Content validation of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (NFLymSI-18) in indolent B-cell non-Hodgkin's lymphoma.

BACKGROUND: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. METHODS: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. RESULTS: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. CONCLUSIONS: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL.

Pharmacokinetics and pharmacodynamics of intravenously and subcutaneously administered pantoprazole in sheep (Ovis aries).

Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.

Pharmacokinetics of nalbuphine administered intravenously and subcutaneously in goats (Capra aegagrus hircus).

The purpose of this study was to evaluate the pharmacokinetics (PK) of intravenously (IV) and subcutaneously (SC) administered nalbuphine in domestic goats. Nalbuphine hydrochloride was administered at 0.8 mg/kg for both IV and SC routes in six goats with a minimum of 10-day washout period between sample collection phases. Eighteen plasma samples were collected over a 36-hour period, analyzed using reverse phase high-performance liquid chromatography (HPLC). Plasma data were analyzed using compartmental and noncompartmental approaches. Following IV nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 - ∞), concentration at time zero (C0), and total body clearance were 120.4 ± 39.1 (min-1 ± SD), 17311.01 ± 7227.32 (min·ng·mL-1 ± SD), 675.6 ± 337.13 (ng·mL-1 ± SD), and 44.5 ± 13.8 (mL·min-1·kg-1 ± SD), respectively. After SC nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 - ∞), and maximum plasma drug concentration were 129 ± 52.9 (min-1 ± SD), 20826.5 ± 14376.2 (min·ng·mL-1), and 368.03 ± 503.78 (ng·mL-1). Calculated bioavailability for the SC route was 138 ± 126 (% ± SD). Nalbuphine in goats is characterized by rapid elimination and high subcutaneous bioavailability and may be a safe analgesic opioid option in goats in the future.

Vitamin D Deficiency in Patients Hospitalized for Heart Failure Living in the Tropics.

Background and Objectives: Vitamin D, as a steroid hormone, has multiple effects on human body and its deficiency has been associated with an increased risk of heart failure (HF) and unfavorable outcomes. The present study investigated the prevalence of vitamin D deficiency (VDD) and its relationship with cardiometabolic parameters in patients hospitalized for HF living in the city of Recife (latitude 8° South). Methods: Analytical cross-sectional study, with men and women aged 40-64 years. The HF group was recruited during hospitalization due to decompensation. A matched control group was recruited from the general endocrine clinics. Vitamin D status was assessed by measuring serum 25-hydroxyvitamin D (25OHD), considering deficiency when 25OHD <20 ng/mL (<50 nmol/L). Results: A total of 243 patients were evaluated (HF group: 161, control group: 82). Lower serum 25OHD levels were observed in the HF group (25.2±9.4 vs. 30.0±7.7ng/mL; p<0.001), as well as a higher prevalence of VDD (27.3% vs. 9.8%; prevalence ratio, 2.80; 95% confidence interval, 1.38-5.67; p=0.002). In patients with HF, VDD was associated with diabetes mellitus (65.9% vs. 41.0%; p=0.005) and female sex (65.9% vs. 44.4%; p=0.015). In the subgroup with VDD, higher values of hemoglobin A1c (7.9% [6.0-8.9] vs. 6.2% [5.7-7.9]; p=0.006) and dyslipidemia were also observed. Conclusions: We found higher rates of VDD in patients hospitalized for HF and this was associated with deleterious laboratory metabolic parameters.

Pharmacokinetics of intraarticular liposomal amphotericin B in goats (Capra aegagrus hircus).

