BMC Womens Health. 2023 Sep 23;23(1):510. doi: 10.1186/s12905-023-02647-y.

ABSTRACT

Endometriosis is a chronic inflammatory disease that occurs in women of reproductive age. Much of the treatment involves hormone therapy that suppresses the proliferation of endometriosis lesions.Objective To compare discontinuation rates of pharmacological treatment with estrogen-progestins and progestins medications. The secondary objective is to evaluate the main side effects of these drugs in patients with endometriosis.Methods This retrospective study analyzed data from 330 patients who attended the Hospital of the State Public Servant of São Paulo from August 1999 to September 2020 and received pharmacological treatment for endometriosis. The data were obtained by review of the files of medical appointments with specialized staff.Results The median treatment time was 18 months, ranging from 1 to 168 months, and 177 patients interrupted the proposed treatment. The combined contraceptives with estrogens and progestins were significantly linked to treatment interruption, with a relative risk of 1,99 (p = 0,005). The most important side effects that resulted in treatment interruption were pain persistence (p = 0,043), weight gain (p = 0,017) and spotting (p < 0,001).

PMID:37741998 | DOI:10.1186/s12905-023-02647-y

J Transl Med. 2023 Sep 23;21(1):661. doi: 10.1186/s12967-023-04541-5.

ABSTRACT

BACKGROUND: The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients.

METHODS: The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium.

RESULTS: JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level.

CONCLUSIONS: The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis.

PMID:37741987 | PMC:PMC10518090 | DOI:10.1186/s12967-023-04541-5

Heart Lung. 2023 Sep 21;63:23-34. doi: 10.1016/j.hrtlng.2023.09.004. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a chronic respiratory disease that affects millions of children worldwide and can impair their quality of life and development. Inhaled glucocorticoids are the mainstay of asthma treatment, but some children require step-up therapy with additional drugs to achieve symptom control. Fluticasone propionate and salmeterol (FSC) has been shown to reduce asthma exacerbations and improve lung function in adults. However, the evidence for its efficacy and safety in children is limited.

OBJECTIVE: This study aims to provide a comprehensive basis for treatment selection by summarizing existing clinical randomized controlled trials (RCTs) on the efficacy of FSC compared to fluticasone propionate (FP) monotherapy in children with asthma who require step-up treatment.

METHODS: Five online databases and three clinical trial registration platforms were systematically searched. The effect size and corresponding 95% confidence interval (CI) were calculated based on the heterogeneity among the included studies.

RESULTS: Twelve RCTs were identified and a total of 9, 859 patients were involved. The results of the meta-analysis revealed that the use of FSC was associated with a greater reduction in the incidence of asthma exacerbations than FP alone when the dose of FP was the same or when the duration of treatment exceeded 12 weeks. In addition, FSC resulted in a greater proportion of time with asthma-free and without the use of albuterol compared to FP alone when the duration of treatment exceeded 12 weeks. No significant differences were observed between FSC and FP alone in the incidence of drug-related adverse events and other adverse events.

CONCLUSION: Both FSC and FP alone are viable options for the initial selection of step-up treatment in asthmatic children. While, FSC treatment demonstrates a greater likelihood of reducing asthma exacerbations which is particularly important for reducing the personnel, social and economic burden in children requiring step-up asthma treatment.

PMID:37740997 | DOI:10.1016/j.hrtlng.2023.09.004

Hu Li Za Zhi. 2023 Oct;70(5):36-43. doi: 10.6224/JN.202310_70(5).06.

ABSTRACT

BACKGROUND: The multiple symptoms of Sjögren's syndrome lead patients affected by this disease to seek medical advice from different medical disciplines and specialists. Diagnoses are often made many years after initial onset, resulting in mental and physical exhaustion and misunderstandings.

PURPOSE: This study was designed to explore the health-seeking experiences of patients with Sjögren's syndrome.

METHODS: Qualitative research methods and purposive sampling were used. Fourteen patients with Sjögren's syndrome were interviewed by the first author, and the collected data were analyzed using content analysis.

RESULTS: Four themes were revealed from the data, including: (1) distressing symptoms; (2) difficulty in diagnosis; (3) concerns about drug side effects; and (4) facing the disease. The participants initially sought medical attention when they began experiencing early onset symptoms that caused discomfort or annoyance. Their doctors' failure to provide proper diagnoses during the long health-seeking process caused a great deal of suffering to the participants. Although related medications should be taken for life, the participants reported taking lower-than-prescribed dosages out of fear of side-effects. The participants explored their process of coping with the disease, which began with denial and ended with acceptance. By learning from their health-seeking process, participants realized that they needed to take proper care of themselves, adapt to life with their disease, and control related symptoms.

