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Alzheimer's disease (AD) often leads to dementia, causing cognitive decline and increased care needs. Rivastigmine (RV) is a key AD treatment, but its brain delivery is limited by the blood-brain barrier (BBB). Aside from oral, olfactory, and intradermal injection (i.d.) routes, the application of polymeric microneedles via the trigeminal nerve on the facial skin as a pretreatment, followed by a solid lipid nanoparticle RV-loaded thermosensitive gel (PMN-SLN-RV-TG), is an alternative to deal with the problems. This study aims to determine the optimal formula for PMN-SLN-RV-TG application and assess its brain delivery ability compared to conventional routes. The optimum SLN-RV formula had a particle size <200 nm and sustained release for 72 h, which was selected for the SLN-RV-TG formulation. SLN-RV-TG was transformed into a gel at normal skin temperature (32-37 °C), with good physical properties and nontoxic behavior. The ideal PMN formula was able to penetrate the dermal layer as an alternative to i.d. administration. Ex vivo dermatokinetics showed significant improvement of PMN-SLN-RV-TG application ( p < 0.05) compared to without PMN application. In vivo pharmacokinetic studies on rats also revealed that the PMN-SLN-RV-TG had superior pharmacokinetic parameters ( C max , AUC, t 1/2 , and MRT) compared to other groups ( p distribution studies of PMN-SLN-RV-TG application exhibited a higher brain:blood ratio than i.v. administration after 5 h, as well as being safe for the brain due to a good histological profile. These results show that PMN-SLN-RV-TG application via the trigeminal nerve on the facial skin has strong potential delivery to the brain for AD treatment.99m Tc showed good physical properties, with a radiochemical yield of >95%. In vivo distribution studies of PMN-SLN-RV-TG application exhibited a higher brain:blood ratio than i.v. administration after 5 h, as well as being safe for the brain due to a good histological profile. These results show that PMN-SLN-RV-TG application via the trigeminal nerve on the facial skin has strong potential delivery to the brain for AD treatment.

Objective: This study was carried out to investigate the effects of mobile application based genetic counseling on the psychosocial well-being of thalassemia patients and caregivers., Methods: A randomized controlled trial was conducted with 80 patients, divided equally between the intervention and control groups. Additionally, 192 caregivers were included, with an equal distribution of 96 in the two groups. The intervention group received mobile application based genetic counseling, while the control received standard routine care. Assessments of quality of life, satisfaction, depression, and anxiety were conducted at baseline (T0), one-month post-intervention (T1), and three months post-intervention (T2). Furthermore, data analysis was performed using the Generalized Estimation Equation Model (GEE) approach in SPSS version 25.0., Results: Mobile application based genetic counseling had significant effects on various aspects of the well-being of thalassemia patients and caregivers. These effects include improvements in quality of life, patient satisfaction, reduction in depression, and alleviation of anxiety (p < 0.05)., Conclusion: Mobile application based genetic counseling showed a significant effect in improving psychosocial well-being among patients and caregivers., Practice Implications: The results obtained practical implications for the integration of genetic counseling interventions, particularly through the application of information technology such as Cyber Gen application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Xanthorrhizol, an important marker of Curcuma xanthorrhiza , has been recognized for its different pharmacological activities. A green strategy for selective xanthorrhizol extraction is required. Herein, natural deep eutectic solvents (NADESs) based on glucose and organic acids (lactic acid, malic acid, and citric acid) were screened for the extraction of xanthorrhizol from Curcuma xanthorrhiza . Ultrasound-assisted extraction using glucose/lactic acid (1:3) (GluLA) gave the best yield of xanthorrhizol. The response surface methodology with a Box-Behnken Design was used to optimize the interacting variables of water content, solid-to-liquid (S/L) ratio, and extraction to optimize the extraction. The optimum conditions of 30% water content in GluLA, 1/15 g/mL (S/L), and a 20 min extraction time yielded selective xanthorrhizol extraction (17.62 mg/g) over curcuminoids (6.64 mg/g). This study indicates the protective effect of GluLA and GluLA extracts against oxidation-induced DNA damage, which was comparable with those obtained for ethanol extract. In addition, the stability of the xanthorrhizol extract over 90 days was revealed when stored at -20 and 4 °C. The FTIR and NMR spectra confirmed the hydrogen bond formation in GluLA. Our study reported, for the first time, the feasibility of using glucose/lactic acid (1:3, 30% water v / v ) for the sustainable extraction of xanthorrhizol.

