Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling.

Diacylglycerol lipase-beta (DAGLß) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLß ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream proinflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to find that disruption of DAGLß in primary macrophages leads to LKB1-AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLß blockade, thereby directly supporting DAGLß-AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy-sensing kinases to mediate cell biological and pain responses.

Stealth Nanocarriers in Cancer Therapy: a Comprehensive Review of Design, Functionality, and Clinical Applications.

Nanotechnology has significantly transformed cancer treatment by introducing innovative methods for delivering drugs effectively. This literature review provided an in-depth analysis of the role of nanocarriers in cancer therapy, with a particular focus on the critical concept of the 'stealth effect.' The stealth effect refers to the ability of nanocarriers to evade the immune system and overcome physiological barriers. The review investigated the design and composition of various nanocarriers, such as liposomes, micelles, and inorganic nanoparticles, highlighting the importance of surface modifications and functionalization. The complex interaction between the immune system, opsonization, phagocytosis, and the protein corona was examined to understand the stealth effect. The review carefully evaluated strategies to enhance the stealth effect, including surface coating with polymers, biomimetic camouflage, and targeting ligands. The in vivo behavior of stealth nanocarriers and their impact on pharmacokinetics, biodistribution, and toxicity were also systematically examined. Additionally, the review presented clinical applications, case studies of approved nanocarrier-based cancer therapies, and emerging formulations in clinical trials. Future directions and obstacles in the field, such as advancements in nanocarrier engineering, personalized nanomedicine, regulatory considerations, and ethical implications, were discussed in detail. The review concluded by summarizing key findings and emphasizing the transformative potential of stealth nanocarriers in revolutionizing cancer therapy. This review enhanced the comprehension of nanocarrier-based cancer therapies and their potential impact by providing insights into advanced studies, clinical applications, and regulatory considerations.

Assessment of the root and canal morphology in the permanent dentition of Saudi Arabian population using cone beam computed and micro-computed tomography - a systematic review.

INTRODUCTION: Root canal treatment procedures require a thorough understanding of root and canal anatomy. The purpose of this systematic review was to examine the morphological differences of teeth root and their canals assessed using cone-beam computed and micro-computed tomography in Saudi Arabian population. METHODOLOGY: An electronic search was conducted in PubMed / Medline, Scopus, Google Scholar, and Web of Science databases until January 2023 to retrieve related studies. "Root canal morphology," "Saudi Arabia," "Micro-CT," and "cone-beam computed tomography" were used as keywords. A modified version of previously published risk of bias assessment tool was used to determine the quality assessment of included studies. RESULTS: The literature search revealed 47 studies that matched the criteria for inclusion, out of which 44 studies used cone beam computed tomography (CBCT) and three were micro-computed tomography (micro-CT) studies. According to the modified version of risk of bias assessment tool, the studies were categorized as low, moderate, and high risk of bias. A total of 47,612 samples were included which comprised of either maxillary teeth (5,412), or mandibular teeth (20,572), and mixed teeth (21,327). 265 samples were used in micro-CT studies while 47,347 teeth samples were used in CBCT studies. Among the CBCT studies, except for three, all the studies were retrospective studies. Frequently used imaging machine and software were 3D Accuitomo 170 and Morita's i-Dixel 3D imaging software respectively. Minimum and maximum voxel sizes were 75 and 300 µm, Vertucci's classification was mostly used to classify the root canal morphology of the teeth. The included micro-CT studies were in-vitro studies where SkyScan 1172 X-ray scanner was the imaging machine with pixel size ranging between 13.4 and 27.4 µm. Vertucci, Ahmed et al. and Pomeranz et al. classifications were applied to classify the root canal morphology. CONCLUSION: This systematic review revealed wide variations in root and canal morphology of Saudi population using high resolution imaging techniques. Clinicians should be aware of the common and unusual root and canal anatomy before commencing root canal treatment. Future micro-CT studies are needed to provide additional qualitative and quantitative data presentations.

