Related Side Research Articles

HPV Infection Causes Dependence on Alternative DNA Damage Response Pathways Providing Cancer Specific Targets for Radiosensitization

Cancer-specific radiosensitization is an attractive approach to improving the efficacy of radiotherapy. However, drugs targeting ubiquitous DNA damage response pathways are not cancer specific and can increase radiation related side effects. Thus, there is an unmet need for tumor specific molecular targets. This approach requires an identification of DNA damage signaling pathways that are unique to cancer cells. We hypothesized that by expressing its genome in the host cells HPV infection can rewire DNA damage signaling making HPV-positive tumor cells dependent on alternative pathways to survive radiation, which can be exploited for radiosensitization of HPV-induced cancers. We have performed a CRISPR/Cas9 screen in HPV-positive SiHa cells that either express HPV16 proteins E6 and E7 or contain a selective knock-out of E6 or E7. We used next-generation sequencing to determine the abundance of gRNA in cells that were mock-treated or irradiated. We identified genes that were required for survival of radiation specifically in the context of E6 or E7 expression. Results of the screen were validated by generating knock-outs of the discovered genes using CRISPR/Cas9. By applying an array of molecular tools to analyze cell survival, cell cycle progression and mitotic progression we assessed the role of these genes in radiation response in HPV-positive cancer cells. We have identified genes that are required for survival of radiation-induced DNA damage in the context of either E6 or E7 expression. We demonstrate that targeting these genes results in hypersensitization of cervical cancer cells to radiation specifically in the presence of E6 or E7. We show that the gene product required for survival in E6-expressing cells is critical for mitotic progression after radiation exposure serving as a member of a protein complex stabilizing the attachment of mitotic spindle to centromeres. We have uncovered specific genes that are critical for DNA damage response and cell survival after radiation exposure in HPV-positive cells. Our findings suggest that expression of the HPV proteins E6 and E7 rewires DNA damage signaling causing dependence on alternative response pathways. We propose that these pathways can be targeted for a tumor-specific radiosensitization of HPV-induced cancers.

Efficacy of Intravenous Ibuprofen and Paracetamol on Postoperative Pain and Tramadol Consumption After Arthroscopic Shoulder Surgery: A Prospective, Randomized, Double-blind Clinical Trial.

Efficient pain management following arthroscopic shoulder surgery plays a crucial role in decreasing pain intensity, tramadol consumption, and related side effects. This study primarily aimed to examine the analgesic impact of intravenous (IV) ibuprofen and paracetamol on postoperative pain intensity. In addition, as secondary objectives, the study assesses tramadol consumption, determine the global satisfaction score (GSS), analyze hemodynamic parameters, and investigate tramadol-related side effects. In this study, we enrolled sixty-four patients who were scheduled to undergo arthroscopic shoulder surgery and met the inclusion criteria of having American Society of Anesthesiologists scores between 1 and 3 and falling within the age range of 18 to 85 years. All participants were managed using IV patient-controlled analgesia. These patients were then randomly assigned in a double-blind manner to two groups: one receiving paracetamol (n=32), and the other receiving ibuprofen (n=32). Demographic information, visual analog scale (VAS) and GSS data, hemodynamics, tramadol consumption, and tramadol-related side effects were recorded. There were no significant differences between the two groups regarding demographics, hemodynamics, GSS scores, and tramadol side effects (respiratory depression, pruritus, urinary retention, and nausea and vomiting). VAS scores of the two groups were similar at postoperative 1st, 6th, and 12th hours. However, group ibuprofen significantly reduced the VAS scores at the postoperative 24th hour (p=0.039). On the other hand, the two groups showed no significant differences in GSS scores. Compared with total tramadol consumption during the postoperative 24-hour period, ibuprofen significantly reduced tramadol consumption (p=0.003). The findings of this study indicate a significant reduction in both pain intensity and tramadol consumption when IV ibuprofen was administered 24 hours following arthroscopic shoulder surgery, in comparison with the use of IV paracetamol.

