Medicina (Kaunas). 2023 Aug 7;59(8):1429. doi: 10.3390/medicina59081429.

ABSTRACT

Background and Aim: Postoperative pain after scoliosis surgery is severe and usually requires long-term intravenous opioid therapy. Local anesthetic options, such as wound infiltration, are limited and include neuraxial analgesia. However, they are rarely used due to side effects and inconsistent efficacy. We report an opioid-sparing multimodal analgesia regimen with bilateral erector spinae plane blocks. This case series evaluated the analgesic effect of the bilateral bi-level erector spinae plane blocks (ESP) in congenital and neurogenic scoliosis surgery. Patients and Methods: Six pediatric patients with congenital or neurogenic scoliosis underwent posterior spinal fusion involving 5 to 12 vertebral levels. Bilateral single-injection ESPB was performed at one or two levels before incision. Preoperatively, patients received intravenous dexamethasone. General anesthesia with endotracheal intubation and volume-controlled ventilation was performed via TIVA with remifentanil and propofol. During and after the procedure, the basic hemodynamic parameters, opioid consumption, pain scores (numerical rating scale/NRS), and possible block complications were monitored. Results: All the patients experienced minimal postoperative pain levels. In addition, on the first day after surgery, they had low opioid requirements with no side effects. Conclusions: ESPB in patients undergoing congenital and neurogenic scoliosis correction surgery seems to be an essential analgesic technique that may reduce both severities of pain and opioid consumption.

PMID:37629719 | PMC:PMC10456815 | DOI:10.3390/medicina59081429

Medicina (Kaunas). 2023 Jul 31;59(8):1406. doi: 10.3390/medicina59081406.

ABSTRACT

Background: Dermal fillers for soft tissue for the treatment of face sagging, volume loss, and wrinkles have become popular among patients of all ages and ethnicities, and their use is becoming increasingly widespread. Aim: the goal of this study was to evaluate the effectiveness and safety of a micro-pulsed, 1444 nm Nd:YAG laser on dermal filler complications, in particular on granuloma management. Methods: A subcutaneous, 1444 nm Nd:YAG laser was used on five female patients (range age 52-68 years) with hyaluronic filler granulomas located on the face (two on the cheek area and three on the lips); three patients had self-injected the filler, buying it online. Before and after the therapy, the patients received a skin ultrasound to determine the form and location of the granulomas and to determine if there had been a full or partial resolution. During this study, all possible adverse effects at the treatment site were monitored. The 5-point Global Aesthetic Improvement Scale (GAIS) (0 point-no change; 1 point-25%, mild improvement; 2 points-50%, moderate improvement; 3 points-75%, good improvement; 4 points-100%, excellent improvement) was recorded at a 3-month follow-up. Results: good results were obtained in the treatment of filler granulomas with the intralesional 1444 nm laser, even if just a single treatment was performed (one intervention was effective for curing granulomas up to 5 mm in diameter). Three patients were satisfied with excellent improvement, and two patients experienced good improvement. The results are functional and aesthetically satisfying, as shown by photographic assessment. At the last follow-up, the granuloma had reduced or completely disappeared in all cases, and no infections, burns, scarring or fibrosis, episodes of severe bleeding, or other serious adverse effects had been reported. All subjects tolerated the post-treatment period well. Conclusions: Our findings showed that granuloma treatment with an intralesional 1444 nm Nd:YAG laser is a minimally invasive, easy, fast, efficient, and low-risk procedure.

PMID:37629696 | PMC:PMC10456612 | DOI:10.3390/medicina59081406

Int J Mol Sci. 2023 Aug 11;24(16):12694. doi: 10.3390/ijms241612694.

ABSTRACT

Contemporary breast cancer management includes surgical resection combined with a multimodal approach, including chemotherapy, radiotherapy, endocrine therapy, and targeted therapies. Breast cancer treatment is now personalised in accordance with disease and host factors, which has translated to enhanced outcomes for the vast majority of patients. Unfortunately, the treatment of the disease involves patients developing treatment-induced toxicities, with cardiovascular and metabolic side effects having negative implications for long-term quality-of-life metrics. MicroRNAs (miRNAs) are a class of small non-coding ribonucleic acids that are 17 to 25 nucleotides in length, which have utility in modifying genetic expression by working at a post-transcriptional cellular level. miRNAs have involvement in modulating breast cancer development, which is well described, with these biomarkers acting as important regulators of disease, as well as potential diagnostic and therapeutic biomarkers. This review focuses on highlighting the role of miRNAs as regulators and biomarkers of disease, particularly in breast cancer management, with a specific mention of the potential value of miRNAs in predicting treatment-related cardiovascular toxicity.

