Effectiveness Of Treatment Research Articles

Effectiveness of post-burn pruritis treatment and improvement of insomnia - a randomized trial.

Post-burn pruritis is difficult to assess and treat. Antihistamines used in its treatment provide little relief. Identification of the itch neuronal pathway has inspired new alternatives including gabapentin in its management. The study compared the effectiveness of cetirizine, gabapentin, and a combination of gabapentin and cetirizine in treating post-burn pruritus. Burn patients were randomly assigned to treatment with Cetirizine (n=23), Gabapentin (n=23), or Cetirizine plus Gabapentin (n=23). Baseline assessment of the intensity or the severity of pruritus was evaluated after which treatment commenced with standard doses of the three study regimens. Quality of sleep was assessed at baseline (day 0) and repeated on day 3, day 7 and day 14. Approximately 97% of participants presented with moderate or severe itch; 69% with acute itch; and majority (94.2%) experienced pruritus between the first and fourth weeks. Gabapentin reduced itch by 92.9% in 14 days compared to cetirizine's 61.8%. The combined effect of cetirizine and gabapentin was comparable to using gabapentin alone. When itch became protracted over 6 weeks, the effectiveness of cetirizine in controlling itch worsened. It reduced itch intensity by only 37.7% whilst gabapentin did so at 89.4%. Itch intensity correlated positively with insomnia and controlling itch intensity improved sleep. Gabapentin was more effective for the treatment of post-burn pruritus than cetirizine. Controlling itch intensity improved sleep. In acute and moderate itch, a low-dose gabapentin could be added if cetirizine is the drug intended for its treatment.

#707 Effectiveness of a personalized approach to the treatment of patients with chronic coronary syndrome with type 2 diabetes and renal dysfunction

Abstract Background and Aims To evaluate the effectiveness of complex personalized treatment of patients with chronic coronary syndrome (CCS) with type 2 diabetes mellitus (T2DM). Method We observed patients with chronic stable angina pectoris III (FC) (Group I, 16) and CV IV FC (Group II, 18) with T2DM who underwent planned stenting of the coronary arteries (SCA). At baseline and after 3 and 6 months, we studied cholesterol, LDL cholesterol and HDL cholesterol, triglycerides (TG), ALT and AST, total bilirubin (TB), polymorphism of the CYP2C19 and 9p21 genes (rs 2383206 and rs 10757272), assessed myocardial viability (ECHOCG, MSCT), an ultrasound of the liver was performed. Against the background of basic therapy (antiplatelet agents, statins, beta blockers, ACE inhibitors), patients received a herbal hepatoprotector. Results Initial lipid parameters in patients with CCS and T2DM: cholesterol—6.9 mmol/l; LDL cholesterol –3.6; HDL cholesterol –1.1; TG –2.5 mmol/l. Parameters of global and regional systolic function were reduced. At the end of observation, lipid content: cholesterol—5.0; LDL cholesterol—2.3; HDL cholesterol –1.18; TG—1.61 mmol/l. Statins and antiplatelet agents were well tolerated, and there were no cases of withdrawal. Enzyme activity (ALT, AST), OB content were within normal values. The genetic studies carried out helped to select the most effective and safe doses of antiplatelet drugs and statins and significantly reduced the risk of complications and drug resistance. The hepatoprotector had a beneficial effect on the condition and function of the liver and improved the tolerability of medications. A personalized approach to the treatment of CCS was carried out taking into account the results of genetic testing with the selection of optimal doses of drugs. When the genotypes of CYP2C19*17 (rs 12248560) CC, ST and TT were distributed, the dose of antiplatelet agents was increased, and when the genotypes of the CYP2C19 gene (rs 4244285) GG, AG and AA were distributed, they were reduced. Assessment of myocardial viability, selection of doses of statins and antiplatelet agents according to individual characteristics, as well as a hepatoprotector increased the effectiveness and safety of treatment. SCA and basic treatment had an impact on the pathogenetic links of CCS, which is especially important in the treatment of patients with concomitant T2DM. Conclusion A personalized approach to the treatment of patients with CCS with T2DM who require SCA, taking into account the functional state and viability of the myocardium, the pharmacogenetic characteristics of the drugs, increases the effectiveness of revascularization, prevents the development of resistance, side effects and complications.

