Specific Dose Research Articles

Binder jetting 3D printing in fabricating pharmaceutical solid products for precision medicine.

Current treatment strategies are moving towards patient-centricity, which emphasizes the need for new solutions allowing for medication tailored to a patient. This can be realized by precision medicine where patient diversity is considered during treatment. However, the broader use of precision medicine is restricted by the current technological solutions and rigid manufacturing of pharmaceutical products by mass production principles. Additive manufacturing of pharmaceutical products can provide a feasible solution to this challenge. In this review, a particular subtype of additive manufacturing, that is, binder jetting 3D printing, is introduced as a solution for fabricating pharmaceutical solid products that can be considered as precision medicine. Technical aspects, practical applications, unique advantages and challenges related to this technique are discussed, indicating that binder jetting 3D printing possesses the potential for fabricating already new product prototypes, where diversity in patient treatment in terms of the needs for specific drug type, dose and drug release can be accounted. To further advance this type of mass customization of pharmaceuticals, multidisciplinary research initiatives are needed not only to cover the engineering aspects but also to bridge these innovations with patient-centric perspectives.

Twenty years of network meta-analysis: Continuing controversies and recent developments.

Network meta-analysis (NMA) is an extension of pairwise meta-analysis (PMA) which combines evidence from trials on multiple treatments in connected networks. NMA delivers internally consistent estimates of relative treatment efficacy, needed for rational decision making. Over its first 20 years NMA's use has grown exponentially, with applications in both health technology assessment (HTA), primarily re-imbursement decisions and clinical guideline development, and clinical research publications. This has been a period of transition in meta-analysis, first from its roots in educational and social psychology, where large heterogeneous datasets could be explored to find effect modifiers, to smaller pairwise meta-analyses in clinical medicine on average with less than six studies. This has been followed by narrowly-focused estimation of the effects of specific treatments at specific doses in specific populations in sparse networks, where direct comparisons are unavailable or informed by only one or two studies. NMA is a powerful and well-established technique but, in spite of the exponential increase in applications, doubts about the reliability and validity of NMA persist. Here we outline the continuing controversies, and review some recent developments. We suggest that heterogeneity should be minimized, as it poses a threat to the reliability of NMA which has not been fully appreciated, perhaps because it has not been seen as a problem in PMA. More research is needed on the extent of heterogeneity and inconsistency in datasets used for decision making, on formal methods for making recommendations based on NMA, and on the further development of multi-level network meta-regression.

Correlation of photopatch positivity with clinical profile in patients with photoallergic dermatitis

Photopatch test (PPT) is designed to diagnose Photoallergic Contact Dermatitis (PACD) using specific dose and wavelength of irradiation. This study is a retrospective analysis of patients with photosensitivity who have undergone photopatch testing. To find the Correlation of photo patch positivity with clinical profile in patients with photoallergic dermatitis. Photo patch testing helps in determining the sensitizing potentials of commonly used day to day agents containing the allergen. Thirty-seven patients who had patch tested between July 2022and June 2023 were analyzed. The patch test antigens comprising 20 common photoallergens from Indian Standard Series were photopatch tested. Of all the patients tested the overall positivity rate was (67.56%). All patients had a characteristic clinical picture of photodermatitis for an variable duration. All patients were engaged in various occupations that involved working outdoors. The exacerbating factors were summer season in 15 (40.54%) patients, insecticides spraying in three (8.1%) and exposure to plant in ten (27%). History of contact with cement was present in six (16.21%) patients. The patients who showed positivity after irradiation was 5 (13.51 %), before and after irradiation was 7 (18.91%), and exacerbated grading after irradiation was 13 (35.13%). The commom allergen showing positivity were parthenium (29.72%), potassium dichromate (13.51%), PPD (10.81%). Apart from these allergens’ fragrance mix, paraben, neomycin sensitivity was also noted in few patients. Significant number of cases belongs to photodermatitis, thereby, finding the cause and the measures to alleviate the symptoms are paramount important. For proper diagnosis, photopatch test is essential and our study emphasis the same which can aid in appropriate management. Cosmetics, sunscreens and drugs like NSAID are found to be the emerging cause for PACD and photopatch series with relevence to above allergen is the need of the hour.

