VasCog 2023: 20 years of research on vascular behavioural and cognitive disorders.

This Commentary describes the 20th Anniversary of VasCog 2023, held in Gothenburg, Sweden.

Determination of plasma properties in liquid jets through time-resolved experiments on third harmonic reflection dynamics.

The study of plasma in liquid jets represents a significant area of research encompassing plasma science, dynamics, and properties. This paper presents experimental studies on plasma formation processes in liquid jets of water, ethanol, and isopropyl based on the dynamics of the third harmonic (TH) reflection from the induced plasma. Through time-resolved experiments, and theoretical estimations using the Keldysh theory, plasma properties including density and frequency for all three media are evaluated. Isopropyl demonstrates the highest values of the characteristics mentioned. These findings hold significant potential for advancing our understanding of plasma-based radiation sources, e.g., terahertz generation.

Association of Multi-Domain Factors with Cognition in the UK Biobank Study.

BACKGROUND: Dementia is a multifactorial syndrome attributable to a combination of vascular risk factors, lifestyle factors and neurodegeneration. However, little is known about the relative contribution of all these factors and their combined effects on cognition among the older population. OBJECTIVE: To examine the association of four domains of risk factors (sociodemographic, vascular risk factors, neuroimaging markers, lifestyle and psychosocial factors) with cognition in older adults. DESIGN: A cross-sectional study. SETTING: Data was obtained from a large-scale population-based study, UK Biobank study, at the first imaging visit assessment. PARTICIPANTS: Participants are citizen or permanent residents of UK, aged 60 years old and above. MEASURES: Cognitive function was assessed using the general cognitive ability score (g-factor score) derived from principal components analysis estimates of six cognitive tests. Associations with cognition were examined using multivariable linear regression for each domain and in combination. RESULTS: The study included 19,773 participants (mean age 68.5 ± 5.3 years SD, 9,726 (49%) male). Participants with lower cognitive scores (poorer cognition) were older, female, non-whites individuals, less educated and more socially deprived than participants with better cognitive scores. Participants with lower cognitive scores also tended to have higher vascular risk factors, lower brain volumes and more adverse lifestyle behaviours. The multivariable analysis found associations between adverse lifestyle and psychosocial factors with poorer cognition, i.e., being obese by measure of body fat percentage, having diabetes, higher white matter hyperintensity volume, increased sedentary screen time watching TV, being socially isolated and having depression were independently associated with poorer cognition. While larger hippocampal volume, having optimal sleep duration, adherence to a heathy diet, current and former alcohol drinking, increased wine consumption and sedentary screen time using a computer were associated with better cognition. CONCLUSION: A combination of adverse lifestyle and psychosocial factors were independently associated with poorer cognition in older adults. Findings in this study can potentially support public health communications to promote cognitive function and independence among older adults. This research has been conducted using the UK Biobank Resource under Application Number 71022.

Phylogenetic Relationships of the Mutualistic Fungi Associated with Macrotermes subhyalinus in Oman.

The symbiotic association between fungus-gardening termites Macrotermes and its fungal symbiont has a moderate degree of specificity-although the symbiotic fungi (Termitomyces) form a monophyletic clade, there is not a one-to-one association between termite species and their fungus-garden associates. Here, we aim to determine the origin and phylogenetic relationships of Termitomyces in Oman. We used sequences of the internal transcribed spacer region (ITS) and the nuclear large subunit ribosomal RNA (LSU rRNA, 25S) gene and analyzed these with sequences of Termitomyces from other geographic areas. We find no evidence for more than a single colonization of Oman by Termitomyces. Unexpectedly, we find Termitomyces in Oman is most closely related to the symbiont of M. subhyalinus in West Africa rather than to those of geographically closer populations in East Africa.

Revision Rotator Cuff Repair With Versus Without an Arthroscopically Inserted Onlay Bioinductive Implant in Workers' Compensation Patients.