A Pilot Study to Evaluate the Use of Automated Nicotine Metabolite Ratio Reporting within Primary Care as an Implementation Strategy to Increase the Use of Tobacco Treatments.

Concerns about safety and effectiveness of tobacco treatments reduce their use. We explored integrating the nicotine metabolite ratio (NMR), and messaging about its potential for improving safety and effectiveness, as a strategy to increase use of tobacco treatments within primary care. Through a prospective cohort design, we explored the effects of integrating NMR testing within primary care on the provision of tobacco treatment; 65 patients completed assessments including NMR before a clinic visit. At the clinic visit, patients' clinicians received an electronic health record alert about the patient's NMR and personalized treatment recommendations to improve effectiveness and safety. Being asked about smoking and advised to quit, and a referral for tobacco treatment or medication prescription, were assessed within 30 days of the appointment and were compared to a usual care cohort (N=85). The NMR and usual care cohorts reported similar rates of being asked about smoking (92.3% vs. 92.9%, p=1.0), being advised to quit (72.3% vs. 74.1%, p=0.85), being referred for tobacco treatment (23.1% vs. 36.5%, p=0.11), and receiving tobacco use medications (20% vs. 27.1%, p=0.34). In the NMR cohort, fast vs. slow metabolizers were more likely to receive medication (26% vs. 0%, p=0.003) and all patients who received varenicline (n=8) were fast metabolizers. NMR results and treatment recommendations did not increase tobacco treatment rates in primary care, although it may increase treatment rates and use of varenicline for fast metabolizers. Future studies could test ways to use the NMR to increase tobacco treatment rates in clinical settings. This study generated a novel implementation strategy, namely an electronic health record alert about patients' NMR and personalized treatment recommendations, in an effort to increase tobacco treatment rates in primary care. While the strategy did not increase tobacco treatment rates, it may have boosted the rate of varenicline prescription for patients who metabolize nicotine faster, aligning with evidence-based practice.

Testing Dynamic Balance in People with Multiple Sclerosis: A Correlational Study between Standard Posturography and Robotic-Assistive Device.

Robotic devices are known to provide pivotal parameters to assess motor functions in Multiple Sclerosis (MS) as dynamic balance. However, there is still a lack of validation studies comparing innovative technologies with standard solutions. Thus, this study's aim was to compare the postural assessment of fifty people with MS (PwMS) during dynamic tasks performed with the gold standard EquiTest® and the robotic platform hunova®, using Center of Pressure (COP)-related parameters and global balance indexes. Pearson's ρ correlations were run for each COP-related measure and the global balance index was computed from EquiTest® and hunova® in both open (EO) and closed-eyes (EC) conditions. Considering COP-related parameters, all correlations were significant in both EO (0.337 ≤ ρ ≤ 0.653) and EC (0.344 ≤ ρ ≤ 0.668). Furthermore, Pearson's analysis of global balance indexes revealed relatively strong for visual and vestibular, and strong for somatosensory system associations (ρ = 0.573; ρ = 0.494; ρ = 0.710, respectively). Findings confirm the use of hunova® as a valid device for dynamic balance assessment in MS, suggesting that such a robotic platform could allow for a more sensitive assessment of balance over time, and thus a better evaluation of the effectiveness of personalized treatment, thereby improving evidence-based clinical practice.

