Multiparametric MRI Scoring System of the Pancreas for the Diagnosis of Chronic Pancreatitis.

BACKGROUND: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP). PURPOSE: Diagnose CP based on multiparametric MRI and MRCP features. STUDY TYPE: Prospective. POPULATION: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation. FIELD STRENGTH AND SEQUENCES: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with variable flip angle, dual-echo Dixon, secretin-enhanced MRCP before and after secretin infusion. ASSESSMENT: Dual-echo fat fraction (FF), T1 relaxation time, extracellular volume (ECV), T1 signal intensity ratio of the pancreas to the spleen (T1 score), arterial-to-venous enhancement ratio (AVR), pancreatic tail diameter (PTD), pancreas volume, late gadolinium enhancement, pancreatic ductal elasticity (PDE), and duodenal filling grade of secretin-enhanced MRCP were measured. STATISTICAL TESTS: Logistic regression analysis generated CP-MRI and secretin-enhanced CP-SMRI scores. Receiver operating characteristics analysis was used to differentiate definite CP from control. Interobserver agreement was assessed using Lin's concordance correlation coefficient. RESULTS: Compared to control, definite CP cohort showed significantly higher dual-echo FF (7% vs. 11%), lower AVR (1.35 vs. 0.85), smaller PTD (2.5 cm vs. 1.95 cm), higher ECV (28% vs. 38%), and higher incidence of PDE loss (6.5% vs. 50%). With the cut-off of >2.5 CP-MRI score (dual-echo FF, AVR, and PTD) and CP-SMRI score (dual-echo FF, AVR, PTD, and PDE) had cross-validated area under the curves of 0.84 (sensitivity 87%, specificity 68%) and 0.86 (sensitivity 89%, specificity 67%), respectively. Interobserver agreement for both CP-MRI and CP-SMRI scores was 0.74. CONCLUSION: The CP-MRI and CP-SMRI scores yielded acceptable performance and interobserver agreement for the diagnosis of CP. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.

Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

Effects of dietary powdered Ficus deltoidea on the growth and health performance of African catfish, Clarias gariepinus production.

Intensive aquaculture causes a decline in the health status of fish, resulting in an increased disease incidence. To counteract this, feed additives have been utilized to improve the growth performance and health of aquaculture species. This work specifically investigates the impact of powdered Ficus deltoidea (FD) on various parameters related to growth, blood parameters, liver and intestine morphology, body proximate analysis, digestive enzymes, antioxidant capacity, and disease resistance to motile Aeromonad Septicemia (MAS) caused by Aeromonas hydrophila infection in African catfish, Clarias gariepinus. Four formulated diets were prepared: T1 (0% FD), T2 (0.5% FD), T3 (0.75% FD), and T4 (1% FD). After 8 weeks, the African catfish's growth performance fed with the T2 diet exhibited a substantial improvement (p < 0.05), along with a remarkably lower (p < 0.05) feed conversion ratio (FCR) when compared to the other treatment groups. Blood parameter analysis revealed notably higher (p < 0.05) levels of white blood cell (WBC), lymphocytosis (LYM), hemoglobin (HGB), albumin (ALB), globulin (GLOB), as well as total protein (TP) in the T2 diet group. While all treatment groups displayed normal intestinal morphology, liver deterioration was observed in groups supplemented with higher FD. The T2 diet group recorded the highest villus length, width, and crypt depth. Protease and lipase levels were also notably improved in the T2 diet group compared to other treatment groups. Additionally, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were remarkably elevated in all FD diet groups than in the control group. The expression of immune-related genes, including transforming growth factor beta 1, heat shock protein 90, nuclear factor kappa-B gene, and lysozyme G, was upregulated in all treatments. Overall, the results of this study indicate that incorporating dietary FD at 0.5% concentration in the diet of African catfish may enhance their productivity in intensive farming.

Genome-Wide and Transcriptome-Wide Association Studies on Northern New England and Ohio Amyotrophic Lateral Sclerosis Cohorts.