The investigation of micro or nano plastics behavior in the environment is essential to minimize the hazards of such pollutants on humans. While the conventional method requires sophisticated procedures and a lot of animal subjects, the nuclear technique confers a sensitive, accurate, and real-time method using radiolabeled micro or nano plastics as a tracer. In this study, polystyrene sulfonate-based microplastic (PSM) was developed with a size of around 3.6 μm, followed by radiolabeling with iodine-131 ( 131 I) or zinc-65 ( 65 Zn) for microplastic radiotracer model. After a stability study in seawater, phosphate buffer saline (PBS), and human serum albumin (HSA) for fifteen days, PSM- 131 I remained stable (>90 %), except in HSA (50-60 % after day-9), while PSM- 65 Zn was unstable (<50 %)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Internal radiotherapy delivers radioactive sources inside the body, near to or into malignant tumours, which may be particularly effective when malignancies are not responding to external beam radiotherapy. A pure beta emitter, 90 Y, is currently used for internal radiotherapy. However, theranostic radionuclide-doped microspheres can be developed by incorporating 153 Sm, which emits therapeutic beta and diagnostic gamma energies. This study investigated the production of high concentrations of samarium-content doped phosphate-based glass microspheres. The glass P60 (i.e. 60P 2 O 5 -25CaO-15Na 2 O) was mixed with Sm 2 O 3 at ratios of 75:25 (G75:Sm25), 50:50 (G50:Sm50) and 25:75 (G25:Sm75) and processed via flame spheroidisation. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) confirmed the microsphere uniformity with significantly high samarium content up to 44 % in G25:Sm75. Via X-ray diffraction (XRD) analysis, samarium-doped microspheres appeared to be glass-ceramic in nature. Mass-loss, size and pH changes were performed over 28 days, revealing a significant increase in samarium microsphere stability. After 15 min of neutron activation (neutron flux 3.01 × 10 13  n.cm -2 .s -1 ), the specific activity of the microspheres (G75:Sm25, G50:Sm50 and G25:Sm75) was 0.28, 0.54 and 0.58 GBq.g -1 , respectively. Therefore, the samarium microspheres produced in this study provide great potential for improving internal radiotherapy treatment for liver cancer by avoiding complex procedures and using less microspheres with shorter irradiation time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We produced spherical gold-198 nanoparticles with an average size of 41 nm, good stability, and high radiochemical purity for a promising single agent of radio-photothermal therapy using Curcuma longa rhizome extract as a reducing and capping agent. The combination of in vitro treatment using gold-198 nanoparticles and irradiation of 980 nm wavelength lasers with a power output of 2 W/cm 2 induced hyperthermia temperature and exhibited enhancement of the percentage dead on MDA-MB-123 cancer cells compared to gold-198 nanoparticles alone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prostate-specific membrane antigen (PSMA) represents a promising target for PSMA-overexpressing diseases, especially prostate cancer-a common type of cancer among men worldwide. In response to the challenges in tackling prostate cancers, several promising PSMA inhibitors from a variety of molecular scaffolds (e.g., phosphorous-, thiol-, and urea-based molecules) have been developed. In addition, PSMA inhibitors bearing macrocyclic chelators have attracted interest due to their favorable pharmacokinetic properties. Recently, conjugating a small PSMA molecule inhibitor-bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator, as exemplified by [ 177 Lu]Lu-PSMA-617 could serve as a molecular imaging probe and targeted radioligand therapy (TRT) of metastatic castration resistant prostate cancer (mCRPC). Hence, studies related to mCRPC have drawn global attention. In this review, the recent development of PSMA ligand-617-labeled with 177 Lu for the management of mCRPC is presented. Its molecular mechanism of action, safety, efficacy, and future direction are also described., Competing Interests: The authors declare no conflict of interests., (©2023 The Authors.)

Curculigo latifolia (family Amaryllidaceae) is used empirically for medicinal purposes. It is distributed throughout Asian countries, especially Indonesia. This study aimed at standardizing the C. latifolia plant, analyzing its phytochemical profile, and evaluating its pharmacological effects. The powder from each organ (root, stem, and leaves) was standardized organoleptically and microscopically. Samples were extracted by graded maceration using hexane, ethyl acetate, and ethanol. The extracts were determined for total phenolic content (TPC) and total flavonoid content (TFC). Antioxidant (radical scavenging and metal ion reduction) and antityrosinase activities were determined by spectrophotometric methods. Extracts were analysed for phytochemical profiles by LC-ESI-MS. The highest TPC and TFC were found in the ethanolic extract of the root organ (68.63 ± 2.97 mg GAE/g) and the ethyl acetate extract of the stem (14.33 ± 0.71 mg QE/g extract). High antioxidant activities were found in the ethanolic root extract (20.42 ± 0.33  µ g/mL) and ethanolic stem extract (45.65 ± 0.77  µ g/mL) by DPPH• and NO• assays, respectively. The ion reduction activity (by CUPRAC assay) was most significant in the ethyl acetate stem extract (390.42 ± 14.49  µ mol GAEAC/g extract). Ethanolic root extract was the most active in inhibiting tyrosinase (IC 50 value of 108.5  µ g/mL). The correlation matrix between TPC and antioxidant activities showed a moderate to robust correlation, whereas the TPC and antityrosinase activity showed a robust correlation. The TFC and antioxidant or antityrosinase activities showed a weak to moderate correlation. The LC-ESI-MS data identified major phenols in the active extracts, including methyl 3-hydroxy-4-methoxy-benzoate, quercetin, 4-O-caffeoylquinic acid-1, and curculigoside. Overall, this study suggests that extracts from the C. latifolia plant offer potent antioxidant and antityrosinase activities, allowing them to be used as natural antioxidants and candidates for skin-lightening compounds., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Syamsu Nur et al.)

Curculigo latifolia is a plant in the Hypoxidaceae family commonly used in herbal medicine. The study objective was to evaluate the antioxidant and anti-elastase properties of C. latifolia extracts in vitro and silico as a candidate for antiaging active ingredients. This study identified secondary metabolites of the hexane (HE), ethyl acetate (EAE), and ethanol extracts (EE) from the root (R), stem (S), and leaf (L) organs by LC-ESI-MS and evaluated in vitro antioxidant and inhibitor elastase activity. An antioxidant evaluation was performed using ABTS, Beta Carotene Bleaching (BCB), and Ferric Reduction Antioxidant Power (FRAP). Evaluation of anti-elastase was carried out using elastase and followed by an in silico study of molecular docking using the target protein elastase (1B0F). Fifteen C. latifolia metabolites were identified in C. latifolia extracts, most of which were phenolic compounds. In antioxidant testing, REE, REAE, SEE, and SEAE extracts showed potent antioxidant activity based on the ABTS, BCB, and FRAP methods. In anti-elastase testing, it was found that SEE, REE, REAE, and RHE extracts gave powerful inhibition of elastase activity (in the ranges of 16.89 to 27.91 µg/mL). The in-silico study demonstrated the potential of the identified metabolites to bind to the target protein 1B0F involved in remodeling the skin aging process. This research concludes that the extracts from C. latifolia have the potential to serve as an active antiaging source., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Berna Elya reports financial support, article publishing charges, equipment, drugs, or supplies, and statistical analysis were provided by the Indonesian Ministry of Higher Education and Culture. Muhammad Hanafi reports a relationship with the National Research and Innovation Agency Republic of Indonesia that includes: consulting or advisory., (© 2023 The Authors.)

