The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting, nor fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in 6 papers and one abstract related to religious fasting (n=129 women) and observational studies in lactating women (n=23, healthy volunteers, fasting). These data reflect two different ‘fasting’ patterns: an acute (18-25h) model in 71 (healthy volunteers, Yom Kippur/Ninth of Av) women and a chronic fasting (Ramadan) model in 81 women. Changes were most related to electrolytes and were moderate, with almost no changes in macronutrients during acute fasting. We therefor conclude that neither short term fasting nor fluid abstention (18-25h) affect human milk macronutrient composition, so that women can be reassured when this topic were raised during consulting. Besides the nutritional relevance, this also matters as clinical research samples – especially to estimate analgo-sedative exposure by lactation - are commonly collected after maternal procedural sedation, associated with maternal fasting and physiology-based pharmacokinetic (PBPK) models assume stable human milk composition.

SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

The aim of the study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection of new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables, considering a p < 0.05 as statistically significant. Multiple logistic regression analysis was used to detect the in-dependent factors associated with TB preventive treatment non-adherence, considering a p < 0.05 as statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: “exposure at school or workplace” (aOR = 3.34), “exposure to an index case without laboratory confirmation of TB” (aOR = 2.07), “immigrant contact” (aOR = 1.81), “male gender” (aOR = 1.75) and “exposure duration <6 hours per week or sporadic exposure” (aOR = 1.60). By contrast, the factor “short-term TB preventive treatment regimen” (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Aluminium bronzes possess a unique combination of high strength and wear and corrosion resistance in aggressive environments; thus, these alloys find wide application in marine, shipbuilding, aviation, railway, offshore platform applications and other fields. Iron-aluminium bronzes (IABs) are the cheapest and most widely used. When the aluminium content is above 9.4 wt%, IAB is biphasic (i.e. it undergoes -transformation) and can be subjected to all heat-treatment types depending on the desired operating behaviour of the bronze component. This article presents correlations (mathematical models) between the primary mechanical characteristics (yield limit, tensile strength, elongation, hardness and impact toughness) and the ageing temperature and time of quench at 920°C in water Cu-11Al-6Fe bronze, obtained using the centrifugal casting method. The microstructure evolution was evaluated depending on the ageing temperature and time changes. Overall, the research was conducted in three successive inter-related stages: a one-factor-at-a-time study, planned experiment, and optimisations. Four optimisation tasks, which have the greatest importance for practice, were formulated and solved. The defined multiobjective optimisation tasks were solved by searching for the Pareto-optimal solution approach. The decisions were made through a nondominated sorting genetic algorithm (NSGA-II) using QstatLab. The optimisation results were verified experimentally. Additional samples were made for this purpose, quenched at 920°C in water and subjected to subsequent ageing with the optimal values of the governing factors (ageing temperature and time) for the corresponding optimisation task. The comparison of the results for the mechanical characteristics with the theoretical optimisation results presents good agreement.

High-strength wastewaters from a variety of sources, including the food industry, domestic septage and landfill leachate, are often hauled to municipal wastewater treatment plants (WWTPs) for co-treatment. Due to their high organic loadings, these wastewaters can cause process upsets in both the WWTP’s liquid and solids treatment trains and consume organic treatment capacity, leaving less capacity available to service customers in the catchment area. A novel pre-treatment method, the Waste Activated Sludge-High Rate (WASHR) process, is proposed to optimize the co-treatment of high-strength wastewaters. The WASHR process combines the contact stabilization and sequencing batch reactor processes. It utilizes waste activated sludge from the municipal WWTP as its biomass source, allowing rapid start-up. Bench scale treatment trials of winery wastewater confirm the WASHR process can reduce loadings on the downstream WWTP’s liquid treatment and solids treatment trains. A case study approach is used to confirm the economic viability and environmental sustainability of the WASHR process compared to direct co-treatment using life cycle cost analyses and greenhouse gas emissions estimates.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

Lithium is the superior first-line treatment for bipolar disorder (BD). Yet the percentage of patients receiving lithium is abysmally low, especially in the USA. Since psychiatrists have failed to place lithium in its appropriate role, we make the case that patients with BD themselves need to be better educated about the unique characteristics and preeminence of the drug so that it can be used more often and appropriately. Lithium has a highly unfavorable popular reputation among would-be patients and many psychiatrists. Thus, a direct appeal to patients with BD appears appropriate to try to remediate this situation. The unique assets of lithium are underappreciated or not well known. Conversely, the side effects profile of lithium are overestimated. Here, we make the case that lithium’s image needs to be revised not only with better and more accurate information but with a wholesale re-naming and rebranding of the drug. We will not only outline the unique qualities and new information about the side effects of the drug but attempt to change some of the terminology conventionally used to refer to lithium so that its use may be appropriately applied earlier and at an increased frequency for patients with BD.

Feline infectious peritonitis (FIP) is a severe and invariably fatal disease affecting both domestic and wild felines with limited effective therapeutic options available. By considering the significant immunomodulatory effects of vitamin E observed in both animal and human models under physiological and pathological conditions, we have provided a full in-silico investigation of vitamin E and related compounds and their effect on the crystal structure of feline infectious peritonitis virus 3C-like protease (FIPV-3CLpro). This work revealed the β-tocotrienol and δ-tocotrienol analogues as inhibitor candidates for this protein, suggesting their potential as possible drug compounds against FIP or their supplementary use with current medicines against this disease.

Our world is rife with challenges, many of which arise from both natural phenomena and human-made issues. While natural problems like diseases and environmental changes often elude our immediate control, a troubling number of today's issues are unintended consequences of human innovations. A striking example is the evolution of drug resistance. The discovery of antibiotics in the early days of modern medicine marked a monumental breakthrough, drastically reducing mortality rates and improving quality of life. Pioneers like Alexander Fleming, who discovered penicillin in 1928, ushered in a new era of medical treatment, transforming healthcare by effectively combating bacterial infections.However, the widespread and often indiscriminate use of these drugs has led to the emergence of drug-resistant pathogens. This natural phenomenon, accelerated by human practices such as overprescription and the misuse of antibiotics in agriculture, exemplifies a double-edged sword—initially celebrated solutions have now become significant challenges. The same drugs that once cured deadly infections are losing efficacy, making us vulnerable to diseases previously thought under control.The inventors of these drugs acted with the intent to save lives and alleviate suffering, unaware of the long-term consequences. Today, the responsibility to address drug resistance lies with us, armed with hindsight and a deeper understanding of microbial resistance complexities. This review explores the origins and evolution of drug resistance, the role of scientific knowledge, and the implications for future actions.

Cancer is a highly heterogeneous disease and remains a global health challenge affecting millions of human lives worldwide. Despite advancements in conventional treatments like surgery, chemotherapy, and immunotherapy, the rise of multidrug resistance, tumor recurrence, and severe side effects necessitates innovative therapeutic approaches. The complex nature of the tumor microenvironment (TME) further compromises the efficacy of traditional chemotherapy drugs. Recently, stimulus-responsive nanomedicines designed to target TME characteristics (e.g., pH, redox, enzymes) have gained attention for their potential to enhance anticancer efficacy while minimizing adverse effects. Among various nanocarriers, hydrogels are an interesting class of nanocarriers used in cancer therapy due to their high water content, adjustable mechanical characteristics, and ability to respond to external/internal stimuli. These properties make hydrogels an ideal nanocarrier for controlled drug release within the TME. This review comprehensively surveys the latest advancements in stimulus-responsive hydrogels for cancer therapy, exploring various stimuli-responsive mechanisms, including biological (e.g., pH, redox), chemical (e.g., enzymes, glucose), and physical (e.g., temperature, light), as well as dual- or multi-stimuli responsiveness. This review will offer novel perspectives on the development of stimulus-responsive hydrogels for cancer therapy.

Skin inflammation associated with chronic diseases has the direct action of keratinocytes in its immunopathogenesis, leading to a series of immune responses. However, there are still no highly targeted treatments, and the development of more specific therapies is highly desirable. In the present work, nanocapsules containing quinizarin (QZ/NC) were developed, evaluating their act in a model of the keratinocytes inflammatory process in vitro with the action of Photodynamic Therapy, analyzing the permeation in a 3D skin model. Physicochemical, stability, cytotoxicity and permeation analyses of the nanomaterials were carried out. The nanocapsules showed desirable physicochemical characteristics and were stable during the analysis period, without spectroscopic modifications. The cell viability test carried out showed no cytotoxicity at the lowest QZ/NC concentrations. The permeation and cellular uptake studies showed the permeation of QZ/NC in 3D skin models and the intracellular incorporation and internalization of the drug, enhancing its action in the drug delivery technique. Promising results were presented using the model developed to induce the inflammatory process in vitro and applying the synthesized nanomaterial in conjunction with PDT, where a decrease in the levels of cytokines analyzed was observed, representing a possible new therapeutic approach for inflammatory skin diseases.

Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior cross-sectional investigation of patients from the Montreal Heart Institute Biobank undergoing allopurinol therapy. Four endpoints were investigated, namely plasma concentrations of oxypurinol, the active metabolite of allopurinol, allopurinol, and allopurinol-riboside, as well as allopurinol daily dosing. A total of 439 participants (mean age 69.4 years; 86.4% male) taking allopurinol (mean daily dose 194.5 mg) and who had quantifiable oxypurinol concentrations were included in the genome-wide analyses. Participants presented multiple comorbidities and received concomitant cardiovascular medications. No association achieved the predefined genome-wide threshold values for any of the endpoints (all p&gt;5 × 10-8). Our results are consistent with prior finding regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, and allopurinol daily dosing. Given the size of this genome-wide study, collaborative investigations involving larger and diverse cohorts may be required to further identify pharmacogenomic determinants of allopurinol and measure their clinical relevance to personalize allopurinol therapy.

Paracetamol, also known as acetaminophen, is one of the most widely used over-the-counter analgesics and antipyretics globally. While generally considered safe when used as directed, excessive or prolonged use of paracetamol can lead to adverse effects on various organ systems within the human body. This comprehensive review explores the physiological mechanisms underlying paracetamol toxicity, its effects on different organs, risk factors for overdose, diagnostic methods, and potential management strategies.

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods utilised often for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This Review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups, so they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission, has many potential benefits. These include reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.

Antibody-drug conjugates (ADCs), a groundbreaking advancement in cancer therapy, synergistically combine the precision of monoclonal antibodies with the potent destruction capabilities of cytotoxic drugs, signifying a new era in the targeted oncological treatments. This comprehensive paper delves into the evolving field of antibody-drug conjugates (ADCs) and their pivotal role in cancer therapy. We have conducted an in-depth exploration of the structural components of ADCs, including target antigens, monoclonal antibodies, chemical linkers, and cytotoxic payloads, each playing a crucial role in determining the efficacy and safety profile of these novel therapies. A detailed market analysis reveals the leading pharmaceutical companies shaping the ADC landscape, reflecting the growing interest and potential in this therapeutic approach. We further dissect the engineering intricacies of ADCs, focusing on their ability to target specific cancer cell antigens while minimizing off-target effects, thus offering a more focused treatment with reduced systemic side effects compared to traditional chemotherapy. This approach holds promise in a heightened therapeutic index and decreased toxicity. The mechanisms and effector functions of ADCs are explored, highlight- ing their multifaceted strategy in combating cancer. We include a comprehensive look at how ADCs operate from initial blood circulation to the induction of apoptosis in cancer cells. We also review several key ADCs currently in use or under investigation, offering insights into their unique mechanisms of action, pharmacokinetics, and clinical implications. The discussion extends to drug creation modalities, focusing on innovative conjugation techniques that enhance ADC homogeneity and therapeutic efficacy. In conclusion, the paper underscores the transformative potential of ADCs in the realm of cancer treatment, marking a shift towards more precise and targeted therapeutic approaches. By offering a thorough analysis of ADC technology, this paper sheds light on the prospects of these groundbreaking therapies in the ongoing fight against cancer.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite the latest advances, a major clinical issue in EOC is the disappointing prognosis related to chemoresistance in almost one-third of cases. Drug resistance relies on heterogeneous cancer stem cells (CSCs), endowed with tumor-initiating potential, leading to relapse. No biomarkers of chemoresistance have been validated yet. Recently, major signaling pathways, micro ribonucleic acids (miRNAs), and circulating tumor cells (CTCs) have been advocated as putative biomarkers and potential therapeutic targets for drug resistance. However, further investigation is mandatory before their routine implementation. In accordance with the increasing rate of therapeutic efforts in EOC, the need for biomarker-driven personalized therapies is growing. This review aims to discuss the emerging hallmarks of drug resistance with an in-depth insight into the underlying molecular mechanisms lacking so far. Finally, a glimpse of novel therapeutic avenues and future challenges will be provided.