Effects of Individualized Exercise on Risk Factors of Metabolic Syndrome: A Scoping Review.

Exercise intervention is effective in alleviating the severity of metabolic syndrome (MetS). However, the results of previous studies on the effect of exercise on MetS have demonstrated considerable individual variability in response to a specific dose of exercise, which was attributed to the lack of a personalized approach to exercise prescription. It is essential to consider individual factors to enhance the effectiveness of exercise in addressing MetS. This scoping review assesses the effectiveness of individualized exercise on the risk factors associated with MetS. Various databases and articles were examined based on eligibility criteria and nine studies were chosen for this review. Personal and adjusted factors were predominantly analyzed to tailor exercise prescriptions to individual needs. This review proposes that personal factors can be classified into three categories: fixed factors, adaptation factors, and response factors, considering both clinical and exercise science perspectives. It also suggests that a two-way communication approach between specialists and individuals is more effective for prescribing exercise to address MetS compared to a one-way method. A one-way communication approach relies solely on an expert's decision, even whether or not he or she fully considers a client's lifestyle and preferences. If the individualized selection of exercise prescriptions is achieved through two-way communication between specialists and subjects, significant improvements can be expected in terms of both MetS severity and exercise adherence.

New insights in animal models of neurotoxicity-induced neurodegeneration.

The high prevalence of neurodegenerative diseases is an unintended consequence of the high longevity of the population, together with the lack of effective preventive and therapeutic options. There is great pressure on preclinical research, and both old and new models of neurodegenerative diseases are required to increase the pipeline of new drugs for clinical testing. We review here the main models of neurotoxicity-based animal models leading to central neurodegeneration. Our main focus was on studying how changes in neurotransmission and neuroinflammation, mainly in rodent models, contribute to harmful processes linked to neurodegeneration. The majority of the models currently in use mimic Parkinson's disease (PD) and Alzheimer's disease (AD), which are the most common neurodegenerative conditions in older adults. AD is the most common age-related dementia, whereas PD is the most common movement disorder with also cases of dementia. Several natural toxins and xenobiotic agents induce dopaminergic neurodegeneration and can reproduce neuropathological traits of PD. The literature analysis of MPTP, 6-OH-dopamine, and rotenone models suggested the latter as a useful model when specific doses of rotenone were administrated systemically to C57BL/6 mice. Cholinergic neurodegeneration is mainly modelled with the toxin scopolamine, which is a useful rodent model for the screening of protective drugs against cognitive decline and AD. Several agents have been used to model neuroinflammation-based neurodegeneration and dementia in AD, including lipopolysaccharide (LPS), streptozotocin, and monomeric C-reactive protein. The bacterial agent LPS makes a useful rodent model for testing anti-inflammatory therapies to halt the development and severity of AD. However, neurotoxin models might be more useful than genetic models for drug discovery in PD but that is not the case in AD where they cannot beat the new developments in transgenic mouse models. Overall, we should work using all available models, either in vivo, in vitro, or in silico, considering the seriousness of the moment and urgency of developing effective drugs.

Antioxidant and Anti-Inflammatory Properties of Quail Yolk Oil via Upregulation of Superoxide Dismutase 1 and Catalase Genes and Downregulation of EIGER and Unpaired 2 Genes in a D. melanogaster Model.

Quail egg yolk oil (QEYO) has a rich history of medicinal use, showcasing heightened antioxidant and bioactive properties in our prior studies. This positions QEYO as a promising candidate for therapeutic and cosmetic applications. In this investigation, QEYO was extracted using ethanol/chloroform and 2-propanol/hexane solvents. GC-MS and FTIR analyses quantified 14 major bioactive compounds in the ethanol/chloroform fraction and 12 in the 2-propanol/hexane fraction. Toxicity evaluations in fruit flies, spanning acute, sub chronic, and chronic exposures, revealed no adverse effects. Negative geotaxis assays assessed locomotor activity, while biochemical assays using fly hemolymph gauged antioxidant responses. Real-time PCR revealed the relative expression levels of the antioxidant and anti-inflammatory genes. FTIR spectra indicated diverse functional groups, and the GC-MS results associated bioactive compounds with the regulation of the anti-inflammatory genes EIGER and UPD2. While no significant change in SOD activities was noted, male flies treated with specific QEYO doses exhibited increased catalase activity and total antioxidant capacity, coupled with a significant decrease in their malondialdehyde levels. This study offers valuable insights into the bioactive compounds of QEYO and their potential regulatory roles in gene expression.

