Application of 3D Printing in Pharmaceutical Sciences, and Evaluation of Administration Routes for Drug-Loaded Composites

3D printing is a novel approach in the pharmaceutical field, but its usage has not been fully established. This method can promote drug therapy and overcome some traditional treatment challenges in different ways that are discussed in this paper. "One-size-fits-all", Large-scale production, and less patient and physician acceptability are some limitations that we will encounter in traditional therapy. Three-dimensional printing of pharmaceutical products is a versatile technology that needs specific attention. Droplet-based, extrusion-based, and laser-assisted 3D printers are three main techniques that can be used in this field. The limitations and advantages of this method have been discussed, highlighting potential innovative pathways towards the possibility of drug carriers’ usage in ink formulas. The administration pathway of drug-loaded composites is another critical issue in drug treatment strategies that have been discussed here. Oral drug delivery as a convenient method of systemic drug administration with significant patient preference is introduced as the most prevalent pathway that has been studied about 3D printed medicines. Finally, essential ethics and future directions of 3D printing in the pharmaceutical and healthcare industries are outlined

The Necessity of Critical Correction of Sharafuddin Maneri’s Maktubat-e-Sadi

In present article, first, Maktubat-e-Sadi as the most important Persian work of Sharafuddin Maneri (1263-1381 AD), the most famous leader of ‘Kubrawiyya Ferdowsiyeh’ tribe in India, is introduced. This work was developed by his fellow named Zeyn Badr Arabi. Then, samples of important and controversial differences between stone print and the ancient version of Maktubat-e-Sadi are proposed in order to determine the need for the critical correction of this work. The results indicated that, based on the “antiquity” and “significance” of Maktubat-e-Sadi and due to the "plurality" of the manuscripts of this work, there are some mistakes made by writers which are referred to in this study. Due to the fact that each of the stone prints has important differences with the old versions of the book in the recording of words and phrases, it is necessary to correct this work in order to achieve a close text similar to what Sharafuddin Maneri has written

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Association of androgen receptor GGN repeat length polymorphism and male infertility in Khuzestan, Iran

Background: Androgens play critical role in secondary sexual and male gonads differentiations such as spermatogenesis, via androgen receptor. The human androgen receptor (AR) encoding gene contains two regions with three nucleotide polymorphic repeats (CAG and GGN) in the first exon. Unlike the CAG repeats, the GGN has been less studied because of technical difficulties, so the functional role of these polymorphic repeats is still unclear. Objective: The goal of this study was to investigate any relationship between GGN repeat length in the first exon of AR gene and idiopathic male infertility in southwest of Iran. Materials and Methods: This is the first study on GGN repeat of AR gene in infertile male in Khuzestan, Iran. We used polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis to categorize GGN repeat lengths in 72 infertile and 72 fertile men. Afterwards we sequenced the PCR products to determine the exact length of GGN repeat in each category. Our samples included 36 azoospermic and 36 oligozoospermic men as cases and 72 fertile men as control group. Results: We found that the numbers of repeats in the cases range from 18 to 25, while in the controls this range is from 20 to 28. The results showed a significant relation between the length of GGN repeat and fertility (p=0.015). The most frequent alleles were alleles with 24 and 25 repeats respectively in case and control groups. On the other hand no significant differences were found between Arab and non-Arab cases by considering GGN repeat lengths (p=0.234). Conclusion: Due to our results, there is a significant association between the presence of allele with 24 repeats and susceptibility to male infertility. Therefore this polymorphism should be considered in future studies to clarify etiology of disorders related to androgen receptor activity

Enhancing flexibility and strength-to-weight ratio of polymeric stents: A new variable-thickness design approach

This paper presents a new design strategy to improve the flexibility and strength-to-weight ratio of polymeric stents. The proposed design introduces a variable-thickness (VT) stent that outperforms conventional polymeric stents with constant thickness (CT). While polymeric stents offer benefits like flexibility and bioabsorption, their mechanical strength is lower compared to metal stents. To address this limitation, thicker polymer stents are used, compromising flexibility and clinical performance. Leveraging advancements in 3D printing, a new design approach is introduced in this study and is manufactured by the Liquid Crystal Display (LCD) 3D printing method and PLA resin. The mechanical performance of CT and VT stents is compared using the Finite Element Method (FEM), validated by experimental tests. Results demonstrate that the VT stent offers significant improvements compared to a CT stent in bending stiffness (over 20%), reduced plastic strain distribution of expansion (over 26%), and increased radial strength (over 10%). This research showcases the potential of the VT stent design to enhance clinical outcomes and patient care.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Materials and Environmen

Ehlers-Danlos Syndrome Type VI in a 17-Year-Old Iranian Boy with Severe Muscular Weakness; A Diagnostic Challenge?