Postendodontic Pain Using Single File System with Different Irrigation Protocols in Single-visit Root Canal Treatment: A Randomized Control Trial.

AIM: To evaluate the intensity of postendodontic pain (PEP) using final irrigation with side-vented needle (SV), EndoActivator (EA), and Ultra X (UX) in single-visit endodontics (SVE) with F-One rotary files. MATERIALS AND METHODS: A total 150 patients indicated for endodontic treatment were selected. Single-visit endodontics treatment was performed under local anesthesia. For the final irrigation protocol, they were divided into three groups: group I (SV), group II (EA), and group III (UX). The severity of PEP was assessed using visual analogue scale (VAS) score after 6, 12, 24, and 48 hours. Analgesics taken by patients, for pain, were also recorded. Finally, the data were tabulated and statistically analyzed using SPSS 20.0 software at a level of significance being 0.05. RESULTS: Postendodontic pain was less in group III (UX) and group II (EA) compared with group I (SV) at 6 and 12 hours, which is statistically significant (p < 0.05). There was no statistically significant difference found after 24 hours and 48 hours. CONCLUSION: The intensity of PEP was minimum in patients treated with EndoActivator and ultrasonic along with single rotary file systems. The incidence of analgesic intake was similar in all three groups. How to cite this article: Kathiria NV, Attur K, Bagda KM, et al. Postendodontic Pain Using Single File System with Different Irrigation Protocols in Single-visit Root Canal Treatment: A Randomized Control Trial. J Contemp Dent Pract 2024;25(2):180-185.

Assessing oral health knowledge among public school children in Saudi Arabian subpopulation.

INTRODUCTION: Oral hygiene is paramount for maintaining optimal oral and physical health, especially among children who are particularly susceptible to dental caries and issues due to dietary habits and inadequate hygiene practices. This study aimed to evaluate the awareness and knowledge of oral health among public school children, analyse their oral hygiene habits, educate parents on the importance of oral health for their children, and implement an oral hygiene educational program in Al-Kharj City, Saudi Arabia. METHODS: Four public elementary schools were selected for the study, with a sample size of 200 school-going children participating. A structured questionnaire was used to assess awareness and knowledge of oral health among the participants. SPSS software version 26 was used for data analysis. Multiple regression analysis and correlation tests was employed to explore the relationships between the different variables measured in the study. RESULTS: The findings revealed a significant lack of awareness regarding oral health among school children. Oral hygiene habits were found to be inadequate in many participants. Overall, the findings highlight the need for targeted interventions aimed at promoting regular dental visits, addressing dental fear, and fostering positive oral hygiene practices among school-going children to improve oral health outcomes in the studied population. CONCLUSION: The study highlighted a critical gap in oral health awareness among school children, underscoring the need for targeted interventions. While the oral hygiene educational program has been implemented and future data will shed light on its effectiveness, preliminary observations suggest that such programs could potentially improve oral health outcomes and overall engagement among students.

In-Vitro Evaluation of Dental Adhesive Bond Strength With Diode Laser Irradiation Before Photopolymerization.