2-Hydroxy-1,4-Naphthoquinone: A Promising Redox Mediator for Minimizing Dissolved Organic Nitrogen and Eutrophication Effects of Wastewater Effluent.

Researchers and engineers are committed to finding effective approaches to reduce dissolved organic nitrogen (DON) to meet more stringent effluent total nitrogen limits and minimize effluent eutrophication potential. Here, we provided a promising approach by adding specific doses of 2-hydroxy-1,4-naphthoquinone (HNQ) to postdenitrification bioreactors. This approach of adding a small dosage of 0.03-0.1 mM HNQ effectively reduced the concentrations of DON in the effluent (ANOVA, p < 0.05) by up to 63% reduction of effluent DON with a dosing of 0.1 mM HNQ when compared to the control bioreactors. Notably, an algal bioassay indicated that DON played a dominant role in stimulating phytoplankton growth, thus effluent eutrophication potential in bioreactors using 0.1 mM HNQ dramatically decreased compared to that in control bioreactors. The microbe-DON correlation analysis showed that HNQ dosing modified the microbial community composition to both weaken the production and promote the uptake of labile DON, thus minimizing the effluent DON concentration. The toxic assessment demonstrated the ecological safety of the effluent from the bioreactors using the strategy of HNQ addition. Overall, HNQ is a promising redox mediator to reduce the effluent DON concentration with the purpose of meeting low effluent total nitrogen levels and remarkably minimizing effluent eutrophication effects.

Design and manufacture a syringe pump for intelligent injection of specific doses of contrast medicine in medical imaging applications

The construction of an Arduino Uno based syringe pump with the ability to measure the patient's body temperature during injection and detect the contrast material bubble has not been done so far. A syringe pump is a device that controls the volume and flow of milliliters to microliters for a certain period of time with very high precision, which gradually pushes the injection piston. This use of syringe pump for drug administration has been done for years. The working principle of this system consists of installing two steel rods to push the syringe piston at a set speed, which works through a coupling system. The advancement of technology has made it possible to use a motor as the driving force of the syringe filled with liquid released through the needle, and the electronic system in this tool is used as a controller. The design using a stepper motor based on Arduino Uno is chosen to adjust the flow rate; the research includes two stages of software and hardware construction. The hardware is implemented with the components needed to build a syringe pump with an Arduino Uno as the brain of the system and a stepper motor as a piston pusher.The flow rate in the syringe pump can be adjusted with the keyboard and displayed on the screen. It is also possible to see the patient's body temperature on the screen, and to detect bubbles in the contrast liquid during injection, we also put a sensor in this device that alerts the operator.

Revisión crítica de los ensayos clínicos publicados sobre la suplementación con vitamina D

ABSTRACT. Vitamin D is supplemented in individuals with or without risk factors for deficiency, although its effects at specific doses and frequency are controversial. In consequence, we aimed to perform an exhaustive review on the effects of vitamin D supplementation in randomized clinical trials in adult patients, grouped by target system and the evaluation criteria established in the objectives, by searching clinical trials published in the last 5 years in PubMed and EBSCO are included, with the keywords "vitamin D supplementation" AND effect, in English or Spanish, excluding participants &lt;19 years Our initial search yielded 91 results from two databases, of which 71 included studies. A total of 24 articles published a significant effect of vitamin D supplementation. Significant effects were identified in 3 of 4 studies in postmenopausal patients on bone density and/or strengthening of the musculoskeletal system. Other statistically significant effects were observed with supplementation in patients with high body mass index, in glucose control and glycosylated hemoglobin levels. We conclude that randomized clinical trials show significant effects in different organs and systems, the effect on glycemic control is promising, even when overrepresenting specific human groups.