Background: The addition of onlay biological grafts to augment difficult rotator cuff repairs has shown encouraging results in a case series. Purpose/Hypothesis: The purpose of this study was to determine whether the addition of an onlay bioinductive implant would improve repair integrity, shear wave elastographic appearance of the repaired tendon and patch, and patient-rated and/or surgeon-measured shoulder function when used in workers' compensation patients undergoing revision arthroscopic rotator cuff repair. We hypothesized that the addition of the bioinductive implant would enhance repair integrity and clinical outcomes compared with standard repair. Study Design: Cohort study; Level of evidence, 3. Methods: A post hoc matched-cohort study was conducted on prospectively recruited workers' compensation patients who received a bioinductive implant for revision rotator cuff repair (n = 19). The control group was selected from consecutive workers' compensation revision rotator cuff repair patients before the introduction of bioinductive implants. Then, they were matched for age and tear size (n = 32). Kaplan-Meier curves were generated to compare the primary outcome of repair integrity between groups. The secondary outcomes were to evaluate the elastographic appearance of the tendon and patch in the bioinductive implant group and to compare patient-rated and surgeon-measured shoulder function between groups preoperatively and at 1 week, 6 weeks, 3 months, and 6 months postoperatively. Results: No major complications associated with the bioinductive implants were identified. Six months after the revision rotator cuff repair, the retear rate in the bioinductive implant group was 16% (3/19), compared with 19% (6/32) in the age- and tear size-matched control group (P = .458). At the final follow-up, the retear rate in the bioinductive implant group was 47% (9/19) at a mean of 14 months compared with 38% (12/32) at a mean of 29 months in the control group (P = .489). The shear wave elastographic stiffness of repaired tendons augmented with the bioinductive implant remained unchanged at 6 m/s from 1 week to 6 months postoperatively, which is lower than the stiffness of 10 m/s in healthy tendons. There were no significant differences in patient-rated or surgeon-measured outcomes between groups 6 months postoperatively. Conclusion: There were no differences in repair integrity or clinical outcomes between workers' compensation patients who underwent revision arthroscopic rotator cuff repair with an onlay bioinductive implant compared to those who underwent standard revision rotator cuff repair.

Reliability of a Novel Preoperative Protocol for Determining Graft Sizes for Superior Capsular Reconstruction Using Plain Film Radiography.

BACKGROUND: Superior capsular reconstruction (SCR) for massive, irreparable rotator cuff tears involves anchoring a graft between the superior glenoid and the greater tuberosity of the humerus. Optimizing the graft size is important. We aimed (1) to evaluate the reliability of plain film radiography in determining graft size for SCR and (2) to create a database to help predict future graft sizes. METHODS: An inter- and intra-rater reliability trial was conducted on 10 and 6 subjects with healthy shoulders, respectively, using plain film radiography to measure the distance between the superior glenoid and the supraspinatus footprint. The subjects were positioned upright with an abduction pillow modified to hold the shoulder at 30° abduction and 45° external rotation, afterwhich a true antero-posterior shoulder radiograph was captured. Thirty subjects were recruited for the database and grouped using the aforementioned protocol. RESULTS: The inter-rater and intra-rater trial agreement was excellent, with intraclass correlation coefficients of 0.94 (95% CI) and 0.76 (95% CI), respectively. Three medio-lateral patch sizes, of 33 mm, 38 mm, and 47 mm, were proposed based on the protocol in 30 subjects. CONCLUSIONS: Plain film radiography demonstrated excellent reliability in measuring the distance between the superior glenoid and the supraspinatus footprint. Three ordinal patch sizes are proposed.

Biomechanical Comparison of Synthetic Polytetrafluoroethylene (PTFE) vs Human Dermal Allograft (HDA), 2 vs 3 Glenoid Anchors, and Suture vs Minitape in Superior Capsule Reconstruction.

Background: Superior capsule reconstruction (SCR) is an option for the treatment of massive, irreparable rotator cuff tears. However, which materials yield the strongest constructs remains undetermined. Purposes: We sought to investigate whether SCR with polytetrafluoroethylene (PTFE) or human dermal allograft (HDA), 2 or 3 glenoid anchors, and suture or minitape resulted in better failure load properties at the patch-glenoid interface. Methods: We conducted a biomechanical study in 30 glenoid-sided SCR repairs in Sawbones models divided into 5 groups. Each was pulled to failure to assess mode of failure, peak load (N), stiffness (N/mm), yield load (N), peak energy (N m), and ultimate energy (N m). The 5 groups were as follows: group 1-PTFE, 2 anchors, and suture; group 2-PTFE, 2 anchors, and minitape; group 3-HDA, 2 anchors, and suture; group 4-HDA, 2 anchors, and minitape; group 5-PTFE, 3 anchors, and minitape. Results: Repairs failed by button-holing of suture/minitape. Group 5 had greater peak load, stiffness, yield load, and peak energy (384 ± 62 N; 24 ± 3 N/mm; 343 ± 42 N; 4 ± 2 N m) than group 3 (226 ± 67 N; 16 ± 4 N/mm; 194 ± 74 N; 2 ± 1 N m) or group 4 (274 ± 62 N; 17 ± 4 N/mm; 244 ± 50 N; 2 ± 1 N m) and greater ultimate energy (8 ± 3 N m) than all other groups. Conclusions: This biomechanical study of SCR repairs in Sawbones models found that yield load was greater in PTFE than HDA, 3 anchors were better than 2, and minitape was no better than suture.

