A systematic review of novel cannabinoids and their targets: Insights into the significance of structure in activity.

To provide a comprehensive framework of the current information on the potency and efficacy of interaction between phyto- and synthetic cannabinoids and their respective receptors, an electronic search of the PubMed, Scopus, and EMBASE literature was performed. Experimental studies included reports of mechanistic data providing affinity, efficacy, and half-maximal effective concentration (EC50). Among the 108 included studies, 174 structures, and 16 targets were extracted. The most frequent ligands belonged to the miscellaneous category with 40.2% followed by phytocannabinoid-similar, indole-similar, and pyrrole-similar structures with an abundance of 17.8%, 16.6%, and 12% respectively. 64.8% of structures acted as agonists, 17.1 % appeared as inverse agonists, 10.8% as antagonists, and 7.2% of structures were reported with antagonist/inverse agonist properties. Our outcomes identify the affinity, EC50, and efficacy of the interactions between cannabinoids and their corresponding receptors and the subsequent response, evaluated in the available evidence. Considering structures' significance and very important effects of on the activities, the obtained results also provide clues to drug repurposing.

Primary extraperitoneal hydatid cyst, a rare differential diagnosis of subdiaphragmatic mass: A case report.

Key Clinical Message: Hydatid cyst is a sly disease that can manifest with a spectrum of symptoms in almost every part of the human body, so it is crucial to be familiar with different scenarios that a patient may present. Abstract: The echinococcus granulosus parasite causes hydatid disease and is common in areas with animal husbandry and agriculture. Here, we report a middle age woman who presented with abdominal pain that further investigation revealed a cyst in subdiaphragmatic area.

Effectiveness of autologous fibrin glue in preventing post-thoracotomy air leaks: a randomized controlled trial.

Introduction: Post-thoracotomy air leaks remain a significant challenge in thoracic surgery. Aim: This randomized controlled trial assessed the efficacy of autologous fibrin glue in reducing air leaks following thoracotomy procedures. Material and methods: Conducted as a single-center, single-blind, randomized clinical trial, the study enrolled adult patients undergoing lung resection or decortication at a thoracic surgery clinic. Participants were randomly assigned to either the intervention group, receiving autologous fibrin glue application during surgery, or the control group, undergoing standard surgical procedures without glue application. Key inclusion criteria were adult patients undergoing elective thoracotomy for lung resection or decortication, while exclusion criteria included patients with severe comorbidities or contraindications to fibrin glue. Results: A total of 40 patients were enrolled and randomized equally to the two groups. The group treated with autologous fibrin glue demonstrated a significant reduction in the duration of air leakage and chest tube drainage, along with a shorter hospital stay, compared to the control group. There were no statistically significant differences in postoperative complications between the groups. Conclusions: The application of autologous fibrin glue during thoracotomy procedures significantly reduces postoperative air leaks and hospitalization duration without increasing complication rates. This finding suggests a beneficial role of fibrin glue in thoracic procedures requiring lung resection or decortication.

Radiographic Investigation of Lumbar Vertebrae in Patients with Flexion and Extension Movement Disorder Syndrome.

Objectives: The kinesiopathology model is a new rehabilitation model classifying, evaluating, and treating patients with non-specific back pain. Sahrmann proposed this model based on movement disorder syndromes. The present cross-sectional study aimed to evaluate the radiograph of the linear and angular displacement of the lumbar spine in patients with lumbar flexion impairment syndrome (LFIS) and lumbar extension impairment syndrome (LEIS). Methods: In this study, 50 adults aged 18-46 years were enrolled, including 25 patients with LFIS and 25 with LEIS. The eligible participants were referred to the radiology department for radiography in the common position of neutral, full extension, and full flexion position while standing. The White and Panjabi's method was used to measure the linear and angular displacements. Moreover, pain intensity was assessed using the visual analogue scale, and functional disability was investigated using a modified Oswestry Disability Questionnaire. Results: The parameter of the linear displacement at the L3-L4 level was significantly different between the two groups (P=0.02). The mean duration of low back pain was longer in the LEIS, compared to the LFIS group (P=0.01). Conclusion: In patients with LEIS, compensatory responses occur that cause less linear displacement at the L3-L4 level, compared to the patients with LFIS. Therefore, it is important to design appropriate exercises to better control the linear displacement at the L3-L4 level during the full range of motion in patients with LFIS.