Transcriptomic analysis of subarachnoid cysts of Taenia solium reveals mechanisms for uncontrolled proliferation and adaptations to the microenvironment

Subarachnoid neurocysticercosis (SANCC) is caused by an abnormally transformed form of the metacestode or larval form of the tapeworm Taenia solium. In contrast to vesicular parenchymal and ventricular located cysts that contain a viable scolex and are anlage of the adult tapeworm, the subarachnoid cyst proliferates to form aberrant membranous cystic masses within the subarachnoid spaces that cause mass effects and acute and chronic arachnoiditis. How subarachnoid cyst proliferates and interacts with the human host is poorly understood, but parasite stem cells (germinative cells) likely participate. RNA-seq analysis of the subarachnoid cyst bladder wall compared to the bladder wall and scolex of the vesicular cyst revealed that the subarachnoid form exhibits activation of signaling pathways that promote proliferation and increased lipid metabolism. These adaptions allow growth in a nutrient-limited cerebral spinal fluid. In addition, we identified therapeutic drug targets that would inhibit growth of the parasite, potentially increase effectiveness of treatment, and shorten its duration.

Myricetin reduces neutrophil extracellular trap release in a rat model of rheumatoid arthritis, which is associated with a decrease in disease severity.

Rheumatoid arthritis (RA) is a chronic disease characterized by joint inflammation and severe disability. However, there is a lack of safe and effective drugs for treating RA. In our previous study, we discovered that myricetin (MC) and celecoxib have a synergistic effect in the treatment of RA. We conducted in vitro and in vivo experiments to further investigate the effects and mechanisms of action of MC. Our findings demonstrated that MC treatment effectively reduced the release of neutrophil extracellular traps (NETs) and alleviated the inflammatory response in RA. Mechanistic studies showed that MC prevents the entry of PADI4 and MPO into the cell nucleus, thereby protecting DNA from decondensation. In a rat arthritis model, MC improved histological changes in ankle joints and suppressed NET-related signaling factors. In conclusion, MC protects the ankle joints against arthritis by inhibiting MPO and PADI4, thereby reducing NET release. The pharmacological mechanism of MC in RA involves the inhibition of NET release.

#530 Cardiorenal effects of dual blockade with ACE inhibitors and ARBs among people with CKD: emulation of a reference trial (ONTARGET) using CPRD

Abstract Background and Aims Cardiovascular disease (CVD) is a leading cause of death globally, and individuals with chronic kidney disease (CKD) are at increased risk. Results from the ONTARGET trial, in conjunction with the ALTITUDE and VA-Nephron-D studies, led to an end of recommendations for dual ACE inhibitor and ARB therapy due to an increase in acute kidney injury. However, these studies had low power to address long-term kidney outcomes and there remains uncertainty about whether dual therapy could be effective at reducing adverse cardiovascular and renal outcomes in patients with CKD. Observational data provides an opportunity to explore such hypotheses in subgroups underrepresented in trials and with power and follow-up enabling estimation of risk of rare outcomes. We aimed to use ONTARGET to perform a reference trial emulation analysis, before extending analysis to explore treatment effectiveness of dual ARB and ACEi use vs ACEi alone in preventing cardiovascular and renal outcomes among those with CKD. Method Using routinely-collected data from the UK Clinical Practice Research Datalink (CPRD) Aurum linked with Hospital Episode Statistics secondary care data, we applied the ONTARGET trial eligibility criteria to patients prescribed an ARB/ACE inhibitor between 1/1/2001-31/7/2019. As the number of patients receiving prescriptions for both medications on the same day was likely to be small in routine care, we used an operational definition to capture dual users. Outcomes included ONTARGET primary cardiovascular composite outcome of cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure and a composite renal outcome of ≥50% reduction in GFR or end-stage kidney disease (ESKD). Within the trial-eligible cohort, outcomes of interest were compared between groups prescribed dual therapy vs ACE inhibitors alone using a propensity-score—weighted time-to-event analysis using a Cox proportional hazards model. Conditional on successfully benchmarking results against the ONTARGET trial, we explored treatment effect heterogeneity by chronic kidney disease (CKD) at baseline, with CKD defined as estimated glomerular rate (eGFR) < 60 ml/min/1.73 m2. Results 412,406 trial-eligible patients in CPRD were included in analysis. Among those with non-missing eGFR at baseline, 37% had CKD (Table 1). We found similar effectiveness of dual therapy and ACE inhibitors in reducing the risk of the primary composite cardiovascular outcome (HR 0.98 (95% CI: 0.93, 1.03), consistent with the ONTARGET trial results (HR 0.99 (95% CI: 0.92, 1.07), with no evidence of heterogeneity by CKD (P-value for interaction = 0.14). However, dual therapy use was associated with a greater risk for the composite renal outcome compared to ACE inhibitor, HR 1.24 (95% CI: 1.14, 1.35), with no evidence of heterogeneity by CKD (P = 0.93) (Fig. 1). Analysing components of the composite renal outcome separately gave consistent results (≥50% reduction in GFR: HR 1.22 (95% CI: 1.12, 1.33); ESKD: HR 1.34 (95% CI: 1.24, 1.57)), as did a post-hoc sensitivity analysis by proteinuria status (no proteinuria: HR 1.28 (95% CI: 1.03, 1.59); proteinuria: 1.27 (95% CI: 1.08, 1.49)). Conclusion We found evidence that dual therapy use was associated with increased risk of renal outcomes in both those with and without CKD at baseline. Applying a reference trial emulation approach and successfully benchmarking findings against ONTARGET, where confounding was not present due to randomisation, provides confidence in the validity of these results.

