Optimizing laccase selection for enhanced outcomes: a comprehensive review.

Despite their widespread applications in sectors such as pulp and paper, textile, food and beverage, pharmaceuticals, and biofuel production, laccases encounter challenges related to their activity and stability under varying reaction conditions. This review accumulates data on the complex interplay between laccase characteristics and reaction conditions for maximizing their efficacy in diverse biotechnological processes. Benefits of organic media such as improved substrate selectivity and reaction control, and their risks such as enzyme denaturation and reduced activity are reported. Additionally, the effect of reaction conditions such as pH and temperature on laccase activity and stability are gathered and reported. Sources like Bacillus pumilus, Alcaligenes faecalis, Bacillus clausii, and Bacillus tequilensis SN4 are producing laccases that are both thermo-active and alkali-active. Additionally, changes induced by the presence of various substances within reaction media such as metals, inhibitors, and organic solvents are also reported. Bacillus pumilus and Bacillus licheniformis LS04 produce the most resistant laccases in this case. Finally, the remarkable laccases have been highlighted and the proper laccase source for each industrial application is suggested. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04015-5.

A short-term economic evaluation of early insulin therapy compared to oral anti-diabetic drugs in order to reduce the major adverse events in type 2 diabetes patients in Iran.

OBJECTIVE: While there are some recommendations about early insulin therapy in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, there is not sufficient evidence on this strategy's cost-effectiveness. This study compared early insulin therapy versus oral anti-diabetic drugs (OADs) for managing T2DMusing a cost-effectiveness analysis approach in Iran. METHODS: In this economic evaluation, a decision analytic model was designed. The target population was newly diagnosed type 2 diabetic patients, and the study was carried out from the perspective of Iran's healthcare system with a one-year time horizon. Basal insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, and Thiazolidinediones (TZDs) were compared in this evaluation. The main outcome for assessing the effectiveness of each intervention was the reduction in the occurrence of diabetes complications. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and deterministic and probabilistic sensitivity analyses were carried out. RESULTS: The DPP-4 inhibitors strategy was the dominant strategy with the highest effectiveness and the lowest cost. Early insulin therapy was dominated (ICER: $-53,703.18), meaning that it was not cost-effective. The sensitivity analyses consistently affirmed the robustness of the base case findings. The probabilistic sensitivity analysis indicated probabilities of 77%, 22%, and 1% for DPP-4 inhibitors, TZDs strategies, and early insulin therapy, respectively, in terms of being cost-effective. CONCLUSION: In terms of cost-effectiveness, early insulin therapy was not cost-effective compared to OADs for managing newly diagnosed T2DM patients. Future studies in this regard, utilizing more comprehensive evidence, can yield more accurate results.

Is Palbociclib a cost-effective strategy in the second-line treatment of metastatic breast cancer in Iran?

BACKGROUND & AIMS: This study evaluates the cost-effectiveness of Palbociclib in the second-line treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in Iran. METHODS: The present economic evaluation used a partitioned survival model (PSM). This model compares lifetime costs and disease outcomes among groups receiving different medication combinations containing Palbociclib, Fulvestrant, Everolimus, Ribociclib, and Abemaciclib as the second-line therapy for HR+/HER2- MBC. The model was conducted from Iran's healthcare perspective, structured with 1-month cycles, and the evaluation time horizon in the base analysis was set to 180 cycles (15 years). Transition probabilities were extracted using the survival curves. The cost information was extracted based on the year 2020. The Quality Adjusted Life Years (QALY) was considered the final outcome unit, and the cost-effectiveness of different combinations is calculated as cost per QALY. The annual discount rate of 5% was considered for costs and QALYs. Two times Iran's GDP per capita (800,000,000 IRR = US$5934) was used as the threshold. Finally, due to the uncertainty of some parameters, deterministic and probabilistic sensitivity analyses were carried out. RESULTS: The base case results showed that the highest cost was for the 'Ribociclib+ Fulvestrant' combination (US$89,629.56), and the lowest price was for the 'Iranian Everolimus + Fulvestrant' combination (US$10,740.09). 'Palbociclib + Fulvestrant' brings about the highest value of 1.456 incremental QALYs compared to other strategies. Finally, the 'Iranian Palbociclib + Fulvestrant' was the cost-effective combination, with an incremental cost-effectiveness ratio (ICER) of US$4,201 compared to other strategies. The base case results were supported by the probabilistic sensitivity analysis. Deterministic sensitivity analysis showed that the cost of Iranian Palbociclib has a threshold of US$582.99. CONCLUSIONS: The 'Iranian Palbociclib + Fulvestrant' combination was cost-effective in second-line therapy for HR+ HER2- MBC in Iran.