AIM: In-vitro evaluation of shear bond strength, mode of failure, and adaptation of fifth-generation (etch-and-rinse), seventh-generation,and eighth-generation self-etch dental adhesives to human dentin with or without diode-laser irradiation before photopolymerization. MATERIALS AND METHODS: Seventy-two extracted human maxillary premolar teeth were collected. The buccal and lingual surfaces of teeth were grounded until dentin was exposed. Test areas of 4 mm diameter were created on both surfaces of teeth to standardize the area of treatment. The samples were then randomly allocated into three groups (n = 24): Group 1 Adper Single Bond 2 Etch-and-Rinse; Group 2 Tetric-N-Bond Universal Self-Etch; Group 3 Prime and Bond Universal Self-Etch dental adhesives were used. Buccal surfaces (sub-groups 'a') of all specimens were irradiated with diode laser before photopolymerization of the adhesive material, and palatal surfaces (sub-groups 'b') were directly photopolymerized without prior diode laser irradiation and restored with composite resin. All specimens were thermocycled. Four specimens from each group were then subjected to scanning electron microscopy (SEM) analysis to examine the adaptation of adhesive to dentin, and the remaining 60 specimens were evaluated for shear bond strength tests, modes of failure at the adhesive-dentin interface, and values were recorded, tabulated, and used for data analysis. A one-way ANOVA test and the Student's t-test were used for statistical analysis. A P value ≤ 0.05 was considered statistically significant. RESULTS: The mean shear bond strength for the groups was: Group 1a (13.96 MPa), 1b (14.95 MPa); Group 2a (10.06 MPa), 2b (10.30 MPa); Group 3a (12.03 MPa), and 3b (10.44 MPa). No statistically significant difference was seen among sub-groups 1a and 3a, 2a and 3a, 2b and 3b as P > 0.05. A significant difference was seen among sub-groups 1b and 3b (P<0.05), 1a and 2a, and 1b and 2b (P<0.01). CONCLUSION: Adper Single Bond 2 without diode-laser irradiation before photopolymerization showed the highest shear bond strength, followed by Adper Single Bond 2 irradiated with diode laser before photopolymerization, with the maximum adaptation of dental adhesive to dentin compared to other adhesives used either with or without diode-laser irradiation.

Comparison of Various Commonly Used Luting Cements on the Success of Composite Inlays Assessed by the Levels of the Microleakage-An In vitro Study.

Introduction: Indirect composite restoration is one of the commonly followed procedures in the posterior teeth. The success of this is dependent on many factors, one being the luting cement. Hence, the current study explores the microleakage of the two luting cements at 2 different times. Materials and Methods: Eighty extracted human teeth were taken, and class II cavities were made that were to receive the composite inlays. They were grouped as supragingival and subgingival, which for further divided as were further subdivided to be observed for marginal leakage at cervical and occlusal margins, at the end of a day and 1 month. Each group had ten specimens. The luting cements that were evaluated were Variolink N and RelyX Unicem. After the composite inlay restoration was done for all the specimens, the sections were put on slides, and a stereomicroscope was used to measure the amount of dye penetration. Leakage was evaluated and compared using Mann-Whitney U test. Results: At the end of 1 day, there was no significant alteration in the microleakage in the occlusal or cervical regions for either region supragingivally or subgingivally between the two luting cements. Significant difference between the two cements at the cervical borders at the end of a month was seen for both the margins. When compared supragingivally and subgingivally at the end of 1 day or at the end of 1 month, there was not a significant difference for any of the cements. Conclusion: Within the constraints of the current investigation, it can be said that there was similar microleakage for both Variolink N and RelyX Unicem at the conclusion of a day's storage time. After a 1-month storage period, RelyX Unicem showed more cervical microleakage than Variolink N.

The Impact of the Gender on the Pulp Vitality Testing for the Various Types of the Conducting Media: An Original Research.

Introduction: To identify gender-based differences in pulpal sensory thresholds in human teeth utilizing various conducting media. Materials and Methods: The study involved 50 participants of both genders equally distributed. The maxillary central incisors were the teeth selected for the intervention. The three conducting media that were put to the test were Colgate Sensitive Pro-Relief Enamel Repair Toothpaste (CS), Himalaya herbals sensitivity toothpaste (HS), and Lignox 2% gel (LG). Subject's sensory threshold readings as well as the Visual analogue scale (VAS) scores were noted at the tiniest sensation they experienced. Following an ANOVA, a post hoc analysis was performed to confirm the significance between the three media. Results: Lox 2% Jelly significantly reduced sensory threshold values compared to the other conducting media (P < 0.001). Comparing the sensory threshold values of the sexes showed that men have greater values. Male and female readings differed significantly in the Lox 2% Jelly group (P = 0.021), whereas Colgate Sensitive Pro-Relief Enamel Repair Toothpaste, Himalaya herbals sensitivity toothpaste (P < 0.001) groups showed highly significant variances. All the three conducting media had a highly significant variance for the VAS scores. (P < 0.001). Conclusion: The conducting material used and gender affect the pulpal sensory thresholds to electric impulses produced by EPT.