Cancer is among the leading causes of death worldwide. Therefore, timely diagnosis and appropriate treatment are very important. There are many disadvantages that come with traditional cancer treatments, such as chemotherapy and radiotherapy. In these treatments, the specific drug concentration affects not only the tumor site but also healthy tissues or organs. One of the foremost promising uses of nanotechnology is in the field of medical technology and specific site targeting can be achieved due to manipulation of materials at a nanometric scale. Nanotechnology offers specific benefits in terms of cancer therapy by enhancing it and reducing its adverse effects by guiding drugs to selectively target cancer cells. In addition, the use of minute amounts of medicine can lead to cost savings. Furthermore, nanoparticles can also be used as imaging agents to improve cancer diagnostics, therapeutics, and treatment management. Thus, this review has focused on the different types of nanoparticles used in cancer therapy, their action mechanisms, and their benefits and applications in diagnosis, imaging, and treatment. This review sums up the parameters that need to be considered when designing systems for cancer therapy while considering the desired characteristics of the nanoparticles from the biological point of view.

(1) Background: Hemispherotomy is the generally accepted treatment for hemispheric drug resistant epilepsy (DRE). Lateral or vertical approaches are performed according to the surgeon's preference. Multiples technical variations have been proposed since Delalande first described his vertical technique. We propose a sub-insular variation of the vertical parasagittal hemispherotomy (VPH) and describe our case series of patients operated on with this procedure. (2) Methods: a continuous series of patients operated on by the senior author (CR) with the modified sub-insular VPH was retrospectively analyzed. We report the demographic pre-operative characteristics, epilepsy and functional outcome as well as the surgical complications.(3) Results: Twenty-five patients were operated on between August 2008 and August 2023, twenty-three of them have at least a 3-month follow-up. On this last group 86,3% of patients were seizure-free. Only two patients developed post-operative hydrocephalus (8.7%), all patients with autonomous preoperative walk and 86,3% of the total series were able to walk without assistance (86.3%) and perform adapted social activities at last follow-up.(4) Conclusion: The modified vertical parasagittal sub-insular hemispherotomy is a successful surgical technique for hemispheric DRE with seizure freedom rates similar to the biggest series reported in the literature. Compared to other series, patients operated with our modified technique had a lower rate of postoperative hydrocephalus and excellent long-term motor and cognitive outcome.

Skin cancer is a disease that reflects most malignant neoplasms worldwide, whose rate of involvement has increased significantly in recent decades. Treatments that offer efficient results with attenuation of adverse reactions and greater patient compliance have been the subject of many systematic investigations. This review aims to qualitatively present published works that showed new strategies to increase the penetration power of natural substances through the skin in the topical treatment against skin cancer. In this sense, nanoengineering mechanisms, the iontophoresis technique, and photodynamic therapy using natural products (NP) contribute to new knowledge about substance carrier strategies in topical treatments against skin cancer.

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1-14 years enrolled March 2019 to December 2020 from five facilities in Kisumu County, Kenya were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for VF (&gt; 1000 copies/ml)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; median age was 9 years (interquartile range (IQR) 7,12), 344 (49%) were female and median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associate with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual class resistance. A history of VF in prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT.

The prevalence of antiviral drugs (AVTs) has seen a substantial increase in response to the COVID-19 pandemic, leading to heightened concentrations of these pharmaceuticals in wastewater systems. The hydrophilic nature of AVTs has been identified as a significant factor contributing to the low degradation efficiency observed in wastewater treatment plants. This characteristic often necessitates the implementation of additional treatment steps to achieve complete degradation of AVTs. Semiconductor-based photocatalysis has garnered considerable attention due to its promising potential in achieving efficient degradation rates and subsequent mineralization of pollutants, leveraging the inexhaustible energy of sunlight. However, in recent years, there have been few comprehensive reports that have thoroughly summarized and analyzed the application of photocatalysis for the removal of AVTs. This review commences by summarizing the types and occurrence of AVTs. Furthermore, it places a significant emphasis on delivering a comprehensive summary and analysis of the characteristics pertaining to the photocatalytic elimination of AVTs. Ultimately, the review sheds light on the identified research gaps and key concerns, offering invaluable insights to steer future investigations in this field.

Background: The clinical outcomes of antiretroviral drugs may be modified by drug interactions; thus, it is important to update the drug interactions in people living with HIV. Aim: To update clinically relevant drug interactions in people living with HIV on antiretroviral therapy. Methods: A systematic review in Medline/PubMed database from July 2017 to December 2022, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. The clinical relevance of drug interaction was grouped into 5 levels according to gravity and probability of occurrence. Results: 361 articles were identified and 148 were included, which allowed the identification of 894 drug interaction pairs. Among these 894 drug pairs, 355 have not been identified previously; and 89 (25.1%) and 72 (20.2%) were of levels 1 and 2, respectively. In addition, for 197 (55.5%) pairs the mechanism was pharmacokinetic. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) with 91 (25.6%) and 76 (21.4%) pairs, respectively were more frequent. Conclusions: In people living with HIV on antiretroviral therapy, we identify 355 new drug interaction pairs, of them 161 (45.3%) are assessed as levels 1 and 2 and thus, clinically relevant; a figure that is lower compared to 2014-2107 update. The pharmacokinetic mechanism is the most frequently identified. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) are the antiretroviral groups with the highest number of clinically relevant drug interactions.

Drug-resistant tuberculosis (DR-TB) is still a major public health concern in South Africa. Mutations in M. tuberculosis can cause varying levels of phenotypic resistance to anti-TB medications. There have been no prior studies on gene mutations and the genotyping of DR-TB in the rural Eastern Cape Province; hence we aimed to identify DR-TB mutations, genetic diversity and allocated lineages among patients in this area. Using Xpert® MTB/RIF, we assessed the rifampin-resistance of sputum samples collected from 1157 patients suspected of having tuberculosis. GenoType MTBDR plus VER 2.0 was used for the detection of mutations causing resistance to anti-TB medications. The next step was to spotlight type 441 isolates. The most prevalent rifampin resistance-conferring mutations were in rpoB codon S531L, in INH-resistant strains, katG gene at codon S315TB and the inhA gene at codon C-15TB had highest mutations; 54.5% and 24.7%, respectively. In addition, 24.6% of strains showed mutations in both the rpoB and inhA genes, while 69.9% of strains showed mutations in both the katG and rpoB genes. Heteroresistance was seen in 17.9% of all cases in the study. According to spoligotyping analysis, Beijing families predominated. Investigating the evolutionary lineages of M. tuberculosis isolates can be done using the information provided by the study's diversity of mutations. In locations where these mutations have been discovered, decision-making regarding standardization of treatment regimens or individualized treatment may be aided by the detection frequency of rpoB, katG, and inhA mutations in various study areas.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancers, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development [1]. Therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options [1-4]. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection [5-7]. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy and targeted agents are occurring.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

Autoimmune disorders and some types of blood cancer originate when B lymphocytes malfunction. In particular, when B cells produce antibodies recognizing the body’s proteins, it leads to various autoimmune disorders. And when B cells of various developmental stages transform into cancer cells, it results in blood cancers, including multiple myeloma, lymphoma, and leukemia. Thus, new methods of targeting B cells are required for various patient groups. Here, we used protein kinase inhibitors alectinib, brigatinib, ceritinib, crizotinib, entrectinib, and lorlatinib previously approved as drugs treating anaplastic lymphoma kinase (ALK)-positive lung cancer cells. We hypothesized that the same inhibitors will efficiently target leukocyte tyrosine kinase (LTK)-positive, actively protein-secreting mature B lymphocytes, including plasma cells. We isolated CD19-positive human B cells from the blood of healthy donors and used two alternative methods to stimulate cell maturation toward plasma cells. Using cell proliferation and flow cytometry assays, we found that ceritinib and entrectinib eliminate plasma cells from B cell populations. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. More generally, we concluded that several drugs previously developed to treat ALK-positive malignant cells can be also used to treat LTK-positive B cells.

Increasing environmental distress is associated with a growing asthma incidence and, with no treatments available, montelukast (MTK) – an antagonist of the cysteinyl leukotrienes receptor 1 – is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions. Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as modulator of leukotriene pathways and systematize the knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

Therapeutic Drug Monitoring (TDM) is potentially a useful tool that can be employed to increase the efficacy and decrease the toxicity of antifungal drugs. The aim of this narrative review is to provide an overview of the current use of TDM in clinical practice, and to present the evidence available regarding its use in proactive clinical settings for preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations in everyday practice. Articles concerning the use of TDM of triazoles in the treatment of fungal infections were retrieved through an electronic search using PubMed. In clinical practice, TDM has an increasingly important role in the management of antifungal drugs as a consequence of the improvement in the knowledge of the pharmacokinetics and pharmacodynamics of these drugs. The currently available evidence shows a direct exposure-response relationship for triazoles, though the PK/PD profile is unpredictable. Current guidelines and treatment consensus statements recommend the proactive TDM of voriconazole, posaconazole, and itraconazole to optimize dosage regimens and improve outcomes for adult and pediatric patients.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

Most recently, an outbreak of severe pneumonia caused by the infection of 2019-nCoV, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Many important aspects about 2019-nCoV remain largely unknown, among which, the limitation of antiviral therapies represents one of the most critical problems. More recently, it was confirmed that human ACE2 is the receptor for the entry of 2019-nCoV into lower respiratory tract epithelial cells. Give this observation, it is thus expected that the virus could be inhibited if we decrease the expression of ACE2. Here by screening two databases, Connectivity Map (CMap) and our JeaMoon Map (JMap), we identified a number of candidate agents that decrease ACE2 expression. CMap analysis identified 5 compounds, among which, Azathioprine is a possible therapeutic strategy for anti-2019-nCoV. Moreover, JMap analysis revealed a number of comounds, biologics, and traditional Chinese medicine, among which, Andrographis, Urtica, Sambucus, Astragalus, valproic acid, butyrate, and epoxomicin represent the most significant and possible strategies for anti-2019-nCoV therapies. This study provides a number of clues and possible therapeutic strategies for 2019-nCoV prevention and treatment.