Predictors of Return to Work Following Primary Arthroscopic Rotator Cuff Repair: An Analysis of 1502 Cases.

BACKGROUND: It is undetermined which factors predict return to work after arthroscopic rotator cuff repair. PURPOSE: To identify which factors predicted return to work at any level and return to preinjury levels of work 6 months after arthroscopic rotator cuff repair. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Multiple logistic regression analysis of prospectively collected descriptive, preinjury, preoperative, and intraoperative data from 1502 consecutive primary arthroscopic rotator cuff repairs, performed by a single surgeon, was performed to identify independent predictors of return to work at 6 months postoperatively. RESULTS: Six months after arthroscopic rotator cuff repair, 76% of patients had returned to work, and 40% had returned to preinjury levels of work. Return to work at 6 months was likely if patients were still working after their injuries but before surgery (Wald statistic [W] = 55, P < .0001), were stronger in internal rotation preoperatively (W = 8, P = .004), had full-thickness tears (W = 9, P = .002), and were female (W = 5, P = .030). Patients who continued working postinjury but presurgery were 1.6 times more likely to return to work at any level at 6 months compared to patients who were not working (P < .0001). Patients who had a less strenuous preinjury level of work (W = 173, P < .0001), worked at a mild to moderate level post injury but presurgery, had greater preoperative behind-the-back lift-off strength (W = 8, P = .004), and had less preoperative passive external rotation range of motion (W = 5, P = .034) were more likely to return to preinjury levels of work at 6 months postoperatively. Specifically, patients who worked at a mild to moderate level postinjury but presurgery were 2.5 times more likely to return to work than patients who were not working, or who were working strenuously postinjury but presurgery (p < 0.0001). Patients who nominated their preinjury level of work as "light" were 11 times more likely to return to preinjury levels of work at 6 months compared to those who nominated it as "strenuous" (P < .0001). CONCLUSION: Six months after rotator cuff repair, patients who continued to work after injury but presurgery were the most likely to return to work at any level, and patients who had less strenuous preinjury levels of work were the most likely to return to their preinjury levels of work. Greater preoperative subscapularis strength independently predicted return to work at any level and to preinjury levels.

Biomechanical and morphological comparison of two interposition graft rotator cuff repair techniques.

BACKGROUND: Interposition graft rotator cuff repair is one option for the treatment of massive, otherwise irreparable rotator cuff tears. It is undetermined how different suturing techniques influence morphology at the patch-tendon interface in interposition rotator cuff repairs, particularly with respect to increased cross-sectional area at the repair site post-exposure to cyclic loading, which may influence healing. We aimed to analyze how the morphology of the grafts used in polytetrafluoroethylene (PTFE) interposition rotator cuff repairs differed according to whether the graft was secured using the multiple mattress technique or the weave technique respectively. METHODS: Twelve PTFE interposition rotator cuff repairs (two groups, n = 6) were cyclically loaded. The thickness, width, cross-sectional area at the individual patches and at the repair site, and patch elongation were compared between repairs using the 'multiple mattress' technique and repairs that used the 'weave' technique. RESULTS: At all loads, repair site cross-sectional area and thickness was greater in the weave group than in the multiple mattress group (P<0.05), despite repair site width being greater in the multiple mattress group (P<0.05). No significant differences in elongation were found between the multiple mattress and weave groups. CONCLUSION: Greater repair site cross-sectional area under cyclic loading was observed in polytetrafluoroethylene interposition rotator repairs that used the weave technique than in those that used the multiple mattress technique. Increased repair site cross-sectional area in the weave group occurred due to increased thickness and decreased width relative to the multiple mattress group. No differences in cross-sectional area were found between groups at the individual patches.

Factors influencing clinical outcomes in superior capsular reconstruction: A scoping review.