Background and Objectives: Amyotrophic lateral sclerosis (ALS) is an age-associated, fatal neurodegenerative disorder causing progressive paralysis and respiratory failure. The genetic architecture of ALS is still largely unknown. Methods: We performed a genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) to understand genetic risk factors for ALS using a population-based case-control study of 435 ALS cases and 279 controls from Northern New England and Ohio. Single nucleotide polymorphism (SNP) genotyping was conducted using the Illumina NeuroChip array. Odds ratios were estimated using covariate-adjusted logistic regression. We also performed a genome-wide SNP-smoking interaction screening. TWAS analyses used PrediXcan to estimate associations between predicted gene expression levels across 15 tissues (13 brain tissues, skeletal muscle, and whole blood) and ALS risk. Results: GWAS analyses identified the p.A382T missense variant (rs367543041, p = 3.95E-6) in the TARDBP gene, which has previously been reported in association with increased ALS risk and was found to share a close affinity with the Sardinian haplotype. Both GWAS and TWAS analyses suggested that ZNF235 is associated with decreased ALS risk. Discussion: Our results support the need for future evaluation to clarify the role of these potential genetic risk factors for ALS and to understand genetic susceptibility to environmental risk factors.

Immune modulation and cecal microbiome changes in broilers fed with fenugreek seeds and Bacillus-based probiotics.

Intensive broiler production systems face challenges like enteric diseases, impacting global food security. Strategies to enhance broiler immunity and gut health, particularly amidst antibiotic growth promoter restrictions, are crucial. The present study investigated the combined effects of fenugreek seeds (FS) and Bacillus-based direct-fed microbials (DFM) on immune-related gene expression in the ileum and alteration of microbial population in the cecum of broiler. The study involved 160 Ross 308 broiler chicks, which were divided into four groups consisting of 5 replicates, each containing eight birds. The chicks were grown for a period of 42 d, during which they had ad libitum access to feed and water. Dietary treatments were: Control (basal diet), FS5 (basal + 5g/kg fenugreek seeds), FS5DFM (basal + 5g/kg fenugreek seeds + 0.1g/kg Bacillus-based DFM), and DFM (basal + 0.1g/kg Bacillus-based DFM). Ileum tissue and cecal contents were collected on d 42 for gene expression and gut microbiome analysis. Ileal gene expression analysis revealed the downregulation of IL-6, IL-8L2, CASP6, PTGS2, and IRF7 in both FSs and DFMs groups compared to the control, suggesting individual immunomodulatory effects. However, avian ß-defensin genes exhibited complex regulation, highlighting the need for further investigation. Cecal microbiome diversity remained stable, with subtle shifts in specific taxa influenced by FSs and DFMs. Interestingly, the combination of the FSs and DFMs uniquely impacted specific taxa, including Clostridiales vadin BB60. These findings suggest that both FSs and DFMs demonstrated potential for improving broiler immunity through inflammation reduction. The combination of FSs and DFMs offers a synergistic effect in immune modulation and specific microbial modulation, warranting further investigation with pathogen challenge models for comprehensive understanding.

Molecular Modes Elucidate the Nuclear Magnetic Resonance Relaxation of Viscous Fluids.

The Bloembergen, Purcell, and Pound (BPP) theory of nuclear magnetic resonance (NMR) relaxation in fluids dating back to 1948 continues to be the linchpin in interpreting NMR relaxation data in applications ranging from characterizing fluids in porous media to medical imaging (MRI). The BPP theory is founded on assuming molecules are hard spheres with 1H-1H dipole pairs reorienting randomly; assumptions that are severe in light of modern understanding of liquids. Nevertheless, it is intriguing to this day that the BPP theory was consistent with the original experimental data for glycerol, a hydrogen-bonding molecular fluid for which the hard-sphere-rigid-dipole assumption is inapplicable. To better understand this incongruity, atomistic molecular simulations are used to compute 1H NMR T1 relaxation dispersion (i.e., frequency dependence) in two contrasting cases: glycerol, and a (non hydrogen-bonding) viscosity standard. At high viscosities, simulations predict distinct functional forms of T1 for glycerol compared to the viscosity standard, in agreement with modern measurements, yet both in contrast to BPP theory. The cause of these departures from BPP theory is elucidated, without assuming any relaxation models and without any free parameters, by decomposing the simulated T1 response into dynamic molecular modes for both intramolecular and intermolecular interactions. The decomposition into dynamic molecular modes provides an alternative framework to understand the physics of NMR relaxation for viscous fluids.

Large scale serum proteomics identifies proteins associated with performance decline and clinical milestones in Duchenne muscular dystrophy.