Many approaches have been developed over time to counter the bioavailability limitations of poorly soluble drugs. With advances in nanotechnology in recent decades, science and industry have been approaching this issue through the formulation of drugs as nanocrystals, which consist of pure drugs and a minimum of surface active agents required for stabilization. They are carrier-free submicron colloidal drug delivery systems with a mean particle size in the nanometer range, typically between 10 and 800 nm. By reducing particle size to nanoscale, the particle surface area available for the molecule dissolution in the direction of dissolution medium is increased, and thus bioavailability is enhanced. This approach has proven successful, as demonstrated by the number of such drug products on the market. R&D and industry have offered many technological solutions to reduce the particle size to nanoscale, and also devised solutions for the handling of particle of nanodimensions, such as methods to accurately measure nanoparticle size and techniques to prevent physicochemical and stability related problems, such as aggregation. The present work provides an overview of the more recent achievements in improving the bioavailability of poorly soluble drugs according to their administration route, and describes the methods developed to overcome physicochemical and stability related problems.

Currently, drug screening is primarily based on human cell culture for initial high-throughput screening, and subsequently, rodent model to confirm the biological effects. However, the mammalian system is known for time-consuming and highly-cost to be difficult to perform high-throughput drug screening, which exists a critical gap between in vitro cell-based models and the in vivo mammalian models. Therefore, the zebrafish could bridge this gap in preclinical toxicity screening along the drug development pipeline because of its efficiency. We aimed to develop an in vivo zebrafish platform for rapid drug screening. Zebrafish, due to its high genomic conservation with mammals and rapid development and differentiation, it has many advantages, such as short life span, large number of offspring and low cost, easy manipulation for generating transgenic species, to serve as animal model for disease-based research. In 96-well microplates, zebrafish embryos were incubated with small molecular compounds that affected bone mineralization. The level of osteogenic mineralization was evaluated by fluorescent dye staining and quantified by image analysis software. Quantitative real time-PCR (qRT-PCR) was performed to evaluate the biological pathways involved in bone metabolism at the molecular level. The system was validated by demonstrating that response to alendronate and Dorsomorphin in zebrafish. In our study, we screened for 24 compounds within the CYCU-1120~1152 chemical library and identified 3 compounds, pentamidine (CYCU-1140), BML-267 (CYCU-1147), and alendronate (CYCU-1152), increased embryonic mineralization; while 6 compounds, RWJ-60475 (CYCU-1126), levamisole HCL (CYCU-1128), tetramisole HCL (CYCU-1129), fenvalerate (CYCU-1132), NSC-663284 (CYCU-1138), and BML-267ester (CYCU-1148), were inhibitory to bone mineralization. We also found that alendronate enhanced the level of bone mineralization by inhibiting osteoclast-related genes. To sum up, our research showed that zebrafish may have potential to be a drug-screening and mechanism-analysis platform for bone mineralization.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

Europium (Eu)-doped fluorapatite (FA) nanorods has a similar biocompatibility with hydroxyapatite (HA) in terms, attracted much attention as cell imaging biomaterials due to their luminescent property. Here, we will discuss the new feature of europium doped fluorapatite (Eu-FA) nanorods as anticancer drug carrier. Eu-FA nanorods was prepared using a hydrothermal method. The morphology, crystal structure, fluorescence and composition are investigated. The specific crystal structure, enabling an effective loading of drug molecules. Doxorubicin (DOX), used as an anticancer model drug, was shown to be effectively loaded onto the surface of the nanorods. The DOX release was fairly pH-dependent, occurring more rapidly at pH 5.5 than pH 7.4 was observed. The intracellular penetration of the DOX-loaded Eu-FA nanorods (Eu-FA/DOX) can be imaged in situ due to the self-fluorescence property. Treatment of melanoma A375 cells with Eu-FA/DOX elicited a more effective apoptosis rate than direct DOX treatment. Overall, Eu-FA show great promise for tracking and treating tumor, may potentially useful as a multifunctional carrier system to effectively load and sustainably deliver drugs.

Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Lead optimization in drug discovery is a crucial phase where initial hits are refined into compounds with improved pharmacological properties. While traditional methods rely on manual experimentation and modifications, AI-driven techniques have revolutionized this process by leveraging big data and predictive modeling. This review explores how AI-driven approaches accelerate lead optimization, showcasing examples like deep neural networks and reinforcement learning. Integration of multi-omic data and experimental validation further enhances AI-driven strategies. The future lies in refining these AI methods, democratizing tools, and interdisciplinary collaboration to streamline drug discovery and address medical needs efficiently.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

As cancer remains resistant to several modes of treatment, novel therapeutics are still under active investigation to overcome treatment inefficacy in cancer. Given the high attrition rate of de novo drug discovery, drug screening, and drug repurposing have offered time- and cost-effective alternative strategies for the identification of potentially effective therapeutics. In contrast to large-scale drug screens, computational approaches for drug repurposing leverage the increasing amounts of biomedical data to predict candidate therapeutic agents prior to testing in biological models. Current studies in drug repurposing for cancer therapy prediction have increasingly focused on the prediction of combination therapies, as combination therapies have numerous advantages over monotherapies. These include increased effect from synergistic interactions, reduced toxicity from lowered drug doses, and a reduced risk of resistance due to multiple non-overlapping mechanisms of action. This review provides a summary of several classes of computational methods used for drug combination therapy prediction in cancer research, including networks, regression-based machine learning, classifier machine learning models, and deep learning approaches, with the goal of presenting current progress in the field, particularly to non-computational cancer biologists. We conclude by discussing the need for further advancements in technologies that incorporate disease mechanisms, drug characteristics, multi-omics data, and clinical considerations to generate effective patient-specific drug combinations, as holistic data integration will inevitably result in optimal targeted therapeutics for cancer.

This paper presents a computational approach designed to construct and query a literature-based knowledge graph for predicting novel drug therapeutics. The main objective is to offer a platform that discovers drug combinations from FDA-approved drugs and accelerates their investigations by domain scientists. Specifically, the paper introduced the following algorithms: (1) an algorithm for constructing the knowledge graph from drug, gene, and disease mentions in the biomedical literature; (2) an algorithm for vetting the knowledge graph from drug combinations that may pose a risk of drug interaction; (3) and two querying algorithms for searching the knowledge graph by a single drug or a combination of drugs. The resulting knowledge graph had 844 drugs, 306 gene/protein features, and 19 disease mentions. The original number of drug combinations generated was 2,001. We queried the knowledge graph to eliminate noise generated from chemicals that are not drugs. This step resulted in 614 drug combinations. When vetting the knowledge graph to eliminate the potentially risky drug combinations, it resulted in predicting 200 combinations. Our domain expert manually eliminated extra 54 combinations which left only 146 combination candidates. Our three-layered knowledge graph, empowered by our algorithms, offered a tool that predicted drug combination therapeutics for scientists who can further investigate from the viewpoint of drug targets and side effects.

Traditional Medicine (TM) is a culturally-rooted healthcare practice, and its use, including for treating illnesses among children, has been reported in many countries. Despite the cultural significance of TM in managing children’s illnesses, evidence suggests that child mortality remains high in many settings. This indicates that the sole use of TM within families and communities might act as a barrier to using biomedical services, contributing to avoidable deaths. Globally, Indonesia is in the top 10 countries with the highest child mortality rates. In addition, Belu is a district in East Nusa Tenggara province, Indonesia that exhibits a high number of child deaths within the last three years. However, the use of TM for the treatment of illnesses among children in Indonesia has received minimal academic attention. This study aimed to understand parental beliefs, knowledge, views, and perceptions of TM and the impact on the use of TM and biomedical services in the treatment of illnesses among their children in Belu district, Indonesia. The participants (n=25) were parents with the real-life experiences of using TM for treating their children’s illnesses. They were recruited using the snowballing sampling technique. Data were collected using in-depth qualitative interviews. A thematic data analysis was performed and guided by a qualitative data analysis framework. The findings were grouped into four main themes: (i) parental beliefs, knowledge, views, and perceptions of TM, (ii) the influence of these factors on parental use of TM and biomedical services for the treatment of children’s illnesses, (iii) social and cultural influences on the use of TM and biomedical services among their children, and (iv) the impact of the sole use of TM or late medical diagnosis on the health condition and the death of children. The findings show that the use of TM is a common practice within families and communities in Belu, however evidence suggests that child mortality remains high in the setting, indicating less effectiveness of the sole use of TM. Thus, there is a need for the development of collaborative models of healthcare programs and service delivery fostering mutual respect and understanding between traditional healers and healthcare professionals, which could significantly contribute to improving parental use of biomedical services for the treatment of their children’s illnesses.

Semisolid casting of Aluminum alloys is growing. For magnesium alloys, Thixomoulding became the dominant process around the world. For aluminium processing, the situation is different as semisolid processing of aluminium is more technically challenging than for magnesium. Today three processes are leading the process implementation, The GISS method, the RheoMetal process and the SEED process. These processes have all strengths and weaknesses and will fit a particular range of applications. The current paper aims at looking at the strengths and weaknesses of the processes to identify product types and niche applications for each process based on current applications and development directions taken for these processes

Abstract: This paper outlines the methodology and results for a two species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA) ) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two species (free-drug and bound-drug) mass transport setup including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of drug between the free and bound-drug states. The model is solved by a 2-D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over our previously developed model using the finite-difference method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 hours (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

Microgreens (young, edible plantlets) are a remarkable opportunity for both consumers, to benefit from health promoting compounds and for applied research, as such organisms have a very high plasticity related to environmental cues, allowing biotechnology development with low costs. Ocimum basilicum species naturally synthesize valuable, phenolic compounds, among which rosmarinic acid is most prominent. Basil plantlets were grown for 10 days under either full spectrum light (white light) or modulated blue:red:far-red:UV spectrum with an additional factorization, by applying fertilisation. Biomass accumulation reached up to 0.8 g/20 plantlets, while chlorophyll fluorescence was in the 0.75 – 0.78 range and remained uniform across treatments, indicating that no significant stress was exerted under modified light treatment. However, total phenolic contents and, in particular, rosmarinic acid contents were markedly enhanced (up to 7.5 mg/g in the red cultivar) under modulated light treatment and fertilization, compared to full spectrum light. Moreover, gene expression was enhanced, 1.3-6.3 fold for genes coding for enzymes involved in phenylpropanoid synthesis patwhays, such as phenylalanine ammonia lyase (PAL), Catechol-O-methyltransferase (COMT) and renin-angiotensin system (RAS). Overall, light modulation coupled with fertilization led to the production of basil microgreens with up to 10% more total phenolics and up to 25% more rosmarinic acid.

The spread of micro- (MPs) and nanoplastics (NPs) in the environment has become a significant environmental concern, necessitating effective removal strategies. In this comprehensive scientific review, we examine the use of magnetic nanoparticles (MNPs) as a promising technology for the removal of MPs and NPs from water. We first describe the issue of MPs and NPs and their impact on the environment and human health. Then the fundamental principles of using MNPs for the removal of these pollutants will be presented, emphasizing that MNPs enable selective binding and separation of MPs and NPs from water sources. Furthermore, we provide a short summary of various types of MNPs that have proven effective in the removal of MPs and NPs. These include ferromagnetic nanoparticles, MNPs coated with organic polymers, as well as nanocomposites and magnetic nanostructures. We also review their properties, such as magnetic saturation, size, shape, surface functionalization and stability, and their influence on removal efficiency. Next, we describe different methods of utilizing MNPs for the removal of MPs and NPs. We discuss their advantages, limitations, and potential for further development in detail. In the final part of the review, we provide an overview of existing studies and results demonstrating the effectiveness of using MNPs for the removal of MPs and NPs from water. We also address challenges that need to be overcome, such as nanoparticle optimization, process scalability, and the removal and recycling of nanoparticles after the completion of the process. This comprehensive scientific review offers an extensive insight into the use of MNPs for the removal of MPs and NPs from water. With improved understanding and the development of advanced materials and methods, this technology can play a crucial role in addressing the issue of MPs and NPs and preserving a clean and healthy environment.