Machine Learning-Driven Analysis of Individualized Treatment Effects Comparing Buprenorphine and Naltrexone in Opioid Use Disorder Relapse Prevention.

A trial comparing extended-release naltrexone and sublingual buprenorphine-naloxone demonstrated higher relapse rates in individuals randomized to extended-release naltrexone. The effectiveness of treatment might vary based on patient characteristics. We hypothesized that causal machine learning would identify individualized treatment effects for each medication. This is a secondary analysis of a multicenter randomized trial that compared the effectiveness of extended-release naltrexone versus buprenorphine-naloxone for preventing relapse of opioid misuse. Three machine learning models were derived using all trial participants with 50% randomly selected for training (n = 285) and the remaining 50% for validation. Individualized treatment effect was measured by the Qini value and c-for-benefit, with the absence of relapse denoting treatment success. Patients were grouped into quartiles by predicted individualized treatment effect to examine differences in characteristics and the observed treatment effects. The best-performing model had a Qini value of 4.45 (95% confidence interval, 1.02-7.83) and a c-for-benefit of 0.63 (95% confidence interval, 0.53-0.68). The quartile most likely to benefit from buprenorphine-naloxone had a 35% absolute benefit from this treatment, and at study entry, they had a high median opioid withdrawal score (P < 0.001), used cocaine on more days over the prior 30 days than other quartiles (P < 0.001), and had highest proportions with alcohol and cocaine use disorder (P ≤ 0.02). Quartile 4 individuals were predicted to be most likely to benefit from extended-release naltrexone, with the greatest proportion having heroin drug preference (P = 0.02) and all experiencing homelessness (P < 0.001). Causal machine learning identified differing individualized treatment effects between medications based on characteristics associated with preventing relapse.

Review Article: DNA Methylation in Cancer Immunity

Background: The transcriptional control of various cell types, especially in the development or functioning of immune system cells involved in either promoting or inhibiting the immune response against cancer, is significantly influenced by DNA or RNA methylation. Multifaceted interconnections exist between immunological or cancer cell populations in the tumor's microenvironment (TME). TME alters the fluctuating DNA (as well as RNA) methylation sequences in these immunological cells to change their development into pro- or anti-cancer cell categories (such as T cells, which are regulatory, for instance). Objective: This review highlights the impact of DNA and RNA methylation on myeloid and lymphoid cells, unraveling their intricate role in immune response orchestration within both oncological and non-oncological milieus. Deciphering this complex transcriptional regulation holds promise for identifying and demonstrating therapeutic avenues that take advantage of the modulation of DNA and RNA methylation with the goal of alleviating the number of cancer-related morbidity and mortality cases. Conclusion: While more research is required towards fully understanding the effectiveness of epigenetic-based treatments aimed at tumor as well as immune cell populations, there is compelling proof that indicates that they will be successful in slowing the advancement of malignancy as well as lowering cancer-related complications as well fatalities.