Despite recent encouraging pharmaceutical and technical breakthroughs in neurosurgical critical care, traumatic brain injury (TBI)-related mortality and morbidity remain substantial clinical issues. Medication of statins was revealed to enhance outcomes following TBI in animal research. In addition to their main role of decreasing serum cholesterol, statins decrease inflammation and enhance cerebral blood flow. However, research on the efficacy of statins in TBI is still limited. This systematic review was conducted to determine the efficacy of statins in enhancing the clinical outcomes of TBI individuals, and specifically investigate the optimal dose and form of statins. The databases of PubMed, DOAJ, EBSCO, and Cochrane were extensively researched. The date of publication within the last fifteen years was the inclusion criterion. Meta-analyses, clinical trials, and randomized controlled trials were prioritized forms of research publications. Ambiguous remarks, irrelevant correlations to the main issue, or a focus on disorders other than TBI were the exclusion criteria. Thirteen research were included in this study. Simvastatin, atorvastatin, and rosuvastatin were the main form of statins discussed in this study. Enhancement of the Glasgow Coma Scale, survival rates, hospital length of stay, and cognitive outcomes were revealed in this study. This study suggests either simvastatin 40 mg, atorvastatin 20 mg, or rosuvastatin 20 mg for 10 days as the optimal therapeutic forms and doses to be applied in the management of TBI. Pre-TBI statin use was linked to lower risk of mortality in TBI individuals compared to nonusers, whereas statin discontinuation was linked to an increase in mortality., Competing Interests: All author declare no conflict of interest., (© 2023 The Authors.)

Thalassemia is the most common genetic disease in Indonesia and is passed on to the next generation following an autosomal recessive Mendelian inheritance pattern. The number of thalassemia sufferers in Indonesia increased from 4896 in 2012 to 8761 in 2018. The latest data in 2019 shows a significant increase to 10,500 patients. Community nurses who work at the Public Health Center, have full roles and responsibilities in carrying out promotive and preventive efforts against thalassemia cases. Promotive efforts that can be carried out are guided by government policies (Ministry of Health, Republic of Indonesia) which stipulate primary efforts in the form of education about thalassemia disease, prevention efforts, and diagnostic tests that can be taken. To optimize the promotive and preventive efforts, community nurses need to collaborate with midwives and cadres at integrated service posts. Interprofessional collaboration between stakeholders can strengthen the government's consideration in making policies for dealing with thalassemia cases in Indonesia., (© 2023 [The Author/The Authors].)

Purpose: The application of contrast and tracing agents is essential for lung imaging, as indicated by the wide use in recent decades and the discovery of various new contrast and tracing agents. Different aerosol production and pulmonary administration methods have been developed to improve lung imaging quality. This review details and discusses the ideal characteristics of aerosol administered via pulmonary delivery for lung imaging and the methods for the production and pulmonary administration of dry or liquid aerosol., Methods: We explored several databases, including PubMed, Scopus, and Google Scholar, while preparing this review to discover and obtain the abstracts, reports, review articles, and research papers related to aerosol delivery for lung imaging and the formulation and pulmonary delivery method of dry and liquid aerosol. The search terms used were "dry aerosol delivery", "liquid aerosol delivery", "MRI for lung imaging", "CT scan for lung imaging", "SPECT for lung imaging", "PET for lung imaging", "magnetic particle imaging", "dry powder inhalation", "nebuliser", and "pressurised metered-dose inhaler"., Results: Through the literature review, we found that the critical considerations in aerosol delivery for lung imaging are appropriate lung deposition of inhaled aerosol and avoiding toxicity. The important tracing agent was also found to be Technetium-99m ( 99m Tc), Gallium-68 ( 68 Ga) and superparamagnetic iron oxide nanoparticle (SPION), while the essential contrast agents are gold, iodine, silver gadolinium, iron and manganese-based particles. The pulmonary delivery of such tracing and contrast agents can be performed using dry formulation (graphite ablation, spark ignition and spray dried powder) and liquid aerosol (nebulisation, pressurised metered-dose inhalation and air spray)., Conclusion: A dual-imaging modality with the combination of different tracing or contrast agents is a future development of aerosolised micro and nanoparticles for lung imaging to improve diagnosis success., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Italian Association of Nuclear Medicine and Molecular Imaging 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: To devise a patient-informed time series model that predicts liver contrast enhancement, by integrating clinical data and pharmacokinetics models, and to assess its feasibility to improve enhancement consistency in contrast-enhanced liver CT scans., Methods: The study included 1577 Chest/Abdomen/Pelvis CT scans, with 70-30% training/validation-testing split. A Gaussian function was used to approximate the early arterial, late arterial, and the portal venous phases of the contrast perfusion curve of each patient using their respective bolus tracking and diagnostic scan data. Machine learning models were built to predict the Gaussian parameters of each patient using the patient attributes (weight, height, age, sex, BMI). Pearson's coefficient, mean absolute error, and root mean squared error were used to assess the prediction accuracy., Results: The integration of the pharmacokinetics model with a two-layered neural network achieved the highest prediction accuracy on the test data (R 2  = 0.61), significantly exceeding the performance of the pharmacokinetics model alone (R 2  = 0.11). Applying the model demonstrated that adjusting the contrast administration directed by the model may reduce clinical enhancement inconsistency by up to 40 %., Conclusions: A new model using a Gaussian function and supervised machine learning can be used to build liver parenchyma contrast enhancement prediction model. The model can have utility in clinical settings to optimize and improve consistency in contrast-enhanced liver imaging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Xanthorrhizol (XTZ), a bisabolene sesquiterpenoid, is abundantly found in the plant Curcuma xanthorrhiza Roxb. Traditionally, C. xanthorrhiza is widely used for the treatment of different health conditions, including common fever, infection, lack of appetite, fatigue, liver complaints, and gastrointestinal disorders. XTZ exhibits wide-ranging pharmacological activities, including anticancer, antioxidative, anti-inflammatory, antimicrobial, and antidiabetic activities, in addition to a protective effect on multiple organs. The present review provides detailed findings on the anticancer activities of XTZ and the underlying cellular and molecular mechanisms., Methods: Literature was searched systematically in main databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with keywords "tumor AND xanthorrhizol" or "cancer AND xanthorrhizol"., Results: Studies show that XTZ has preventive and therapeutic activities against different types of cancer, including breast, cervical, colon, liver, lung, oral and esophageal, and skin cancers. XTZ regulates multiple signaling pathways that block carcinogenesis and proliferation. In vitro and in vivo studies showed that XTZ targets different kinases, inflammatory cytokines, apoptosis proteins, and transcription factors, leading to the suppression of angiogenesis, metastasis, and the activation of apoptosis and cell cycle arrest., Conclusion: The potential anticancer benefits of XTZ recommend further in vivo studies against different types of cancer. Further, XTZ needs to be confirmed for its toxicity, bioavailability, protective, antifatigue, and energy booster activities. Future studies for the therapeutic development of XTZ may be directed to cancer-related fatigue., (Copyright © 2022. Published by Elsevier GmbH.)