Constructing amphipathic molecular layer to assists de-solvation process for dendrite-free Zn anode

Due to the excellent safety feature, substantial theoretical capacity and abundant zinc reserves in the earth's crust, Aqueous Zn-ion batteries (AZIBs) are promising as the next generation energy storage system. However, the problem of dendrite growth and the related side reactions in Zn surface limit their further development and application. Herein, an amphipathic molecular layer (Polyacrylic Acid, named as PAA) is constructed on Zn surface to hinder the side reactions and zinc dendrites by intervening the de-solvation process. It is found that the rich hydroxyl group in polyacrylic acid is very hydrophilic. On the contrary, hydrocarbon group on the other side is nearly hydrophobic. The amphiphilic PAA molecular layer on Zn surface results in lower de-solvation energy barrier, thus inhibits the decomposition of water and related side reactions. Additionally, the accumulate abundant negative charge at the interface of polyacrylic acid and Zn surface can attract homogeneous deposition of Zn atoms. Using only 0.01 M PAA as additive in 2.0 M ZnSO4 electrolyte. Zn||Zn symmetric cells expresses a superior cycling stability of 4643 h (5 mA cm−2, 1 mAh cm−2). This study provides new insights into the long-life AZIBs modulated by amphipathic molecular layer.

Medicinal Plant-rich Diet: A Potential Therapeutic Role in Colorectal Cancer.

Colorectal cancer is estimated to become the leading cause of cancer death worldwide. Since most of the available therapies affect vital organs such as heart and liver, herbal remedies as a substitute therapy have been reported in several evidence-based studies. Medicinal plants exhibit a diverse range of bioactive elements known for their medicinal properties, such as anti-inflammatory, anticancer, antioxidant, and antimicrobial effects. Phytochemicals present in medicinal plants significantly trigger different signaling pathways, contributing to their therapeutic activities. This review covers a comprehensive summary of the therapeutic potential of an herbal diet in treating colorectal cancer and other ailments. Special attention will be given to exploring the interactions of medicinal plants with the microbiota and their associations with cancer pathways. A medicinal plant rich in bioactive compounds is a therapeutic option for colorectal cancer and potent cardioprotective and hepatoprotective agents. These bioactive compounds have demonstrated the ability to impede the growth of cancerous cells and trigger apoptosis. Our findings suggest that pomegranate, garlic, soybean, olive, green tea, papaya, and grapes are potential medicinal plants for combating cancer and related side effects. Bioactive compounds can modulate the gut microbiota's metabolism, and short-chain fatty acid production shows cardioprotective effects and reduces the risk of colorectal cancer. Hence, it can be stated that the interaction between a medicinal plant-rich diet and the gut microbiota plays a crucial role in preventing colorectal cancer and cardiac arrest.

“Diplomacy of Heads of State”: Chinese Media about Xi Jinping’s Visit to Russia in March 2023

The visit of the President of the People’s Republic of China to the Russian Federation attracted a lot of attention from the Chinese media, which was manifested in a large number of publications on this topic in the media and social networks. The purpose of the study was to analyze news reports and messages on the Weibo social network about the state visit of the President of the People’s Republic of China to the Russian Federation and determine its role in strengthening bilateral relations between China and Russia. For the first time, the main principles of China’s foreign diplomacy, implemented in a particular state visit, were considered by the example of how they were perceived by public opinion. A content analysis of news reports from mainstream Chinese media showed that this diplomatic move is highly appreciated. The authors of the publications noted the high significance and effectiveness of this visit. A statistical analysis of publications on the Weibo social network showed that public opinion also generally assesses Xi Jinping’s visit to Russia positively, paying attention to the content side of Russian-Chinese relations. In general, strengthening and deepening the comprehensive strategic partnership between China and Russia in the new era is a strategic choice made by countries based on the domestic political and domestic economic situation, which is in line with the fundamental interests of the peoples of the two countries and the development trend of international relations. The results of the study showed that China has always pursued an independent foreign policy, and promoting the development of Russian-Chinese relations at a high level is a strategic choice made by China, taking into account its internal development and overall diplomatic strategy.