PMID:37628874 | PMC:PMC10454054 | DOI:10.3390/ijms241612694

Int J Mol Sci. 2023 Aug 9;24(16):12587. doi: 10.3390/ijms241612587.

ABSTRACT

Due to the progressive ageing of the human population, the number of cancer cases is increasing. For this reason, there is an urgent need for new treatments that can prolong the lives of cancer patients or ensure them a good quality of life. Although significant progress has been made in the treatment of cancer in recent years and the survival rate of patients is increasing, limitations in the use of conventional therapies include the frequent occurrence of side effects and the development of resistance to chemotherapeutic agents. These limitations are prompting researchers to investigate whether combining natural agents with conventional drugs could have a positive therapeutic effect in cancer treatment. Several natural bioactive compounds, especially polyphenols, have been shown to be effective against cancer progression and do not exert toxic effects on healthy tissues. Many studies have investigated the possibility of combining polyphenols with conventional drugs as a novel anticancer strategy. Indeed, this combination often has synergistic benefits that increase drug efficacy and reduce adverse side effects. In this review, we provide an overview of the studies describing the synergistic effects of curcumin, a polyphenol that has been shown to have extensive cytotoxic functions against cancer cells, including combined treatment. In particular, we have described the results of recent preclinical and clinical studies exploring the pleiotropic effects of curcumin in combination with standard drugs and the potential to consider it as a promising new tool for cancer therapy.

PMID:37628772 | PMC:PMC10454892 | DOI:10.3390/ijms241612587

Genes (Basel). 2023 Aug 11;14(8):1609. doi: 10.3390/genes14081609.

ABSTRACT

Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) contribute to the occurrence of metformin side effects. The aim of the present study was to identify intronic genetic variants modifying the occurrence of metformin side effects and to replicate them in individuals with T2DM and in women with PCOS. We performed Next Generation Sequencing (Illumina Next Seq) of 115 SNPs in a discovery cohort of 120 metformin users and conducted a systematic literature review. Selected SNPs were analysed in two independent cohorts of individuals with either T2DM or PCOS, using 5'-3'exonucleaseassay. A total of 14 SNPs in the organic cation transporters (OCTs) showed associations with side effects in an unadjusted binary logistic regression model, with eight SNPs remaining significantly associated after appropriate adjustment in the discovery cohort. Five SNPs were confirmed in a combined analysis of both replication cohorts but showed different association patterns in subgroup analyses. In an unweighted polygenic risk score (PRS), the risk for metformin side effects increased with the number of risk alleles. Intronic SNPs in the OCT cluster contribute to the development of metformin side effects in individuals with T2DM and in women with PCOS and are therefore of interest for personalized therapy options.

PMID:37628660 | PMC:PMC10454417 | DOI:10.3390/genes14081609

Biomolecules. 2023 Aug 18;13(8):1264. doi: 10.3390/biom13081264.

ABSTRACT

The number of patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is increasing globally and is raising serious concerns regarding the increasing medical and economic burden incurred for their treatment. The progression of NASH to more severe conditions such as cirrhosis and hepatocellular carcinoma requires liver transplantation to avoid death. Therefore, therapeutic intervention is required in the NASH stage, although no therapeutic drugs are currently available for this. Several anti-NASH candidate drugs have been developed that enable treatment via the modulation of distinct signaling cascades and include a series of drugs targeting peroxisome proliferator-activated receptor (PPAR) subtypes (PPARα/δ/γ) that are considered to be attractive because they can regulate both systemic lipid metabolism and inflammation. Multiple PPAR dual/pan agonists have been developed but only a few of them have been evaluated in clinical trials for NAFLD/NASH. Herein, we review the current clinical trial status and future prospects of PPAR-targeted drugs for treating NAFLD/NASH. In addition, we summarize our recent findings on the binding modes and the potencies/efficacies of several candidate PPAR dual/pan agonists to estimate their therapeutic potentials against NASH. Considering that the development of numerous PPAR dual/pan agonists has been abandoned because of their serious side effects, we also propose a repositioning of the already approved, safety-proven PPAR-targeted drugs against NAFLD/NASH.

