Design, Synthesis, Characterization, and Molluscicidal Activity Screening of New Nicotinonitrile Derivatives against Land Snails, M. cartusiana.

A new series of nicotinonitrile derivatives 2-7 was designed and synthesized from the starting material (E)-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (1) to assess their molluscicidal activity. The newly synthesized nicotinonitrile compounds 2-7 were characterized based on FTIR, 1H-NMR, and 13C-APT NMR spectra as well as elemental microanalyses. The target compounds 2-7 were screened for their toxicity effect against M. cartusiana land snails and were compared to Acetamiprid as a reference compound. The results demonstrated that the nicotinonitrile-2-thiolate salts 4a and 4b had good mortality compared with that of Acetamiprid. The results of the in vivo effect of the prepared nicotinonitrile molecules 2, 4a, and 4b on biochemical parameters, including AChE, ALT, AST, and TSP, indicated a reduction in the level of AChE and TSP as well as an increase in the concentration of transaminases (ALT and AST). A histopathological study of the digestive gland sections of the M. cartusiana land snails was carried out. The nicotinonitrile-2-thiolate salts 4a,b showed vacuolization, causing the digestive gland to lose its function. It could be concluded that the water-soluble nicotinonitrile-2-thiolate salts 4a,b could be adequate molluscicidal molecules against M. cartusiana land snails.

Relationship between mechanical properties and crystal structure in cocrystals and salt of paracetamol.

Objectives were to study mechanical properties of various solid forms of paracetamol and relate to their crystal structures. Paracetamol form I (PRA), its cocrystals with oxalic acid (PRA-OXA) and 4,4-bipyridine (PRA-BPY) and hydrochloride salt (PRA-HCL) were selected. Cocrystals and salt were scaled-up using rational crystallization methods. The resulting materials were subjected to different solid-state characterizations. The powders were sieved and 90-360 µm sieve fraction was considered. These powders were examined by scanning electron microscopy (SEM) and densities were determined. Tablets were made at applied pressures of 35-180 MPa under controlled conditions and the tablet height, diameter and hardness were measured. Tensile strength and porosity of the tablets were estimated using well known models. Crystal structures of these systems were visualized and slip planes were identified. Cocrystal and salt of PRA were physically pure. Sieved powders had comparable morphologies and particle size. The apparent and theoretical densities of powders were similar, but no clear trends were observed. The tensile strengths of these compacts were increased with increasing pressure whereas tabletability decreased in the order oxalic acid > PRA-HCL ≈ PRA-OXA > BPY > PRA-BPY. Tablet tensile strength decreases exponentially with increasing porosity with the exception of PRY-BPY and BPY. Slip plane prediction based on attachment energies may not be independently considered. However, it was possible to explain the improved mechanical properties of powders based on the crystal structure. Cocrystallization and salt formation have introduced structural features that are responsible for improved tableting properties of PRA.

Lumbar Disc Degeneration Is Linked to Dorsal Subcutaneous Fat Thickness at the L1-L2 Intervertebral Disc Level Measured by MRI.

BACKGROUND: Obese individuals have a higher risk of degenerative disc disease (DDD). Currently, body mass index is not sensitive enough to differentiate between muscle and fat distribution, and obesity-related health issues are linked to the way body fat is distributed. Therefore, this study aims to investigate the association between the dorsal subcutaneous fat thickness (DSFT) of the lumbar spine, an alternative measurement tool of body fat distribution, and DDD. METHODS: A total of 301 patients with DDD and 123 participants without the disease were recruited. Using length functions of magnetic resonance imaging (MRI) console, the DSFT of L1 to S1 intervertebral disc levels was measured in mid-sagittal spin-echo T2 weighted image. The Mann-Whitney U test and Chi-squared test (X2) were utilized to examine any variations between the case and control groups. Logistic regression models were built to explore the association of the DSFT with DDD. RESULTS: The logistical regression model showed a positive association between DDD and DSFT [OR: 1.30, 95% CI: 1.02-1.64, p = 0.03]. In the stratified logistic regression analysis, a positive association was found between DDD and DSFT among younger participants and females [OR young: 1.48; 95% CI (1.02-2.20); p = 0.04-OR female: 1.37; 95% CI (1-1.88); p = 0.05]. CONCLUSIONS: Younger females with thicker DSFT at the L1-L2 level are more likely to develop DDD. This suggests that increased DSFT may be a contributing factor to DDD.

Macrophage activation in response to shape memory polymer foam-coated aneurysm occlusion devices.

Brain aneurysms can be treated with embolic coils using minimally invasive approaches. It is advantageous to modulate the biologic response of platinum embolic coils. Our previous studies demonstrated that shape memory polymer (SMP) foam coated embolization coils (FCC) devices demonstrate enhanced healing responses in animal models compared with standard bare platinum coil (BPC) devices. Macrophages are the most prevalent immune cell type that coordinate the greater immune response to implanted materials. Hence, we hypothesized that the highly porous SMP foam coatings on embolic coils activate a pro-regenerative healing phenotype. To test this hypothesis, we analyzed the number and type of infiltrating macrophages in FCC or BPC devices implanted in a rabbit elastase aneurysm model. FCC devices elicited a great number of infiltration macrophages, skewed significantly to a pro-regenerative M2-like phenotype 90 days following implantation. We devised an in vitro assay, where monocyte-derived macrophages were placed in close association with FCC or BPC devices for 6-72 h. Macrophages encountering SMP FCC-devices demonstrated highly mixed activation phenotypes at 6 h, heavily skewing toward an M2-like phenotype by 72 h, compared with macrophages encountering BPC devices. Macrophage activation was evaluated using gene expression analysis, and secreted cytokine evaluation. Together, our results demonstrate that FCC devices promoted a pro-regenerative macrophage activation phenotype, compared with BPC devices. Our in vitro findings corroborate with in vivo observations that SMP-based modification of embolic coils can promote better healing of the aneurysm site, by sustaining a pro-healing macrophage phenotype.