Assessment of the Micro-Tensile Strength of the Composites for the Various Antioxidants: An In Vitro Study.

Introduction: The application of the antioxidants after the teeth are bleached has been advocated to fasten the restorative process post-bleaching. The motive of this study was to examine and assess the micro-tensile binding strength of bleached enamel to the resin using a variety of antioxidant solutions. Finding the reason for the tooth fracture was the secondary outcome measured. Materials and Methods: An in vitro study was planned with 100 human extracted teeth, with 20 in each group with one as controls and 4 others tested for the antioxidants sodium ascorbate, epigallocatechin gallate, chitosan, and proanthocyanidin application. The bond strength of bleached enamel to the resin was well as the failure type was assessed after the values were noted and compared using the ANOVA and Tukey's methods keeping P < 0.05 as significant. Results: Epigallocatechin gallate specimens displayed the maximum micro-tensile bond strength under the investigational circumstances, whereas controls displayed the lowest micro-tensile bond strength. There was statistical alteration in micro-tensile bond strengths between all the groups except between epigallocatechin gallate vs chitosan and sodium ascorbate vs proanthocyanidin. High statistical significance was seen between the control and the antioxidant groups as well as between sodium ascorbate and epigallocatechin gallate and chitosan. Conclusion: The antioxidant chemicals significantly augmented the bond strength of bleached enamel to the resin that had been bleached. Also, when compared to the other experimental groups, epigallocatechin gallate and chitosan treatment displayed the greatest mean bond strength values.

Comparison of the Photofunctionalization and Platelet-Rich Plasma in the Immediate Implants.

Introduction: Many adjuvant methods have been researched to enhance the immediate implant success in the recent times. The study's goal was to compare the aesthetic and biological results of immediate dental implants in the aesthetic zone to standard tapered root form implants that had not undergone pre-treatment with platelet-rich plasma or photofunctionalization. Materials and Methods: The study used a randomized controlled trial as its design. Ninety subjects were chosen at random and placed into three groups: a control group, a case group, and a group that needed replacement of their maxillary anterior teeth right away following extraction. The interventional groups received the "Platelet-Rich Plasma (PRP)" or "Photofunctionalization (PF)" group before the implant placement. After the delayed loading approach, the prosthesis was given after 6 months. At the second and fourth weeks, as well as 2, 4, 6, and 12 months (P 0.05), follow-up was conducted. The success and survival rate, aesthetic, and biological outcomes were assessed. One-way ANOVA was used to compare outcomes, and repeated-measures ANOVA was used to assess intragroup variations over baseline and follow-up. Results: The distal, mesial, and mean marginal bone loss as well as the aesthetic scores for pink and white did not differ significantly between groups. The implant stability however was significantly higher in the PF and PRP groups as compared to the controls. A single implant failed in all the three groups. The success percentage was similar for all the groups. Conclusion: The stability of immediate dental implants pre-treated with PRP or PF differed statistically significantly than the subjects in the control group, while other parameters remained the similar between the groups.

Recent investigations into deborylative (thio-/seleno-) cyanation of aryl boronic acids.

In this review, we intend to summarize the most important discoveries in the deborylative (thio-/seleno-) cyanation of aryl boronic acids from 2006 to the end of 2023. Thus, the review is divided into three parts. The first section focuses exclusively on cyanation of aryl boronic acids into aryl nitriles. The second section covers the available literature on the synthesis of aryl thiocyanates through thiocyanation of respective aryl boronic acids. The third will discuss selenocyanation of aryl boronic acids into aryl selenocyanates.

NiOx/PANI nanocomposite doped carbon paste as electrode for long-term stable and highly efficient perovskite solar cells.