PMID:37627329 | PMC:PMC10452531 | DOI:10.3390/biom13081264

Biomolecules. 2023 Aug 16;13(8):1256. doi: 10.3390/biom13081256.

ABSTRACT

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment.

PMID:37627321 | PMC:PMC10452377 | DOI:10.3390/biom13081256

Biomolecules. 2023 Aug 11;13(8):1239. doi: 10.3390/biom13081239.

ABSTRACT

Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular damage. Notably, oxidative stress plays a critical role in the pathogenesis of a number of oral mucosal diseases, including oral mucositis, which remains one of cancer treatments' most common side effects. We have shown previously that oral keratinocytes are remarkably sensitive to oxidative stress, and this may hinder the development and reproducibility of epithelial cell-based models of oral disease. Here, we examined the oxidative stress signatures that parallel oral toxicity by reproducing the initial events taking place during cancer treatment-induced oral mucositis. We used three oral epithelial cell lines (an immortalized normal human oral keratinocyte cell line, OKF6, and malignant oral keratinocytes, H357 and H400), as well as a mouse model of mucositis. The cells were subjected to increasing oxidative stress by incubation with hydrogen peroxide (H2O2) at concentrations of 100 μM up to 1200 μM, for up to 24 h, and ROS production and real-time kinetics of oxidative stress were investigated using fluorescent dye-based probes. Cell viability was assessed using a trypan blue exclusion assay, a fluorescence-based live-dead assay, and a fluorometric cytotoxicity assay (FCA), while morphological changes were analyzed by means of a phase-contrast inverted microscope. Static and dynamic real-time detection of the redox changes in keratinocytes showed a time-dependent increase of ROS production during oxidative stress-induced epithelial injury. The survival rates of oral epithelial cells were significantly affected after exposure to oxidative stress in a dose- and cell line-dependent manner. Values of TC50 of 800 μM, 800 μM, and 400 μM were reported for H400 cells (54.21 ± 9.04, p < 0.01), H357 cells (53.48 ± 4.01, p < 0.01), and OKF6 cells (48.64 ± 3.09, p < 0.01), respectively. Oxidative stress markers (MPO and MDA) were also significantly increased in oral tissues in our dual mouse model of chemotherapy-induced mucositis. In summary, we characterized and validated an oxidative stress model in human oral keratinocytes and identified optimal experimental conditions for the study of oxidative stress-induced oral epithelial toxicity.

PMID:37627304 | PMC:PMC10452318 | DOI:10.3390/biom13081239

Pharmaceuticals (Basel). 2023 Aug 15;16(8):1161. doi: 10.3390/ph16081161.

ABSTRACT

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.

PMID:37631076 | DOI:10.3390/ph16081161

Pharmaceuticals (Basel). 2023 Aug 10;16(8):1137. doi: 10.3390/ph16081137.

ABSTRACT

Phytoestrogens (PEs) are plant-based compounds that can interact with estrogen receptors and are mainly used to treat menopausal complaints. However, the safety of products with assumed phytoestrogenic activity is not fully understood. This study aimed to identify plant species with assumed phytoestrogenic activity, review existing literature on their use and safety, and critically evaluate adverse reaction (AR) reports of single-herb, multi-herb, and mixed-multiple products, as submitted to the Netherlands Pharmacovigilance Centre Lareb and to VigiBase of the World Health Organization (WHO). In the Lareb database, the most commonly reported plant species to cause ARs (total of 67 reports) were Actaea racemosa L. (black cohosh) (47.8%), Humulus lupulus L. (hops) (32.8%), and Glycine max (L.) Merr. (soybean) (22.4%). In the VigiBase database (total of 21,944 reports), the top three consisted of Glycine max (L.) Merr. (71.4%), Actaea racemosa L. (11.6%), and Vitex agnus-castus L. (chaste tree) (6.4%). In the scoping review (total of 73 articles), Actaea racemosa L. (30.1%), Glycine max (L.) Merr. (28.8%), and Trifolium pratense L. (13.7%) were the most frequently mentioned plant species. ARs were most frequently reported in the system organ classes "gastrointestinal disorders", "skin and subcutaneous tissue disorders", "reproductive system and breast disorders", and "general disorders and administration site conditions". Furthermore, from the scoping review, it appeared that the use of products with assumed phytoestrogenic activity was associated with postmenopausal bleeding. It was concluded that, while the potential benefits of products with assumed phytoestrogenic activity have been extensively pursued, the potential occurrence of ARs after using these products is less well understood. This study highlights the need for further investigation and careful monitoring of these products to better understand their effects and ensure the safety and well-being of individuals using them.