Researchers are increasingly concerned about microplastics (MPs) since they have proven to be detrimental to the environment and humans. They not only contribute to the accumulation of plastics in the environment, but they can also help spread micropollutants through absorption. MPs have entered the environment through a variety of channels, including direct discharge through human activities, the textile industry, and wastewater treatment systems. Wastewater treatment plants (WWTPs) are seen as the final line of defense, forming a barrier between MPs and the environment. The most common MPs found in wastewater are polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), and polystyrene. The purpose of this study is to investigate and measure the efficacy of conventional and advanced technologies in removing microplastic. The fate of MPs in WWTPs and their impact on various wastewater treatment processes will be thoroughly examined. Both conventional and advanced methods of treatment will be discussed. Conventional methods include coagulation/flocculation, sedimentation, and filtration. Advanced treatment methods that will be discussed include membrane bioreactors, rapid sand filtration, electrocoagulation, and photocatalytic degradation. Despite the high removal of MPs, WWTPs remain an important entry point into aquatic and terrestrial systems due to the large volumes involved and the quantity of sludge reused through land application. Also, the complex interactions between MPs and other environmental pollutants may broaden MPs' effects on wastewater treatment processes, which have yet to be fully researched. Furthermore, potential issues with MP removal from treatment procedures and microplastic remediation techniques in drinking water was discussed.

Acne Vulgaris is a multifactorial skin disorder affecting many adolescents involving a complex array of factors. Previous extensive research has delved into the correlation between acne outbreaks and specific diet consumption, and while there have been a variety of treatment indications for decreasing acne in patients, many do not involve the significant impact a holistic approach can take. This case reports on the relationship between cystic acne and dietary habits, presenting a possible treatment approach for acne vulgaris by eliminating dairy consumption.

This review article explores the transformative impact of Artificial Intelligence (AI) on glaucoma care, focusing on advancements in diagnosis, monitoring, and treatment algorithms. AI technologies have revolutionized the field of ophthalmology by enhancing the accuracy and efficiency of diagnosing glaucoma. Furthermore, AI-powered monitoring systems enable continuous and personalized patient care, facilitating early detection of disease progression. Integrating AI algorithms in treatment protocols promises individualized and optimized therapeutic strategies for better management of glaucoma. This comprehensive review elucidates AI applications' current state and future directions in transforming glaucoma care, emphasizing the potential benefits of improving patient outcomes.

In recent decade water pollution by micropollutants is an increasing environmental concern. Since 2019, due to COVID-19 pandemic, increased stormwater pollution by chlorine based disinfectants has been determined. Research aimed to treat of chlorine contaminated stormwater after outdoors spaces disinfection are very limited. Runoff from disinfected areas and residual chlorine present in stormwater are transported to surface water bodies. Residual chlorine reacts with dissolved organic compounds in water and results the formation of environmentally toxic disinfection by-products. Studies present event low residual chlorine concentrations may pose a risk to aquatic flora and fauna. In this study the efficiency of different filter materials, including peat, wood chips, sawdust (column tests) and ceramzites Leca, Pollytag, Polski, Ceski (batch tests), in retaining residual chlorine were tested in laboratory scale batch and flow through experiment. The best efficiency to retain chlorine presented sawdust (96 %) and ceramzite Leca (76 %). The plants abilities to reduce pollution by chlorine was analyzed in raised garden bed. Research results will contribute to future studies aimed to retain various micropollutants in stormwater using remediation technologies.

With the ongoing amendment of the EU legislation on the treatment of urban wastewater, stricter requirements for the removal of pollutants are expected, which calls for the need for innovative wastewater treatment technologies. Biological systems are still the first choice. The survey of typical bioreactors applied in wastewater treatment is presented. Wastewater treatment objective, bio-chemical environment and microbial growth are selected as a main criterion for classification of these bioreactors. Hydraulic and kinetic aspects are considered, advantages and drawbacks of these bioreactors regarding the selection of appropriate type of the reactor as well as regarding operation of reactors are mentioned. The aim of this paper is to provide operators and designers with a brief overview of selected traditional and advanced processes, reactors, and technologies for nutrient removal from municipal wastewater. Another goal is to discuss the possibilities and limitations to comply with more strict effluent standards. From the evaluation of the published papers, it follows that the currently applied traditional methods of nutrients removal have the potential to convey also with the expected stricter limits.

Tick-borne diseases are among the most common vector-borne diseases. These include various infections caused by viruses, bacteria, rickettsiae, spirochetes and protozoa. The aim of our review is to present the relationship between the clinico-epidemiological aspect of some of the emergency tick-borne diseases and their diagnosis, treatment and prevention. We will review three diseases- anaplasmosis, babesiosis and ehrlichiosis. Anaplasmosis and ehrlichiosis are caused by small gram-negative obligate intracellular alphaproteobacteria in the order Rickettsiales, family Anaplasmataceae. The prognosis of disease depends on early diagnosis and proper treatment. The symptoms of anaplasmosis largely overlap with those of ehrlichiosis. Babesiosis is a malaria-like disease that is caused by intraerythrocytic protozoa. Like malaria, the disease proceeds with hemolysis and its severity is determined by the parasitemia. Treatment of babesiosis involves the use of antimalarial agents and antibiotics, most commonly in a combination. Understanding the clinical, epidemiological and laboratory characteristics of tick-borne diseases is crucial for their prevention, diagnosis and treatment.

Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic on the management of imRMDs. Materials and Methods: Systematic literature search of PubMed, Cochrane and Embase databases, including studies with adult patients on the influence of the COVID-19 pandemic on management of imRMDs. There were no restrictions regarding to study-design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and, in case of disagreement, consensus was reached after discussion. Results: A total of 5969 potentially relevant studies were found, and, after title, abstract and full-text screening, 35 studies were included with data from 182’746 patients and 2018 rheumatologists. Non-availability of drugs, e.g., hydroxychloroquine and tocilizuab, was frequent (16–69% of patients). Further, medication non-adherence was reported among patients with different RMDs and between different drugs in 4–46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g. reducing dose of steroids or cessation of biological disease-modifying antirheumatic drugs). Physical in-office consultations and laboratory testing decreased and as a consequence newly implemented remote consultations increased greatly with an increase of up to 80%. Conclusion: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. Influences were wide-ranging, affecting availability of pharmacies, adherence to medication or medication changes, doctor visits and laboratory testing. New systems of care were set up, including virtual clinics and video consultations. These new forms of health care delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics.

Galectins play a role in lung cancer oncogenic pathways including apoptosis, t-cell immune responses, and tumor metastasis. Biomarkers that diagnose, prognose, and assist with treatment remain important, and galectins represent biomarkers that have the potential to impact lung cancer management through these pathways. Using enzyme-linked immunosorbent assay (ELISA) we examined galectin-1, -3, and -9 levels from lung cancer patient serum. Through comprehensive chart review: patient demographics, staging information, tumor biology, treatment data, and outcomes including overall survival (OS) and metastasis were retrospectively collected. Galectin levels were then compared to these numerous factors. Galectin-1, -3, and -9 levels did not correlate with cancer stage, however galectin-3 levels were lower in small cell lung cancer (SCLC) and squamous cell lung cancer than in adenocarcinoma. There was no correlation between galectin levels and previous treatment or future metastasis. Patients that had an abnormal galectin-1 level had decreased OS. Furthermore, patients with curative surgically resectable NSCLC with abnormal galectin-1 levels had decreased OS, but there was no difference in those with SCLC or that were non-resectable treated palliatively. These findings provide insight into galectin levels in various lung cancer histology and highlight the potential for galectin-1 to assist in prognosis of surgically resectable NSCLC.

Bowel intussusception is a rare cause of acute or subacute abdomen in adults. The frequency, etiology, symptoms, diagnosis and treatment of the disease differ significantly in comparison to the pediatric population. In adult patients, the cause of the intussusception in the majority of the cases is an underlying intestinal tumor (benign or malign), leading in a complete or incomplete mechanical ileus with corresponding symptoms. Diagnosis via imaging modalities may be challenging and is sometimes set only after exploratory laparotomy. Surgical treatment in adult patients is most of the times mandatory, because it aims not only to reverse the intussusception but also to treat the underlying cause of the disease. We present 4 cases of adult intussusception that were treated surgically and discuss the crucial points in the management of this disease through a review of the literature.

(1) Background: It is crucial to provide safe and knowledgeable healthcare practices because no research has been done on the knowledge and usage patterns of NSAIDs among the Hail population. (2) Method: Structured questionnaires were utilized to gather data from 399 individuals in Hail, Saudi Arabia for the cross-sectional analysis. The study assessed participants' knowledge regarding NSAIDs, patterns of use, reasons for use, and awareness of potential side effects. (3) Results: In the study, the gender distribution indicated that 170 participants (42.61%) were male, while 229 (57.39%) were female. Gender, occupation, and marital status showed non-significant associations (p>0.01), except for menstrual cycle and joint pain, where marital status displayed significant associations. Age had significant associations with muscle pain, menstrual cycle, and joint pain (p<0.01). Education and monthly income exhibited non-significant associations for all the reasons. The regression analysis demonstrated that gender played a significant role, with females having higher odds of knowledge (AOR = 1.75, 95% CI 1.10-2.88) than males. Age also had a notable impact, with individuals aged 50-59 (AOR = 0.21, 95% CI 0.07-0.66) exhibiting lower odds of knowledge. Education holding a Ph.D (AOR = 3.50, 95% CI 0.54-22.51) and business as an occupation (AOR = 6.12, 95% CI 1.10-35.10) had significantly higher odds of knowledge while housewives (AOR = 0.76, 95% CI 0.25-2.27) had lower odds. Meanwhile, >50% of the participants had knowledge of adverse events related to the use of NSAIDs while 25% had no knowledge. Moreover, 59 (25.766%) participants reported discomfort with the use of NSAIDs. In addition, 50% and >75% of participants’ considered NSAIDs can cause peptic ulcers and damage kidneys, respectively (4) Conclusions: This study shed light on the knowledge and patterns of NSAIDs use in the population of Hail, Saudi Arabia. While NSAIDs are commonly utilized for pain management, there exists a need for improved public awareness regarding potential risks and safe usage practices. Healthcare providers and policymakers should consider these insights to develop targeted educational initiatives and healthcare interventions to promote safe and informed NSAID utilization in the region.

Staphylococcus aureus(S. aureus) is associated with mastitis in dairy cows, this study investigates the therapeutic effect of maggot antimicrobial peptides on S. aureus induced mastitis in mice. The maggot AMP was isolated and purified, tested for antimicrobial activity, and used to treat a pathological model of rat mastitis. The concentration of 1.5mg/（Kg. BW）AMP was selected as intramammary treatment in S. aureus-induced mastitis in mice. The mice were divided into four groups of 30 mice each: group I (healthy control), group II (disease control), group III (AMP), and group IV (ciprofloxacin). To evaluate the therapeutic efficacy of maggot AMP in mastitis induced by S. aureus based on clinical presentation, mammary gland structure, bacterial load, histopathology, and cure. During the 7-day treatment period, all the mice in Group II died in the afternoon of the fifth day, and the clinical signs of the mice in Group III began to improve on the third day, as evidenced by the gradual recovery of the mice's mental status, dietary intake, and water intake. During the treatment period, the bacterial load count of Group III was significantly lower than that of Group II but higher than that of Group IV, while the bacterial load count of Group III gradually decreased and approached that of Group IV from the fifth to the seventh day. The levels of TNF-α in groups III and IV were significantly lower than those in group II, suggesting that maggot AMP has a certain inhibitory effect on TNF-α. Treatment with AMP@ 1.5 mg/(Kg. BW) showed restoration of clinical signs, reduced bacterial load, and lower TNF-α levels in mice, leading to significant improvement in histopathological changes as compared to disease controls. The final cure rate was 40% for mice in Group III compared to 70% for mice in Group IV, compared to all mice in Group II that died. From this study, it can be concluded that maggot AMP can be used as a potential alternative treatment option to antibiotics for the treatment of bovine mastitis.