Microbe-pesticide interactions: Soil enzyme analysis and bacterial degradation of chlorpyrifos

With the objective of understanding microbe—pesticide interactions in soil, the effect of pesticides alone and in combination on the activities of amylase, cellulase, and invertase was assessed in black, and red soils collected from the groundnut (Arachis hypogaea L.) cultivated fields of Andhra Pradesh, India. In addition, the potential bacteria that can break down chlorpyrifos was identified using biochemical assays and a partial 16S rRNA gene sequence analysis. Soil enzymes were analyzed using standard procedures described elsewhere. The activities of amylase, cellulase, and invertase were solely dependent on the dose of pesticides used in the current study. Enzyme activities were significantly increased at the level of 2.5 or 5.0 kg ha–1, whereas increases in the concentration of pesticides at 7.5–10 kg ha−1 were lethal to the enzyme activities in both soils at 10-day incubation. The effective combination for the increase in the activities of amylase, cellulase, and invertase were monocrotophos + mancozeb. Mineral salts medium with 50 ppm chlorpyrifos as a carbon source had the greatest growth of the bacteria (i.e. Pseudomonas citronellolis strain CF3) at 14th h of incubation with OD value of 0.24 at 660 nm, and the same strain could eliminate 75% of the chlorpyrifos within 24 h from the medium. Based on the present study it was concluded that insecticides used alone or in combination with fungicides at specific doses (2.5 or 5.0 kg ha−1) improved the amylase, cellulase, and invertase activities, which are involved in the carbon cycle in soils. Pseudomonas citronellolis strain CF3 is a potential bacterium in the remediation of chlorpyrifos-contaminated sites.

Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.

Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by cytochrome P450 (CYP) 2B6 enzyme. Several other enzymes are also involved in its bioactivation and affect its kinetics. Previous studies have shown the effect of the enzymes' genetic polymorphisms on Cy kinetics and its clinical outcome. These results were controversial primarily because of the involvement of several interacting enzymes in the Cy metabolic pathway, which can also be affected by several clinical factors as well as other drug interactions. In this review article, we present the effect of CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating enzyme, as well as discussing all previously reported enzymes and clinical factors that can alter Cy efficacy. Additionally, we present explanations for key Cy side effects related to the nature and site of its bioactivation. Finally, we discuss the role of busulphan in conditioning regimens in the Cy metabolic pathway as a clinical example of drug-drug interactions involving several enzymes. By the end of this article, our aim is to have provided a comprehensive summary of Cy pharmacogenomics and the effect on its kinetics. The utility of these findings in the development of new strategies for Cy personalized patient dose adjustment will aid in the future optimization of patient specific Cy dosages and ultimately in improving clinical outcomes. In conclusion, CYP2B6 and several other enzyme polymorphisms can alter Cy kinetics and consequently the clinical outcomes. However, the precise quantification of Cy kinetics in any individual patient is complex as it is clearly under multifactorial genetic control. Additionally, other clinical factors such as the patient's age, diagnosis, concomitant medications, and clinical status should also be considered.

Mechanisms of exercise intervention in type 2 diabetes: a bibliometric and visualization analysis based on CiteSpace.

Type 2 diabetes (T2D) is a common chronic metabolic disease, and its prevalence is increasing globally. Exercise is crucial for T2D management, yet many aspects of its mechanisms remain unclear. This study employs CiteSpace to reveal research hotspots and frontier issues in exercise intervention for T2D. A literature review spanning from January 1, 2013 to December 31, 2022, was conducted using the Web of Science Core Collection (WoSCC), with keywords including "exercise," "type 2 diabetes," and "mechanisms." We analyzed network diagrams generated by CiteSpace, which depicted relationships among countries, authors, and keywords. This study includes 1,210 English papers from 555 journals, affiliated with 348 institutions across 80 countries/regions. Notably, the United States, China, and the United Kingdom account for nearly half of all publications. The University of Copenhagen leads in publication volume, followed by Harvard Medical School and the University of Colorado. Key authors include Kirwan, John P (Case Western Reserve University), Malin, Steven K (Rutgers University), and Pedersen, Bente Klarlund (University of Copenhagen). Based on co-occurrence analysis of keywords, it is evident that terms such as "disease," "glucagon-like peptide 1," and "cardiovascular risk factor" exhibit high intermediary centrality. The analysis highlights ongoing investigations into molecular mechanisms, such as β-cell function enhancement, exerkines, and epigenetic mechanisms. Emerging areas include exercise response heterogeneity, circadian rhythm regulation, transcription factors, neurotrophic factors, and mitochondrial function. Future studies should prioritize understanding interactions between different exercise mechanisms and optimizing exercise prescriptions for T2D. Exercise prescriptions are crucial for effective interventions. Collaboration between countries and institutions is essential to understand the influences of different genetic backgrounds and environmental factors. Currently, a combination of aerobic and resistance training is considered the optimal form of exercise. However, considering time efficiency, high-intensity interval training (HIIT) has gained widespread attention and research due to its ability to achieve similar exercise effects in a shorter duration. Additionally, circadian rhythm regulation may affect the exercise outcomes of diabetic individuals at different times of the day, particularly concerning the specific types, doses, and intensities used for precision intervention in T2D.