PMID:37631050 | DOI:10.3390/ph16081137

Nutrients. 2023 Aug 20;15(16):3655. doi: 10.3390/nu15163655.

ABSTRACT

Cancer therapy is often associated with severe side effects such as drug induced weight loss, also known as chemotherapy-induced cachexia. The aim of this study was to investigate the effects of a multispecies probiotic (OMNi-BiOTiC® 10 AAD) in a chemotherapy mouse model. A total of 24 male BALB/c mice were gavage-fed with the probiotic formulation or water, once a day for 3 weeks. In the third week, the mice received intraperitoneal cyclophosphamide. At euthanasia, the organs were dissected, and serum was sampled for cytokine analysis. Tight junction components, myosin light chain kinase, mucins, and apoptosis markers were detected in the ileum and colon using histological analyses and qRT-PCR. Lipolysis was analyzed by enzymatic activity assay, Western blotting analyses, and qRT-PCR in WAT. The fecal microbiome was measured with 16S-rRNA gene sequencing from stool samples, and fecal volatile organic compounds analysis was performed using gas chromatography/mass spectrometry. The probiotic-fed mice exhibited significantly less body weight loss and adipose tissue wasting associated with a reduced CGI58 mediated lipolysis. They showed significantly fewer pro-inflammatory cytokines and lower gut permeability compared to animals fed without the probiotic. The colons of the probiotic-fed animals showed lower inflammation scores and less goblet cell loss. qRT-PCR revealed no differences in regards to tight junction components, mucins, or apoptosis markers. No differences in microbiome alpha diversity, but differences in beta diversity, were observed between the treatment groups. Taxonomic analysis showed that the probiotic group had a lower relative abundance of Odoribacter and Ruminococcus-UCG014 and a higher abundance of Desulfovibrio. VOC analysis yielded no significant differences. The results of this study indicate that oral administration of the multispecies probiotic OMNi-BiOTiC® 10 AAD could mitigate cyclophosphamide-induced chemotherapy side effects.

PMID:37630845 | DOI:10.3390/nu15163655

J Clin Med. 2023 Aug 12;12(16):5260. doi: 10.3390/jcm12165260.

ABSTRACT

Children who sustain major injuries are at risk of receiving insufficient pain relief and sedation, which can have physical and psychological repercussions. Heightened emotional distress can increase the likelihood of developing symptoms of post-traumatic stress. Providing sufficient analgesia and sedation for children with major trauma presents specific challenges, given the potential for drug-related adverse events, particularly in non-intubated patients. The current literature suggests that a relatively low percentage of pediatric patients receive adequate analgesia in pre-hospital and emergency department settings following major trauma. There are only sparse data on the safety of the provision of analgesia and sedation in children with major trauma in the pre-hospital and ED settings. The few studies that examined sedation protocols in this context highlight the importance of physician training and competency in managing pediatric airways. There is a pressing need for prospective studies that focus upon pediatric major trauma in the pre-hospital and emergency department setting to evaluate the benefits and risks of administering analgesia and sedation to these patients. The aim of this narrative review was to offer an updated overview of analgesia and sedation management in children with major trauma in pre-hospital and ED settings.

PMID:37629302 | DOI:10.3390/jcm12165260

BMC Public Health. 2023 Aug 25;23(1):1636. doi: 10.1186/s12889-023-16578-8.