Lameness is a significant welfare concern in goats. Amphotericin B is used via intraarticular (IA) administration in models to study experimentally induced lameness in large animals. The main objective of this study was to estimate plasma pharmacokinetic (PK) parameters for amphotericin B in goats after a single IA administration. Liposomal amphotericin B was administered to ten Kiko-cross goats at a dose of 10 mg total (range: 0.34-0.51 mg/kg) via IA administration into the right hind lateral distal interphalangeal joint. Plasma samples were collected over 96 h. Amphotericin B concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive PK parameters. Following single IA administration, maximum plasma concentration was estimated at 54.6 ± 16.5 ng/mL, and time to maximum concentration ranged from 6 to 12 h. Elimination half-life was estimated at 30.9 ± 16.5 h, and mean residence time was 45.1 ± 10.4 h. The volume of distribution after IA administration was 13.3 ± 9.4 L/kg. The area under the curve was 1481 ± 761 h*ng/mL. The achieved maximum concentration was less than the observed concentrations for other species and routes of administration. Further research is needed into the pharmacodynamics of IA liposomal amphotericin B in goats to determine specific research strategies.

2-Ferrocenyl-2-[(2-ferrocenylethen-yl)(morpholin-4-yl)meth-yl]-1,3-di-thiol-ane.

The mol-ecular structure of 2-ferrocenyl-2-[(2-ferrocenylethen-yl)(morpholin-4-yl)meth-yl]-1,3-di-thiol-ane, [Fe2(C5H5)2(C19H21NOS2)] or C29H31Fe2NOS2, has the ferrocenyl fragments in a trans disposition with respect to the vinyl group. One of the methyl-ene groups is disordered over two sites with occupancies of 0.782 (13):0.218 (13). In the crystal, cyclo-penta-dienyl-C-H⋯O(morpholin-yl) inter-actions feature within helical chains parallel to the c-axis direction. The chains are connected by methyl-ene- and cyclo-penta-dienyl-C-H⋯O(cyclo-penta-dien-yl) inter-actions.

Proteomic study of gamma-oryzanol preventive effect on a diet-induced non-alcoholic fatty liver disease model.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease associated with obesity and diabetes prevalence. The use of natural compounds has become an attractive approach to prevent NAFLD and its progression. Gamma-oryzanol (Orz) is a natural compound whose beneficial effects on chronic metabolic diseases have been reported. Therefore, we aimed to investigate the preventive effect of Orz on the hepatic proteome in a diet induced NAFLD model. Wistar rats were randomly distributed into three experimental groups (n=6/group) according to the diet received for 30 weeks: Control group, high sugar-fat (HSF) group, and HSF+Orz group. The isolated Orz was added to the chow at the dose of 0.5% (w/w). We evaluated the nutritional profile, characterized the presence of steatosis through histological analysis, triglyceride content in liver tissue and hepatic inflammation. Next, we performed label-free quantitative proteomics of hepatic tissue. Network analysis was performed to describe involved protein pathways. NAFLD induction was characterized by the presence of hepatic steatosis. Orz prevented lipid accumulation. The compound prevented alterations of the hepatic proteome, highlighted by the modulation of lipid metabolism, inflammation, oxidative stress, xenobiotic metabolism, and the sirtuin signaling pathway. It was possible to identify key altered pathways of NAFLD pathophysiology modulated by Orz which may provide insights into NAFLD treatment targets.

Habitat complexity influences neuron number in six species of Puerto Rican Anolis.

Elucidating the selective forces shaping the diversity of vertebrate brains continues to be a major area of inquiry, particularly as it relates to cognition. Historically brain evolution was interpreted through the lens of relative brain size; however, recent evidence has challenged this approach. Investigating neuroanatomy at a finer scale, such as neuron number, can provide new insights into the forces shaping brain evolution in the context of information processing capacity. Ecological factors, such as the complexity of a species' habitat, place demands on cognition that could shape neuroanatomy. In this study, we investigate the relationship between neuron number and habitat complexity in three brain regions across six closely related anole species from Puerto Rico. After controlling for brain mass, we found that the number of neurons increased with habitat complexity across species in the telencephalon and 'rest of the brain,' but not in the cerebellum. Our results demonstrate that habitat complexity has shaped neuroanatomy in the Puerto Rican anole radiation and provide further evidence of the role of habitat complexity in vertebrate brain evolution.