Background: The Ehlers-Danlos syndrome type VI (EDSVI) is an autosomal recessive connective tissue disease which is characterized by severe hypotonia at birth, progressive kyphoscoliosis, skin hyperelasticity and fragility, joint hypermobility and (sub-)luxations, microcornea, rupture of arteries and the eye globe, and osteopenia. The enzyme collagen lysyl hydroxylase (LH1) is deficient in these patients due to mutations in the PLOD1 gene. Case Presentation: We report a 17-year-old boy, born to related parents, with severe kyphoscoliosis, scar formation, joint hypermobility and multiple dislocations, muscular weakness, rupture of an ocular globe, and a history of severe infantile hypotonia. EDS VI was suspected clinically and confirmed by an elevated ratio of urinary total lysyl pyridinoline to hydroxylysyl pyridinoline, abnormal electrophoretic mobility of the a-collagen chains, and mutation analysis. Conclusion: Because of the high rate of consanguineous marriages in Iran and, as a consequence thereof, an increased rate of autosomal recessive disorders, we urge physicians to consider EDS VI in the differential diagnosis of severe infantile hypotonia and muscular weakness, a disorder which can easily be confirmed by the analysis of urinary pyridinolines that is highly specific, sensitive, robust, fast, non-invasive, and inexpensive

Impact of Dialysis on Open Cardiac Surgery

Background: Dialysis patients frequently have coronary artery disease but are regarded as high risk patients for coronary artery bypass grafting (CABG). Methods: Between February 2002 and September 2006, seventeen dialysis-dependent patients underwent isolated CABG at our center. CABG was performed under cardiopulmonary bypass (CPB) for all the patients. All cases had been maintained on hemodialysis and the duration of preoperative hemodialysis ranged from 6 to 24 months (mean 13.4±6.4). The patients’ characteristics, clinical and operative data as well as perioperative and mid-term outcome were reviewed. Results: All patients were men with a mean age of 53±8.4 years. Mean preoperative ejection fraction was 45.5%±10.4% (range 25 to 60 %). One internal mammary graft was used in 16 (94.1%) patients. Cardiopulmonary bypass and aortic cross-clamp times were 71.3±18.7 and 40.5±8.3 minutes respectively. The more frequent complication was prolonged mechanical ventilation in 2 (11.7%), there was no perioperative mortality. In mid-term follow-up (mean time: 11.8±9.5 months) the mid-term mortality rate was 20% (3 patients). Conclusion: CABG in chronic renal dialysis patients can be accomplished with acceptable short and mid-term morbidity and mortality

Anticancer property of lanthanide sulfate nanostructure against neuroblastoma-neuro2a cell line

A novel lanthanum (III) complex with 8-Hq = 8-hydroxy quinoline and phen-dione = 1,10-phenanthroline-5,6-dione was synthesized using the reflux method. The complex was characterized using elemental analyses, cyclic voltammetry technique, electronic absorption spectroscopy, H-NMR spectroscopy, X-ray powder diffraction, and scanning electron microscopy. Then, La2O2(SO4) nanostructure (NS La-s) was obtained from the lanthanum (III) complex as a precursor after calcination at 700 °C for 4 h. The thermal stability of nanostructure was determined by the thermal gravimetric method. SEM results showed that the morphology of La2O2(SO4) was spiral-like. The cytotoxicity of La-s NS was studied using cell viability assay on neuroblastoma-N2a cell line culture. The results ranked the cytotoxicity activity of La-s NS in N2a cell line to IC50 = ~ 22 μg mL−1