First study on the molecular prevalence of caprine arthritis encephalitis virus in goats in Babylon, Iraq.

Background and Aim: Caprine arthritis encephalitis virus (CAEV) is a virus that affects goats all over the world and causes enormous economic losses; as a result, screening for the disease is a priority, especially in Iraq. The present study aimed to estimate the prevalence of CAEV in infected goats using the précised PCR method in Babylon, Iraq. Materials and Methods: A total of 85 blood samples from goats aged 1 month to ≥6 years were analyzed for CAEV infections using molecular methods. The polymerase chain reaction primer was designed to amplify a 573 bp region of the proviral pol gene. Results: The CAEV tests revealed that five out of 85 goats were positive for CAEV. There were no significant differences in CAEV infection according to goat sex and significant differences according to age. Conclusion: Based on these results, the present study is the first molecular survey to confirm the current CAEV genome in an Iraqi goat flock.

Obesity-Dependent Adipokine Chemerin Suppresses Fatty Acid Oxidation to Confer Ferroptosis Resistance.

Clear cell renal cell carcinoma (ccRCC) is characterized by accumulation of neutral lipids and adipogenic transdifferentiation. We assessed adipokine expression in ccRCC and found that tumor tissues and patient plasma exhibit obesity-dependent elevations of the adipokine chemerin. Attenuation of chemerin by several approaches led to significant reduction in lipid deposition and impairment of tumor cell growth in vitro and in vivo. A multi-omics approach revealed that chemerin suppresses fatty acid oxidation, preventing ferroptosis, and maintains fatty acid levels that activate hypoxia-inducible factor 2α expression. The lipid coenzyme Q and mitochondrial complex IV, whose biogeneses are lipid-dependent, were found to be decreased after chemerin inhibition, contributing to lipid reactive oxygen species production. Monoclonal antibody targeting chemerin led to reduced lipid storage and diminished tumor growth, demonstrating translational potential of chemerin inhibition. Collectively, the results suggest that obesity and tumor cells contribute to ccRCC through the expression of chemerin, which is indispensable in ccRCC biology. SIGNIFICANCE: Identification of a hypoxia-inducible factor-dependent adipokine that prevents fatty acid oxidation and causes escape from ferroptosis highlights a critical metabolic dependency unique in the clear cell subtype of kidney cancer. Targeting lipid metabolism via inhibition of a soluble factor is a promising pharmacologic approach to expand therapeutic strategies for patients with ccRCC.See related commentary by Reznik et al., p. 1879.This article is highlighted in the In This Issue feature, p. 1861.

A retrospective analysis of hospitalisation for diseases of the pulp and periapical tissues in NHS Grampian 2011-2015: geographic, socioeconomic and increased primary care availability effects.

Objectives A study of hospital admissions for diseases of pulp and periapical tissues in NHS Grampian and the effects of socioeconomic, geographic location and primary dental care availability on hospital admissions.Design Retrospective analysis of hospitalisation data from NHS Grampian Health Intelligence database for the five-year period (1 January 2011 to 31 December 2015), if their primary diagnosis was disease of the pulp or periapical tissues. The influence of the Scottish Index of Multiple Deprivation (SIMD) scores on hospital admissions for pulp or periapical diseases were assessed and compared. Data from general dental practitioners (GDPs) providing primary care were obtained from the National Services Scotland practitioner services board.Results There were 963 admissions to NHS Grampian hospitals over the five-year period. The most frequent hospitalisation admission code was K047 'periapical abscess without sinus', accounting for 59.3% of all admissions. Hospital admissions decreased from 185 in 2011 to 122 in 2015, and coincided with a 50% rise in the number of GDPs providing primary care dentistry within the region (171 in 2011 to 256 in 2015). SIMD 5 (least deprived) had the greatest number of admissions (68) in 2011 compared with the most deprived (11). In 2015, SIMD 4 had the most admissions (41) compared to SIMD 1 (12).Conclusion A reduction in hospital admissions for pulp/periapical abscesses appears to coincide with an increase in GDPs providing primary care dental services. Barriers to providing dental treatment in primary care should be minimised to reduce the burden of care on NHS hospitals for preventable dental diseases such as periapical abscesses.

Powder Compression Properties of Paracetamol, Paracetamol Hydrochloride, and Paracetamol Cocrystals and Coformers.

The objective was to study the relationship between crystal structure, particle deformation properties, and tablet-forming ability for the monoclinic form of paracetamol (PRA), 2 cocrystals and a salt crystal of PRA in addition to 2 coformers (oxalic acid and 4,4'-bipyridine). Thus, the structure-property-performance relationship was investigated. Analytical powder compression was used for determination of effective plasticity, as inferred from the Heckel yield pressure and the Frenning parameter, and the elastic deformation was determined from in-die tablet elastic recovery. The plasticity could not be linked to the crystal lattice structure as crystals containing zig-zag layers displayed similar plasticity as crystals containing slip planes. In addition, crystals containing slip planes displayed both high and low plasticity. The mechanical properties could not be linked to the tablet-forming ability as the tablet tensile strength, unexpectedly, displayed a tendency to reduce with increased plasticity. Furthermore, the elastic deformation could not explain the tablet-forming ability. It was concluded that no relationship between structure-property-performance for PRA and its cocrystals and salt could be established. Thus, it was indicated that to establish such a relationship, an improved knowledge of crystallographic structure and interparticle bonding during compaction is needed.