ABSTRACT

BACKGROUND: Household air pollution is the major public health problem in developing countries. Pregnant women spent the majority of their time at home and are the most affected population by household air pollution. Exploring the perception of pregnant women on adverse health effects is important to enhance the mitigation strategies. Therefore, this study aim to explore the pregnant women's perceptions about health effects of household air pollution in rural Butajira, Ethiopia.

METHODS: A phenomenological qualitative study design was conducted among 15 selected pregnant women. All interviews were carried out at the participants´ house and audio-recorded while housing and cooking conditions were observed and appropriate notes were taken for each. The collected data were transcribed verbatim and translated into the English language. Then, the data were imported into Open code software to manage the overall data coding processes and analyzed thematically.

RESULTS: Study participants perceived that respiratory problems such as coughing, sneezing and asthma and eye problem were the major health problem caused by household air pollution among pregnant women. Study participants also mentioned asphyxiated, abortion, reduces weight, and hydrocephalus was caused by household air pollution on the foetus. Study participants perceived that financial inability, spouse negligence, autonomy and knowledge level of the women were the barriers to tackling household air pollution. Study participant also suggested that opening the door and window; using improved cookstove and reduce workload were the perceived solution for household air pollution.

CONCLUSIONS: This study explores pregnant women's perceptions on health effects of household air pollution. The finding of this study was important to deliver suitable intervention strategies to mitigate household air pollution. Therefore, educating the women on way of mitigating household air pollution, improving existing structure of the house and minimize the time to stay in the kitchen is important to mitigate household air pollution exposure.

PMID:37626318 | DOI:10.1186/s12889-023-16578-8

Sci Rep. 2023 Aug 25;13(1):13907. doi: 10.1038/s41598-023-40832-z.

ABSTRACT

Hepatocellular carcinoma (HCC) is a fatal tumor which is usually diagnosed at advanced stage. Molecular targeted drugs were used recently to treat HCC, however, due to serious side effects, mainly cardiotoxicity and emergence of resistance, there is demanding to explore new chemotherapeutics. 10 novel thiazoloquinoxaline derivatives coupled with different sulfonamide moieties 4(a-j) were designed and synthesized fulfilling pharmacophoric features of VEGFR-2 inhibition. Structures of all new compounds were verified via spectral and microanalytical data. After carrying in-vitro VEGFR-2 assay for compounds 4(a-j); sulfapyridine and sulfamethoxazole derivatives 4d and 4f showed potential inhibitory effect [61.04 and 83.35 nM], respectively, comparable to standard sorafenib [51.41 nM]. Both were then further evaluated for their cytocidal activity against HepG2 cell-line and against myocardium cells using H9C2 cell-line. As a result, only sulfapyridine derivative 4d exhibited a significant inhibition of HepG2 cells viability [IC50 = 4.31 μM]. Furthermore, it showed relatively lower cytotoxic impact against normal H9C2 myocardium cells [IC50, 33.47 μM] compared to that of sorafenib [IC50, 98.07 μM]. In-vivo study was carried out to determine myocardium safety of compound 4d on irradiated mice (8 Gy). In-vivo results of sulfapyridine derivative 4d showed normal cardiac enzyme function (CK) and serum catalase activity with significant reductions in LDH, cardiac TNF-α and caspase-9 levels, alongside with its efficacy in suppressing the expression of hepatic VEGF. In conclusion, sulfapyridine derivative 4d could be considered a promising candidate as VEGFR-2 inhibitor with less myocardium side effect.

PMID:37626064 | PMC:PMC10457369 | DOI:10.1038/s41598-023-40832-z

Int J Environ Res Public Health. 2023 Aug 11;20(16):6558. doi: 10.3390/ijerph20166558.

ABSTRACT

Children with short stature can experience a range of burdens due to their chronic condition. However, little is known about parents' experiences dealing with their child's short stature and the potential caregiving burdens and concerns they may face. We aim to review the literature on health-related quality of life (HRQOL), caregiving burden, and special needs among parents caring for a child with isolated growth hormone deficiency (IGHD) or idiopathic short stature (ISS). Using pre-defined inclusion and exclusion criteria, we systematically searched for literature using PubMed and Web of Science from its inception to December 2022. We identified 15 articles assessing HRQOL, special needs, or caregiving burdens in parents of IGHD/ISS children. The main problems included concerns about the future, organizational issues, side effects from growth hormone treatment, and social stigmatization. Furthermore, two studies assessed parents' special needs to cope with caregiving stress, mainly the dialogue between them and their families or parent support groups. This review outlines parental burdens, needs, and resources when caring for an IGHD/ISS child. Furthermore, it provides information about previously used measures appraising parents' special needs and underlines the need for disease-specific measurements.