Prevalence of vitamin B12 deficiency in patients treated with metformin

Background/Aim: Metformin has been associated with vitamin B 12 (cobalamin) deficiency, pushing scientific societies such as the American Diabetes Association and the European Association for the Study of Diabetes to emphasise the need for screening B 12 levels, without specific metformin doses or exposure durations triggering this screening. Robust data regarding the prevalence of B 12 deficiency in metformin-treated patients in Portugal are currently lacking. Aim of this study was to identify the prevalence of B 12 deficiency in a sample of diabetic patients taking metformin. Secondary objectives were determining the minimum dose and minimum and median time exposure time leading to this deficiency and identifying the average duration of metformin use in the patients with this deficiency. Methods: Descriptive and cross-sectional observational study was performed on a sample of 79 users from a population of 714 diabetic patients on metformin. Inclusion criteria comprised individuals aged 18 or older, receiving metformin for at least 1 month and voluntarily participating in the study. Exclusion criteria included a history of gastrectomy or B 12 supplementation. Results: A prevalence of 25.3 % of vitamin B 12 deficiency was identified in the study sample. Minimum doses of 500 mg of metformin per day and a minimum exposure period of 1 year were associated with B 12 deficiency. An average exposure time of 5.33 years was identified. Conclusion: These results align with the prevalence described in the few international studies and should alert physicians to potential clinical manifestations of this deficiency, such as anaemia and neurological symptoms like neuropathy.

Metadichol, a Natural Ligand for the Expression of Yamanaka Reprogramming Factors in Human Cardiac, Fibroblast, and Cancer Cell Lines

The reprogramming of somatic cells into embryonic-like stem cells requires the activation of four essential transcription factors, referred to as the Yamanaka factors: Sox2, Oct4, Klf4, and c-Myc. However, the utilization of these genes and viral vectors for their delivery presents a risk of carcinogenesis, which renders induced pluripotent stem cell (iPSC) lines unsuitable for clinical applications. Typically, direct reprogramming involves the use of viral vectors to induce the expression of these factors. In contrast, metadichol, a novel approach, enhances the expression of Yamanaka factors in cells using a dose ranging from 1 pg to 100 ng, thereby preventing the need for viral vectors. This non-viral method renders cellular reprogramming safer and more clinically viable. Treatment with metadichol within the specific dose range resulted in a substantial augmentation of the fibroblast expression of OCT4, SOX2, KLF4, KLF2, and Nanog, which was confirmed through qRT-PCR and western blot analyses. The expression levels of OCT4, KLF4, Nanog, and Sox2, exhibited an increase of 4.01-, 3.51-, 1.26-, and 2.5-fold, respectively, compared to the controls. Notably, A549 and Colo-205 cancer cells demonstrated a marked elevation in expression levels. The reprogramming of primary human cancer cells presents considerable challenges. However, in triple-negative primary breast cancer cells, metadichol treatment led to the substantial upregulation of the expression levels of OCT4, KLF4, Nanog, and Sox2 by 19.6-, 8.07-, 2.45-, and 6.91-fold, respectively, across the dose range of 1 pg to 100 ng. Klotho, an antiaging gene that is modulated by metadichol, down regulates TP53, a crucial factor for the production of somatic cell iPSCs. Additionally, metadichol enhances the availability of vitamin C, which is essential for generating iPSCs from somatic cells. Increased levels of alkaline phosphatase, indicative of cellular differentiation, were observed in the treated group compared to the controls. Metadichol is a nontoxic nanoemulsion that is derived from long-chain C26–C28 alcohols from food sources and activates Yamanaka factors across various cell types without requiring the use of viral or CRISPR-based methodologies, thus substantially advancing somatic cell reprogramming.