CONCLUSIONS / IMPLICATIONS FOR PRACTICE: To facilitate the early diagnosis of Sjögren's syndrome, healthcare professionals should improve their awareness of this condition and refer patients with related symptoms to rheumatologists and immunologists. Effective early diagnosis and treatment can help these patients reduce the time and effort involved in unproductive doctor's visits, allowing them to better continue as productive members of society and to maintain a good quality of life.

PMID:37740263 | DOI:10.6224/JN.202310_70(5).06

BMC Infect Dis. 2023 Sep 22;23(1):624. doi: 10.1186/s12879-023-08612-2.

ABSTRACT

BACKGROUND: Various factors influence tuberculosis preventive treatment (TPT) decisions thus it is important to understand the health beliefs and concerns of patients before starting TPT to ensure treatment compliance. This study aims to explore facilitators and barriers for TPT among patients diagnosed with Latent Tuberculosis infection (LTBI) attending six primary healthcare clinics in Selangor, Malaysia.

METHOD: In-depth interviews were conducted face-to-face or via telephone among patients with a clinical diagnosis of LTBI using a semi-structured topic guide developed based on the common-sense model of self-regulation and literature review. Audio recordings of interviews were transcribed verbatim and analysed thematically.

RESULTS: We conducted 26 In-depth interviews; Good knowledge of active tuberculosis (TB) and its associated complications, including the perceived seriousness and transmissibility of active TB, facilitates treatment. LTBI is viewed as a concern when immune status is compromised, thus fostering TPT. However, optimal health is a barrier for TPT. Owing to the lack of knowledge, patients rely on healthcare practitioners (HCPs) to determine their treatment paths. HCPs possessing comprehensive knowledge play a role in facilitating TPT whereas barriers to TPT encompass misinterpretation of tuberculin skin test (TST), inadequate explanation of TST, and apprehensions about potential medication side effects.

CONCLUSIONS: Knowledge of LTBI can influence TPT uptake and patients often entrust their HCPs for treatment decisions. Improving knowledge of LTBI both among patients and HCPs can lead to more effective doctor-patient consultation and consequently boost the acceptance of TPT. Quality assurance should be enhanced to ensure the effective usage of TST as a screening tool.

PMID:37740196 | PMC:PMC10517541 | DOI:10.1186/s12879-023-08612-2

Sci Rep. 2023 Sep 22;13(1):15850. doi: 10.1038/s41598-023-43252-1.

ABSTRACT

Recent evidence has demonstrated that both acute and chronic exposure to particulate air pollution are risk factors for respiratory tract infections and increased mortality from sepsis. There is therefore an urgent need to establish the impact of ambient particulate matter (PM) on innate immune cells and to establish potential strategies to mitigate against adverse effects. PM has previously been reported to have potential adverse effects on neutrophil function. In the present study, we investigated the impact of standard urban PM (SRM1648a, NIST) and PM2.5 collected from Chiang Mai, Thailand, on human peripheral blood neutrophil functions, including LPS-induced migration, IL-8 production, and bacterial killing. Both NIST and the PM2.5, being collected in Chiang Mai, Thailand, increased IL-8 production, but reduced CXCR2 expression and migration of human primary neutrophils stimulated with Escherichia coli LPS. Moreover, PM-pretreated neutrophils from vitamin D-insufficient participants showed reduced E. coli-killing activity. Furthermore, in vitro vitamin D3 supplementation attenuated IL-8 production and improved bacterial killing by cells from vitamin D-insufficient participants. Our findings suggest that provision of vitamin D to individuals with insufficiency may attenuate adverse acute neutrophilic responses to ambient PM.

PMID:37740033 | PMC:PMC10516903 | DOI:10.1038/s41598-023-43252-1

Clin Nutr ESPEN. 2023 Oct;57:665-675. doi: 10.1016/j.clnesp.2023.08.023. Epub 2023 Aug 22.