P11.01.A BASELINE TOTAL BRAIN VOLUME PREDICTS FOR POORER QUALITY OF LIFE AND REDUCED OVERALL SURVIVAL AFTER CRANIAL RADIOTHERAPY IN OLDER PATIENTS WITH GLIOBLASTOMA (GBM): RESULTS FROM THE PROSPECTIVE BRITER STUDY

Abstract BACKGROUND GBM incidence peaks in the 7th and 8th decades, with median life expectancy of 3-6 months. Treatment decisions finely balance benefit to side-effects and worsening quality of life (QoL). Short-course partial brain radiotherapy, +/- chemotherapy, extends survival compared to supportive care but there is no validated evidence for prediction of individual risk of acute radiotherapy related side effects. We aimed to consider putative MRI markers of brain resilience and their relationship to change in QoL amongst older patients being treated for GBM with cranial radiotherapy. MATERIAL AND METHODS BRITER, a prospective multicentre observational trial, recruited patients with newly diagnosed GBM aged ≥ 65 planned for cranial radiotherapy. Baseline MRI scans were analysed for: relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)), contralateral medial temporal lobe volume, number and volume of T1 white matter hypointensities, and Fazekas' scale of white matter change. Radiotherapy treatment volumes were obtained from planning software. RESULTS 126 patients were enrolled from 12 UK centres; mean age 72 years (range 65-83); 67% men, 33% women. 4% had a radiological diagnosis, 19% biopsy and 77% had debulking surgery. 21% received palliative radiotherapy alone (25% 30Gy/6#, 75% 40Gy/15#), 79% received radiotherapy with concurrent TMZ (47% 40Gy/15#, 53% 60Gy/30#). Median OS was 11.3 months. 56 participants completed all MRI sequences and QoL data points. After accounting for age, sex, treatment and baseline MoCA score, there was a significant relationship between baseline CSF:TIV ratio and change in QoL score. For each unit point of increase in CSF:TIV ratio, there was a corresponding decrease in EORTC QLC C30 QoL score by a factor of 1.27 (coefficient -1.27, 95% CI -3.24 to -0.19 p=0.02). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV ratio was related to risk of non-attendance (OR 1.35, 95% CI 1.01-1.80, p=0.04). Cox regression models were fitted for time to death in 88 participants who had analysable baseline MRI sequences. Baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19-1.66, p<0.001). CONCLUSION This unique prospective study indicates that baseline imaging parameters can predict the impact of cranial radiotherapy on QoL and OS. Due to frailty, there was a significant attrition rate in data return. 29% of participants were too unwell by 8 weeks post treatment to attend hospital, also predicted by baseline imaging. These results promote and enable discussion of individualised treatment options with older patients with GBM, differentiating those who are likely to suffer reduced QoL and short survival rather than benefit from radiotherapy

Judicial protection of workers' labor rights: problems of implementation

The object of the study was the legal relations arising between the subjects of labor law regarding the protection of the labor rights of employees. The subject of the study includes theoretical and practical foundations of judicial protection of workers' labor rights. The author analyzes the judicial method of protecting the labor rights of employees, and also identifies problematic aspects of their practical application. In particular, the author noted that the employee, being the most vulnerable party of labor relations, needs more protection from the state. As a result, the current system of restoring balance in labor relations is mostly focused on protecting the labor rights of employees. The main conclusions of the study are: 1. Judicial practice on the protection of workers' labor rights is very extensive and diverse, but its essence basically boils down to one thing: an employer, being interested in obtaining the best labor resources at minimal financial costs, will always strive to protect the interests of his business, regardless of the requirements of the legislator. 2. The effectiveness of all methods of protecting labor rights often largely depends on the reasonable behavior of the employee until the moment of conflict with the employer. 3. Being a more vulnerable side of labor relations, an employee, when applying to the court, claims a special attitude due to the possible lack of knowledge of all the subtleties of legislative regulation of labor relations. As a consequence, if there are contradictions in the position of an employee and an employer, the court seeks to promote the former as a priority. At the same time, such a position in no way infringes on the rights of the employer. 4. One of the urgent problems of protecting the labor rights of employees in recent years is the substitution of labor relations with civil relations with the self-employed. The solution may be the introduction of relevant provisions in the Federal Law on the self-employed, the Tax Code of the Russian Federation and the Labor Code of the Russian Federation.

Public awareness of side effects of systemic steroids in Asir region, Saudi Arabia.