Carbon-based perovskite solar cells (PSCs) have emerged as a hopeful alternative in the realm of photovoltaics. They are considered promising due to their affordability, remarkable durability in humid environments, and impressive electrical conductivity. One approach to address the cost issue is to use affordable counter electrodes in PSCs that do not require organic hole transport materials (HTMs). This study utilized an innovative and economical method to create NiOx/PANI nanocomposites. Later, these nanoparticles were integrated into a carbon paste to act as an HTM. This incorporation is intended to optimize charge extraction, improve interfacial contact, align energy levels, reduce energy loss, minimize charge recombination, and protect the perovskite (FAPbI3) surface from degradation. The optoelectronic properties of these devices were investigated, and all cells showed improved efficiency compared to control cells. The NiOx/PANI doped carbon (NiOx/PANI+CE) exhibited excellent performance due to strong hole conductivity, well-aligned energy levels, and the formation of stepwise band alignment at the perovskite interface.

Evaluation of systemic inflammation in seizure phenotypes following meningioma resection.

PURPOSE: To investigate the association between perioperative peripheral blood inflammatory markers and seizures in patients who have undergone meningioma resection. MATERIALS AND METHODS: A single neurosurgery tertiary centre blood bank database was screened to extract pre-operative and post-operative white cell count (WCC), neutrophils, lymphocytes, monocytes, platelets and neutrophil-lymphocyte ratio (NLR) and derived NLR (dNLR). All patients who underwent resection of meningioma from 2012 to 2020 were eligible. Patients were excluded if they had an inflammatory condition, peri-operative infection, medical illness or operative complication. RESULTS: 30 patients suffered pre-operative seizures only, 16 experienced de novo post-operative seizures within 1 year and 42 patients did not experience seizures throughout their treatment timeline. Patients with post-operative de novo seizures had a significantly higher WCC when compared those who never had a seizure (7.1 vs. 4.8x109/L, p =.048, 95 % 1.96 to 5.60). However, this difference of WCC was poorly predictive of de novo seizures at one year (AUC 0.61). dNLR was significantly higher in patients with continued post-operative seizures than in patients in which seizures were terminated with tumour resection (1.2 vs. 0.1, p =.035, 95 % 1.47 to 2.29). dNLR was predictive of seizures at one year with an 87.5 % sensitivity and 82.1 % specificity. CONCLUSIONS: There is a significantly higher post-operative systemic white cell count response in patients who suffered de novo seizures after meningioma resection. Peripheral blood markers have the potential to predict seizures in patients with meningioma.

Predicting the employment of teledentistry in clinical practice by the Saudi dental community using a theoretical model.

Introduction: There are very few scholastic studies applying a theory-driven methodology to analyse the employment of teledentistry in clinical practice by the Saudi dental community. The objective of this research was to predict the employment of teledentistry in clinical practice by the Saudi dental community using the UTAUT (Unified Theory of Acceptance and Use of Technology) model. Methods: A countrywide survey was executed from November 2022 to April 2023 among the dental community (pre-graduate students, graduates, post-graduate students, general dentists, and specialist dentists) involved in clinical practice. The survey employed the UTAUT model, which has four fundamental constructs: performance expectancy (PE), effort expectancy (EE), social influence (SI) and facilitating conditions (FC). These constructs are known to impact the user's behavioural intention (BI). The four fundamental constructs were independent, and BI was the dependent variable. A Likert scale with five scores was used to record each variable. Descriptive statistics were used to describe all the constructs. Cronbach's alpha scores were used to measure the inner consistency of the Likert scale. Simple linear regression and multiple linear regression were used to determine the correlation between all the constructs and the overall model's prediction. The Statistical Package for the Social Sciences was applied for analysis. The study had 80% power and an alpha threshold of .05. Results: The electronic survey was sent to 3000 participants, out of whom 2143 responded (response rate = 71.43%). PE (R2= 26%, p < .01) was the most significant predictor of the Saudi dental community BI to employ teledentistry in clinical practice, followed by SI (R2= 24%, p < .01), EE (R2= 19%, p < .01) and FC (R2= 6%, p < .01). With statistically significant predictive power, the UTAUT model explained 32% of the variance in the BI (R2= 0.32, p < .01). Conclusions: Each UTAUT construct and the entire model were significantly correlated with the employment of teledentistry in clinical practice by the Saudi dental community. PE had the most salient correlation, followed by SI, EE and FC. The participants have perceived the benefits of teledentistry, increasing the future likelihood of its utilisation. The Saudi government could consider the UTAUT constructs to promote teledentistry in tandem with Vision 2030.