Optimal delivery of RNA interference by viral vectors for cancer therapy.

In recent years, there has been a surge in the innovative modification and application of the viral vector-based gene therapy field. Significant and consistent improvements in the engineering, delivery, and safety of viral vectors have set the stage for their application as RNA interference (RNAi) delivery tools. Viral vector-based delivery of RNAi has made remarkable breakthroughs in the treatment of several debilitating diseases and disorders (e.g., neurological diseases); however, their novelty has yet to be fully applied and utilized for the treatment of cancer. This review highlights the most promising and emerging viral vector delivery tools for RNAi therapeutics while discussing the variables limiting their success and suitability for cancer therapy. Specifically, we outline different integrating and non-integrating viral platforms used for gene delivery, currently employed RNAi targets for anti-cancer effect, and various strategies used to optimize the safety and efficacy of these RNAi therapeutics. Most importantly, we provide great insight into what challenges exist in their application as cancer therapeutics and how these challenges can be effectively navigated to advance the field.

Tension pneumothorax caused by the ruptured hydatid cyst of the lung.

Hydatid cyst disease puts a significant burden on the health of humans every year. The lung is the second most common organ of implantation of Echinococcus larvae. Due to the importance of early diagnosis of tension pneumothorax, this paper provides four cases of hydatid disease that presented with tension pneumothorax.

Tracheal hemangioma: a case report and literature review.

Hemangiomas are the most common vascular tumors in children. Although hemangiomas are common, they are rarely seen in areas like the trachea and larynx.The most common clinical manifestations in tracheal hemangiomas are stridor and respiratory distress. The main diagnostic method is bronchoscopy. Other imaging techniques like computed tomography scans and MRIs are also helpful. Various treatment options are now used for treating the disease, including beta blockers like propranolol, local and systemic steroids, and surgical resection. Case presentation: An 8-year-old boy with the chief complaint of severe progressive dyspnea and a history of neonatal postbreastfeeding cyanosis was admitted. On physical examination, he had tachypnea, and stridor was heard upon auscultation. There was no history of fever, chest pain, or coughing. He underwent a rigid bronchoscopy followed by a neck computed tomography scan. The results indicated a soft tissue mass with a vascular nature. An MRI of the neck confirmed the diagnosis of tracheal hemangioma. The mass was not resectable during surgery; hence, angioembolization was carried out. Treatment was successful and there was no recurrence on the follow-up. Clinical discussion: Based on the findings in this literature review tracheal hemangiomas present with stridor, progressive respiratory distress, dyspnea, hemoptysis, and chronic coughs. Advanced tracheal hemangiomas commonly do not reduce in size by themselves and need treatment. A close follow-up ranging from 3 months to 1 year is recommended. Conclusion: Although tracheal hemangiomas are rare they should be considered in the differential diagnosis of severe dyspnea and stridor.

Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies.

The large coding potential of vaccinia virus (VV) vectors is a defining feature. However, limited regulatory switches are available to control viral replication as well as timing and dosing of transgene expression in order to facilitate safe and efficacious payload delivery. Herein, we adapt drug-controlled gene switches to enable control of virally encoded transgene expression, including systems controlled by the FDA-approved rapamycin and doxycycline. Using ribosome profiling to characterize viral promoter strength, we rationally design fusions of the operator element of different drug-inducible systems with VV promoters to produce synthetic promoters yielding robust inducible expression with undetectable baseline levels. We also generate chimeric synthetic promoters facilitating additional regulatory layers for VV-encoded synthetic transgene networks. The switches are applied to enable inducible expression of fusogenic proteins, dose-controlled delivery of toxic cytokines, and chemical regulation of VV replication. This toolbox enables the precise modulation of transgene circuitry in VV-vectored oncolytic virus design.