Corticosteroids have been used since the 50s and it represent the most important and frequently used class of anti-inflammatory and immunosuppressive drugs for the treatment of several diseases such as numerous neoplastic, asthma, allergy, rheumatoid arthritis, and dermatological disorders. This study aims to determine the public awareness of side effects of systemic steroids in Asir region, Saudi Arabia. A descriptive cross-sectional web-based study was used. An online questionnaire was developed by the study researchers based on the literature review and consultations of the field experts. The questionnaire included the following components: Participants demographic data, medical history, and steroids use. Also, it covered participants awareness regarding systemic steroids and side effects. A total of 439 participants fulfilling the inclusion criteria completed the study questionnaire. Ages ranged from 18 to 65 years with mean age of 26.1 ± 13.9 years old, of those, 227 (51.7%) respondents were males. Around 346 (78.8%) had poor overall awareness level while only 93 (21.2%) had good awareness regarding systematic steroids. The study also showed that awareness was significantly higher among young aged participants in the health care field and among those who previously used steroids. Two hundred and eighty two (64.2%) of the respondents reported previous use of steroids. In conclusion, the current study showed that nearly one out of each five people know about systemic steroids and related side effects which is below the satisfactory level. Higher awareness was observed with regards drug associated side effects and long-term use consequences.

The rationale and guiding principles to design a psychiatric curriculum for primary care nurses of India.

The National Mental Health Survey reports a huge treatment gap for all mental disorders. There is an acute shortage of mental health professionals in India. Hence, there is a dire need to support task-shift interventions by nurses in providing non-pharmacological interventions for persons suffering from mental health issues. The traditional psychiatric nursing curriculum emphasizes nurses' knowledge and skills rather than their competency in providing mental health care. We designed an innovative, digitally driven, modular-based primary care psychiatry program for nurses (PCPP-N) to incorporate mental health with physical health and emphasize redesigning nursing practice. In this paper, we discuss the rationale and guiding principles behind designing the curriculum of PCPP-N. The PCPP-N program is based on nine guiding principles to provide skill-based, pragmatic, and feasible modules of a higher collaborative care quotient (CCQ) and translational quotient (TQ) that are essential for upskilling primary care nurses. In this program, nurses are trained through telemedicine-based 'on-consultation training' augmented with collaborative video consultations. A tele-psychiatrist/tele-psychiatric nurse will demonstrate how to screen, identify, and plan treatment for patients with psychiatric disorders from patients coming for general medical care using the manual Clinical Schedules of Primary care psychiatry Nursing (CSP-N). The CSP-N manual includes a screener, simplified diagnosing guidelines relevant for nurses and primary care settings, nursing management, pharmacological management, and related side effects, counseling, and follow-up guidelines. This program helps the nurses in identifying the most commonly prevalent adult psychiatric disorders presenting to primary care. This PCPN curriculum contains pragmatic modules with higher CCQ and TQ. This curriculum is dynamic as the learning is interactive. Upskilling primary care nurses in integrating mental health with physical health may reduce the mental health burden. Further, the policymakers and administrators plan to integrate mental health along with physical health in national health programs.

A STUDY TO ASSESS THE PATTERN OF CONSUMPTION AND AWARENESS REGARDING USE OF CAFFEINE AND ENERGY DRINKS AMONG NURSING STUDENTS IN SELECTED NURSING COLLEGE AT DEHRADUN, UTTARAKHAND

A STUDY TO ASSESS THE PATTERN OF CONSUMPTION AND AWARENESS REGARDING USE OF CAFFEINE AND ENERGY DRINKS AMONG NURSING STUDENTS IN SELECTED NURSING COLLEGE AT DEHRADUN, UTTARAKHAND

The Effect of Patient Safety Experience on Patient Satisfaction of Patients Using Outpatient Health Services in Hospitals/Clinics

Objectives: The aim of this study is to identify outpatients’ experiences of patient safety, patient satisfaction levels, and examine the factors influencing on patients’ satisfaction. Methods: Data from the Survey on the Experience with Healthcare Service in 2021 were used for this secondary analysis. Data from 6,027 patients aged over 20 who experienced outpatient health services in hospitals or clinics were analyzed. Logistic regression analysis was carried out to explore as influential factors which are patient characteristics, health-related characteristics, and their experiences of patient safety. Results: Generally, the level of patient satisfaction was high as 90.6% of participants were satisfied with the received outpatient care. High patient satisfaction was related to gender (females), job (housewives), education level (below secondary education level) and perceived health status (good status). Besides, those who experience being educated the side effects related to the medications or no checking the safety facilities of medical institutions were more likely to satisfy with the outpatient care. Conclusions: It is revealed that demographic and health-related characteristics, and patient safety experiences affected patients’ satisfaction with outpatient health services. To improve overall patients’ satisfaction with outpatient care, it is needed to enhance nonclinical patient safety activities such as explaining medication related side effects for patients.