PMID:37623144 | PMC:PMC10454502 | DOI:10.3390/ijerph20166558

Dan Med J. 2023 Aug 10;70(9):A02230072.

ABSTRACT

INTRODUCTION: Post-operative pain following open heart surgery is a clinical challenge usually requiring significant amounts of opioids. Long-acting local infiltration anaesthesia may effectively reduce post-operative opioid consumption and improve recovery. The trial is a publicly funded, double-blinded, randomised, placebo-controlled trial evaluating the effect of long-acting local infiltration anaesthesia in open heart surgery.

METHODS: Two Danish centres are planning to randomise 100 patients undergoing coronary artery bypass grafting to treatment with long-acting infiltration anaesthesia or placebo. We compare an active solution of bupivacaine, adrenaline, clonidine and dexamethasone with saline placebo. The primary outcome measure is the accumulated opioid use within the first 24 post-operative hours. Secondary outcome measures include evaluation of respiratory function, patient-reported pain scores, mobilisation, opioid-associated side effects and long-term opioid consumption.

CONCLUSION: This trial will define whether the use of long-acting infiltration anaesthesia during heart surgery may reduce acute and prolonged post-operative opioid consumption. Reduction of opioid-related adverse effects may improve recovery.

FUNDING: The trial is supported by public grants (Dansk Selskab for Anæstesiologi og Intensiv Medicin: 40,000 DKK; Regionernes Medicin og Behandlingspulje 2022: 686,000 DKK). The work of I. S. Modrau is supported by an unrestricted grant from the Health Research Foundation of the Central Denmark Region.

TRIAL REGISTRATION: EudraCT 2021-005886-41.

PMID:37622639

Biomed Res Int. 2023 Aug 16;2023:9933283. doi: 10.1155/2023/9933283. eCollection 2023.

ABSTRACT

Numerous disorders go untreated owing to a lack of a suitable drug delivery technology or an appropriate therapeutic moiety, particularly when toxicities and side effects are a major concern. Treatment options for microbiological infections are not fulfilled owing to significant adverse effects or extended therapeutic options. Advanced therapy options, such as active targeting, may be preferable to traditional ways of treating infectious diseases. Niosomes can be defined as microscopic lamellar molecules formed by a mixture of cholesterol, nonionic surfactants (alkyl or dialkyl polyglycerol ethers), and sometimes charge-inducing agents. These molecules comprise both hydrophilic and hydrophobic moieties of varying solubilities. In this review, several pathogenic microbes such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Plasmodium, Leishmania, and Candida spp. have been evaluated. Also, the development of a proper niosomal formulation for the required application was discussed. This review also reviews that an optimal formulation is dependent on several aspects, including the choice of nonionic surfactant, fabrication process, and fabrication parameters. Finally, this review will give information on the effectiveness of niosomes in treating acute microbial infections, the mechanism of action of niosomes in combating microbial pathogens, and the advantages of using niosomes over other treatment modalities.

PMID:37621700 | PMC:PMC10447041 | DOI:10.1155/2023/9933283

Curr Med Chem. 2023 Aug 25. doi: 10.2174/0929867331666230825104254. Online ahead of print.

ABSTRACT

Cancers are a huge threat to human life and health. Every year, many people suffer and die from various cancers, and numerous resources have been used to combat cancer. Due to several disadvantages of anticancer agents, such as drug-induced side effects, drug resistance, etc., there are still wide gaps in their ability to conquer cancer. Therefore, there is an urgent need to discover and develop many novel chemotypes to suppress cancer. In this review, we mainly focus on the anticancer potency of two representative sorts of carbazole-based compounds: carboline derivatives and diazacarbazole derivatives. Diazacarbazole derivatives, which have not been fully explored yet, might bring us a new vision and a valuable opportunity for overcoming the enormous hurdle we are now facing in the cancer campaign. We also provide several synthetic approaches for constructing the critical skeletons of the carbazole-based tricyclic compounds.

