensifying malabsorption achieves significant long-term excess weight loss. The optimal surgical option should be personalized, considering eating behavior and psychological issues, surgical anatomy of the bypass, and anesthetic and surgical risks.
Sexual selection reveals a cost of pathogen resistance undetected in life‐history assays

Mechanisms of resistance to pathogens and parasites are thought to be costly and thus to lead to evolutionary trade‐offs between resistance and life‐history traits expressed in the absence of the infective agents. On the other hand, sexually selected traits are often proposed to indicate “good genes” for resistance, which implies a positive genetic correlation between resistance and success in sexual selection. Here I show that experimental evolution of improved resistance to the intestinal pathogen Pseudomonas entomophila in Drosophila melanogaster was associated with a reduction in male sexual success. Males from four resistant populations achieved lower paternity than males from four susceptible control populations in competition with males from a competitor strain, indicating an evolutionary cost of resistance in terms of mating success and/or sperm competition. In contrast, no costs were found in larval viability, larval competitive ability and population productivity assayed under nutritional limitation; together with earlier studies this suggests that the costs of P. entomophila resistance for nonsexual fitness components are negligible. Thus, rather than indicating heritable pathogen resistance, sexually selected traits expressed in the absence of pathogens may be sensitive to costs of resistance, even if no such costs are detected in other fitness traits.
New discoveries for an old drug: a review of recent olanzapine research

ABSTRACT Objective: Based on a substantial literature, olanzapine appears to be one of the most efficacious antipsychotics marketed in the United States, with only clozapine clearly more advantageous. However, olanzapine is marred by an equally substantial literature demonstrating a metabolic burden of olanzapine, particularly for weight gain. With the publication of successful strategies to limit olanzapine induced weight gain, a reassessment of the clinical utility of olanzapine appears warranted. The purpose of this paper is to review recent evidence for olanzapine, highlighting use in both schizophrenia and other conditions, safety and supporting the use of olanzapine above 20 mg/day, focusing on studies published since our previous reviews in 2008 and 2009. Data Sources: The US National Library of Medicine’s PubMed resource (https://www.ncbi.nlm.nih.gov/pubmed/) was searched using the text word ‘olanzapine’ for all English-language articles published between 2008 to July 2019, inclusive with a specific focus on double-blind randomized controlled trials and meta-analyses. In addition, we examined the review articles for other reports of interest that may have been missed by our initial search. Data Extraction: The studies were evaluated based on efficacy and safety data. Results: Use of olanzapine may be decreasing but remains common overall. Evidence continues to support both the relative efficacy advantage and weight gain/metabolic disadvantages of olanzapine in schizophrenia, and recent research supports olanzapine’s use in treating anorexia nervosa and chemotherapy-induced nausea. The evidence for high dose olanzapine dosages >20 mg remains limited. Non-pharmacological options, such as dietary counseling and exercise, appear to be efficacious in addressing antipsychotic-induced weight gain. Topiramate, metformin and possibly the olanzapine-samidorphan combination also appear helpful. Conclusions: Olanzapine remains a useful antipsychotic, but requires with careful monitoring. Further research is needed to compare the different options available to mitigate olanzapine-induced weight gain and to evaluate potential synergism between pharmacological and non-pharmacological treatments.