Waist to height ratio as a simple tool for predicting mortality: a systematic review and meta-analysis.

BACKGROUND: The association of central obesity with higher rates of mortality is not well studied. This study evaluates the association between waist-to-height ratio (WHtR), as a measure of central obesity, with mortality. METHODS: Documents were retrieved from PubMed, Web of Science, Scopus, and Google Scholar databases until May 2022. Data were extracted from cohort studies reporting effect size (hazard ratio (HR)) regarding the association between WHtR as a continuous (per 1 SD increment) or categorical (highest/lowest) measure and all-cause and cause-specific mortality. Screening of included studies was performed independently by two authors. Moreover, the quality assessment of included studies was performed based on the Newcastle-Ottawa assessment scale. Finally, random effect meta-analysis was performed to pool the data, and the outcomes' certainty level was assess based on the GRADE criteria. RESULTS: Of the 815 initial studies, 20 were included in the meta-analysis. Random effect meta-analysis showed that in the general population, the all-cause mortality HRs for categorical and continuous measurements of WHtR increased significantly by 23% (HR:1.23; 95% CI: 1.04-1.41) and 16% (HR:1.16; 95% CI: 1.07-1.25), respectively. Moreover, the hazard of cardiovascular (CVD) mortality increased significantly for categorical and continuous measurements of WHtR by 39% (HR:1.39; 95% CI: 1.18-1.59) and 19% (HR:1.19; 95% CI: 1.07-1.31). The quality assessment score of all included studies was high. CONCLUSIONS: Higher levels of WHtR, indicating central obesity, were associated with an increased hazard of CVD and all-cause mortality. This measure can be used in the clinical setting as a simple tool for predicting mortality.

Cost-benefit analysis of stroke rehabilitation in Iran.

BACKGROUND: The economic evaluation of medication interventions for stroke has been the subject of much economic research. This study aimed to examine the cost-benefit of multidisciplinary rehabilitation services for stroke survivors in Iran. METHODS: This economic evaluation was conducted from the payer's perspective with a lifetime horizon in Iran. A Markov model was designed and Quality-adjusted life years (QALYs) were the final outcomes. First, to evaluate the cost-effectiveness, the incremental cost-effectiveness ratio (ICER) was calculated. Then, using the average net monetary benefit (NMB) of rehabilitation, the average Incremental Net Monetary Benefit (INMB) per patient was calculated. The analyses were carried out separately for public and private sector tariffs. RESULTS: While considering public tariffs, the rehabilitation strategy had lower costs (US$5320 vs. US$ 6047) and higher QALYs (2.78 vs. 2.61) compared to non-rehabilitation. Regarding the private tariffs, the rehabilitation strategy had slightly higher costs (US$6,698 vs. US$6,182) but higher QALYs (2.78 vs. 2.61) compared to no rehabilitation. The average INMB of rehabilitation vs non-rehabilitation for each patient was estimated at US$1518 and US$275 based on Public and private tariffs, respectively. CONCLUSION: Providing multidisciplinary rehabilitation services to stroke patients was cost-effective and has positive INMBs in public and private tariffs.

The efficacy of topical aminophylline in local fat reduction: A systematic review.