Fibroset™ and neuromuscular pain: a multicentric, real world, observational, post-marketing surveillance study in Indian patients suffering from neuromuscular pain

Background: Neuromuscular disease (NMD) is a condition due to abnormality or damage to muscles and nerves causing painful symptoms. Symptomatic management involves use of conventional painkillers, but desirable relief is not achieved due to multimodal pathophysiology of disease. This study evaluated the efficacy and safety of Fibroset™ tablets in subjects with neuromuscular pain. Methods: Subjects with neuromuscular pain, previously unsatisfied with standard therapies, were enrolled. Subjects were advised to take Fibroset™ one tablet BID for 2 weeks with their standard therapy. Efficacy was evaluated on pain, stiffness, swelling, weakness, tenderness, and difficulty in activity of daily living (ADL) as per the visit schedule. Tolerability of therapy was also evaluated. Results: 59 patients were enrolled in study and 46 patients were included in the final analysis. Fibroset™ supplementation significantly reduced all evaluated parameters (p<0.05 vs baseline). The mean pain score from 2.50 to 0.89, while mean stiffness score was reduced to 0.55 from 1.87 at end of study. The mean swelling score was reduced to 0.81 from 2.04, while the mean weakness score was reduced to 0.64 from baseline score of 1.79. The mean tenderness score was reduced from baseline score of 1.90 to 0.65 and the mean ADL score was reduced to 0.63 from baseline score of 2.00. No treatment related side effects were observed. Conclusions: Fibroset™ is a potentially effective and safe therapy for subjects with neuromuscular pain. It can be used to reduce symptoms in patients with unsatisfactory results with conventionally standard care therapy.

Effect of acupressure on pain among older female patients undergoing extracorporeal shock wave lithotripsy: A randomized controlled clinical trial

Background and aimUrinary stones are highly prevalent among older people. Extracorporeal lithotripsy is one of the commonly used treatment methods, but it causes pain. Acupressure is a non-pharmacological therapeutic method that is effective in relieving pain among patients with various health conditions. This study aimed to investigate the effect of acupressure on pain among female older people undergoing extracorporeal lithotripsy. MethodThis randomized controlled clinical trial was conducted on 66 older female patients undergoing extracorporeal lithotripsy. They were enrolled in the study through convenient sampling and were assigned to the intervention and control groups through the block randomization method. The intervention group underwent acupressure for 16 min which was repeated twice with an interval of 20 min, but the control group received only touch without any pressure for the same period. The McGill Pain Questionnaire and Visual Analogue Scale were completed 60 min before the intervention and immediately after lithotripsy. FindingsBefore the intervention, no statistically significant difference in the quality and intensity of pain between the two groups was observed (p > 0.05). However, after acupressure, the mean scores of quality and intensity of pain decreased significantly (p < 0.001) in the intervention group compared with the control group. ConclusionAcupressure as a complementary and alternative medicine can reduce pain and suffering among older people undergoing extracorporeal lithotripsy. It can be included in the routine therapeutic measures for relieving pain and suffering during noninvasive methods for older people and reducing their need for medication use and avoiding related pharmacological side effects.

Utility of Ultrasound-Guided Erector Spinae Plane Blocks for Postoperative Pain Management Following Thoracolumbar Spinal Fusion Surgery.