Background: It is undetermined how effective superior capsule/capsular reconstruction (SCR) is, and which factors influence clinical outcomes. Questions/purposes: (1) To identify which factors influence outcomes in SCR, (2) to evaluate the effect of graft integrity on clinical outcomes, and (3) to compare SCR to other procedures for irreparable rotator cuff tears. Methods: PubMed and EMBASE databases were searched for clinical SCR studies. Data on specific factors that influenced outcomes, that compared outcomes between intact/torn graft groups, or compared SCR to alternative treatments for irreparable tears were extracted by two investigators. Random-effects meta-analysis was performed to compare outcomes between intact vs torn SCR grafts. Results: 394 articles were identified. 100 full-text articles were screened. 13 studies were included for scoping review. Eight studies were meta-analyzed. Better clinical scores were found in younger patients, with intact/repairable subscapularis, without acetabulization/arthritis, who played sports. In patients with irreparable tears without arthritis, SCR produced similar clinical scores at 2 years as shoulder arthroplasty and partial infraspinatus repair, and greater improvements in ASES and Constant scores than latissimus dorsi tendon transfer. Intact grafts produced better VAS (mean difference [MD] = 0.97, 95% confidence interval [-1.45-0.50], P < 0.0001, I 2 = 67%, n [patients] = 261), ASES (MD = 8.29, [2.89-13.70], P = 0.003, I 2 = 74%, n = 281), external rotation (MD = 4.49, [0.36-8.61], P = 0.03, I 2 = 0%, n = 240), and acromiohumeral distance (MD = 2.45, [0.96-3.94], P = 0.001, I 2 = 92%, n = 260) than torn grafts. Conclusions: Patients who underwent SCR for irreparable rotator cuff tears were more likely to have better clinical outcomes if they were younger, had intact/repairable subscapularis, without acetabulization/arthritis, played sports and had intact grafts.

Sports Participation After Reverse Total Shoulder Replacement.

Background: Reverse total shoulder replacement (RTSR) is becoming a popular and reliable treatment for rotator cuff arthropathy. However, little is known about the ability to participate in sports after surgery. Purpose: To determine to what extent RTSR will allow patients to participate in sporting activities and identify the associated factors that could affect postoperative sports participation. Study Design: Case series; Level of evidence, 4. Methods: Data were collected prospectively from patients who underwent RTSR over a 10-year period from April 2009 to May 2019. Patients were assessed before surgery, at 6 months after surgery, and at the final follow-up. Patients were asked within a validated shoulder questionnaire to rank their current highest level of sports participation, overall shoulder status, frequency of pain, level of pain, and functional levels. Their shoulder range of motion and strength were assessed before surgery and at 6 months after surgery. Results: The study included 108 shoulders (106 patients). The mean age was 74 years (range, 51-88 years), with 44 men and 64 women. The mean follow-up was 4 years. Overall shoulder satisfaction, frequency and levels of pain, and shoulder function improved significantly at 6 months and 4 years (P < .0001). External rotation, abduction, and forward flexion range of motion improved significantly at 6 months (P < .05 for all). The strength of internal rotation, external rotation, abduction, and adduction improved significantly at 6 months (P < .001 for all). The rate of return to sports was 67% at 6 months and 48% at 4 years. Multiple significantly associated factors were identified with return to sports at 6 months, including sex and age. Conclusion: The rate of return to sports after RTSR is high. Around two-thirds of patients can return to sports at 6 months postoperatively, although the results slightly deteriorate over time (48% at 4 years).

Arterial Spin-Labeling Parameters and Their Associations with Risk Factors, Cerebral Small-Vessel Disease, and Etiologic Subtypes of Cognitive Impairment and Dementia.