Targeted Ferroptosis-Immunotherapy Synergy: Enhanced Antiglioma Efficacy with Hybrid Nanovesicles Comprising NK Cell-Derived Exosomes and RSL3-Loaded Liposomes.

Ferroptosis therapy and immunotherapy have been widely used in cancer treatment. However, nonselective induction of ferroptosis in tumors is prone to immunosuppression, limiting the therapeutic effect of ferroptosis cancer treatment. To address this issue, this study reports a customized hybrid nanovesicle composed of NK cell-derived extracellular versicles and RSL3-loaded liposomes (hNRVs), aiming to establish a positive cycle between ferroptosis therapy and immunotherapy. Thanks to the enhanced permeability and retention effect and the tumor homing characteristics of NK exosomes, our data indicate that hNRVs can actively accumulate in tumors and enhance cellular uptake. FASL, IFN-γ, and RSL3 are released into the tumor microenvironment, where FASL derived from NK cells effectively lyses tumor cells. RSL3 downregulates the expression of GPX4 in the tumor, leading to the accumulation of LPO and ROS, and promotes ferroptosis in tumor cells. The accumulation of IFN-γ and TNF-α stimulates the maturation of dendritic cells and effectively induces the inactivation of GPX4, promoting lipid peroxidation, making them sensitive to ferroptosis and indirectly promoting the occurrence of ferroptosis. This study highlights the role of the customized hNRV platform in enhancing the effectiveness of synergistic treatment with selective delivery of ferroptosis inducers and immune activation against glioma without causing additional side effects on healthy organs.

Selected cannabis cultivars modulate glial activation: in vitro and in vivo studies

IntroductionMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination and axonal loss. Cannabis, an immunomodulating agent, is known for its ability to treat MS effectively. However, due to variations in the profile of secondary metabolites, especially cannabinoids, among cannabis cultivars, the effectiveness of cannabis treatment can vary, with significant variability in the effects on different biological parameters. For screening available cultivars, cellular in vitro as well as pre-clinical in vivo assays, are required to evaluate the effectiveness of the wide range of chemical variability that exists in cannabis cultivars. This study evaluated comparatively three chemically diverse cannabis cultivars, CN2, CN4 and CN6, containing different ratios of phytocannabinoids, for their neuroinflammatory activity in MS model.Materials and methodsIn vitro experiments were performed with lipopolysaccharide (LPS)-activated BV-2 microglia and primary glial cells to evaluate the effect of different cannabis cultivars on nitric oxide (NO) and inflammatory cytokines, as well as inducible nitric oxide synthase (iNOS) protein expression. An in vivo experiment using the experimental autoimmune encephalomyelitis (EAE) MS model was conducted using Myelin oligodendrocyte glycoprotein (MOG) as the activating peptide. The cannabis extracts of the cultivars CN2, CN4, CN6 or vehicle, were intraperitoneally injected with clinical scores given based on observed symptoms over the course of study. At the end of the experiment, the mice were sacrificed, and splenocyte cytokine secretion was measured using ELISA. Lumbar sections from the spinal cord of treated MS mice were evaluated for microglia, astrocytes and CD4+ cells.ResultsExtracts of the CN2 cultivar contained tetrahydrocannabinolic acid (THCA) and tetrahydrocannabinol (THC) without cannabidiol (CBD), and a number of monoterpenes. CN4 contained cannabidiolic acid (CBDA) and tetrahydrocannabidiolic acid (THCA), with significant amounts of THC: CBD in a 1:1 ratio, as well as sesquiterpenes and some monoterpenes; and CN6 contained primarily CBDA and THCA, as well as THC and CBD in a 2:1 ratio, with some sesquiterpenes and no monoterpenes. All extracts were not cytotoxic in glial cells up to 50 µg/ml. Dose dependent inhibition of LPS-induced BV2 as well as primary microglial NO secretion confirmed the anti-inflammatory and anti-oxidative activity of the three cannabis cultivars. CN2 but not CN4 reduced both astrocytosis and microglial activation in lumbar sections of EAE mice. In contrast, CN4 but not CN2 significantly decreased the secretion of TNFα and Interferon γ (IFNγ) in primary splenocytes extracted from EAE mice.ConclusionsWhile both cannabis cultivars, CN2 and CN4, significantly reduced the severity of the clinical signs throughout the course of the study, they modulated different inflammatory mediators and pathways, probably due to differences in their phytocannabinoid composition. This demonstrates the differential potential of cannabis cultivars differing in chemotype to regulate neuroinflammation and their potential to treat MS.