Serum biomarkers are promising minimally invasive outcome measures in clinical studies in Duchenne muscular dystrophy (DMD). However, biomarkers strongly associated with clinical progression and predicting performance decline are lacking. In this study we aimed to identify serum biomarkers associated with clinical performance and able to predict clinical milestones in DMD. Towards this aim we present a retrospective multi-center cohort study including serum samples and clinical data collected in research participants with DMD as part of a natural history study at the University of Florida (UF) and real-world observations at Leiden University Medical Center (LUMC) between 2009-2022. The 7K SomaScan® assay was used to analyse protein levels in in individual serum samples. Serum biomarkers predicted age at loss of ambulation (LoA), age at loss of overhead reach (OHR) and age at loss of hand to mouth function (HTM). Secondary outcomes were the association of biomarkers with age, corticosteroid (CS) usage, and clinical performance based on the North Star Ambulatory Assessment (NSAA), 10 meter run velocity (10mrv), 6 minute walk (6MWT) and Performance of the Upper Limb (PUL2.0). A total of 716 serum samples were collected in 79 participants at UF and 74 at LUMC (mean[SD] age; 10.9[3.2] vs 8.4[3.4]). 244 serum proteins showed an association with CS usage in both cohorts independent of CS type and regimen, including MMP3 and IGLL1. 318 probes (corresponding to 294 proteins) showed significant associations with NSAA, 10mrv, 6MWT and/or PUL2.0 across both cohorts. The expression of 38 probes corresponding to 36 proteins such as RGMA, EHMT2, ART3, ANTXR2 and DLK1 was associated with risk of both lower and upper limb clinical milestones in both the LUMC and UF cohort. In conclusion, multiple biomarkers were associated with CS use, motor function and upper lower and upper limb disease milestones in DMD. These biomarkers were validated across two independent cohorts, increasing their likelihood of translation for use within the broader DMD population.

Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort.

INTRODUCTION: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort. METHODS: The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up. RESULTS: The mean ± SD COPPS was 8.4 ± 1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r = 0.15, P = 0.01; duration: r = 0.16, P = 0.01) and pancreas-related hospitalizations (number: r = 0.15, P = 0.02; duration: r = 0.13, P = 0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalizations. All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, P = 0.004; duration, P = 0.007) and pancreas-related hospitalizations (number, P = 0.02; duration, P = 0.04). The prevalence of continued drinking at follow-up ( P = 0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment ( P = 0.02) and follow-up ( P < 0.05) was higher in the moderate and high groups. DISCUSSION: Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.

New insights into the early morphological evolution of sea turtles by re-investigation of Nichollsemys baieri, a three-dimensionally preserved fossil stem chelonioid from the Campanian of Alberta, Canada.

The early evolution of Pan-Chelonioidea (sea turtles) is poorly understood. This is in part due to the rarity of undeformed skulls of definitive early stem chelonioids. In this work, we redescribe the holotype of Nichollsemys baieri using µCT scans and segmentations of the skull. This fossil is the best 3D preserved skull of any Campanian sea turtle, and includes partial "soft tissue" preservation. Nichollsemys is morphologically similar but clearly distinct from Toxochelys spp., and both show a mosaic of plesiomorphic and derived chelonioid features. The internal cranial anatomy documents the presence of derived characters in Nichollsemys baieri that are absent in Toxochelys spp., such as the loss of the epipterygoids and the rod-like shape of the rostrum basisphenoidale. Among the numerous plesiomorphic characters is the presence of a splenial bone, which was unnoticed before. An updated phylogenetic analysis retrieves Nichollsemys baieri as a non-protostegid early stem chelonioid in a slightly more crownward position than Toxochelys latiremis. Our phylogeny includes macrobaenids and protostegids as pan-chelonioids, and we find unorthodox results for dermochelyids. Thus, although Nichollsemys baieri provides important new insights into the early morphological evolution of sea turtles, much work remains to be done. As a completely 3D preserved specimen, we included Nichollsemys baieri into a recent landmark-based skull shape dataset of turtles. Morphospace analysis reveals an intermediate position between cryptodires and crown chelonioids. Based on these data, we also predict that Nichollsemys baieri was still capable of neck retraction, constraining the loss of this trait to more crownward pan-chelonioids. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-024-00323-8.