BACKGROUND AND PURPOSE: Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation. MATERIALS AND METHODS: Three hundred ninety patients with a diagnosis of no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia were recruited from the memory clinic. Cerebral microbleeds and lacunes were categorized into strictly lobar, strictly deep, and mixed-location and enlarged perivascular spaces into the centrum semiovale and basal ganglia. Total and region-specific white matter hyperintensity volumes were segmented using FreeSurfer. CBF (n = 333) and the spatial coefficient of variation (n = 390) were analyzed with ExploreASL from 2D-EPI pseudocontinuous arterial spin-labeling images in white matter (WM) and gray matter (GM). To analyze the effect of demographic and vascular risk factors as well as the location and severity of cerebral small-vessel disease markers on arterial spin-labeling parameters, we constructed linear regression models, whereas logistic regression models were used to determine the association between arterial spin-labeling parameters and cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia. RESULTS: Increasing age, male sex, hypertension, hyperlipidemia, history of heart disease, and smoking were associated with lower CBF and a higher spatial coefficient of variation. Higher numbers of lacunes and cerebral microbleeds were associated with lower CBF and a higher spatial coefficient of variation. Location-specific analysis showed mixed-location lacunes and cerebral microbleeds were associated with lower CBF. Higher total, anterior, and posterior white matter hyperintensity volumes were associated with a higher spatial coefficient of variation. No association was observed between enlarged perivascular spaces and arterial spin-labeling parameters. A higher spatial coefficient of variation was associated with the diagnosis of vascular cognitive impairment no dementia, Alzheimer's disease, and vascular dementia. CONCLUSIONS: Reduced CBF and an increased spatial coefficient of variation were associated with cerebral small-vessel disease, and more specifically lacunes, whereas cerebral microbleeds and white matter hyperintensities were associated with WM-CBF and GM spatial coefficient of variation. The spatial coefficient of variation was associated with cognitive impairment and dementia, suggesting that hypoperfusion might be the key underlying mechanism for vascular brain damage.

Ultrasound-guided repair of the distal biceps tendon.

Surgical repair of the distal biceps tendon rupture can be a challenge, especially when patients present with a retracted tendon. The tendon stump is often difficult to find and retrieve. In this aticle, we described a technique using ultrasound imaging at the start of the procedure. Under ultrasound guidance, a breast biopsy needle is used to help localize and mark the retracted tendon edge as well as the distal rupture site. Ultrasound is also used to mark important neurovascular structures at risk to help speed up exposure and avoid complications.

Oil-based mud cutting as an additional raw material in clinker production.

Oil-Based Mud (OBM) cutting is a hazardous by-product generated during oil-well drilling. Its chemical composition suggests that it might be suitable as a raw material in cement manufacturing. It is rich in calcium oxide, silica, and aluminium oxide, which are the major oxides in raw materials for cement manufacturing. In this research, OBM cutting is used as a constituent of the raw meal for cement clinker production. Raw meal mixtures were prepared by mixing different ratios of raw materials increasing OBM content. The impact of the addition of OBM cutting on the resulting clinker has been investigated. The results demonstrate that OBM cutting could be recycled in the manufacturing of Portland cement clinker. Clinker prepared using OBM cutting had very similar properties to that prepared from limestone. This result could represent an opportunity for solving an environmental problem. The addition of OBM cutting lowers the calcination temperature, and increases the rate of carbonate dissociation. However, it also leads to a higher free lime in clinker, which is a result of the presence of trace elements, such as barium. Overall, its use as a raw material in cement production could provide a cost-effective, environment-friendly route for the management of OBM cutting.

Towards saving freshwater: halophytes as unconventional feedstuffs in livestock feed: a review.

Water represents 71% of all earth area and about 97% of this water is salty water. So, only 3% of the overall world water quantity is freshwater. Human can benefit only from 1% of this water and the remaining 2% freeze at both poles of earth. Therefore, it is important to preserve the freshwater through increasing the plants consuming salty water. The future prosperity of feed resources in arid and semi-arid countries depends on economic use of alternative resources that have been marginalized for long periods of time, such as halophytic plants, which are one such potential future resource. Halophyte plants can grow in high salinity water and soil and to some extent during drought. The growth of these plants depends on the contact of the salted water with plant roots as in semi-desert saline water, mangrove swamps, marshes, and seashores. Halophyte plants need high levels of sodium chloride in the soil water for growth, and the soil water must also contain high levels of salts, as sodium hydroxide or magnesium sulfate. There are many uses for halophyte plants, including feed for animals, vegetables, drugs, sand dune stabilizers, wind shelter, soil cover, wetland cultivation, laundry detergents, and paper production. This paper will focus on the use of halophytes as a feed additive for animals. In spite of the good nutritional value of halophytes, some anti-nutritional factors as nitrates, nitrite complexes, tannins, glycosides, phenolic compounds, saponins, oxalates, and alkaloids may be present in some of them. The presence of such anti-nutritional agents makes halophytes unpalatable to animals, which tends to reduce feed intake and nutrient use. Therefore, the negative effects of these plants on animal performance are the only objection against using halophytes in animal feed diets. This review article highlights the beneficial impact of considering halophytes in animal feeding on saving freshwater and illustrates its nutritive value for livestock from different aspects.

NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib.

NF-E2-related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy.

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells.

Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2.HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single antibody alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target.

Estimating the melting point, entropy of fusion, and enthalpy of fusion of organic compounds via SPARC.

The entropy of fusion, enthalpy of fusion, and melting point of organic compounds can be estimated through three models developed using the SPARC (SPARC Performs Automated Reasoning in Chemistry) platform. The entropy of fusion is modelled through a combination of interaction terms and physical descriptors. The enthalpy of fusion is modelled as a function of the entropy of fusion, boiling point, and flexibility of the molecule. The melting point model is the enthalpy of fusion divided by the entropy of fusion. These models were developed in part to improve SPARC's vapour pressure and solubility models. These models have been tested on 904 unique compounds. The entropy model has a RMS of 12.5 J mol(-1) K(-1). The enthalpy model has a RMS of 4.87 kJ mol(-1). The melting point model has a RMS of 54.4°C.

NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies.

NF-E2 related factor-2 (NRF2) is an essential transcription factor for multiple genes encoding antioxidants and detoxification enzymes. NRF2 is implicated in promoting cancer therapeutic resistance by its detoxification function and crosstalk with proproliferative pathways. However, the exact mechanism of this intricate connectivity between NRF2 and growth factor induced proliferative pathway remains elusive. Here, we have demonstrated that pharmacological activation of NRF2 by tert-butylhydroquinone (tBHQ) upregulates the HER family receptors, HER2 and HER3 expression, elevates pAKT levels, and enhances the proliferation of ovarian cancer cells. Preactivation of NRF2 also attenuates the combined growth inhibitory effects of HER2 targeting monoclonal antibodies, Pertuzumab and Trastuzumab. Further, tBHQ caused transcriptional induction of HER2 and HER3, while SiRNA-mediated knockdown of NRF2 prevented this and further caused transcriptional repression and enhanced cytotoxicity of the HER2 inhibitors. Hence, NRF2 regulates both HER2 and HER3 receptors to influence cellular responses to HER2 targeting monoclonal antibodies. This deciphered crosstalk mechanism reinforces the role of NRF2 in drug resistance and as a relevant anticancer target.

Evaluate the Effect of Commercially Available Denture Cleansers on Surface Hardness and Roughness of Denture Liners at Various Time Intervals.

BACKGROUND AND OBJECTIVE: Chemical cleansing by denture cleansers is first choice for denture plaque control. The most common problems while using denture cleansers are hardening, porosity, odor sorption, water sorption, solubility, and colour change, bacterial and fungal growth. Chemical cleansing procedures have been found to have an effect on the physical and mechanical properties of denture liners. Thus, this study was conducted to evaluate the effect of commercially available denture cleansers on surface hardness and roughness of acrylic and silicon based denture liners at various time interval. METHOD: Two autopolymerising denture liners Kooliner (acrylic) and GC reline soft (silicon) were tested with two commercially available denture cleansers, polident and efferdent plus. Total of 120 specimens were prepared and all the specimens were divided into six groups based on the relining materials and denture cleansers used. Surface hardness and surface roughness was tested using Shore A durometer and profilometer respectively at the end of day 1, day 7, day 30 and day 90. All the specimens were stored in artificial saliva throughout the study. Cleanser solution was prepared daily by adding Polident and Efferdent plus denture cleanser tablet into 250ml of enough very warm (not hot) water. Acrylic and silicon liner groups were cleansed in a solution of denture cleanser and water for 15 minutes daily, rinsed with water and stored in artificial saliva at room temperature. The data was analyzed with one way ANOVA and independent t-test. RESULT: The acrylic soft lining showed gradual hardening and increase in surface roughness after immersion in denture cleanser and also with time. Acrylic liner material showed maximum hardness and roughness with Polident followed by Efferdent plus and water (control group). Silicone lining material showed a slight difference in hardness and roughness between the test group and control group. There was a slight increase in hardness in all the groups with time. Very slight increase in mean surface roughness of all the silicon liner groups from day 1 to day 90 was observed. A statistically significant change was noted between and within the all silicon liner groups on day 7, day 30 and day 90. CONCLUSION: The average surface hardness and surface roughness were lower in silicon liner material than acrylic liner material. Maximum surface roughness was noted by Polident followed by Efferdent Plus and Water for both acrylic liner group and silicon liner group.