Mesoporous gamma-alumina (MGA) was synthesized for neutron-activated 99 Mo adsorbent. Acid functionalization of the MGA was carried out to enhance the Mo adsorption capacity and the 99 Mo breakthrough profile. The acid-treated MGA has a more positive particle charge, rougher surface, smaller particle and pore size, larger surface area, and wider pore distance. The acid-treated MGA has a Mo adsorption capacity of 82.8 ± 6.3 mg Mo/g and resulted in 99m Tc eluate with the 99 Mo breakthrough at the acceptable level., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Biomass discharged from primary industries can be converted into methane by fermentation. This methane is used for generating electricity with solid oxide fuel cells (SOFCs). This methane fermentation provides H 2 S, which reduces the efficiency of SOFCs even at a level as low as a few parts per million. It has been experimentally reported that a nitrogen (N)-doped graphene-based material known as pyridinic N removes H 2 S via an oxidation reaction compared with another graphene-based material known as oxidized N. To understand this experimental result, we investigated H 2 S adsorption on pyridinic N and oxidized N by a density functional theory analysis and further examined the activation barrier of dissociation reactions. We found that the adsorption of H 2 S on pyridinic N is more stable than that on oxidized N. In addition, the H 2 S dissociation reaction occurs only on pyridinic N., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Antidesma is a genus of plants, and its several species are known to have antidiabetic properties. Leaves of Kayu Tuah ( Antidesma celebicum Miq) have been proven to have the best α -glucosidase inhibition ability compared to other species in the Antidesma genus, as evidenced by the in vitro α -glucosidase inhibition test. However, no scientific studies have reported its antidiabetic properties and toxicity in vivo. Therefore, this research managed to verify the antidiabetic features and safety of ethanolic extract of A. celebicum leaves (EEAC) in Sprague-Dawley rats. Male rats (170-280 g) were induced diabetic with streptozotocin (35 mg/kg BW) and fed a high-fat diet comprising 24% fat, whereas control group rats were given a standard diet. Rats were treated with EEAC at 200 and 400 mg/kg BW doses for 28-days and 60 mg/kg BW acarbose for the control group. Determination of antidiabetic properties was done by analyzing lipid profiles as well as fasting blood glucose. After confirming the antidiabetic properties of EEAC, the toxicological assessment was determined using the fixed-dose method. General behavior changes, appearance, signs of toxicity, mortality, and body weight of animals were marked down during the observation period. When the treatment period ended, hematological, biochemical, and histological examinations of liver, kidneys, and heart sections were performed. The results confirmed that EEAC reduced fasting blood glucose levels and stepped forward lipid profiles of rats. Also, all animals survived, and no obvious destructive outcomes were noticeable during the study. As EEAC has promising results toward hyperglycemia and hyperlipidemia and has been proven safe through toxicity tests, it can be concluded that EEAC has good potential to be further developed into antidiabetic drugs., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Raysa Y. Pratiwi et al.)

Background: The COVID-19 pandemic has become a global public health issue, and the roles of nurses are very much needed in providing nursing services in the current situation. The enforcement of appropriate nursing diagnoses for patients with COVID-19 is also fundamental in determining proper nursing care to help the patients achieve maximum health., Objective: This study aimed to describe and analyze nursing diagnoses in patients with COVID-19 treated in the isolation rooms and ICUs., Methods: This study used a secondary data analysis from hospital medical record data of patients with COVID-19 from early December 2020 to the end of February 2021. Data were selected using a cluster random sampling technique and analyzed using descriptive statistics., Results: The results showed that the signs and symptoms of the patients with COVID-19 that often appeared were fever, cough, shortness of breath, and decreased consciousness. The common nursing diagnoses in the hospitalized patients with COVID-19 were hyperthermia, ineffective airway clearance, gas exchange disorder, self-care deficit, spontaneous ventilation disorder, spontaneous circulation disorder, knowledge deficit, and shock risk., Conclusion: This study offers an insight into nursing practices in the hospital setting, which can be used as a basis for nurses to perform complete nursing assessments and nursing diagnoses during the pandemic., Competing Interests: The authors declare that they have no conflict of interest in this study., (© The Author(s) 2022.)