Rheumatoid arthritis (RA) occurs more frequently in women than in men, and the studies that have addressed clinical and prognostic differences between sexes are scarce and have contradictory results and methodological problems. The present work aims to evaluate sex and gender-related differences in the clinical expression and prognosis of RA as well as the impact on psychosocial variables, coping behavior, and healthcare use and access. By identifying between-sex differences and gender-related outcomes in RA, it may be possible to design tailored therapeutic strategies that consider the differences and unmet needs. Being sex, together with age, the most relevant biomarker and health determinant, a so-called personalized medicine approach to RA must include clear guidance on what to do in case of differences.

Telemonitoring and telerehabilitation have shown promise in delivering individualized healthcare remotely. We introduce STASISM, a Sensor-Based Telerehabilitation and Telemonitoring System, in this work. This platform has been created to facilitate individualized telerehabilitation and telemonitoring for those who need rehabilitation or ongoing monitoring. To gather and analyze pertinent and validated physiological, kinematic, and environmental data, the system combines a variety of sensors and data analytic methodologies. The platform facilitates customized rehabilitation activities based on individual needs, allows for remote monitoring of patients' progress, and offers real-time feedback. To protect the security of patient data and to safeguard patient privacy, STASISM also provides secure data transmission and storage. The platform has the potential to significantly improve the accessibility and efficacy of telerehabilitation and telemonitoring programs, enhancing patients' quality of life and allowing healthcare professionals to provide individualized care outside of traditional clinical settings/

(1) Background: Spontaneous isolated intramural hematoma of the superior mesenteric artery (SIHSMA) is a rare entity often considered as a subset of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). It is characterized by a completely thrombosed false lumen with or without ulcer-like projection with computed tomography (CT) imaging. The recent literature describes few reports with a relatively short-term follow-up. The natural course, prognosis, and treatment options for SIHSMA still lack consensus. We present two cases of acute abdominal pain in a young man due to IMH of the superior mesenteric artery with an extensive literature review. (2) Case report: A 46-year-old male patient was submitted to an urgent CTA for acute abdominal pain, showing the presence of an isolated dissection of the superior mesenteric artery, determining significant stenosis of the vessel with collateral vessel patency. The patient referred to a recent COVID-19 infection, whose course was paucisymptomatic. He was treated conservatively with antiplatelet therapy and corticosteroid treatments, and, after a few days, the symptomatology completely regressed; also, 2-month- control CTA showed the complete IMH regression and the absence of any signs of residual stenosis. The second patient is a 61-year-old male patient who was submitted to an urgent CTA for acute abdominal pain, showing the presence of an isolated dissection of the superior mesenteric artery, not determining significant vessel stenosis. He was treated conservatively with antiplatelet therapy and corticosteroid treatment, and after a few days, the symptomatology completely regressed, and the radiological control showed a complete dissection regression. (3) Conclusion: SISHSMA is a rare entity of vascular pathology, and conservative management represents the best medical strategy. We propose corticosteroid treatment as one of the most appropriate tools in the conservative treatment of SISHSMA.

(1) Background: Melanoma is the most aggressive tumor located at the skin level and the man-agement of this pathology requires a correct staging as well as a modern oncological treatment, adapted to each patient. The main objective of the study is to determine the variability of lymphatic drainage in the case of melanomas located on the trunk; (2) Methods: This retrospective study in-cluded 62 cases of melanoma located on the trunk operated between July 2019 and March 2023 in which SLNB was performed and a total of 84 lymph node were excised; (3) Results: Patients had an average age of 54.5 years old, while melanomas had a mean Breslow index of 2.3 mm. The distri-bution of trunk melanomas was: upper trunk 54 cases, lower trunk 30 cases (64.3 % vs. 35.7%). The type of anesthesia chosen was general anesthesia in 53 cases, respectively spinal anesthesia in 9 cases (85.5% vs. 14.5%, p<0.001). The number of sentinel lymph nodes was 54 for melanomas lo-cated on the upper trunk, 8 cervical and 46 axillary, respectively 30 sentinel lymph nodes in cases of melanomas of the lower trunk, 16 at the axillary level and 14 at the inguinal level; (4) Conclusions: Lymph node involvement in melanoma represents an important prognostic factor and the different lymphatic drainage pathways in relation to the location of the primary tumor represents an im-portant objective in the management of this pathology.

Titanium (Ti) and Ti-based alloys are commonly used in dental implants, and surface modifications of dental implants are important for achieving osseointegration (i.e., direct connection between the implant surface and bone). This study investigated the effect of an eco-friendly etching solution—a hydrogen peroxide–sodium bicarbonate mixture—on the surface properties and contact angles of and osteoblast adhesion and proliferation on Ti surfaces. Disk-shaped Ti specimens were prepared using different surface treatments (machining, sandblasting, and sandblasting/acid-etching), and they were immersed in the etching solution and then ultrasonically cleaned. Surface characterization was performed using scanning electron microscopy, digital microscopy, contact angle analysis, and X-ray photoelectron spectroscopy. MG-63 osteoblasts were cultured on the specimens, and their adhesion to the specimen surface and their proliferation were examined using staining and the MTT assay, respectively. Additional etching with the etching solution caused the formation of nano/micro hierarchical structures, increased the surface roughness, and enhanced the hydrophilicity. Osteoblast adhesion and proliferation were found to improve on the modified surfaces. The eco-friendly etching method has the potential to enhance the biological properties of Ti implant surfaces and to thereby improve the dental implant performance.

In the field of orthodontics, providing patients with accurate treatment time estimates is of utmost importance. As orthodontic practices continue to evolve and embrace new advancements, incorporating machine learning (ML) methods becomes increasingly valuable in improving orthodontic diagnosis and treatment planning. This study aimed to develop a novel ML model capable of predicting the orthodontic treatment duration based on essential pre-treatment variables. Patients who completed comprehensive orthodontic treatment at the Indiana University School of Dentistry were included in this retrospective study. Fifty-seven pre-treatment variables were collected and used to train and test 9 different ML models. The performance of each model was assessed using descriptive statistics, intraclass correlation coefficients, and one-way analysis of variance tests. Random Forest, Lasso, and Elastic Net were found to be the most accurate, with a mean absolute error of 7.27 months in predicting treatment duration. Extraction decision, COVID, intermaxillary relationship, lower incisor position, and additional appliances were identified as important predictors of treatment duration. Overall, this study demonstrates the potential of ML in predicting orthodontic treatment duration using pre-treatment variables.

: Microbial fuel cell (MFCs) devices utilise the metabolic processes of bacteria to generate electricity from various organic substrates. Due to the enormous amount of energy that organic waste produces, scientists are highly interested in advanced MFCs. MFCs serve as a multidisciplinary research platform at the engineering and natural sciences intersection. MFCs have various uses besides being used as energy sources, such as sensing capabilities. Despite showing considerable promise, only a few marine sediment MFCs have been deployed in real-world applications to supply current for low-power devices. It is now required to maintain track of the work being done by research groups worldwide and regularly compile significant discoveries due to the rising quantity of research publications. Review papers are a traditional beginning point for a literature review for new scholars. This review is a fast reckoner that directs readers to pertinent reviews and research publications detailing significant advances in microbial fuel cell research during the previous two decades. An overview of key advances in MFC research over the past two decades is provided as a quick reference in this review article. In addition, the report identifies research gaps that, if filled, could bring this technology closer to real-world use.

Metal fabrications experience complex physical metallurgical processes during additive manufacturing, leading to residual stress and coarse microstructure with directional growth. It significantly affects the comprehensive performance of the fabrications, which limits the application of additive manufacturing. Ultrasonic impact treatment (UIT), as a strengthening means to assist additive manufacturing, can effectively improve the stress state and refine the microstructure and the comprehensive performance. This paper introduces the effect of UIT on AM metal fabrications on microstructure morphology, stress distribution, surface roughness, internal defects, and comprehensive performance to gain a deeper understanding of the role of UIT on additively manufactured metal fabrications, which is based on the working principle and effect of process parameters. In addition, the strengthening mechanism of UIT in additive manufacturing is described from the perspective of surface plastic deformation and substructure formation, providing support for the shape and property control of metal fabrications in the process of additive manufacturing assisted by UIT. Finally, the issues that need to be studied in depth on UIT in additive manufacturing are summarized, and an outlook on future research directions is taken.

Feline infectious peritonitis (FIP), caused by the feline coronavirus (FCoV), is a devastating dis-ease in cats. Based on its antigenicity, FCoV can be divided into two serotypes: FCoV-I and FCoV-II. Furthermore, according to its pathogenicity, FCoV can be divided into feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). There are numerous factors that affect the pathogenesis of FIP, among which host immunity and viral genetics can play an es-sential role in the development of FIP. Owing to the lack of specific symptoms, existing individual diagnostic methods can only support the suspicion of FIP, and multiple diagnostic methods and test data need to be combined to make a diagnosis. Although there are still no effective FIPV vaccines or commercial drugs available in the market, various studies have shown that some compounds can be used for treatment. Therefore, FIP is no longer incurable in cats

Neonicotinoids (NEOs) have become the most widely used insecticides in the world since the mid-1990s. According to Chinese dietary habits, rice and water are usually heated before being consumed, but the information about the alteration through the heat treatment process is very limited. In this study, the parents of NEOs (p-NEOs) accounted for >99% of the total NEOs mass (∑NEOs) in both uncooked (median: 66.8 ng/g) and cooked (median: 41.4 ng/g) rice samples from Guangdong Province, China, while the metabolites of NEOs (m-NEOs) involved in this study accounted for less than 1%. We aimed to reveal the concentration changes of NEOs through heat treatment process, thus, several groups of rice and water samples from Guangdong were cooked and boiled, respectively. Significant (p < 0.05) reductions in acetamiprid, imidacloprid (IMI), thiacloprid, and thiamethoxam (THM) have been observed after the heat treatment of the rice samples. In water samples, the concentrations of THM and dinotefuran decreased significantly (p < 0.05) after the heat treatment. These results indicate the degradation of p-NEOs and m-NEOs during the heat treatment process. However, the concentrations of IMI increased significantly in tap water samples (p < 0.05) after heat treatment process, which might be caused by the potential IMI precursors in those industrial pesticide products. The concentrations of NEOs in rice and water can be shifted by the heat treatment process, so this process should be considered in relevant human exposure studies.

The cavovarus deformity is characterized by a pathologic longitudinal arch elevation caused by a severe hindfoot varus and forefoot equinus deformity. This disorder includes multiple anomalies and therapies and affects 25% of the population. Cavus feet usually indicate neurologic illness, which affects sensory and motor nerves. Clinical and radiological evaluations are needed to establish each patient's optimum therapy. Failure to identify a neurologic illness may lead to inappropriate surgical treatment, recurrence, and reconstructive failure. In progressive anomalies, surgical procedures must be performed quickly in a phased protocol to prevent the malalignment from worsening. Soft tissue surgeries, osteotomies, and arthrodesis are surgical options for patients. To aid and lead practitioners in selecting the most appropriate therapy for their patients daily, we have included the most common therapeutic options currently available in this article.