Morning light treatment for inflammatory bowel disease: a clinical trial.

Inflammatory bowel disease (IBD) affects over 3million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD. We will recruit sixty-eight individuals with biopsy-proven IBD and clinical symptoms and randomize them to 4-weeks of morning light treatment or 4-weeks of treatment as usual (TAU), with equivalent study contact. Patient-reported outcomes (IBD-related quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Our primary objective will be to test the effect of morning light treatment versus TAU on IBD-related quality of life and our secondary objectives will be to test the effects on clinician-rated disease activity, depression, and sleep quality. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome, and biological sex. Morning light treatment may be an acceptable, feasible, and effective adjunctive treatment for individuals with active IBD suffering from impaired health-related quality of life. The study protocol was registered on ClinicalTrials.gov as NCT06094608 on October 23, 2023, before recruitment began on February 1, 2024.

Experimental study on dewatering and reinforcement of dredged slurry treated by PHDs-PVDs under step vacuum preloading

Nowadays, the utilization of prefabricated vertical drains (PVDs) or prefabricated horizontal drains (PHDs) in combination with vacuum preloading (VP) has emerged as a prevalent and effective strategy for treating dredged slurry. Nevertheless, both of these methods possess certain inherent limitations. In this study, three groups of parallel model experiments are conducted to compare the effectiveness of PVDs, PHDs and PHDs-PVDs under step VP in treating dredged slurry. Firstly, the water discharge, settlement and pore water pressure are monitored during the experiments. Then, the shear strength and water content of the soil at various locations after experiments are measured and the soil profiles at different cross sections are gauged. Additionally, soil excavation is conducted to evaluate the deformation characteristics of PHDs and PVDs. Finally, a scanning electron microscopy analysis is to assess the clogging of filter membranes. The results indicate that the proposed method can combine the advantages of both PHDs and PVDs, effectively enhancing the treatment effectiveness of the slurry. These findings elucidate the dewatering and reinforcement mechanism of PHDs-PVDs-VP and provide valuable insights for its practical engineering application.

Mycobacterium Tuberculosis Resistance — Stages of Drug Resistance Formation (Review)

The review contains an analysis of the latest research on molecular genetic aspects of the formation of resistance in tuberculosis patients to avoid it during use of modern treatment programs. Objective — to assess the situation with the evolution of resistance of Mycobacteria tuberculosis and the stages of drug resistance development using materials from available databases. Materials and methods. The research has been completed for the period from 2014 to 2024. The next stage with the establishment of a systemic topological and metric computer analysis of the results allowed us to see the most informative sections of the research topic that are clearly associated with the formation mechanisms of drug-resistance in pulmonary tuberculosis. The most complete database of available literary sources was obtained (about 50 out of 502 analyzed arrays). Results and discussion. Ukraine is among the thirty countries with a high burden of tuberculosis with multiple drug resistance (MDR-TB). The main threat to the effectiveness of tuberculosis treatment in Ukraine is late detection of the disease and determining the sensitivity of the pathogen, which is the main prerequisite for prescribing adequate treatment. The situation with MDR-TB in Ukraine remains difficult in the conditions of war against the background of the COVID-19 pandemic. Thus, the total number of such cases for 2023 was 1,955 patients, of which 1,326 were new cases. The number of cases of tuberculosis with extended resistance (XDR-TB) was 228, of which 136 patients were diagnosed for the first time. Conclusions. The question of studying the genetic aspects of the formation of drug resistance of M. tuberculosis with the determination of the role of polymorphic variants of genes encoding xenobiotic metabolism systems in tuberculosis infection remains relevant to understand the mechanisms of interaction in the process of implementing hereditary information at the holistic level of the organism in order to increase the effectiveness of treatment and prevent the formation of resistance.