An accessory mediastinal thyroid: A case report.

Various differential diagnoses and etiologies exist for mediastinal masses. One of the most uncommon is the ectopic mediastinal goiter. It is crucial for a clinician, especially cardiothoracic surgeons, to think about it when encountering such masses.

Hydatid cyst of the middle mediastinum complicated by fistulated ascending aorta: A case report and review of the literature.

Clinicians must pay attention to the clinical presentation and consequences of hydatid cysts in rare sites. Cysts close to the aorta require planning and assistance of a cardiac or vascular surgeon before surgical intervention can be considered.

Fatty acid transport protein inhibition sensitizes breast and ovarian cancers to oncolytic virus therapy via lipid modulation of the tumor microenvironment.

Introduction: Adipocytes in the tumour microenvironment are highly dynamic cells that have an established role in tumour progression, but their impact on anti-cancer therapy resistance is becoming increasingly difficult to overlook. Methods: We investigated the role of adipose tissue and adipocytes in response to oncolytic virus (OV) therapy in adipose-rich tumours such as breast and ovarian neoplasms. Results: We show that secreted products in adipocyte-conditioned medium significantly impairs productive virus infection and OV-driven cell death. This effect was not due to the direct neutralization of virions or inhibition of OV entry into host cells. Instead, further investigation of adipocyte secreted factors demonstrated that adipocyte-mediated OV resistance is primarily a lipid-driven phenomenon. When lipid moieties are depleted from the adipocyte-conditioned medium, cancer cells are re-sensitized to OV-mediated destruction. We further demonstrated that blocking fatty acid uptake by cancer cells, in a combinatorial strategy with virotherapy, has clinical translational potential to overcome adipocyte-mediated OV resistance. Discussion: Our findings indicate that while adipocyte secreted factors can impede OV infection, the impairment of OV treatment efficacy can be overcome by modulating lipid flux in the tumour milieu.

Identifying, classifying and prioritizing factors affecting human errors in the mine design process: A mixed methods research.

BACKGROUND: Mines are often home to many dangers with a high rate of accidents and occupational diseases. One of the most effective ways to prevent these adverse incidents is to identify and control the influential factors causing human error in design and the ensuing negative consequences. OBJECTIVE: This study aimed to explore, categorize and prioritize factors affecting human errors in the mine design process. METHODS: The study has a mixed-method design combining qualitative and quantitative data. In the qualitative phase, the required data were collected by conducting semi-structured interviews with 12 surface mine designers. The causes of errors were extracted and categorized by the latent content analysis using MAXQDA2022 software. The identified causes in the qualitative phase were sent to expert designers in Q tables, and the data were analyzed by factor analysis. RESULTS: Of the identified codes in the qualitative phase, 40 main themes in five different categories (individual, organizational, external, task, and environmental factors) were determined as causes. The results of the quantitative phase suggest the existence of four different mental patterns regarding the causes of design errors (DEs). The data analysis also shows that organizational and personal factors, particularly supervision and inspection, experience, and technical knowledge, were the strongest causes of DEs and environmental (hotness, coldness, indoor air quality, and noise) and external (work-family conflict) factors being the weakest ones. CONCLUSION: This study not only identifies and categorizes the causes of design errors in the mining industry but also suggests some control strategies for these errors based on the mental patterns of the experts.

Reactive Blue 19 dye removal by UV-LED/chlorine advanced oxidation process.