Andrographis paniculata , Syzygium cumini , and Caesalpinia sappan are used as traditional medicines to treat diabetes mellitus. Therefore, this study aims to examine the antidiabetic effects and the acute toxicity of combined extract (1:1:1) of A. paniculata , S. cumini , and C. sappan (ASCE). The antidiabetic effect was tested using the rats model, induced by a high-fat diet and a double dose of streptozotocin injection of 35 mg/kg BW. Subsequently, diabetic rats in the experimental group were treated with 75 mg/kg BW and 150 mg/kg BW of ASCE, and those in the diabetic control group were treated with metformin 250 mg/kg BW. After seven days of treatment, fasting blood glucose (FBG), pancreatic β-cells numbers, and lipid profiles were used to analyze the antidiabetic effect. The results showed that the administration of 150 mg/kg BW ASCE significantly reduced FBG ( p < 0.01), cholesterol levels ( p < 0.05), LDL levels ( p < 0.05), but not triglycerides, compared to diabetic control, this effect was comparable to metformin treatment. In addition, the pancreatic β-cells numbers were likely increased after ASCE treatment in a dose-dependent manner. The oral administration of a single dose of ASCE was safe up to 5000 mg/kg BW and did not result in any significant difference in body weight, relative organ weight, hematological and biochemical parameters compared with the control group. Therefore, it can be concluded that ASCE has a potential antidiabetic effect and can be safely developed as alternative medicine., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Real-time performance is important in rule-based continuous spatiotemporal query processing for risk analysis and decision making of target objects collected by sensors of combat vessels. The existing Rete algorithm, which creates a compiled node link structure for executing rules, is known to be the best. However, when a large number of rules are to be processed and the stream data to be performed are large, the Rete technique has an overhead of searching for rules to be bound. This paper proposes a hashing indexing technique for Rete nodes to the overhead of searching for spatiotemporal condition rules that must be bound when rules are expressed in a node link structure. A performance comparison evaluation experiment was conducted with Drool, which implemented the Rete method, and the method that implemented the hash index method presented in this paper. For performance measurement, processing time was measured for the change in the number of rules, the change in the number of objects, and the distribution of objects. The hash index method presented in this paper improved performance by at least 18% compared to Drool.

The Superconducting Analyzer for MUlti-particles from RAdioIsotope (SAMURAI) Pion-Reconstruction and Ion-Tracker Time Projection Chamber (SπRIT TPC) was designed to enable measurements of heavy ion collisions with the SAMURAI spectrometer at the RIKEN radioactive isotope beam factory and provides constraints on the equation of state of neutron-rich nuclear matter. The SπRIT TPC has a 50.5 cm drift length and an 86.4 × 134.4 cm 2 pad plane with 12 096 pads that are equipped with the generic electronics for TPCs. The SπRIT TPC allows for an excellent reconstruction of particles and provides isotopic resolution for pions and other light charged particles across a wide range of energy losses and momenta. The details of the SπRIT TPC are presented, along with discussion of the TPC performance based on cosmic rays and charged particles emitted in heavy ion collisions.

Brain tumors are challenging to handle and cause severe mortality and morbidity. The primary therapy for brain tumors, a combination of radiotherapy, chemotherapy (i.e temozolomide), and corticosteroids, is considered inadequate to improve patients' clinical conditions and associated with many adverse effects. There is an urgent need for new compounds or repurposing of existing therapies, which could improve brain tumor patients' prognosis. Metformin, commonly used for type 2 diabetes medication, has been examined for its protective action in cancer, reducing cancer risk and cancer-related mortality. However, its effect on cancer is still in rigorous debate. This study examines recent studies on the effects of metformin in primary brain tumor patients through systematic reviews. The literature search was performed on PubMed, ScienceDirect, and SpringerLink databases for articles published between 2013 and 2020. We selected clinical studies comparing the therapeutic outcomes of brain tumor therapy with and without metformin. The clinical benefits of the drug were assessed through the overall survival (OS) and progression-free survival (PFS) of brain tumor patients. Those studies demonstrated that the combination of metformin with temozolomide given post-radiotherapy resulted in better OS and PFS . Nonetheless, the efficacy and safety of metformin need further clinical testing in the wider population., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

The volume and value of fish catches by Indonesia's small-scale fisheries have declined significantly since national government restrictions on travel and social distancing were imposed in response to the COVID-19 pandemic. Using a digital data collection system (OurFish), that records purchases by fish traders from small-scale fishers, data was collected across 82 coastal communities in Southeast Sulawesi. We found that the number of active fishers and traders declined by more than 90% after the onset of the pandemic and the average weight of catch per fishing trip increased across fishers. Although the average price per kilogram of fish declined after the pandemic began, fishers that were able to maintain fishing had on average higher catches and therefore daily catch value was maintained. High value fisheries that usually enter export supply chains were more negatively impacted compared with lower value species that are commonly sold to local markets. We interviewed 185 small scale fishers and fish traders across 20 of the 82 communities in Southeast Sulawesi province, recording the perceived level of impact on local fisheries and the fish trade, causes of this impact and proposed coping strategies. Over 50% of both fishers and fish traders believed low demand for fish from traders and a decline in the price received for fish were disrupting their lives. Approximately 75% of both male and female fishers are coping by continuing to fish, highlighting that there were few alternative livelihoods available at the time of the interviews. Our results provide key insights into the vulnerability of small-scale fishing communities to impacts of the COVID-19 pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