A taxonomic backbone for the Plumbaginaceae (Caryophyllales).

A taxonomic backbone of the Plumbaginaceae is presented and the current state of knowledge on phylogenetic relationships and taxon limits is reviewed as a basis for the accepted taxon concepts. In total, 4,476 scientific names and designations are treated of which 30 are not in the family Plumbaginaceae. The Plumbaginaceae are subdivided in three tribes with 26 genera and 1,179 accepted species. Two subgenera, 17 sections, two subsections and 187 infraspecific taxa are accepted. At the species and infraspecific level 2,782 synonyms were assigned to accepted taxa, whereas 194 names were excluded from the core checklist (i.e., unplaced taxa, infrageneric subdivisions with still uncertain application, names of verified uncertain application, invalid horticultural names, excluded names from other families, other excluded designations, and unresolved names). The EDIT Platform for Cybertaxonomy was utilized as the tool to compile and manage the names and further taxonomic data under explicit taxon concepts. Secundum references are given in case taxon concepts were taken from the literature, whereas this study serves as reference for newly circumscribed taxa. The family's division into the tribes Aegialitideae, Limonieae, and Plumbagineae departs from earlier two-subfamily classifications, prompted by recent phylogenetic findings that challenge the subfamilial affinity of Aegialitis. The genus Acantholimon was extended to include Gladiolimon, as currently available phylogenetic and morphological data support this merger. In Limonium, all accepted species could be assigned to sections and subsections or the "Mediterranean lineage", respectively, making use of the phylogenetic distribution of their morphological characters and states. A new combination and/or status is proposed for Dyerophytumsocotranum, Limoniumthymoides, Limonium×fraternum, Limonium×rossmaessleri, and Limoniumsect.Jovibarba. Special attention is given to nomenclatural issues, particularly for Staticenomenambiguum to resolve the names under accepted names. The use of artificial groupings like "aggregates", "complexes" and "species groups" in alpha-taxonomic treatments is discussed. The taxonomic backbone will receive continued updates and through the Caryophyllales Taxonomic Expert Network, it contributes the treatment of the Plumbaginaceae for the World Flora Online.

DMNP as an Effective Cage for Ln3+: A Spectroscopic and Thermodynamic Study.

Dimethoxynitrophenyl-EDTA (DMNP) is a popular calcium cage that is frequently used to investigate the role of Ca2+ in signaling processes in vivo. Lanthanides have been used in Ca2+ biomimetics due to similarities in coordination properties of Ln3+ and Ca2+ that may enable fluorescence and NMR studies of functional and structural properties of Ca2+ binding proteins. In this study, we show that Tb3+, Eu3+, and Nd3+ bind strongly to DMNP in a 1:1 ratio. Isothermal titration calorimetric measurements of Ca2+ displacement by Ln3+ in DMNP provide the equilibrium binding constants for Ln3+DMNP complexation with association constants, K11 = (1.2 ± 0.7) × 1012 M-1 for Eu3+, (2.5 ± 1.7) × 1012 M-1 for Nd3+, and (2.8 ± 0.8) × 1012 M-1 for Tb3+. The kinetics and thermodynamics of Ca2+, Mg2+, and Tb3+ release from DMNP were characterized using photothermal beam deflection (PBD). Ligand release from the DMNP cage was rapid and occurred within 10 µs upon cage photofragmentation and was associated with similar reaction volume and enthalpy changes that can be attributed to the photoreleased ion solvation. In the case of Ca2+DMNP photodissociation at subsaturating Ca2+ concentrations, we observed a slower phase with a lifetime of 300 µs that we attribute to Ca2+ rebinding to unphotolyzed DMNP. These results demonstrate that DMNP can serve as an effective photolabile cage for oxophilic Ln3+ that has similar coordination properties to Ca2+ and Mg2+.

Relationship between serum uric acid, nocturnal hypertension and risk for preeclampsia in high-risk pregnancies.