Background and aims: Some studies have reported that the topical forms with aminophylline as the active ingredient appear to be relatively effective on local fat burning while having no/minimal side effects. This systematic review accumulates all of the data on the local fat-burning potency of aminophylline topical formulation. Methods: Documents were retrieved from PubMed, Web of Science, and Scopus databases until Aug 2022. Data were extracted from clinical trials reporting the reduction in thigh or waist circumference as a result of using topical forms containing aminophylline. Screening of included studies was performed independently by two authors and the quality assessment of included studies was performed based on the Cochrane Collaboration's approach. Results: Of the 802 initial studies, 5 studies were included in the systematic review. Several concentrations of aminophylline were used in different studies. Most studies administred the topical formulation on participants' one thigh, and the other thigh was considered to be the control for comparing the fat reduction amount. Except for one study, all other studies reported that all participants lost more fat on the treated area than the control groups. The amount of fat reduction differed in studies regarding their different aminophylline concentrations and administration routines. In the case of side effects, except for some studies reporting skin rashes, other studies reported no significant side effects at all. Conclusions: Aminophylline topical formulation offers a safe, effective, and much less invasive alternative to cosmetic surgery for localized fat reduction. It seems that the 0.5% concentration, administered five times a week for five weeks is the most potent concentration. However, more high-quality clinical trials are needed to verify this conclusion. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022353578.

Tenecteplase in managing acute ischemic stroke: a long-term cost-utility analysis in Iran.

BACKGROUND & AIMS: The advantage of tenecteplase (TNK) over alteplase (ALT) in managing acute ischemic stroke (AIS) has been reported, but the cost-effectiveness of these two strategies has not received as much attention. The objective of this study was to compare TNK and ALT for the management of AIS patients in Iran in terms of cost-effectiveness. METHODS: This study was carried out from the payer's perspective in Iran, with a lifetime horizon. A full economic evaluation model was designed as a decision tree and a Markov model. After defining different Markov states, each health state was assigned a utility value, and quality-adjusted life year (QALY) was estimated using that value. The incremental cost-effectiveness ratio (ICER) was ultimately used for evaluating the comparative cost-effectiveness. Both deterministic and probabilistic sensitivity analyses were carried out. RESULTS: Compared to ALT, TNK can save approximately 4333.81 USD, and is able to increase one unit of QALY while saving approximately 17,450.29 USD. So, Base-case results showed that TNK strongly dominates ALT. Moreover, the base case results were strongly confirmed by deterministic and probabilistic sensitivity analysis. CONCLUSIONS: Base-case and sensitivity analysis showed that TNK is the dominant strategy compared to ALT for the management of AIS patients.

The modulatory role of dopamine receptors within the hippocampal cornu ammonis area 1 in stress-induced analgesia in an animal model of persistent inflammatory pain.

The intrinsic pain inhibitory mechanisms can be activated by fear, anxiety, and stress. Stressful experiences produce analgesia, referred to as stress-induced analgesia (SIA). Major components of the limbic system, including the ventral tegmental area, nucleus accumbens, amygdala, and hippocampus, are involved in the SIA. In this study, we tried to understand the role of dopamine receptors in the cornu ammonis area 1 (CA1) of the hippocampus in the forced swim stress (FSS)-induced analgesia. Stereotaxic surgery was unilaterally performed on 129 adult male Wistar rats weighing 220-280 g. SCH23390 (0.25, 1, and 4 µg/0.5 µl saline) or sulpiride (0.25, 1, and 4 µg/0.5 µl DMSO), as D1- and D2-like dopamine receptor antagonists, respectively, were microinjected into the CA1 area, 5 min before exposure to FSS for a 6-min period. The vehicle groups received saline or DMSO instead of SCH23390 or sulpiride, respectively. The formalin test was done using formalin injection (50 µl; 2.5%) into the plantar surface of the rat's hind paw immediately after exposure to FSS. The results demonstrated that FSS produces analgesia during the early and late phases of the formalin test. However, intra-CA1 microinjection of SCH23390 or sulpiride attenuated the FSS-induced analgesia in both phases of the formalin test. This study provides new insight into the role of D1- and D2-like dopamine receptors in the CA1 area in the FSS-induced analgesia during persistent inflammatory pain.