The primary objective of this study is to determine if ultrasound-guided erector spinae plane blocks (ESPB) prior to thoracolumbar spinal fusion reduces opioid consumption in the first 24 hours postoperatively. Secondary objectives include ESPB effects on administration of opioids, utilization of intravenous patient-controlled analgesia (IV-PCA), pain scores, length of stay, and opioid related side effects. A retrospective cohort analysis was performed on consecutive, adult patients undergoing primary thoracolumbar fusion procedures. Demographic and baseline characteristics including diagnoses of chronic pain, anxiety, depression, and preoperative use of opioids were collected. Surgical data included surgical levels, opioid administration, and duration. Postoperative data included pain scores, opioid consumption, IV-PCA duration, opioid-related side effects, ESPB-related complications, and length of stay (LOS). Statistical analysis was performed using chi-squared and t-test analyses, multivariable analysis, and covariate adjustment with propensity score. A total of 118 consecutive primary thoracolumbar fusions were identified between October 2019 and December 2021 (70 ESPB, 48 no-block [NB]). There were no significant demographic or surgical differences between groups. Median surgical time (262.50 mins vs 332.50 mins, p = 0.04), median intraoperative opioid consumption (8.11 OME vs 1.73 OME, p = 0.01), and median LOS (152.00 hrs vs 128.50 hrs, p = 0.01) were significantly reduced in the ESPB group. Using multivariable covariate adjustment with propensity score analysis only intraoperative opioid administration was found to be significantly less in the ESPB cohort. ESPB for thoracolumbar fusion can be performed safely in index cases. There was a reduction of intraoperative opioid administration in the ESPB group, however the care team was not blinded to the intervention. Extensive thoracolumbar spinal fusion surgery may require a different approach to regional anesthesia to be similarly effective as ESPB in isolated lumbar surgeries.

Differences in Coronavirus disease - 19 vaccination related side effects in patients with ulcerative colitis and Crohn's disease in Japan.

It has been recommended that individuals with inflammatory bowel disease (IBD) be vaccinated against Coronavirus disease -19 (COVID-19). Recently, we documented the incidence of side effects (SEs) after COVID-19 immunization among individuals with IBD in Japan. However, the study did not show differences between the types of IBD or the patients' clinical backgrounds. In this survey, we aimed at investigating whether the frequency of SEs differed among patients with IBD. A cross-sectional survey was conducted among adult patients with IBD at Kobe University between March 2022 and September 2022. Total 195 patients, including 134 with ulcerative colitis (UC) and 61 with Crohn's disease (CD), completed the questionnaire and were included in the analysis. Of these, 92.3%, 91.3% and 44.1% received the initial, second and third dose of the COVID-19 vaccine, respectively. The frequency of local symptoms following the initial, second and third dose of thevaccine was comparable between patients with UC and CD (69.6% vs. 72.7%, 64.2% vs. 69.1% and 63.5% vs. 73.9%, respectively). Muscle pain after the initial and second doses of the COVID-19 vaccine was more common among patients treated with corticosteroids (58.1% vs. 37.6% and 60.0% vs. 31.8%, p < 0.05). Female sex, younger age and current or former smoking were associated with an increased incidence of fever or chills after the initial dose of thevaccine (p < 0.05). In contrast, corticosteroid use was identified as a factor associated with an increased incidence of muscle pain after the initial dose of vaccine (p < 0.05). The use of corticosteroids could increase the risk of muscle pain following COVID-19 vaccination. Additionally, factors such as female sex, younger age and current or former smoking can affect the incidence of fever or chills. This information should encourage patients with IBD to get vaccinated against COVID-19.

Targeted Metabolomics Analysis Suggests That Tacrolimus Alters Protection against Oxidative Stress.

Tacrolimus (FK506) is an immunosuppressant that is experiencing a continuous rise in usage worldwide. The related side effects are known to be globally dose-dependent. Despite numerous studies on FK506, the mechanisms underlying FK506 toxicity are still not well understood. It is therefore essential to explore the toxicity mediated by FK506. To accomplish this, we conducted a targeted metabolomic analysis using LC-MS on the plasma samples of patients undergoing FK506 treatment. The aim was to identify any associated altered metabolic pathway. Another anti-calcineurin immunosuppressive therapy, ciclosporin (CSA), was also studied. Increased plasma concentrations of pipecolic acid (PA) and sarcosine, along with a decrease in the glycine/sarcosine ratio and a tendency of increased plasma lysine was observed in patients under FK506 compared to control samples. Patients under CSA do not show an increase in plasma PA compared to the control samples, which does not support a metabolic link between the calcineurin and PA. The metabolomics changes observed in patients under FK506 highlight a possible link between FK506 and the action of an enzyme involved in both PA and sarcosine catabolism and oxidative pathway, the Peroxisomal sarcosine oxidase (PIPOX). Moreover, PA could be investigated as a potential biomarker of early nephrotoxicity in the follow-up of patients under FK506.