In recent years, advanced oxidation processes (AOPs) have indicated the greatest potential in the removal of stable organic compounds, including dyes. In this study, the ultraviolet light-emitting diodes (UV-LEDs) combined with chlorine was evaluated to remove Reactive Blue 19 (RB19) dye from aqueous solution. The effect of key experimental parameters including pH, initial chlorine concentration, initial dye concentration, and reaction time on the performance of UV-LED irradiation, UV-LED/chlorine, and the chlorination method for the removal of RB19 was studied in this research. Results showed that, more than 99% of RB19 was removed after 30 min of reaction time under optimized conditions (pH = 5, [chlorine] = 300 µM, and [RB19] = 20 mg L-1) with apparent kinetic rate constant (kapp) of 17.1 × 10-2 min-1 in UV-LED/chlorine process. However, for the chlorination method, removal efficiency was 64.7% (kapp = 3.41 × 10-2 min-1) with an apparent kinetic rate constant of 0.0341 min-1. Results also showed that UV-LED irradiation is not effective at all in removing RB19. The scavenging assay showed that OH• radicals (67.23%) had the highest contribution in RB19 removal in UV-LED/chlorine process while Cl• (17.82%) and [Formula: see text] (8.56%) had a minor role in the degradation of the dye. The RB19 degradation kinetics analysis revealed that the processes of UV-LED/chlorine and chlorination degradation followed the pseudo-first-order kinetic model. In this study, the impact of chloride, nitrate, bicarbonate, carbonate, sulfate, and sulfite anions on the performance of the process was investigated. It indicated that sulfite anion has the most negative impact on the RB19 removal process. By evaluating the synergistic effect between UV-LED lamp and chlorine, a synergy index of 5.0 was obtained for the UV-LED/chlorine process. The results presented that the UV-LED/chlorine process has a better performance than each of them alone and has the necessary efficiency for RB19 removal. Measuring COD reported its removal efficiency of 98% during the UV-LED/chlorine process under optimized conditions. Experiments continued with textile factory wastewater and indicated 30.9% of its COD removed after treatment when 1.0 µM chlorine was used.

Primary retroperitoneal hydatid cyst, a rare novel differential diagnosis of retroperitoneal masses: A case report.

The presence of primary retroperitoneal hydatid cysts is rare, even in endemic areas. The authors report a young man with a retroperitoneal hydatid cyst who underwent total cystectomy. The surgeons should suspect hydatid cysts in case of any abdominal cysts, especially in endemic areas, and avoid any spillage and puncture.

Branched-chain amino acids regulate intracellular protein turnover in porcine mammary epithelial cells.

Dietary supplementation with branched-chain amino acids (BCAAs) to lactating sows has been reported to enhance their milk production, but the underlying mechanisms remain largely unknown. This study was conducted with porcine mammary epithelial cells (PMECs) to test the hypothesis that individual BCAAs or their mixture stimulates protein synthesis and inhibit proteolysis in PMECs. Cells were cultured at 37 °C in customized Dulbecco's modified Eagle medium containing 5 mmol/L D-glucose, 1 mmol/L L-phenylalanine, L-[ring-2,4-3H]phenylalanine, 0.1 (control), 0.25, 0.5, 1, or 2 mmol/L L-leucine, L-isoleucine or L-valine or an equimolar mixture of the three BCAAs. The culture medium also contained physiological concentrations of other amino acids found in the plasma of lactating sows. Proliferation, protein synthesis, proteolysis, ß-casein production, the mechanistic target of rapamycin (mTOR) signaling, and the ubiquitin-proteasome pathway were determined for PMECs. Cell proliferation and abundances of phosphorylated mTOR, eukaryotic translation initiation factor 4E-binding protein 1, and ribosomal protein S6 kinase ß-1 proteins increased (P < 0.05), but abundances of ubiquitinated protein and 20S proteasome decreased (P < 0.05) when extracellular concentrations of L-leucine, L-isoleucine, L-valine, or an equimolar mixture of BCAAs were increased from 0.1 to 2 mmol/L. Compared with the control, 0.25, 0.5, 1 or 2 mmol/L BCAAs enhanced (P < 0.01) protein (including ß-casein) synthesis, while decreasing (P < 0.05) proteolysis in PMECs in a dose-dependent manner. Collectively, our results indicate that physiological concentrations of BCAAs regulate protein turnover in mammary epithelial cells to favor net protein synthesis through stimulating the mTOR signaling pathway and inhibiting the ubiquitin-proteasome pathway.