PMID:37622700 | DOI:10.2174/0929867331666230825104254

BMC Psychiatry. 2023 Aug 24;23(1):623. doi: 10.1186/s12888-023-05112-0.

ABSTRACT

OBJECTIVE: Previous studies have shown that transcranial direct current stimulation(tDCS) led to an improvement of cognitive function in patients with schizophrenia, but rare study has explored the effect of tDCS on long-term hospitalized chronic schizophrenia with tardive dyskinesia (TD). The present research explored if cognitive function in patients with long-term hospitalized chronic schizophrenia with TD could be improved through tDCS.

METHODS: This study is a randomized, double-blind, sham-controlled clinical trial. Of the 52 patients, 14 dropped out, and 38 completed the experiment. Thirty-eight patients on stable treatment regimens were randomly assigned to receive active tDCS(n = 21) or sham stimulation(n = 17) on weekdays of the first, third, and fifth weeks of treatment. Patients performed the Pattern Recognition Memory (PRM) and the Intra/Extradimensional Set Shift (IED) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and the end of week 3, week 5. Clinical symptoms were also measured at the baseline and the fifth week using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). Side effects of tDCS were assessed with an experimenter-administered open-ended questionnaire during the whole experiment.

RESULTS: There were no significant differences in PRM and IED performance metrics, SANS total score and PANSS total score between active and sham tDCS groups at the end of week 5 (p > 0.05). Furthermore, there was a significant difference in the adverse effects of the tingling sensation between the two groups (p < 0.05), but there was no significant difference in other side effects (p > 0.05).

CONCLUSION: According to these findings, no evidence supports using anodal stimulation over the left dorsolateral prefrontal cortex to improve cognitive function in patients with long-term hospitalized chronic schizophrenia with TD.

PMID:37620825 | DOI:10.1186/s12888-023-05112-0

BMC Public Health. 2023 Aug 24;23(1):1615. doi: 10.1186/s12889-023-16548-0.

ABSTRACT

BACKGROUND: Widely published findings from the COVID-19 pandemic show adverse effects on body mass index (BMI) and behavioral health in both adults and children, due to factors such as illness, job loss, and limited opportunity for physical and social activity. This study investigated whether these adverse effects were mitigated in adolescents from military families, who are universally insured with consistent access to healthcare, and who generally have at least one parent who must adhere to physical and mental fitness as a condition of employment.

METHODS: We conducted a cohort study using two groups of adolescents receiving care in the U.S. Military Health System during the COVID-19 pandemic; one for changes in Body Mass Index (BMI) and the second for changes in behavioral health diagnoses, using TRICARE claims data. Beneficiaries (160,037) ages 13 to 15 years in fiscal years 2017-2018, were followed up during October 2020 to June 2021.

RESULTS: Among the BMI cohort, 44.32% of underweight adolescents moved to healthy weight, 28.48% from overweight to obese, and 3.7% from healthy weight to underweight. Prevalence of behavioral disorders showed an overall 29.01% percent increase during the study period, which included in mood (86.75%) and anxiety (86.49%) disorders, suicide ideation (42.69%), and suicide attempts (77.23%). Decreases in percent change were observed in conduct disorders (-15.93%) and ADD/ADHD (-8.61%).

CONCLUSIONS: Adolescents in military families experienced adverse health outcomes during the pandemic at approximately the same rates as those in non-military families, suggesting that universal insurance and military culture were not significantly mitigating factors. Obesity and underweight present significant opportunities to intervene in areas such as exercise and food access. Decreased conduct disorders and ADD/ADHD may reflect lower prevalence due to favorable home environment, or lower rates of diagnosis and referral; however, increased rates of anxiety, mood disorders, suicide ideation and attempt are especially concerning. Care should be taken to ensure that adolescents receive consistent opportunity for physical activity and social interaction, and those at risk for suicide should receive active monitoring and appropriate referral to behavioral healthcare providers.

PMID:37620800 | DOI:10.1186/s12889-023-16548-0