Quantitative proteomics study of carnosine effect in an animal model of Western diet-induced nonalcoholic fatty liver disease.

The nonalcoholic fatty liver disease (NAFLD), which is closely related to westernized dietary (WD) patterns, displays a rising epidemiological and economic burden. Since there is no pharmacological therapy approved for this disease, mechanistic studies are warranted. In this work, we investigated the action of carnosine (CAR), a natural dipeptide with several protection roles against oxidative stress in the liver of NAFLD rats. NAFLD was induced by WD-rich sugars and fat, verifying the histological evidence of steatosis. As intraperitoneal administration of CAR reversed liver steatosis, the protein profiles of NAFLD liver and CAR NAFLD liver were evaluated by label-free proteomics approach. A total of 2531 proteins were identified and the 230 and 276 were significantly up- and downregulated, respectively, by CAR treatment of NAFLD rats and involved in fundamental pathways such as oxidative stress and lipid metabolism. Perilipin 2 and apolipoprotein E, components of the plasma membrane of vesicle, resulted in highly downregulated in the CAR-treated NAFLD liver. The advanced bioanalytical approach demonstrated the efficacy of CAR in overcoming the main symptoms of NAFLD, ameliorating the steatosis in the liver.

Influence of vascular imaging acquisition at local stroke centers on workflows in the drip-n-ship model: a RACECAT post hoc analysis.

BACKGROUND: The influence of vascular imaging acquisition on workflows at local stroke centers (LSCs) not capable of performing thrombectomy in patients with a suspected large vessel occlusion (LVO) stroke remains uncertain. We analyzed the impact of performing vascular imaging (VI+) or not (VI- at LSC arrival on variables related to workflows using data from the RACECAT Trial. OBJECTIVE: To compare workflows at the LSC among patients enrolled in the RACECAT Trial with or without VI acquisition. METHODS: We included patients with a diagnosis of ischemic stroke who were enrolled in the RACECAT Trial, a cluster-randomized trial that compared drip-n-ship versus mothership triage paradigms in patients with suspected acute LVO stroke allocated at the LSC. Outcome measures included time metrics related to workflows and the rate of interhospital transfers and thrombectomy among transferred patients. RESULTS: Among 467 patients allocated to a LSC, vascular imaging was acquired in 277 patients (59%), of whom 198 (71%) had a LVO. As compared with patients without vascular imaging, patients in the VI+ group were transferred less frequently as thrombectomy candidates to a thrombectomy-capable center (58% vs 74%, P=0.004), without significant differences in door-indoor-out time at the LSC (median minutes, VI+ 78 (IQR 69-96) vs VI- 76 (IQR 59-98), P=0.6). Among transferred patients, the VI+ group had higher rate of thrombectomy (69% vs 55%, P=0.016) and shorter door to puncture time (median minutes, VI+ 41 (IQR 26-53) vs VI- 54 (IQR 40-70), P<0.001). CONCLUSION: Among patients with a suspected LVO stroke initially evaluated at a LSC, vascular imaging acquisition might improve workflow times at thrombectomy-capable centers and reduce the rate of futile interhospital transfers. These results deserve further evaluation and should be replicated in other settings and geographies.

Randomized trial comparing standard versus light intensity parent training for anxious youth.