Transcranial photobiomodulation therapy improves cognitive test scores in dogs with presumptive canine cognitive dysfunction (CCD): A case series of five dogs

Background: Canine cognitive dysfunction (CCD) is considered the canine version of human Alzheimer’s disease (AD). As with AD, CCD is a multifactorial and progressive neurodegenerative disorder for which effective treatment options are continuously being sought. Transcranial photobiomodulation (tPBMT), or transcranial laser therapy, has shown promise as a treatment for cognitive impairment in rodent AD investigations and several human AD clinical trials. Aim: The purpose of this prospective case series was to evaluate the effect of transcranial photobiomodulation (tPBMT) on cognitive scores when applied to senior dogs with CCD over a 60-day period. Methods: Five senior (&gt;9-year-old) dogs with moderate (16-33) to severe (&gt;33) cognitive scores were enrolled. Owners were instructed on the use of a Class IM laser device and administered a specific dose of laser energy transcranially to both sides of the patient’s head, 3 times per week for one month and 2 times per week for a second month. No additional therapeutic measures aimed at enhancing cognitive ability were permitted during the 60-day evaluation time. Baseline cognitive scores were compared with scores obtained at 30-and 60-days post-treatment. Results: Cognitive scores showed improvement in 4/5 dogs at 30 days (27.6% reduction) and all dogs at 60 days (43.4% reduction). There were no adverse effects attributable to tPBMT. Conclusion: Results of our small case series suggest that tPBMT may improve cognitive scores in dogs with moderate to severe CCD by 30 days of application and the improvement is sustained at 60 days. Further studies are needed to ascertain optimal tPBMT protocols for CCD.

Comparative Study of Image Quality and Radiation Dose between 120kVp Filtered Back Projection and 80kVp Iterative Reconstructed Computed Tomography Images

Background: Iterative Reconstruction techniques have been shown to produce diagnostically acceptable images at low doses to the patient. This study aimed to compare the image quality and radiation dose between 120kVp Filtered Back Projection and 80kVp Iterative Reconstructed (SAFIRE) CT images.Methods: This cross-sectional study was performed on patients referred for CT Urography examinations for various clinical indications to the Department of Radiology and Imaging, Tribhuvan University Teaching Hospital. Data were collected for a period of four months (From August to November 2019) after approval from the Institutional Review Committee of the Institute of Medicine. Convenience sampling was employed and a total of 96 examinations were included. Among them 48 were male and 48 were female. Data were obtained from the 128-slice MDCT Siemens Somaton Definition AS+ CT scanner. Venous phase scans were obtained with Protocol A (120kVp and Filtered Back Projection) and non-contrast scans were obtained with Protocol B (80kVp and SAFIRE). The mAs (tube current-time product) was fixed at 200 for both protocols.Results: There was a 72.5% reduction in Size Specific Dose Estimate (SSDE) in Protocol B compared to Protocol A. However, there was a 13.17% increase in noise in Protocol B compared to Protocol A. Image quality evaluation showed a 98.95% acceptability for the low dose i.e. Protocol B images.Conclusion: CT using low kVp (80kVp) and low current (200mAs) along with an iterative reconstruction algorithm (SAFIRE) can provide diagnostically acceptable images at very low doses for examinations of the Urinary tract

Radiation attenuation of fly ash and rice husk ash-based geopolymers as cement replacement in concrete for shielding applications