ХРОНОФИЗИОТЕРАПИЯ – НОВОЕ НАПРАВЛЕНИЕ В МЕДИЦИНСКОЙ БИОФИЗИКЕ

The study is aimed at solving the issues of increasing the efficiency and safety of treatment for a wide range of diseases based on the developed chronobiological approach to managing the functional state of the body. The approach is based on the following chronobiological patterns: 1. the principle of the rhythm of biological processes in living organisms; 2. the principle of conjugation of bioprocesses and their biorhythms; 3. the principle of chrono-management of living organisms by regulating their biorhythms; 4. the phenomenon of assimilation of external rhythms by living organisms. According to the principle of rhythm, all biological processes in the body have their own biorhythms. This means that bioprocesses and their biorhythms are interdependent and obey the conjugation principle. Therefore, in case of a disease, a violation of bioprocesses in the body is accompanied by a deviation of their biorhythms from the norm – desynchronosis. From this it follows that it is possible to treat diseases not only by pharmacotherapy methods by restoring disturbed bioprocesses, but also by chronophysiotherapy methods by correcting their biorhythms and eliminating desynchronosis. This is the principle of chrono-management of living organisms. However, at present, there is no hardware methods for the treatment of desynchrony on the therapy market. To implement this principle, based on the phenomenon of mastering external rhythms and the principle of conjugation of bioprocesses and their biorhythms, a technology of chronophysiotherapy has been developed. Chronotechnology includes a method of resynchronizing physiotherapy of biorhythms of a sick organism and a chronophysiotherapy apparatus. The frequency component of the EMF is used as an external synchronizer. The apparatus simultaneously implements two treatment functions: chronotherapy and magnetotherapy. The function of chronotherapy implements the developed method of treatment, the therapeutic factor of which is the frequency of EMF from the corresponding range of biorhythms of a healthy organism. And the function of magnetotherapy implements an auxiliary method, the therapeutic factor of which is the magnetic component of the EMF. The device has no side effects on the body and as a result of complex chronomagnetic therapy, the effectiveness of treatment on it reaches 95%.

Cryopreserved bone flaps from decompressive craniectomies: a microbiological analysis.

Surgical site infection (SSI) is a serious complication after cranioplasty. Due to the relatively frequent occurrence of post-cranioplasty SSI, the utility of autologous bone flap swab cultures surrounding cryopreservation as a reliable predictor has been the subject of an ongoing debate. This bicentric study aims to contribute to this topic by conducting an in-depth analysis of bone flaps obtained via decompressive craniectomies. This study had three major aims: assessments of 1) bacterial contamination of bone flaps after decompressive craniotomy, 2) impact of cryoconservation on contamination rates and 3) potential effectiveness of anti-infective treatment to reduce the germ load prior to cranioplasty. Cryopreserved bone flaps from two centers were used. Microbiological cultivations of swabs prior to and after cryopreservation were taken and assessed for aerobic and anaerobic growth over a 14-day incubation period. Additionally, in a subset of bone flaps, swab testing was repeated after thorough rinsing with an anti-infectant (octenidine-phenoxyethanol) followed by saline. All 63 bone flaps (patients median age at surgery: 59years) were obtained via decompressive craniectomies. Swabs done prior to cryopreservation revealed a 54% infection rate with Propionibacterium acnes being the most common microorganism in 65% of those cases. After thorough disinfection of the preserved bone flaps, all but one case showed no bacterial growth in swab testing. Furthermore, no relevant risk factors for bacterial contamination could be identified. This retrospective study showed the common presence of bacterial growth in cryopreserved bone flaps before and after freezing. Rinsing with octenidine-phenoxyethanol and saline effectively prevented bacterial growth in a notable percentage of cases, suggesting a potential strategy to reduce contamination. However, persistent bacterial growth in some cases underscores the need for further research to optimize antiseptic measures during autologous cranioplasty.