OBJECTIVE: To examine the efficacy of the parent-led intervention Supportive Parenting for Anxious Childhood Emotions (SPACE) relative to a low-dose version of the protocol among children and adolescents with clinically significant anxiety and/or obsessive-compulsive disorder (OCD). METHOD: 68 youth (7-17) with anxiety/OCD and their parents were randomized to receive 12 weekly telehealth SPACE sessions (SPACE-Standard) or bibliotherapy plus 4 telehealth sessions over 12 weeks (SPACE-light). After screening, assessments were conducted via videoconferencing at baseline, post-treatment, and one-month follow-up. Independent evaluators were blind to treatment condition. RESULTS: Treatment condition did not predict whether a participant responded to the intervention (SPACE-Standard = 70%; SPACE-Light = 68%), nor was treatment condition a predictor of anxiety severity, parent-reported anxiety, or parent-/child-reported functional impairment at post-treatment or one-month follow-up. Youth in SPACE-Light self-reported higher post-treatment anxiety than youth in SPACE-standard, though this was no longer significant at one-month follow-up. Parent-reported family accommodation total change scores were associated with anxiety severity at post-treatment across both arms. CONCLUSION: This is the second randomized controlled trial (RCT) evaluating SPACE and provides further support for the efficacy of this intervention both in standard and low-dose formats. This study provides support for parent-led anxiety treatment targeting family accommodation as a primary mechanism of change and extends evidence of efficacy to a more clinically diverse sample. TRIAL REGISTRATION: ClinicalTrials.gov Registry: NCT04922502.https://classic. CLINICALTRIALS: gov/ct2/show/NCT04922502.

Serious bleeds in pediatric persons with hemophilia A on emicizumab prophylaxis.

Background: Clinical trials have shown success in bleed prevention with emicizumab, but real-world data on the effectiveness of emicizumab in preventing serious bleeds in the pediatric population are lacking. Objectives: To report real-world data on the effectiveness of Emicizumab in pediatric persons with hemophilia A. Methods: We completed a retrospective chart review of 37 pediatric male patients aged ≤18 years on emicizumab prophylaxis for a median duration of 30.5 months at Children's Medical Center in Dallas, Texas. Results: We identified 4 pediatric persons with severe hemophilia A with and without inhibitors who experienced a provoked or unprovoked serious bleed requiring hospitalization. Conclusion: This study highlights that serious bleeds, both provoked and unprovoked, can occur in pediatric persons with severe hemophilia A. These findings are important for clinicians to provide appropriate counseling/education and recommendation of treatment for pediatric persons with severe hemophilia A through shared decision making. Up-titration of emicizumab or factor VIII replacement needs consideration in persons with hemophilia with suboptimal bleeding control or who participate in activities categorized as moderate- to high-risk activities.

Efficacy and safety of deep sclerectomy with uveoscleral implant plus collagen matrix implant overcoming the superficial scleral flap in glaucoma surgery.

AIM: To assess the efficacy and safety of non-penetrating deep sclerectomy (NPDS) with uveoscleral implant plus subconjunctival and intrascleral collagen matrix overcoming the superficial scleral flap lips (modified deep sclerectomy technique, DS) and minimal use of mitomycin C in glaucoma surgery. METHODS: A retrospective review of 47 consecutive glaucoma patients who underwent NPDS with DS between January 2017 and May 2018. Best-corrected visual acuity, intraocular pressure (IOP), post-operative need for glaucoma medications, visual field mean deviation (MD), re-interventions, needling revisions and laser goniopuncture were noted. Absolute success was defined as IOP≤18 mm Hg without topical medication. Relative success was defined as the same criteria but with the addition of any antihypertensive medication. IOP over 18 mm Hg on two consecutive follow-up visits was considered as a failure. RESULTS: Fifty-two eyes of 47 patients were evaluated. Mean preoperative IOP was 25.37±6.47 mm Hg, and decreased to 15.04±4.73 at 12mo and 12.21±4.1 at 24mo (all P<0.0001). Requirement for topical medications dropped from a mean of 3.06±0.25 per patient to 0.51±0.99 and 1.11±1.23 respectively after 12 and 24mo (all P<0.0001). No medications were required in 45.5% of patients after 24mo. Relative and absolute success rate at 24mo were 85.5%±5% and 48.5%±7.4%, respectively. CONCLUSION: DS is a safe and effective non-penetrating glaucoma surgery variation. It aims to retain the patency of all pathways created for aqueous humor drainage: the intrascleral bleb, the supraciliary space and the open communication between intrascleral and subconjunctival compartments.