Due to the economic and environmental cost of producing cement for concrete, research into the use of alternative materials such as geopolymers for the partial replacement of cement has become popular. In an attempt to understand the effect of such replacement on the shielding behavior of concrete, this study evaluated and analyzed the gamma-ray interaction parameters of fly ash- and rice husk ash-based geopolymers (G-RHA-F1, G-RHA-F2, G-RHA-F3, and G-RHA-F4). The mass attenuation coefficient (μρ), mass energy absorption coefficient (μenρ), effective atomic number (Zeff), specific gamma-ray dose constant (Г), dose rate (Dr), and photon buildup factors (BFs) were computed for photon energies within 15,000 eV and 15,000 keV. The evaluated parameters showed differences in value for the materials. For G-RHA-F1, G-RHA-F2, G-RHA-F3, and G-RHA-F4, μρ values are within the range 0.0208–6.5169 cm2/g, 0.0208–6.3631 cm2/g, 0.0209–6.70611 cm2/g, and 0.0208–6.2149 cm2/g, respectively. The corresponding ranges of are 0.0155–5.9433 cm2/g, 0.0155–5.7934 cm2/g, 0.0156–6.4016 cm2/g, and 0.0155–5.6775 cm2/g, accordingly. Fly ash slightly improved the gamma photon absorption capacity of the geopolymers, especially at the low energies. The investigated geopolymers have relatively higher photon absorption cross-sections relative to some existing polymers and shielding glasses. They could therefore be used to construct effective concrete shields.

The effect of eight weeks of resistance training with tribulus terrestris on the apoptosis mechanism in the heart tissue of rats exposed to stanozolol

Introduction: Abuse of androgenic-anabolic steroids (AAS) has irreversible effects on the heart in athletes. On the other hand, the beneficial effects of tribulus terrestris (T) have been shown to reduce cardiovascular risks. Therefore, the aim of this study was to investigate the effect of eight weeks of resistance training (RT) with T on the apoptosis mechanism in the heart tissue of rats exposed to stanozolol (S). Methods: in this experimental study 35 male rats were divided into 7 groups of 5 rats including: 1) sham (normal saline) (Sh), 2) S, 3) S+100 mg/kg T (ST100), 4) S+50 mg/kg T (ST50), 5) S+RT (SRT), 6) S+RT+100 mg/kg T (SRTT100), and 7) S+RT+50 mg/kg T (SRTT50). During eight weeks, groups 5-7 performed three sessions of RT pre week, and groups 3, 4, 6, and 7 received specific doses of T daily. In order to analyze the research findings, the Shapiro-Wilk, one-way ANOVA with Tukey’s post- hoc tests were used in SPSS21 software (P≤0.05). Results: RT reduced gene expression of CRP, cytochrome-c, AIF-1 and caspase-9 in the heart tissue (P=0.001); 50 and 100 mg/kg T reduced gene expression of CRP, cytochrome-c, AIF-1 (P=0.001) so that 100 mg/kg T has more favorable effect than 50 mg/kg T (P=0.001). Also, RT with T had interactive effects on reducing the genetic expression of CRP, cytochrome-c, AIF-1 and caspase-9 (P=0.001). Conclusion: RT and T consumption seem to have synergistic effects in reducing the apoptotic pathway markers in the heart tissue of rats exposed to the supra-physiologic dose of S.

Comparison on removal performance of virus, antibiotic-resistant bacteria, cell-associated and cell-free antibiotic resistance genes, and indicator chemicals by ozone in the filtrated secondary effluent of a sewage treatment plant