Electrochemical DNA-nano biosensor for the detection of Goserelin as anticancer drug using modified pencil graphite electrode.

Goserelin is an effective anticancer drug, but naturally causes several side effects. Hence the determination of this drug in biological samples, plays a key role in evaluating its effects and side effects. The current studies have concentrated on monitoring Goserelin using an easy and quick DNA biosensor for the first time. In this study, copper(II) oxide nanoparticles were created upon the surface of multiwalled carbon nanotubes (CuO/MWCNTs) as a conducting mediator. The modified pencil graphite electrode (ds-DNA/PA/CuO/MWCNTs/PGE) has been modified with the help of polyaniline (PA), ds-DNA, and CuO/MWCNTs nanocomposite. Additionally, the issue with the bio-electroanalytical guanine oxidation signal in relation to ds-DNA at the surface of PA/CuO/MWCNTs/PGE has been examined to determination Goserelin for the first time. It also, established a strong conductive condition to determination Goserelin in nanomolar concentration. Thus, Goserelin's determining, however, has a 0.21 nM detection limit and a 1.0 nM-110.0 µM linear dynamic range according to differential pulse voltammograms (DPV) of ds-DNA/PA/CuO/MWCNTs/PGE. Furthermore, the molecular docking investigation highlighted that Goserelin is able to bind ds-DNA preferentially and supported the findings of the experiments. The determining of Goserelin in real samples has been effectively accomplished in the last phase using ds-DNA/PA/CuO/MWCNTs/PGE.

Urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI) and plasmin as novel biomarkers in early diagnosis of lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, with multi systematic affection. Lupus nephritis (LN) is the most frequent cause of renal damage in SLE patients with variable presentations that may progress to end stage renal failure. Coagulation disorders are frequently reported in SLE and LN with higher mortality rates. Renal biopsy is an invasive process, and the existing indicators for LN diagnosis and activity are unreliable. New urinary biomarkers with significant validity, safety, and accuracy are the current focus of most studies. Our study sought to assess the value of urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI), and plasmin as biomarkers for the early identification and detection of LN and its activity. This was a cross-sectional study, included 100 subjects (80 SLE patients, and 20 healthy controls), they were recruited from the Internal Medicine department, Rheumatology and Nephrology units and outpatient's clinics at Assiut University hospital between the period of 2020 and 2022. All patients underwent full history taking, clinical evaluation, and activity scoring calculation and laboratory investigations. The results showed that the best diagnostic accuracy of LN was observed with TFPI (90% accuracy, sensitivity 80% and specificity 95% with p <0.001 at cutoff point of >193.2 ng/ml), followed by uTF (75.4% overall accuracy at cut off point of >12.6 ng/ml, sensitivity 90% and specificity 68% with p < 0.001) and plasmin (70.3% accuracy at cut off point of >30.5 ng/ml, sensitivity 55% and specificity 78% with p < 0.001). Urinary TFPI was the best predictor of LN occurrence with odd ratio of 4.34, (p < 0.001). In conclusion urinary TFPI could be used as a diagnostic marker for LN with high accuracy and an early predictor of LN.

N-oleoyl alanine attenuates nicotine reward and spontaneous nicotine withdrawal in mice.