Exposure keratopathy and its associated risk factors in patients undergoing general anesthesia in nonocular surgeries.

INTRODUCTION: The most common eye injury during and after general anesthesia is corneal abrasion which can occur at any time after anesthesia and even up to 24 h after it. The aim of this study was to investigate the incidence and factors associated with corneal injury in patients undergoing nonocular surgery. METHODS: This was a descriptive cross-sectional study. A total of 170 patients, who were admitted to the operating room and met the inclusion criteria, were selected through simple nonprobability sampling. Data collection forms were used in order to assess the incidence of corneal injury and its related risk factors. The National Eye Institute scale with fluorescein paper and cobalt blue light by slit lamp were utilized to examine exposure keratopathy. RESULTS: Overall, the results showed that the incidence of keratopathy immediately after eye care removal was found to be 64.7% in the operating room, 65.9% in the recovery room, and 41.2% in 24 h after the surgery. Smokers' patients and drug abusers under general anesthesia underwent endotracheal intubation, received more opioids preoperatively, and had more perioperative bleeding and fluid intake. Moreover, in patients who had received more oxygen flow in the recovery room; the rate of keratopathy was higher. CONCLUSION: Smoking, drug usage, and receiving endotracheal intubation are the risk factors of keratopathy. Therefore, for high-risk patients and procedures, it is indispensable to both obtain preoperative information and take intraoperative precautions in order to prevent eye injuries. Future studies are needed to demonstrate these finding.

Dietary supplementation with branched-chain amino acids enhances milk production by lactating sows and the growth of suckling piglets.

BACKGROUND: Under current dietary regimens, milk production by lactating sows is insufficient to sustain the maximal growth of their piglets. As precursors of glutamate and glutamine as well as substrates and activators of protein synthesis, branched-chain amino acids (BCAAs) have great potential for enhancing milk production by sows. METHODS: Thirty multiparous sows were assigned randomly into one of three groups: control (a corn- and soybean meal-based diet), the basal diet + 1.535% BCAAs; and the basal diet + 3.07% BCAAs. The ratio (g/g) among the supplemental L-isoleucine, L-leucine and L-valine was 1.00:2.56:1.23. Diets were made isonitrogenous by the addition of appropriate amounts of L-alanine. Lactating sows had free access to drinking water and their respective diets. The number of live-born piglets was standardized to 9 per sow at d 0 of lactation (the day of parturition). On d 3, 15 and 29 of lactation, body weights and milk consumption of piglets were measured, and blood samples were obtained from sows and piglets 2 h and 1 h after feeding and nursing, respectively. RESULTS: Feed intake did not differ among the three groups of sows. Concentrations of asparagine, glutamate, glutamine, citrulline, arginine, proline,  BCAAs, and many other amino acids  were greater (P < 0.05) in the plasma of BCAA-supplemented sows and their piglets than those in the control group. Compared with the control, dietary supplementation with 1.535% and 3.07% BCAAs increased (P < 0.05) concentrations of free and protein-bound BCAAs, glutamate plus glutamine, aspartate plus asparagine, and many other amino acids in milk; milk production by 14% and 21%, respectively; daily weight gains of piglets by 19% and 28%, respectively, while reducing preweaning mortality rates by 50% and 70%, respectively. CONCLUSION: Dietary supplementation with up to 3.07% BCAAs enhanced milk production by lactating sows, and the growth and survival of their piglets.