Post-stroke epileptic seizures: risk factors, clinical presentation, principles of diagnosis and treatment

Post-stroke developing epileptic seizures represent a severe complication aggravating post-stroke condition. Epilepsy can exacerbate cognitive, psychopathological, somatic disorders resulting from cerebrovascular and comorbid diseases. Despite that post-stroke epilepsy (PSE) is a rather common type of acquired structural epilepsy, the issues related to diagnosis and management often raise difficulties for clinicians. Patients with severe strokes affecting brain, cortex, acute symptomatic seizures and intracerebral hemorrhage are at greater risk of developing PSE. Timely neurophysiological, neuroradiological research methods, assessed blood biomarkers as well as prognostic models provide information that complements PSE clinical risk factors. The management of post-stroke acute and long-term (late) symptomatic seizures differs markedly. At the same time, the choice of an optimal anticonvulsant drug should be based not only on its effectiveness, but also on related side effects, pharmacodynamics as well as an impact on concomitant diseases. Drug interactions, especially between anticonvulsants and anticoagulants or antiplatelet agents also affect a choice of treatment, which should be taken into consideration for management of PSE patients.

Intracellular ROS production and apoptotic effect of quinoline and isoquinoline alkaloids on the growth of Trypanosoma evansi

Trypanosoma evansi, a hemoflagellate poses huge economic threat to the livestock industry of several countries of Asia, Africa, South America and Europe continents of the world. Limited number of available chemical drugs, incidents of growing drug resistance, and related side effects encouraged the use of herbal substitutes. In the present investigation, the impact of six alkaloids of quinoline and isoquinoline group was evaluated on the growth and multiplication of Trypanosoma evansi and their cytotoxic effect was examined on horse peripheral blood mononuclear cells in an in vitro system. Quinine, quinindine, cinchonine, cinchonidine, berbamine and emetine showed potent trypanocidal activities with IC50/24 h values 6.631 ± 0.244, 8.718 ± 0.081, 16.96 ± 0.816, 33.38 ± 0.653, 2.85 ± 0.065, and 3.12 ± 0.367 µM, respectively, which was comparable to the standard anti-trypanosomal drug, quinapyramine sulfate (20 µM). However, in the cytotoxicity assay, all the drugs showed dose dependent cytotoxic effect and quinine, berbamine and emetine showed selectivity index more than 5, based of ration of CC50 to IC50. Among the selected alkaloids, quinidine, berbamine and emetine exhibited higher apoptotic effects in T. evansi. Likewise, drug treated parasites showed a dose-dependent and time-dependent increase in reactive oxygen species (ROS) production. Therefore, increased apoptosis in combination with ROS generation could be responsible for the observed trypanocidal effect which could be further evaluated in T. evansi-infected mice model.

Effectiveness of Adjunctive High-Dose Infliximab Therapy to Improve Disability-Free Survival Among Patients With Severe Central Nervous System Tuberculosis: A Matched Retrospective Cohort Study.

Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse. We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome. Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted. Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings.

A Phenomenological Study to Explore the Lived Experience of Patient Living with Mental Illness

Abstract Background: A broad understanding of patient’s mental health problem is important to deliver effective and patient-centered mental health interventions. Patients with mental illness feel frustrated when they will not be listened by the health professional. People living with mental illness have different problems which are unheard by the society because of various stereotypes regarding mental illness. Objective: The objective of this study was to describe the experience of the patient living with mental illness. Methodology: The research approach used was qualitative and the research design was hermeneutic phenomenological design. With the help of purposive sampling technique, the data were collected from 20 patients through the interview technique. Results: The study results were described into three emergent themes such as patient’s perception about the cause of their mental illness, patient’s experience of their symptoms, and patient’s understanding of their positive and negative experiences of their treatment. Conclusion: The study indicated that mentally ill persons experience many changes in their lives but manage to develop coping skills. Patients had both positive and negative experiences while living with mental illness. The experience of stigma and discrimination, dependence on prescribe medication and its related side effects, loss, and fear, all contributed to the hazy reality of living with mental illness.