White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue that’s primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear. This review aims to evaluate the emerging evidence on the crosstalk between adiposity and the immune-tumour microenvironment in BC, its progression and treatment resistance. Adiposity, and by extension subclinical inflammation, are associated with metabolic dysfunction and changes in the immune-tumour microenvironment in BC. In oestrogen receptor positive (ER+) breast tumours, it is proposed that these changes are mediated via a paracrine interaction between macrophages and preadipocytes leading to elevated aromatase expression and secretion of pro-inflammatory cytokines and adipokines in the breast tissue in patients who are obese or overweight. In HER2+ breast tumours, WAT inflammation has been shown to be associated with resistance to trastuzumab mediated via MAPK or PI3K pathways. Furthermore, adipose tissue in patients with obesity is associated with upregulation of immune checkpoints on T-cells that is partially mediated via immunomodulatory effects of leptin and has been paradoxically associated with improved responses to immunotherapy in several cancers. In conclusion, evidence suggests that body composition and metabolic status are associated with patient outcomes. To optimise patient stratification and personalisation of treatment, prospective studies are required to evaluate the role of body composition and metabolic parameters in metabolic immune reprogramming with and without immunotherapy in patients with BC.

Coagulation is the most sensitive step in drinking water treatment. Underdosing may not yield the required water quality, whereas overdosing may result in higher costs and excess sludge. Traditionally, the coagulant dosage is set based on bath experiments performed manually. Therefore, this test does not allow real-time dosing control, and its accuracy is subject to operator experience. Alternatively, solutions based on machine-learning (ML) have been evaluated as a computer-aided alternative. Despite these advances, there is open debate on the most suitable ML method applied to the coagulation process, capable of the most highly accurate prediction. This study addresses this gap, where a comparative analysis between ML methods was performed. As a research hypothesis, a novel data-driven fuzzy inference system (FIS) should provide the best performance due to its ability to deal with uncertainties inherent to complex processes. Although ML methods have been widely investigated, only a few studies report hybrid neuro-fuzzy systems applied to coagulation. Thus, to the best of our knowledge, this is the first study thus far to address the accuracy of this novel data-driven FIS for such application. The novel FIS provided the smallest error (0.86), indicating a promising alternative tool for real-time and highly accurate coagulant dosing in drinking water treatment.

The COVID-19 pandemic initiated a race to determine the best measures to control the disease and to save as many people as possible. Efforts to implement social distancing, the use of masks, and massive vaccination programs turned out to be essential in reducing the devastating effects of the pandemic. Nevertheless, the high mutation rates of SARS-CoV-2 challenge the vaccination strategy and maintain the threat of new outbreaks due to the risk of infection surges and even lethal variations able to resist the effects of vaccines and upset the balance. Most of the new therapies tested against SARS-CoV-2 came from already available formulations developed to treat other diseases, so they were not specifically developed for SARS-CoV-2. In parallel, the knowledge produced regarding the molecular mechanisms involved in this disease was vast due to massive efforts worldwide. Taking advantage of such a vast molecular understanding of virus genomes and disease mechanisms, a targeted molecular therapy based on siRNA specifically developed to reach exclusive SARS-CoV-2 genomic sequences was tested in a non-transformed human cell model. Since coronavirus can escape from siRNA by producing siRNA inhibitors, a complex strategy to simultaneously strike both the viral infectious mechanism and the capability of evading siRNA therapy was developed. The combined administration of the chosen produced siRNA proved to be highly effective in successfully reducing viral load and keeping virus replication under control, even after many days of treatment, unlike the combinations of siRNAs lacking this anti-anti-siRNA capability. Additionally, the developed therapy did not harm the normal cells, which was demonstrated because, instead of testing the siRNA in nonhuman cells or in transformed human cells, a non-transformed human thyroid cell was specifically chosen for the experiment. The proposed siRNA combination deeply reduced the viral load throughout the experiment and allowed cellular recovery, thus representing a potential innovation, to be considered as an additional weapon for therapy of COVID-19 and even other infectious diseases.

As the scarcity of potable water increases, recycling of treated wastewater is increasing. Small-scale, decentralized treatment can be implemented to serve local populations by keeping water within their boundaries and within reach for reuse, particularly in less dense, non-urban communities. Availability of cellular networks and high-speed internet connectivity, along with significant reduction in cost, allows ongoing monitoring of decentralized treatment systems at a central location. In this paper a decentralized treatment system using micro nanobubble aeration, moving media and membranes is able to produce reusable water with low energy consumption, thereby allowing the use of solar energy in places with unreliable electrical supply. The treatment system, which uses no external chemicals, is able to operate unattended and deliver clear, disinfected water with non-detect suspended solids, BOD5 less than 10 mg/L and nutrients below 5 mg/L.

The spray drying process causes the buildup of an unspecified and unique pattern of wall deposits on the wall. The powder recovery of fruit juice by spray dryer is associated with stickiness problems because of the nature of food which contains low molecular weight sugars and organic acids, which have a low glass transition temperature (T_g). The surface properties of oxygen plasma treated-PTFE substrate were evaluated by using the different parameters of Plasma Enhanced Chemical Vapour Deposition (PECVD) prior to spray drying analysis. In this study, the fabrication method of nearly perfect superhydrophobic surfaces through plasma treatment with oxygen gas was generated and utilized. The plasma-treated PTFE were deposited from a fixed flow rate of oxygen gas with 30 cm³/min by varying the deposition time from 1 to 15 minutes to induce the hydrophobic surface of the PTFE substrate. The characterization techniques used to determine the morphology and chemical bonding of the substrate are field emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FTIR), respectively. The hydrophobicity of the glass samples was determined by the water droplet contact angle. Sample prepared at radio frequency (RF) power of 90W for 15 minutes duration of treatment time showed porous and spongy like microstructure which correlates with the best performance of a good contact angle which creates the superhydrophobicity regime (171^o). Surface morphology analysis using scanning electron microscopy (SEM) showed changes in its roughness in the surface-treated glass substrate. The success of this method produced a huge potential for solving most of the food processing issues which relate to biofouling (e.g., powder stickiness) that would otherwise struggle to improve high productivity and recovery.

As the problem of traction injuries to brachial plexus is a common one and of high socio-economic significance, the analysis of the surgical outcomes in patients with this pathology is significant for neurosurgery, neurology, traumatology-orthopedics, and rehabilitation. The aim of the research is to compare the short-term outcomes of using various surgical methods for managing patients with closed traction injuries of brachial plexus. Material and methods. The research involved 61 patients with closed traction injury of brachial plexus divided into two groups homogeneous in sex, age and severity of their neurological deficit: Group I – 33 patients who underwent microsurgical neurolysis, Group II – 28 patients who underwent microsurgical neurolysis combined with one-level electrostimulation. The dynamic assessment of clinical and functional status of upper limbs was performed using scale methods and electrophysiological monitoring. Results. The research revealed a more evident recovery of the upper limb function in Group II patients suggesting the method of microsurgical neurolysis combined with electrostimulation to be preferable in case of closed traction injuries to brachial plexus. Conclusion. The combination of microsurgical neurolysis with one-level electrostimulation improves the short-term outcomes of surgical treatment in patients with closed traction injuries of brachial plexus due to a sooner decrease in pain in postoperative period, and positive dynamics of clinical and electrophysiological parameters.

Background The spread of COVID-19 continues, the mutation of SARS-COV-2 is still difficult to control, and the need for antiviral drugs to treat COVID-19 remains urgent. The use of arbidol in the treatment of COVID-19 is limited and controversial. Methods To clarify the efficacy of arbidol on COVID-19, we collected 25 cases and 178 related studies. We analyzed the treatment information of arbidol based on the obtained cases, expanded the scope of the study, and collected current studies on the treatment of COVID-19 in various databases for in-depth analysis. Results History analysis showed that arbidol was effective (76% cure rate) compared with other drugs. However, compared with other antiviral drugs or standard therapy, the arbidol group had no significant advantage in reducing the time to negative virus transformation, length of hospital stays, or improvement in CT (MD=0.22, 95%CI -0.29-0.73; MD = 0.61, 95% CI 1.46 to 2.67; RR=1.15, 95%CI 0.88-1.50); Analysis of adverse events showed no significant difference between the arbidol group and the other groups (RR=0.82, 95%CI 0.25-2.71). Conclusion Our study showed that arbidol had no significant effect on COVID-19, but showed a slight advantage in CT improvement and adverse events. Our study objectively evaluated the efficacy of arbidol in the treatment of COVID-19 and provided some guidance for arbidol in the treatment of COVID-19.

Bacterial vaginosis (BV), the most common cause of vaginal discharge, is characterized by a shift in the vaginal microbiota from lactobacillus dominance to a diverse array of facultative and strict anaerobic bacteria which form a multi-species biofilm on vaginal epithelial cells. The rate of recurrence after therapy is high, often >60%. While the BV biofilm itself likely contributes to recurrent and/or refractory disease after treatment by reducing antimicrobial penetration, antimicrobial resistance in BV-associated bacteria including those, both within the biofilm and the vaginal canal, may be the result of independent, unrelated bacterial properties which are discussed in this paper. Our current recommendations for the treatment of refractory and recurrent BV are also provided.

This paper deals with investigation of changes in geopolymer wettability with increasing mass fraction of high-carbon fly ash and surface treatment by cold atmospheric plasma (CAP). In this study, multiple samples of geopolymers were prepared, including those with 5% and 10% of high-carbon fly ash from coal-fired power station. Wettability of samples was then measured before and after plasma treatment, both on surface and cut surface. While addition of fly ash only had low effect on the wettability, as in most cases, it only lowered the initial contact angle without speeding up the speed of soaking for compact geopolymer and actually slowed the soaking for foamed geopolymer, plasma treatment had significant impact and made the geopolymer hydrophobic.

The granulomatous cheilitis (GC) presents a heterogeneous group of disorders characterised by a granulomatous inflammation/reaction of the lips to various stimuli. Numerous etiologies have been proposed, including genetic, immunologic, allergic and infectious. Among the secondary causes of GC, a distant infection by Mycobacterium tuberculosis should be considered. The GC could be the clinical presentation of a tuberculide resulting from a hypersensitivity reaction to an underlying focus of active or latent tuberculosis infection (LTBI). This communication describes a woman diagnosed with GC related to LTBI, who responded well to antituberculosis treatment.

Children with leukaemia experience difficulties adapting to medical procedures and to the chemotherapy’s adverse effects. Study’s objectives were to identify which coping strategies could be associated with the treatments’ factors and with the dosage of sedation analgesic drugs during bone marrow aspirates. 125 patients (M = 6.79 years; SD = 3.40), majority with acute lymphoblastic leukemia (90.4%) and their parents received, one month after diagnosis, the PPCI. Data on the severe treatment effects and on the dosage of drugs in sedation-analgesia were also collected. An ANCOVA model (R2=0.25) showed that, weighing the age factor (F=3.47; df=3; p=0.02), the number of episodes of fever (F=4.78; df=1; p=0.03), nausea (F=4.71; df=1; p=0.03) and mucositis (F=5.81; df=1; p=0.02) influenced the use of distraction. Cognitive self-instructions (R2=0.22) were influenced by the number of hospitalizations (F=5.14; df=1; p=0.03) and mucositis (F=8.48; df=3; p=0.004) and by child’s age (F=3.76; df=3; p=0.01). Children who sought parental support more frequently (F=9.7; df=2; p=0.0001) and who tended not to succumb to a catastrophic attitude (F=13.33; df=2; p=0.001) during the induction treatment phase required lower drug dosages, especially propofol. The clinical application of these results could be to encourage the use of cognitive self-instructions and search for social support.