BACKGROUND: As nicotine dependence represents a longstanding major public health issue, new nicotine cessation pharmacotherapies are needed. Administration of N-oleoyl glycine (OlGly), an endogenous lipid signaling molecule, prevents nicotine-induced conditioned place preference (CPP) through a peroxisome proliferator-activated receptor-alpha (PPARα) dependent mechanism, and also ameliorated withdrawal signs in nicotine-dependent mice. Pharmacological evidence suggests that the methylated analog of OlGly, N-oleoyl alanine (OlAla), has an increased duration of action and may offer translational benefit. Accordingly, OlAla was assessed in nicotine CPP and dependence assays as well as its pharmacokinetics compared to OlGly. METHODS: ICR female and male mice were tested in nicotine-induced CPP with and without the PPARα antagonist GW6471. OlAla was also assessed in nicotine-dependent mice following removal of nicotine minipumps: somatic withdrawal signs, thermal hyper-nociception and altered affective behavior (i.e., light/dark box). Finally, plasma and brain were collected after administration of OlGly or OlAla and analyzed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: OlAla prevented nicotine-induced CPP, but this effect was not blocked by GW6471. OlAla attenuated somatic and affective nicotine withdrawal signs, but not thermal hyper-nociception in nicotine-dependent mice undergoing withdrawal. OlAla and OlGly showed similar time-courses in plasma and brain. CONCLUSIONS: The observation that both molecules showed similar pharmacokinetics argues against the notion that OlAla offers increased metabolic stability. Moreover, while these structurally similar lipids show efficacy in mouse models of reward and dependence, they reduce nicotine reward through distinct mechanisms.

Early Detection of Renal Complication in Children With Sickle Cell Disease: A Single Center Prospective Study.

INTRODUCTION: This observational cross-sectional study aimed to identify predictors of renal complications in pediatric patients with sickle cell disease (SCD) at King Salman Armed Forces Hospital, Tabuk, Saudi Arabia, over six months from February 2023 to July 2023. The study evaluated microalbuminuria as an early indicator of renal injury and explored its correlations with clinical and laboratory parameters and abdominal ultrasound (US) findings. METHODS: Included were pediatric patients aged 1 to 14 years with confirmed SCD, excluding those with acute infections or pre-existing renal diseases. Data from 100 patients' electronic medical records were analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States), with a significance set at p ≤ 0.05. RESULTS: The mean age was 7.6 ± 3.3 years, with 51 males and 49 females; 11 were diagnosed with Hb-S-beta thalassemia. Hydroxyurea (HU) compliance was high, with only four non-compliant patients, though all took folic acid. Among 42 tested for albuminuria, all had negative results (<30 mg/g creatinine). A significant association was found between SCD diagnosis and kidney, ureter, and bladder (KUB) US results (p=0.008), with abnormal KUB findings more prevalent in the Hb-S-beta thalassemia group. Patients with abnormal KUB results had significantly lower mean weight (p=0.024). Additionally, Hb-S-beta thalassemia patients had lower mean weight than hemoglobin SS (HGSS) patients (p=0.04). Though not statistically significant, Hb-S-beta thalassemia patients had higher mean systolic blood pressure (p=0.053). CONCLUSION: Significant associations were identified between SCD diagnosis type and renal US results, with lower body weight emerging as a potential predictor of renal complications. High HU compliance and its impact on renal outcomes warrant further investigation. Routine monitoring of microalbuminuria and KUB US may aid early detection of renal complications in pediatric SCD patients. Further studies with larger sample sizes are recommended to validate these findings and develop comprehensive renal protective strategies.

The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/ß-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.

Bariatric surgery discovering unexpected silent gastric cancer: a case report.

This research paper discusses a case in which stomach cancer was incidentally discovered during a bariatric surgery procedure. Bariatric surgery is well-known for its significant effects on weight loss and overall health enhancement, and its prevalence has been rising globally. While its primary aim is weight reduction, it also offers the chance for surgeons to detect and manage other medical conditions. In this specific case, a patient scheduled for bariatric surgery was incidentally discovered with stomach cancer, underscoring the significance of comprehensive operative assessments and vigilant monitoring during surgery.