Due to the widespread appearance of viruses, antibiotic-resistant bacteria (ARBs), and antibiotic resistance genes (ARGs) in the aquatic environment, more powerful oxidation processes such as ozonation are needed to enhance the efficiency of their inactivation and removal during wastewater treatment. However, information is lacking on the elimination rates of viruses, ARBs, cell-associated ARGs (ca-ARGs), and cell-free ARGs (cf-ARGs) during ozonation. This study examined the kinetics and dose-dependent inactivation of a virus (MS2 coliphage) and an ARB (Ampicillin-resistant [AmpR] E. coli) and the removal of ca- and cf-ARGs (plasmid-encoded blaTEM) by ozonation in a filtered secondary effluent (SE) of a municipal sewage treatment plant (STP). In addition, the ozonation kinetics of carbamazepine (CBZ) and metoprolol (MTP)—ubiquitous organic micropollutants with different removal rate constants—were also investigated in order to monitor their effectiveness as indicators for the abovementioned biological risk factors. Our results showed that ozonation was an efficient way to remove MS2, AmpRE. coli, ARGs, CBZ, and MTP. We investigated the kinetics of their inactivation/removal with respect to exposure in terms of CT (dissolved ozone concentration C and contact time T) value, and found their inactivation/removal constants were in the following order: MS2 (8.66 ×103 M−1s−1) ≈ AmpRE. coli (8.19 ×103 M−1s−1) > cf-ARG (3.95 ×103 M−1s−1) > CBZ (3.21 ×103 M−1s−1) > ca-ARG (2.48×103 M−1s−1) > MTP (8.35 ×102 M−1s−1). In terms of specific ozone dose, > 5-log inactivation of MS2 was observed at > 0.30 mg O3/mg DOC, while > 5-log inactivation of AmpRE. coli was confirmed at 1.61–2.35 mg O3/mg DOC. Moreover, there was almost no removal of ca-ARG when the specific ozone dose was < 0.68 mg O3/mg DOC. However, 2.86–3.42-log removal of ca-ARG was observed at 1.27–1.31 mg O3/mg DOC, while 1.14–1.36-log removal of cf-ARG was confirmed at 3.60–4.30 mg O3/mg DOC. As alternative indicators, > 4-log removal of CBZ was observed at > 1.00 mg O3/mg DOC, while > 2-log removal of MTP was confirmed at > 2.00 mg O3/mg DOC. Thus, it was observed that inactivation of E. coli needs a greater ozone dose to achieve the same level of inactivation of AmpRE. coli; for ARGs, cf-ARG can persist longer than ca-ARG if low dosages of ozone are applied in the filtrated SE, CBZ might act as an indicator with which to monitor the inactivation of viruses and ARBs, while MTP might act as an indicator with which to monitor removal of ARGs. Moreover, cf-ARG cannot be neglected even after ozonation due to the possibility that ca-ARGs can become cf-ARGs during ozonation and be discharged with the final effluent, posing a potential risk to the receiving environment.

Chemical Analysis of the Antihyperglycemic, and Pancreatic α-Amylase, Lipase, and Intestinal α-Glucosidase Inhibitory Activities of Cannabis sativa L. Seed Extracts.

Cannabis is considered (Cannabis sativa L.) a sacred herb in many countries and is vastly employed in traditional medicine to remedy numerous diseases, such as diabetes. This research investigates the chemical composition of the aqueous extracts from Cannabis sativa L. seeds. Furthermore, the impact of these extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase enzymes is evaluated, as well as their antihyperglycemic effect. Analysis of the chemical composition of the aqueous extract was conducted using high-performance liquid chromatography with a photodiode array detector (HPLC-DAD). In contrast, the ethanol, hexanic, dichloromethane, and aqueous extract compositions have been established. Additionally, the inhibitory effects of ethanolic, dichloromethane, and aqueous extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase activities were evaluated in vitro and in vivo. The results of HPLC analysis indicate that the most abundant phenolic compound in the aqueous cannabis seed extract is 3-hydroxycinnamic acid, followed by 4-hydroxybenzoic acid and rutin acid. Moreover, administration of ethanolic and aqueous extracts at a dose of 150 mg/Kg significantly suppressed postprandial hyperglycemia compared to the control group; the ethanolic, dichloromethane, and aqueous extracts significantly inhibit pancreatic α-amylase and lipase, and intestinal α-glucosidase in vitro. The pancreatic α-amylase test exhibited an inhibition with IC50 values of 16.36 ± 1.24 µg/mL, 19.33 ± 1.40 µg/mL, 23.53 ± 1.70 µg/mL, and 17.06 ± 9.91 µg/mL for EAq, EDm, EET, and EHx, respectively. EET has the highest inhibitory capacity for intestinal α-glucosidase activity, with an IC50 of 32.23 ± 3.26 µg/mL. The extracts inhibit porcine pancreatic lipase activity, demonstrating their potential as lipase inhibitors. Specifically, at a concentration of 1 mg/mL, the highest inhibition rate (77%) was observed for EDm. To confirm these results, the inhibitory effect of these extracts on enzymes was tested in vivo. The oral intake of aqueous extract markedly reduced starch- and sucrose-induced hyperglycemia in healthy rats. Administration of the ethanolic extract at a specific dose of 150 mg/kg significantly reduced postprandial glycemia compared with the control group. It is, therefore, undeniable that cannabis extracts represent a promising option as a potentially effective treatment for type 2 diabetes.