Purpose: To determine whether pre-surgical treatment using long-acting somatostatin analogues (SSAs) may improve surgical outcomes in acromegaly. Methods: Retrospective study of 48 patients with acromegaly operated by endoscopic transsphenoidal approach and for first time. Surgical remission was evaluated based on the 2010 criteria. Results: Most patients, 83.3% (n=40), harboured macroadenomas and 31.3% (n=15) invasive pitu-itary adenomas. Fourteen patients were treated with lanreotide LAR and 6 with octreotide LAR, median monthly doses of 97.5 [range 60-120] and 20 [range 20-30] mg, respectively, for at least 3 months preoperatively. Presurgical variables were comparable between pre-treated and un-treatred patients (P>0.05). Surgical remission was more frequent in those pre-treated with monthly doses ≥90 mg of lanre-otide or ≥30 mg of octreotide than in untreated or pre-treated with lower doses (OR=4.64, P=0.025). However, no differences were found between pre-treated and untreated patients when lower doses were included or between those treated for longer than 6 months compared to those untreated or pre-treated for shorter than 6 months. Similarly, no differences were found either in terms of surgical or endocrine complications (OR=0.65, P=0.570)), independently of the doses and the duration of SSA treatment (P>0.05). Conclusions: The dose of SSAs is a key factor during pre-surgical treatment, since the beneficial effects in surgical remission were observed with monthly doses equal or higher than 90 mg of lanreotide and 30 mg of octreotide, but not with lower doses.

Abstract: As a risk factor, obesity is a threat to human well-being and related metabolic disorders such as diabetes mellitus and dyslipidemia. adipogenesis is defined as the proliferation and maturation of adipocyte predecessor cells to adipocyte. As the adipogenesis process decides adipocyte production, it may be considered a therapeutic target for obesity and obesity-related disorders. White adipose tissue abnormal expansion increases the size and number of adipocytes. For that reason, this review aims to spot the molecular mechanisms implicated in adipogenesis that lead to application in the therapeutic targets. Keywords: adipogenesis, signaling pathways, anti-obesity treatment, obesity

The mechanical engineering requires heat treatment after rough machining to reach the mechanical strength, but the heat treatment can induce workpiece deformation, so that the workpiece cannot be reworked. In this study, the plasma was integrated with a lathe, and the on line heat treatment was performed to achieve the mechanical strength and hardness, so as to reduce the machining process and handling. However, for on line heat treatment, it is important to study the machine and plasma parameters of the lathe and plasma, and the research method is used eventually to optimize the process, reduce the machining cost and machining error. The variable factors in surface on line real-time heat treatment are revolution, feed rate and current, the objective function is the hardness of mechanical properties. In the screening experiment, the interaction of factors was discussed using full factorial experiment. The Central Composite Design was combined with the Lack-of-Fit test for optimization experiment, the R2 coefficient was used to determine whether the regression model is appropriate. The optimum parameters were derived from the contour diagram and response surface diagram. The experimental results show that the significant factors include revolution, feed rate and current, the optimum parameters include revolution 168rpm, feed rate 0.068mm/rev and current 86A. The experimental results of optimum parameters show that the surface hardness is increased from 306HLD to 806HLD, the surface hardening effect is enhanced by 163%, so the on line real-time heat treatment equipment has a best hardening effect.

The article discusses the results of investigations performed during a thermo-mechanical treatment of forgings made of chromium-molybdenum 42CrMo4 grade steel. The treatment was realized during a regular series production. The forging process was combined with a heat treatment carried out directly after forging on a specially adapted station. Such a production technology will make it possible to eliminate the step of repeated heating of the forgings. On the example of an element of a steering gear, it was demonstrated how it is possible to perform an isothermal annealing process starting from the temperature at which the trimming of the forgings ends. During the cooling of the forgings, it is enough to maintain the temperature at the proper level in order for the exothermal phase transformation of austenite into pearlite to take place. With an appropriate design of the processing line, the heat released during the transformation could be used to maintain the applied temperature, thus limiting the consumption of energy needed to power the devices. The test results show that, with the properly selected temperature of isothermal annealing, it is possible to obtain an equilibrial ferritic-pearlitic structure in the required hardness scope. Introducing such a solution into the industrial practice would allow significant savings of the energy used for the heat treatment.

Control of Theileria equi, the primary cause of equine theileriosis, is largely reliant on acaracide use and chemosterilization with imidocarb dipropionate (ID). However, it is currently unknown if ID is effective against Theileria haneyi, the recently identified second causative agent of equine theileriosis, or if the drug maintains effectiveness against T. equi in the presence of T. haneyi co-infection. The purpose of this study was address these questions using ID treatment of the following three groups of horses: 1. Five T. haneyi infected horses; 2. Three T. haneyi-T. equi infected horses; and 3. Three T. equi-T. haneyi infected horses. Clearance was first evaluated using nPCR for each Theileria sp. on peripheral blood samples. ID failed to clear T. haneyi in all three groups of horses, and failed to clear T. equi in 2/3 horses in group two. For definitive confirmation of infection status, horses in groups two and three underwent splenectomy post-treatment. The T. equi-nPCR-positive horses in group two developed severe clinical signs and were euthanized. Remaining horses exhibited moderate signs consistent with T. haneyi. Our results demonstrate that ID therapy lacks efficacy against T. haneyi, and T. haneyi-T. equi co-infection may interfere with ID clearance of T. equi.

Control of Theileria equi, the primary cause of equine theileriosis, is largely reliant on acaracide use and chemosterilization with imidocarb dipropionate (ID). However, it is currently unknown if ID is effective against Theileria haneyi, the recently identified second causative agent of equine theileriosis, or if the drug maintains effectiveness against T. equi in the presence of T. haneyi co-infection. The purpose of this study was address these questions using ID treatment of the following three groups of horses: 1. Five T. haneyi infected horses; 2. Three T. haneyi-T. equi infected horses; and 3. Three T. equi-T. haneyi infected horses. Clearance was first evaluated using nPCR for each Theileria sp. on peripheral blood samples. ID failed to clear T. haneyi in all three groups of horses, and failed to clear T. equi in 2/3 horses in group two. For definitive confirmation of infection status, horses in groups two and three underwent splenectomy post-treatment. The T. equi-nPCR-positive horses in group two developed severe clinical signs and were euthanized. Remaining horses exhibited moderate signs consistent with T. haneyi. Our results demonstrate that ID therapy lacks efficacy against T. haneyi, and T. haneyi-T. equi co-infection may interfere with ID clearance of T. equi.

The management of carbapenem-resistant infections is often based on colistin, tigecycline, aminoglycosides and their combinations. However, in a recent systematic review we found that Gram-negative bacteria (GNB) co-resistant to carbapanems, aminoglycosides, colistin and tigecycline (CACT-resistant) are increasingly being reported worldwide. Clinical data to guide the treatment of CACT-resistant GNB are scarce and based exclusively on few case reports and small case series but seem to indicate that appropriate (in vitro active) antimicrobial regimens, including newer antibiotics and synergistic combinations, may be associated with lower mortality. In this review we consolidate the available literature to inform clinicians dealing with CACT-resistant GNB about treatment options by considering the mechanisms of resistance to carbapenems. In combination with rapid diagnostic methods that allow fast detection of carbapenemase production, the approach proposed in this review may guide a timely and targeted treatment of patients with infections by CACT-resistant GNB. Specifically, we focus on the three most problematic species, namely Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Several treatment options are currently available for CACT-resistant K. pneumonia. Newer β-lactam-β-lactamase combinations, including the combination of ceftazidime/avibactam with aztreonam against metallo-β-lactamase-producing isolates, appear to be more effective compared to combinations of older agents. Options for P. aeruginosa (especially metallo-β-lactamase-producing strains) and A. baumannii remain limited. Synergistic combination of older agents (e.g. colistin- or fosfomycin-based synergistic combinations) may represent a last resort option but their use against CACT-resistant GNB requires further study.

Plastics are naturally hydrophobic materials so, in order to employ flotation for the separation of plastic mixtures, the use of appropriate wetting agents is mandatory. In this work, the effect of pretreatment with alkaline solutions of sodium hydroxide on the floatability of four plastics (PET, PS, PMMA and PVC) was studied. The influence of NaOH concentration, treatment time and temperature of the alkaline solution, and influence of particle size was analyzed. Results showed that alkaline treatment had a strong effect on PET floatability, some effect on floatability of PMMA and PVC and no effect on floatability of PS. Plastics floatability decreased with the increase of NaOH concentration, temperature and treatment time of the alkaline solution. Based on flotation behavior of simple plastics, flotation separation after alkaline treatment of bi-component mixtures of PET with PS and PVC was achieved efficiently. The best separation was obtained for PET/PS mixture, a floated with a grade of 98% in PS and a sunk with a grade of 100% in PET. PET/PMMA mixture led to the worst separation. For PET/PMMA and PET/PVC mixtures, flotation separation improved with the decrease of the particles size.

The shortage of donor organs is a major global concern. Organ failure requires the transplantation of functional organs. Organ donors are preserved in warm or cold ischemia. Ischemia and reperfusion damage the organs, due to the lack of oxygen during the ischemia step and the oxidative stress during the reperfusion step. Different methodologies were developed to prevent or diminish the level of injuries. Preservation solutions were first developed, followed by the addition of chemical compounds. In addition of inhibitors of mitogen activated protein kinase, inhibitors of the proteasome, mesenchymal stem cells started to be used 13 years ago to prevent or diminish the organ’s injuries. Mesenchymal stem cells (e.g bone marrow stem cells, adipose derived stem cells) have proven to be powerful tools in repairing damaged organs. This review will focus on the use of some bone marrow stem cells, adipose derived stem cells and umbilical cord stem cells on preventing or decreasing the injuries due to ischemia-reperfusion.

In 2014, the outbreak of adenoviral pneumonia occurred in Korean military training center. However, there is limited data on characteristics of fever and its response to antipyretics therapy in immunocompetent adults with adenoviral positive community-acquired pneumonia (CAP). Medical records of patients who were admitted to Armed Forces Chuncheon Hospital for treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. We evaluated demographics, clinico-laboratory findings and radiologic findings at admission were compared between adenovirus positive (Adv) group and adenovirus negative (non-Adv) group. Out of 251 military personnel with CAP during the study periods, 67 were classified into Adv group while 184 were Non-Adv group. Patients with Adv group had a longer duration of fever after admission and symptom onset. Adv group patients had a higher mean temperature at admission and more observed over 40 and 39 to 40℃. Adv group patients had more commonly observed no response to antipyretic treatment and adverse events after antipyretics use. Length of hospital stay had no significant difference between two groups and no patient died in both groups. In our study, Adv positive CAP in patients with immunocompetent military personnel had distinct characteristics of fever and response to antipyretic treatment.

In this investigation steel P355NH has been successfully cladded with Inconel 625 through the method of explosive welding. Explosively welded bimetal clad-plate was subjected to the two separated post weld heat treatment processes: stress relief annealing (at 620oC for 90 minutes) and normalizing (at 910oC for 30 minutes). In order to analyze the microstructure of the joint in the as-welded state and to investigate the influence of the post weld heat treatment on it, the light and scanning electron microscope observations and microhardness analysis have been performed. The examination of the diffusion zone microstructure has been performed by using the scanning transmission electron microscope. It was stated that obtained joint has characteristic wavy-shape geometry with the presence of the melted zones and severe deformed grains of both joined materials. Strain hardening of the materials in joint zone was established with microhardness analysis. In both of the heat treatments the changes in the grain structure have been observed. The normalizing heat treatment has the most significant impact on the microstructure of the joint as well as the concentration of the chemical elements in the joint zone. It was reported that due to normalizing the diffusion zone has been formed together with precipitates in the joint zone. The analysis of the diffusion zone images leads to the conclusion that the diffusion of alloying elements from Inconel 625 to steel P355NH takes place along the grain boundaries with additional formation of the voids in this area. The precipitates in Inconel 625 in the joint zone are two type of carbides – chromium-rich and molybdenum-rich. Scanning transmission electron microscope observation of the grain microstructure in the diffusion zone shows that this area consists of equiaxed grains (from the side of Inconel 625 alloy) and columnar grains (from the side of steel P355NH).