Introduction: Researchers usually use herbal combinations to explore and develop traditional medicine to obtain additional benefits in the treatment of diseases, including diabetes. This study aims to evaluate the hypoglycemic effect of the combination of Andrographis paniculata (Burm. f.) Wall ex Nees and Caesalpinia sappan Linn extract (APCSE) on diabetes-induced rats. There has not been sufficient research on this combination; however, single extract studies of these plants have been widely conducted., Materials and Methods: Male Sprague Dawley rats (160-200 g) were induced by injecting a low dose of streptozotocin (35 mg/kg BW) twice and fed with a high-fat diet containing 25% fat, whereas control animals received only standard feed. Rats were treated with APCSE at doses of 100 mg and 200 mg/kg BW for seven days and compared to the APE and CSE groups treated with the extract at 100 mg, respectively. For the control group, rats were treated with metformin with a dose of 250 mg/kg. The antihyperglycemic and antihyperlipidemic effects were determined by measuring blood glucose levels and lipid profiles (cholesterol, triglycerides, HDL, and LDL). To assess the impact of the extract on pancreatic and adipose tissue, the number of pancreatic beta cells and adipocytes was evaluated through histopathological and immunohistochemical study. Results and Discussion . In a nonfasting state, the blood glucose change in APCSE 200 mg was 18.65% and was significantly lower from the DM group. However, a single extract of APE and CSE showed lower fasting blood glucose levels compared to the combined extract. Lipid profiles show no significant differences in cholesterol levels between groups; however, all treatment groups, including metformin, showed higher triglyceride levels. The APE-treated group showed significantly lower HDL and LDL, whereas CSE only showed lower LDL. The β -cell number was significantly higher after treatment with single extract CSE. The CSE and the combined extract groups showed hyperplasia adipocytes., Conclusion: The combined extract of APCSE has a moderate antihyperglycemic effect; however, a single extract may have better potential than the combined extract., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Febrika Wediasari et al.)

Objective: To determine the correlation between patient attributes and contrast enhancement in liver parenchyma and demonstrate the potential for patient-informed prediction and optimization of contrast enhancement in liver imaging., Methods: The study included 418 chest/abdomen/pelvis computed tomography scans, with 75% to 25% training-testing split. Two regression models were built to predict liver parenchyma contrast enhancement over time: first model (model A) utilized patient attributes (height, weight, sex, age, bolus volume, injection rate, scan times, body mass index, lean body mass) and bolus-tracking data. A second model (model B) only used the patient attributes. Pearson coefficient was used to assess predictive accuracy., Results: Weight- and height-related features were found to be statistically significant predictors (P < 0.05), weight being the strongest. Of the 2 models, model A (r = 0.75) showed greater accuracy than model B (r = 0.42)., Conclusions: Patient attributes can be used to build prediction model for liver parenchyma contrast enhancement. The model can have utility in optimization and improved consistency in contrast-enhanced liver imaging.

Aim: This research aimed to study the effect of leaf extract of cashew as a bioactive compound in feed on the morphology of the small intestine in Jawa Super chicken ( Gallus gallus domesticus )., Materials and Methods: This study used 72 1-day-old Jawa Super chicks reared for a further 16 days. We used a randomized complete design, in which basal feed was supplemented with ethanolic extract of cashew leaves at 0 g/kg feed (control), 1.25 g/kg feed (P1), 2.5 g/kg feed (P2), 5 g/kg feed (P3), 10 g/kg feed (P4), and 20 g/kg feed (P5). Parameters observed included growth performance, chicken morphometry, and morphology of the small intestine, comprising the length and width of the villi, the depth of the crypt, and the number and size of goblet cells in the duodenum, jejunum, and ileum. Data analysis was conducted using one-way ANOVA followed by Duncan's test, with significance defined as p<0.05., Results: Ethanolic extract of cashew leaf significantly increased body weight, feed efficiency, body morphometry, villus length, crypt depth, number of goblet cells, and extent of goblet cell area of the small intestine at 16 days. The morphological results from the small intestine showed that P4 and P5 were significantly better than control., Conclusions: Cashew leaf ethanolic extract mixed with 10 g/kg basal feed is effective as a natural feed supplement for Jawa Super chickens.

Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in L-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as L-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of L-arginine bioavailability and NO 2 - were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas L-arginine levels were significantly reduced, and these changes were followed by reductions in NO 2 - levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with L-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma L-arginine and NO 2 - levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.

Oxidative stress is widely known to play a role in asthma. However, the contribution of xanthine oxidoreductase (XOR) as a source of the superoxide anion radical (O2－) in oxidative stress associated with asthma has not yet been examined in detail. Here we investigated pathophysiological changes in XOR in an experimental model of asthma induced by the house dust mite Dermatophagoides farinae (Df). In the lungs of Df-treated mice, the production of O2 － from XOR increased and the nitrite concentrations decreased, whereas the protein expression of XOR remained unchanged. Moreover, the protein expression levels of XOR and the hydrogen peroxide (H2O2) concentrations in bronchoalveolar lavage fluid (BALF) were higher in the Df-treated mice than in saline-treated mice. Immunohistochemically, although XOR was highly localized in the bronchial epithelial cells of the saline-treated mice, immunostaining for XOR was absent in the bronchial epithelium of Df-treated mice. These results suggest that oxidative stress is up-regulated by increases in the conversion of the dehydrogenase form (xanthine dehydrogenase; XDH) of XOR to the oxidase form (xanthine oxidase; XOD).