Mushroom-derived bioactive components with definite structures in alleviating the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is a complicated neurodegenerative condition with two forms: familial and sporadic. The familial presentation is marked by autosomal dominance, typically occurring early in individuals under 65years of age, while the sporadic presentation is late-onset, occurring in individuals over the age of 65. The majority of AD cases are characterized by late-onset and sporadic. Despite extensive research conducted over several decades, there is a scarcity of effective therapies and strategies. Considering the lack of a cure for AD, it is essential to explore alternative natural substances with higher efficacy and fewer side effects for AD treatment. Bioactive compounds derived from mushrooms have demonstrated significant potential in AD prevention and treatment by different mechanisms such as targeting amyloid formation, tau, cholinesterase dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, neurotrophic factors, ER stress, excitotoxicity, and mitochondrial dysfunction. These compounds have garnered considerable interest from the academic community owing to their advantages of multi-channel, multi-target, high safety and low toxicity. This review focuses on the various mechanisms involved in the development and progression of AD, presents the regulatory effects of bioactive components with definite structure from mushroom on AD in recent years, highlights the possible intervention pathways of mushroom bioactive components targeting different mechanisms, and discusses the clinical studies, limitations, and future perspectives of mushroom bioactive components in AD prevention and treatment.

Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120mg (+ 60mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20mg oral (+ 10mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12months post-randomisation or death, whichever occurs first. This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. Trial registered on Australian New Zealand Clinical Trials Registry. ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

Biomimetic cascade-released hydrogel scaffolds from microfluidics for efficient T cell recruitment and expansion

Adoptive T-cell immunotherapy has shown powerful therapeutic effects in cancer treatment. Attempts to implement T cell therapy have tended to focus on providing T cells with specific targeting and sufficient activation to enhance their tumor killing ability. Although biomaterial-based scaffolds can provide necessary molecular cues for T cell activation, efficient stimulation necessitates more attention on the reconstruction of natural T cell activation processes. Here, we present a novel biomimetic scaffold with cascade-released capacity for T-cell recruitment and activation. Core-shell structured hydrogel scaffolds are fabricated by single-step microfluidic electrospray, and chemokines and stimulatory antibodies are compartmentalized in the shell and core, respectively. Benefiting from the heterogeneity in the microstructure and swelling degree of the core and shell hydrogels, chemokine peptides are robustly released to recruit tumor-reactive T cells, and stimulatory antibodies are continuously released to support T cell proliferation. Such biomimetic recruitment and activation processes contribute to the formation of T cell clusters, which enhances their proliferation and infiltration in tumor tissues. Owing to the high expression of cytotoxic receptor and chemokine receptor, the activated T cells exhibit potent antitumor activity in vitro and in vivo. These features demonstrate that the cascade-released hydrogel scaffolds are promising for the local recruitment and activation of tumor-reactive T cells.

Polycationic Photosensitizers as Effective Anticancer Agents That Destroy Cancer Stem Cells, Cancer Vascularization and Induce Protective Desmoplastic Reaction around Lung Cancers

PDT using PSs based on polycationic derivatives of synthetic bacteriochlorin against Lewis lung carcinoma provides effective inhibition of tumor growth with an increase in the lifespan and survival of mice in the group. PDT with polycationic photosensitizers destroys CSCs and tumor neovascularization, and activates the desmoplastic reaction. These results open up new opportunities for increasing the effectiveness of treatment and reducing the incidence of relapses and metastases after PDT.