The fatigue strength of the hot work steel depends on various factors, including the mechanical, properties and behavior and bulk and the surface under layer, the microstructural features as well as heat treatments. The influence of a series of heat treatments on the fatigue strength of H13 hot work steel was investigated. Different preheating, quenching and tempering treatments were applied to four sets of specimens and fatigue tests were conducted at room temperature using a rotating bending test machine. All heat treatments resulted in a certain improvement of the fatigue strength. Highest fatigue strength obtained by applying a double tempering heat treatment (first tempering at 550 °C for two hours and second tempering at 610 °C for two hours) after initial preheating and quenching. One tempering treatment (550 °C for two hours after preheating and quenching) did not significantly improve the fatigue strength.

Development of carbon nanomaterials for adsorption thus removal of organic pollutants from water is a progressive research subject. In this regard, carbon nanomaterials with bifunctionality towards polar and non-polar or even amphiphilic undesired materials is indeed attractive for further study and implementation. Here, we created carbon buckypaper adsorbents comprising amphiphilic (oxygenated amorphous carbon (a-COx)/graphite (G)) nanofilaments that can dynamically adsorb organic biomolecules (i.e. urease enzyme) and thus purify the wastewaters of relevant industries. Given the dynamic conditions of the test, the adsorbent was highly efficient in adsorption of the enzyme (88%) while permeable to water (2382 L.h-1.m-2), thus holds a great promise for further development and upscaling. A subsequent citric acid functionalization declined selectivity of the membrane to urease, implying the biomolecules adsorb mostly via graphitic domains rather than oxidized, polar amorphous carbon ones. The devised platform i.e. the urease functionalized buckypaper is optimally conductive (13 S.cm-1) and can be further employed as a biosensor. Accordingly, water treatment can be linked to biosensing via a nanostructured membrane.

Natural spa springs are diffused all over the world and their use in pools is known since ancient times. This review underlines the cultural and social spa context focusing on hygiene issues, public health guidelines and emerging concerns regarding water management in wellness or recreational settings. The question of the "untouchability" of therapeutic natural waters and their incompatibility with traditional disinfection processes is addressed considering the demand for effective treatments that would respect the natural properties. Available strategies and innovative treatments are reviewed, highlighting potentials and limits for a sustainable management. Alternative approaches comprise nanotechnologies, photocatalysis systems, advanced filtration. State of the art and promising perspectives are reported considering the chemical-physical component and the biological natural complexity of the spa water microbiota.

Several common and functional genes are known to contribute to responsiveness to blood pressure (BP) therapy. BP therapy is typically guided by algorithms that do not include a patient’s genetic information. This study aimed to determine the impact of a multi-organ genetic panel on BP response to pharmacotherapy. Eighty-six patients completed one study visit consisting of a buccal swab collection, measurement of office BP, and a medical chart review for BP history. Genes analyzed included those that encode for one drug metabolizing enzyme, renal Na+ handling, vascular, and cardiac function. Relationships between genotype and control of BP (<140/<90), ∆ systolic BP, ∆ diastolic BP, and ∆ mean arterial BP were assessed. SLC12A3 resulted in a significant association between the target drug and the functional genotype for BP control (<140/<90 cut off) (p<0.05). Conversely, three of five renal genotypes were associated with BP control using 120/80 as a cut-off (p<0.05). Three of four cardiac genotypes were associated with the BP control at <140/<90, with one being statistically significant (position 49 of ADRB1). Only one vascular genotype was predictive of blood pressure control at <140/<90. We found a significant drop in mean BP from baseline in six genes, three important in the diuretic response and three in β-blockade (p<0.05 on target drug vs. not). These results demonstrate that a multi-gene panel for renal Na+ handling, vascular function, and cardiac output may influence the BP response to therapy, but larger studies with more statistical power are needed.

This study explored the effects of cryogenic treatment on the microstructure, hardness, and wear-resistance of diamond-like carbon (DLC) by cryogenically treating NAK 80 mold steel coated with DLC. Raman spectroscopy analyzed the structure of the DLC film. Nanoindenter analyzed the hardness and Young’s modulus of the film, and their relationship determined the wear resistance. Wear test assessed the wear rate and friction coefficient of the DLC film. The results showed that cryogenic treatment increased the rate of carbide precipitation and refined the grain structure. Raman spectroscopy indicated that the Raman intensity rate (I_D/I_G) of treated DLC films was smaller than those without cryogenic treatment. When the sp3 bond increased, the hardness and wear-resistance of the DLC film also increased.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by swelling in at least one joint. Owing to an overactive immune response, extra-articular manifestations are observed in certain cases, with interstitial lung disease (ILD) being the most common. Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is characterized by chronic inflammation of the interstitial space, which causes fibrosis and the scarring of lung tissue. Controlling inflammation and pulmonary fibrosis in RA-ILD is important because they are associated with high morbidity and mortality. Pirfenidone and nintedanib are specific drugs against idiopathic pulmonary fibrosis and have shown efficacy against RA-ILD in several clinical trials. Immunosuppressants and disease-modifying antirheumatic drugs (DMARDs) with antifibrotic effects have also been used to treat RA-ILD. Immunosuppressants moderate the overexpression of cytokines and immune cells to reduce pulmonary damage and slow the progression of fibrosis. DMARDs with mild antifibrotic effects target specific fibrotic pathways to regulate fibrogenic cellular activity, extracellular matrix homeostasis, and oxidative stress levels. Therefore, specific medications are required to effectively treat RA-ILD. In this review, the commonly used RA-ILD treatments are discussed based on their molecular mechanisms and clinical trial results. In addition, a computational approach is proposed to develop specific drugs for RA-ILD.

Wound infection is a common complication of chronic wounds. It can impair healing, which may not occur without external help. Antimicrobial dressings (AMDs) are a type of external help to infected chronic wounds. In this study, highly porous membranes made of only chitosan and containing the antiseptic polyhexanide (poly(hexamethylene biguanide); PHMB) were prepared by cryogelation, aiming to be used in AMDs. These membranes exhibited high water swelling capacity, fast water absorption and high water vapor transmission. The best drug loading method involved simultaneous loading by soaking in a PHMB solution and sterilization by autoclaving, resulting in sterilized, drug-loaded membranes. The drug release kinetics was comparable to that of a commercial PHMB-releasing AMD assayed under the same conditions. These membranes exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are bacterial species commonly found in infected wounds, and blood clotting activity. The obtained results suggest that these membranes may be suitable for use in the development of AMDs.

The COVID-19 was described as a respiratory illness, however further studies recognize it as a complex heterogeneous multisystemic disorder. Global efforts have been proposed to combat COVID-19, emerging diverse therapeutic options, in which discovering new drug therapies, development of vaccines and drug repurposing have been considered the most promising approaches to fight the virus. This study aimed to repurpose known drugs for use against the COVID-19, finding better therapeutic options. Seventeen biological databases were used in this study. The genetic algorithm (GA) was performed for a set of drug target classes and COVID-19 proteins as input, whose drug candidates are obtained according to the target similarities found in the target-target similarity predictive network, resulting in a drug-target interaction network. Thus, recommended drugs correspond to the union of the drug subsets found during each GA execution. Twenty-eight drugs were indicated to be the best therapeutic targets for the virus, in special, the Cyclosporine drug was administered as adjuvant to steroid treatment for COVID-19 patients which showed positive outcomes, reducing mortality in moderate and severe cases. The drugs found have used to treat other diseases, evidencing that the COVID-19 is a multisystemic disorder and suggests that the viruses’ mechanism of action presents some comorbidity with other human diseases. Evidence shows that the drugs found in this research might act together to fight the virus in a broader fashion, however further studies including in vitro and in vivo experiments are needed to find the best combination of these drugs.

Drug repurposing, the practice of utilizing existing drugs for novel clinical indications, has tremendous potential for improving human health outcomes and increasing therapeutic development efficiency. The goal of multidisease multitarget drug repurposing, also known as shotgun drug repurposing, is to develop platforms that assess the therapeutic potential of each existing drug for every clinical indication. Our Computational Analysis of Novel Drug Opportunities (CANDO) platform for shotgun multitarget repurposing implements several pipelines via large scale modelling and simulation of interactions between comprehensive libraries of drugs/compounds and protein structures. In these pipelines, each drug is described by an interaction signature that is then compared to all other signatures that are then sorted and ranked based on similarity. Pipelines within the platform are benchmarked based on their ability to recover known drugs for all indications in our library, and predictions are generated based on the hypothesis that (novel) drugs with similar signatures may be repurposed for the same indication(s). The drug-protein interactions in the platform used to create the drug-proteome signatures may be determined by any screening or docking method but the primary approach used thus far has been an in house similarity docking protocol. In this study, we calculated drug-proteome interaction signatures using the publicly available molecular docking method Autodock Vina and created hybrid decision tree pipelines that combined our original bio- and cheminformatic approach with the goal of assessing and benchmarking their drug repurposing capabilities and performance. The hybrid decision tree pipeline outperformed the corresponding two docking-based pipelines it was synthesized from, yielding an average indication accuracy of 13.3% at the top10 cutoff (the most stringent), relative to 10.9% and 7.1% for its constituent pipelines, and a random control accuracy of 2.2%. We demonstrate that docking based virtual screening pipelines have unique performance characteristics and that the CANDO shotgun repurposing paradigm is not dependent on a specific docking method. Our results also provide further evidence that multiple CANDO pipelines can be synthesized to enhance drug repurposing predictive capability relative to their constituent pipelines. Overall, this study indicates that pipelines consisting of varied docking based signature generation methods can capture unique and useful signal for accurate comparison of drug-proteome interaction signatures, leading to improvements in the benchmarking and predictive performance of the CANDO shotgun drug repurposing platform.

Nanotechnology has enabled the development of novel therapeutic strategies such as targeted nanodrug delivery systems, control and stimulus-responsive release mechanisms, and the production of theranostic agents. As a prerequisite for the use of nanoparticles as drug delivery systems, the amount of loaded drug must be precisely quantified, a task for which two approaches are currently used. However, both approaches suffer from the inefficiencies of drug extraction and of the solid-liquid separation process, as well as from dilution errors. This work describes a new, reliable, and simple method for direct drug quantification in polymeric nanoparticles using attenuated total reflection Fourier transform infrared spectroscopy, which can be adapted for a wide variety of drug delivery systems. Silk fibroin nanoparticles and naringenin were used as model polymeric nanoparticle carrier and drug, respectively. The specificity, linearity, detection limit, precision and accuracy of the spectroscopic approach were determined in order to validate the method. A good linear relation was observed within 0.00 to 7.89 % of naringenin relative mass with an R2 of 0.973. The accuracy was determined by the spike and recovery method. Results showed an average 104% recovery. The limit of detection and limit of quantification of the drug loading content were determined to be 0.3 and 1.0 %, respectively. The method's robustness is demonstrated by the notable similarities between the calibrations carried out in two different equipment and institutions.