Changes in l-arginine metabolism, including increased arginase levels and decreased nitric oxide production, are involved in the pathophysiology of asthma. In this study, using an intranasal mite-induced NC/Nga mouse model of asthma, we examined whether administration of l-arginine ameliorated airway hyperresponsiveness and inflammation by altering l-arginine metabolism. Experimental asthma was induced in NC/Nga mice via intranasal administration of mite crude extract (50 µg/day) on 5 consecutive days (days 0-4, sensitization) and on day 11 (challenge). Oral administration of l-arginine (250 mg/kg) was performed twice daily on days 5-10 for prevention or on days 11-13 for therapy. On day 14, we evaluated the inflammatory airway response (airway hyperresponsiveness, the number of cells in the bronchoalveolar lavage fluid, and the changes in pathological inflammation of the lung), arginase expression and activity, l-arginine bioavailability, and the concentration of NOx, the end products of nitric oxide. Treatment with l-arginine ameliorated the mite-induced inflammatory airway response. Furthermore, l-arginine administration attenuated the increases in arginase expression and activity and elevated the NOx levels by enhancing l-arginine bioavailability. These findings indicate that l-arginine administration may contribute to the improvement of asthmatic symptoms by altering l-arginine metabolism.

Objective: Even though diabetes patients exhibit an increased oxidative stress, its correlation with diabetic nephropathy is not fully understood. The purpose of this study was to determine whether lipid peroxidation marker correlates well with eGFR and UACR in type 2 diabetes mellitus patients., Methods: We collected urine and serum samples of Indonesian type 2 diabetes mellitus outpatients with normo- and microalbuminuria at a Local Government Clinic (from ages: 39-74 years). Urinary 8-iso-PGF2α was measured by ELISA, the serum malondialdehyde by TBARS assay, and urinary albumin by BCG albumin assay. eGFR was calculated using the corrected-Cockcroft-Gault (CG), MDRD, and CKD-EPI equation. Other necessary data were obtained through questionnaires., Results: The results showed that the increasing level of malondialdehyde was mildly correlated with the decline in eGFR (MDRD). In contrary, there was a significant positive correlation between 8-iso-PGF2α concentration and eGFR based on the corrected-CG, MDRD study, and CKD-EPI equation (r=0.457, p<0.001; r=0.424, p<0.001; r=0.443, p<0.001). This relationship still persisted in the normoalbuminuric subjects (n=43) (r=0.491, p=0.001; r=0.461, p=0.002; r=0.455, p=0.002). The multivariate analysis showed that 8-iso-PGF2α together with fasting plasma glucose was the most predictive factor for the high 2-quantile eGFR (adjusted OR 1.001, (95% CI, 1.000-1.001)). However, there was no significant correlation between UACR with malondialdehyde (r=0.268, p=0.050) and 8-iso-PGF2α(r=-0.030, p=0.808). UACR itself was inversely correlated with eGFR based on the corrected-CG, the MDRD, and CKD-EPI (r=-0.232, p<0.05; r=-0.228, p<0.05; r=-0.232, p<0.05)., Conclusions: Increased 8-iso-PGF2α and malondialdehyde in type 2 diabetes mellitus patients may play a role in the pathophysiologic significance of diabetic nephropathy, even while considering the effect of potential confounders., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The associations of serum arginase I with serum L-arginine, serum 3-nitrotyrosine, and fractional exhaled nitric oxide (FENO) were evaluated cross-sectionally in healthy Japanese workers. The serum median (minimum-maximum) levels of arginase I, 3-nitrotyrosine, and FENO in healthy people (n = 130) were 14.6 (0.94-108.1) ng/mL, 81.0 (0.27-298.6) pmol/mg protein, and 14.0 (5.0-110.0) parts per billion, respectively. Significant correlations of arginase I with FENO, L-arginine, 3-nitrotyrosine, and percent predicted forced expiratory volume in 1 s (FEV1 (% predicted)) were observed, and correlations of FENO with immunoglobulin E (IgE), NOx, arginase I, and sex and allergy were also observed. By multiple regression analysis, arginase I showed positive associations with FENO and 3-nitrotyrosine, and a negative association with L-arginine; and FENO showed positive associations with IgE and NO2(-) + NO3(-) (NOx), and a negative association with L-arginine, as well as an association with sex. Moreover, logistic regression analysis showed linear inverse associations of arginase I and 3-nitrotyrosine with L-arginine, and showed linear positive associations of FENO with IgE and NOx. It was concluded that serum arginase I might regulate serum L-arginine and 3-nitrotyrosine via L-arginine, and that IgE or NOx might regulate FENO in a healthy Japanese population.

Objective: We reported previously that serum arginase I increased in asthmatic patients and was associated with oxidative stress in a small healthy population. However, the exact association of arginase I with oxidative stress is not known. The present study aimed to analyze the association of arginase I with oxidative stress in a larger healthy population by a newly established ELISA., Design and Methods: The new ELISA for the measurement of human arginase I was established by generating recombinant arginase I protein in human arginase I gene-transfected Escherichia coli via an ARG1 cDNA fragment-inserted vector and -specific antibody in rabbits. Serum arginase I was evaluated in a cross-sectional study on a healthy population (n=721) by comparing a commercial ELISA kit with the new ELISA., Results: The mean levels of serum arginase I were 20.3 ± 0.7 ng/mL and 4.7 ± 0.2 ng/mL using the commercial ELISA kit and the new ELISA, respectively. Arginase I was correlated with WBC, RBC, hs-CRP, 8-OHdG, HDL-c, ALT, and BMI. Logistic regression analysis showed independent positive associations of arginase I with WBC, RBC, and urinary 8-OHdG and inverse independent associations with serum insulin and age. The association of arginase I with hs-CRP was not independent., Conclusion: The independent associations of arginase I with urinary 8-OHdG and serum insulin may reflect its involvement in oxidative stress and diabetes mellitus., (© 2013.)