To analyze the possible association between serum uric acid (SUA) and nocturnal hypertension and to evaluate the ability of these variables (alone or in combination) to predict preeclampsia (PE) we conducted a historical cohort study in 532 high-risk pregnancies. Women were divided according to SUA values and nocturnal blood pressure (BP) into four groups: 1- normal SUA and nocturnal normotension; 2- high SUA and nocturnal normotension; 3- normal SUA and nocturnal hypertension and 4- high SUA and nocturnal hypertension. High SUA was defined by the top quartile values and nocturnal hypertension as BP ≥ 120/70 mmHg, using ambulatory blood pressure monitoring (ABPM), during nocturnal rest. Risks for PE were compared using logistic regression. SUA had a weak but significant correlation with daytime systolic ABPM (r = 0.11, p = 0.014), daytime diastolic ABPM (r = 0.13, p = 0.004), nighttime systolic ABPM (r = 0.16, p < 0.001) and nighttime diastolic ABPM (r = 0.18, p < 0.001). Also, all ABPM values were higher in women with high SUA. The absolute risk of PE increased through groups: 6.5%, 13.1%, 31.2%, and 47.9% for groups 1, 2, 3, and 4, respectively, p < 0.001. Compared with Group 1, Group 3 (OR 6.29 95%CI 3.41-11.60), but not Group 2 (OR 2.15 95%CI 0.88-5.24), had statistically significant higher risk for PE. Group 4 (women with both, high SUA and nocturnal hypertension) had the highest risk (OR 13.11 95%CI 6.69-25.70). Risks remained statistically significant after the adjustment for relevant variables. In conclusion, the combination of SUA > 4 mg/dL and nocturnal BP > 120/70 mmHg implies a very high risk to developed PE.

Discoloration of textile dyes by spent mushroom substrate of Agaricus bisporus.

The textile industry discharges up to 5 % of their dyes in aqueous effluents. Here, use of spent mushroom substrate (SMS) of commercial white button mushroom production and its aqueous extract, SMS tea, was assessed to remove textile dyes from water. A total of 30-90 % and 5-85 % of the dyes was removed after a 24 h incubation in SMS and SMS tea, respectively. Removal of malachite green and remazol brilliant blue R was similar in SMS and its tea. In contrast, removal of crystal violet, orange G, and rose bengal was higher in SMS, explained by sorption to SMS and by the role of non-water-extractable SMS components in discoloration. Heat-treating SMS and its tea, thereby inactivating enzymes, reduced dye removal to 8-58 % and 0-31 %, respectively, indicating that dyes are removed by both enzymatic and non-enzymatic activities. Together, SMS of white button mushroom production has high potential to treat textile-dye-polluted aqueous effluents.

Effects on Lung Tissue After Breast Cancer Radiation: Comparing Photon and Proton Therapies.

Purpose: In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes. Patients and Methods: A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12-month time points. Results: Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever-smokers but not in never-smokers. Conclusion: Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.

Circulating angiotensin-(1-7) is decreased in patients with isolated nocturnal hypertension.

Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1-7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ±â€Š16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1-7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1-7) and Ang II levels. Logistic regression showed significant association in Ang-(1-7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.

Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology.

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.

The cranial and postcranial morphology of Hutchemys rememdium and its impact on the phylogenetic relationships of Plastomenidae (Testudinata, Trionychidae).

Hutchemys rememdium is a poorly understood softshell turtle (Trionychidae) from the mid Paleocene of the Williston Basin of North America previously known only from postcranial remains. A particularly rich collection of previously undescribed material from the Tiffanian 4 North American Land Mammal Age (NALMA) of North Dakota is here presented consisting of numerous shells that document new variation, some non-shell postcrania, and cranial remains, which are described based on 3D models extracted from micro-CT data. Although the observed shell variation weakens previously noted differences with the younger species Hutchemys arctochelys from the Clarkforkian NALMA, the two taxa are still recognized as distinct. Parsimony and Bayesian phylogenetic analyses reaffirm the previously challenged placement of Hutchemys rememdium within the clade Plastomenidae, mostly based on novel observations of cranial characters made possible by the new material and the micro-CT data. The new topology supports the notion that the well-ossified plastron of plastomenids originated twice in parallel near the Cretaceous/Paleogene boundary, once in the Hutchemys lineage and once in the Gilmoremys/Plastomenus lineage. Hutchemys rememdium is notable for being the only documented species of trionychid in the mid Paleocene of the Williston Basin. The presence of multiple individuals in a carbonaceous claystone indicates this taxon lived in swamps and lakes and its expanded triturating surface suggests it had a durophagous diet. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-024-00315-8.