4,6-Diferrocenyl-5-(morpholin-4-yl)-1,2,3-triazine.

The structure of the title Fe complex, [Fe(C5H5)2(C17H16N4O)], was determined at 130 K, and has ortho-rhom-bic (Pna21) symmetry. It is of inter-est with respect to the class of triazine heterocyclic compounds: the triazine ring is substituted by two ferrocenyl and one morpholine groups. The crystal structure features C-H⋯O and C-H⋯N non-classical hydrogen bonds.

The Amoebicidal Activity of Diferrocenyl Derivatives: A Significant Dependence on the Electronic Environment.

Amoebiasis is the second leading cause of death worldwide associated with parasitic disease and is becoming a critical health problem in low-income countries, urging new treatment alternatives. One of the most promising strategies is enhancing the redox imbalance within these susceptible parasites related to their limited antioxidant defense system. Metal-based drugs represent a perfect option due to their extraordinary capacity to stabilize different oxidation states and adopt diverse geometries, allowing their interaction with several molecular targets. This work describes the amoebicidal activity of five 2-(Z-2,3-diferrocenylvinyl)-4X-4,5-dihydrooxazole derivatives (X = H (3a), Me (3b), iPr (3c), Ph (3d), and benzyl (3e)) on Entamoeba histolytica trophozoites and the physicochemical, experimental, and theoretical properties that can be used to describe the antiproliferative activity. The growth inhibition capacity of these organometallic compounds is strongly related to a fine balance between the compounds' redox potential and hydrophilic character. The antiproliferative activity of diferrocenyl derivatives studied herein could be described either with the redox potential, the energy of electronic transitions, logP, or the calculated HOMO-LUMO values. Compound 3d presents the highest antiproliferative activity of the series with an IC50 of 23 µM. However, the results of this work provide a pipeline to improve the amoebicidal activity of these compounds through the directed modification of their electronic environment.

Bone Mineral Density, Trabecular Bone Score and Fractures in Patients Hospitalized for Heart Failure.

BACKGROUND: This study aimed to evaluate the bone mineral density (BMD), trabecular bone score (TBS), and fracture history of middle-aged patients hospitalized for heart failure (HF), as well as analyze the association of these factors with cardiometabolic parameters and muscle strength. METHODS: A cross-sectional study with patients aged 40 to 64 years hospitalized for HF was performed. Dual energy X-ray absorptiometry was performed to obtain BMD and TBS. Fracture history, handgrip strength (HGS), and clinical and laboratory cardiometabolic parameters of the patients were evaluated. RESULTS: Altogether, 109 patients were evaluated (female 50.5%). Medians and interquartile ranges for age and length of hospital stay were 58.0 (53.0-61.0) years and 20.0 (11.0-32.0) days, respectively. Osteoporosis was observed in 15.6% of the patients, low TBS was observed in 22.8%, and 6 patients had a history of fragile fracture. No differences between the sexes regarding BMD (p=0.335) or TBS (p=0.736) classifications were observed. No association was observed between low BMD and HF classification (p>0.05) regarding the ejection fraction, ischemic etiology, or New York Heart Association Functional Classification. However, there was a significant association between high serum parathyroid hormone (PTH) and the presence of osteoporosis (62.5 [37.2-119.0] pg/mL vs. 34.2 [25.0-54.1] pg/mL; p=0.016). There was a negative correlation between serum PTH and TBS (r=-0.329, p=0.038) and a higher frequency of reduced HGS in patients with low TBS (92.3% vs. 50.0%; p=0.009). CONCLUSIONS: We found relevant frequencies of osteoporosis and bone microarchitecture degradation in middle-aged patients with HF, which were related to high serum PTH concentrations.