Nitric oxide (NO) is produced from the conversion of L-arginine by NO synthase (NOS) and regulates a variety of processes in the gastrointestinal tract. Considering the increased activity of arginase in colitis tissue, it is speculated that arginase could inhibit NO synthesis by competing for the same L-arginine substrate, resulting in the exacerbation of colitis. We examined the role of arginase and its relationship to NO metabolism in dextran sulfate sodium (DSS)-induced colitis. Experimental colitis was induced in mice by administration of 2.5% DSS in drinking water for 8 days. Treatment for arginase inhibition was done by once daily intraperitoneal injection of N(ω)-hydroxy-nor- arginine (nor-NOHA). On day 8, we evaluated clinical parameters (body weight, disease activity index, and colon length), histological features, the activity and expression of arginase, L-arginine content, the expression of NO synthase (NOS), and the concentration of NO end-product (NOx: nitrite + nitrate). Administration of nor-NOHA improved the worsened clinical parameters and histological features in DSS-induced colitis. Treatment with nor-NOHA attenuated the increased activity of arginase, upregulation of arginase Ι at both mRNA and protein levels, and decreased the content of L-arginine in colonic tissue in the DSS-treated mice. Conversely, despite the decreased expression of NOS2 mRNA, the decreased concentration of NOx in colonic tissues was restored to almost normal levels. The consumption of L-arginine by arginase could lead to decreased production of NO from NOS, contributing to the pathogenesis of the colonic inflammation; thus, arginase inhibition might be effective for improving colitis.

Recently, arginase is suggested to regulate nitric oxide production by competing with nitric oxide synthase for the same substrate, L-arginine, in experimental asthma. We investigated the role of arginase and its relationship to nitric oxide production after spinal cord injury. Rats were subjected to laminectomy and complete transection of their spinal cords (injury group) or laminectomy only (sham group). In the injury group, arginase I was increased in the macrophages at the transection edge, and the peak was observed 48 h after spinal cord injury. However, nitric oxide production decreased significantly in the injury group despite increased nitric oxide synthase2 mRNA expression compared with the sham group. We also demonstrated the reduction in L-arginine concentrations, which was inversely associated with changes in arginase activity. Therefore, arginase appeared to regulate nitric oxide production by consuming L-arginine. The regulation of arginase activity and L-arginine levels may improve nitroxidative stress and reduce tissue damage in spinal cord injury.

Pelvic computed tomography was used to evaluate 74 women with persistent puerperal infection. There was at least one abnormal roentgenographic finding in 57, and these are correlated with clinical and surgical findings. In 16 women, a palpable pelvic mass was seen on tomography, however, masses not appreciated clinically were visualized in another 29 women, and in five, a clinically palpable mass was not visualized by tomography. In 12 women who had a normal pelvic examination, septic pelvic thrombophlebitis was diagnosed by tomography. Over-all, there was poor correlation with roentgenographic findings and uterine incisional necrosis and dehiscence. We conclude that pelvic tomography is useful to evaluate some women with persistent puerperal infection, but that these studies must be correlated with clinical findings.

Sonographic and radiographic fidings were reviewed in 27 patients with hepatic amebiasis. Sonography usually demonstrated nonspecific, peripheral, hypoechoic lesions. The only diagnostic sonographic appearance was a combination of a hypoechoic lesion and diaphragmatic disruption, which was found in four patients. About 50% of the patients had accompanying radiographic abnormalities that were nondiagnostic. These included elvation of the right hemidiaphragm, basilar pulmonary infiltrates, and pleural effusions. Liver abscesses occasionally grew during the first 2 weeks of treatment even though the patients were responding well to medical therapy. Lesions frequently became more anechoic and better defined on follow-up examinations. Successfully treated abscesses may calcify rather than diminish.

Stab wounds to the back present a diagnostic problem, since missed occult abdominal injuries can lead to serious morbidity. In a prospective study of 205 patients, the authors evaluated the usefulness of abdominal computed tomography (CT) in assessment of low-velocity penetrating injury to the back. CT results were classified into three groups. Category 1 included injuries limited to superficial subcutaneous tissue (n = 174); category 2, injuries to the retroperitoneal compartment (n = 18); and category 3, injuries within the peritoneal cavity (n = 13). Fifty patients underwent surgery, including 30 with category 1 injuries, nine with category 2 injuries, and eleven with category 3 injuries. CT categorization of injury, compared with surgical findings in these 50 patients, had a sensitivity of 85% and specificity of 93%. The CT interpretation was considered correct if it demonstrated peritoneal penetration or retroperitoneal injury potentially requiring surgery. The remaining 155 patients were managed nonoperatively, and none had late complications. Abdominal CT is a reliable diagnostic tool in the evaluation of penetrating injury to the back.

Thirty-two (32) patients with primary hyperparathyroidism (17 with prior localization surgery, 15 without) were studied by a combination of computed tomography (CT), ultrasound (US), nuclear medicine (NM), and magnetic resonance imaging (MRI) for parathyroid adenoma localization. The sensitivity and true-positive ratio of each imaging technique and various combinations of techniques were evaluated. Of the 28 proven parathyroid adenomas (27 by surgery, 1 by digital subtraction angiography), 24 were imaged by two techniques, 19 by three techniques, and 10 by all four imaging techniques. The sensitivities were NM (65%), CT (76%), US (77%), and MRI (81%). The differences between true-positive ratios of 82%, 64%, 71%, and 77%, respectively, were not statistically significant. If multiple techniques were considered as a single test (i.e., a positive localization requires two or more tests to be positive at the same location), then sensitivity for a two-study combination was 79% and true-positive ratio 86%. Three techniques showed a sensitivity of 63% and a true-positive ratio of 92%, four modalities 40% and 100%, respectively. There was no significant difference in the various combinations of techniques employed (e.g., CT and US, US and MR, NM and MR, etc.). Thus, there appears to be an advantage in performing multiple techniques (regardless of which combination is selected) until two tests are positive at the same location.