ABSTRACT

BACKGROUND & AIMS: Rice Bran Arabinoxylan Compound (RBAC) results from an enzymatic modification of rice bran, which is reported to have immunomodulatory, anti-oxidant, and anti-inflammatory effects by regulating the production of pro-inflammatory cytokines. The current systematic review and meta-analysis aimed to determine the hepatic adverse effects of RBAC by assessing the effect through liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

METHODS: In the present study, the Medline (PubMed), Web of Sciences, and Scopus databases were searched for relevant publications from the beginning to October 2022. The meta-analysis was based on the Mixed effect model to generate the mean effect sizes in weighted mean differences (WMD) and the 95% confidence intervals (95%CI). The heterogeneity was assessed using the Cochrane Chi-squared test, and the analysis of Galbraith plots was applied.

RESULTS: Subgroup meta-analysis on five eligible randomized controlled trials (n = 239) showed a significant decrease in serum AST regarding RBAC supplementation in powder form (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170), three months and more supplementation duration (WMD (95%CI) = -3.71 (-5.95, -1.48) U/L; P-value = 0.001, I2 (%) = 29.9; P heterogeneity = 0.240) and studies with a good quality (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170).

CONCLUSIONS: In conclusion, RBAC supplementation seems to not have any hepatic adverse effects and its supplementation as powder or for three months and more may decrease serum AST levels. However, we need further studies to confirm the results.

REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYZES: CRD42022361002, registration time: 29/09/2022.

PMID:37739721 | DOI:10.1016/j.clnesp.2023.08.023

Clin Nutr ESPEN. 2023 Oct;57:575-586. doi: 10.1016/j.clnesp.2023.08.005. Epub 2023 Aug 5.

ABSTRACT

The food industry has always sought to produce products enriched with vitamins, probiotics, polyphenols, and other bioactive compounds to improve physiological function, enhance nutritional value, and provide health. These compounds are essential for human health, and their deficiency can lead to adverse effects. Therefore, food enrichment is an important strategy to improve the nutritional value and, in some cases, improve the quality of food. Recently, functional foods have been very popular around the world. Among food products, dairy products constitute a major part of people's diet, and due to the high consumption of dairy products, including yogurt, the enrichment of this product effectively reduces or prevents diseases associated with nutritional deficiencies. Most consumers generally accept yogurt due to its high nutritional value and low price. So, it can be considered a good candidate for enrichment with micronutrients and probiotics. In recent years, using functional foods to prevent various diseases has become a popular topic for research. In this study, the effect of fortified yogurt in preventing diseases and improving deficiencies has been investigated, and it has been proven that super healthy yogurt has a positive effect on human health.

PMID:37739708 | DOI:10.1016/j.clnesp.2023.08.005

Clin Nutr ESPEN. 2023 Oct;57:305-310. doi: 10.1016/j.clnesp.2023.07.013. Epub 2023 Jul 13.

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to decrease hepatic transaminases, steatosis, and in some studies, hepatic fibrosis. However, the safety and efficacy of SGLT2i has not been tested in patients who have moderate to severe hepatic fibrosis.

METHODS: In a retrospective study of sixty patients with moderate to severe hepatic fibrosis (kPa estimated by Fibroscan > 10), SGLT2i were prescribed on top of other oral anti-hyperglycemic medications. The safety and efficacy of SGLT2i were evaluated. Using the Fibroscan, CAP scores (decibel/meter), and liver stiffness measurement (LSM) (kPa, kilopascals) were examined before and after treatment.

RESULTS: The mean age of the T2DM patients was 54.7 ± 10.3 years, and the mean duration of T2DM was 8.3 ± 7.1 years. SGLT2i were given from 3 to 36 months. After treatment, a decrease in glycated hemoglobin (HbA1c), and hepatic transaminases (SGOT and SGPT) was recorded. Upon follow up, CAP and kPa scores decreased significantly. Importantly, no adverse drug reaction, such as balanoposthitis, vulvovaginitis, urosepsis, and postural drop in blood pressure, were reported in any patient.

CONCLUSION: In this retrospective cohort study, patient with T2DM and moderate to severe hepatic fibrosis, use of SGLT2i is safe with respect to common adverse effects & may have contributed to improved hepatic profile.

PMID:37739673 | DOI:10.1016/j.clnesp.2023.07.013

Br J Nurs. 2023 Sep 21;32(17):S4-S12. doi: 10.12968/bjon.2023.32.17.S4.

ABSTRACT

Myeloma is an aggressive B-cell malignancy resulting from an uncontrolled production of plasma cells in the bone marrow. A multitude of drugs and combinations of drugs are now approved for use to treat this complex disease and nurses require knowledge and skills in recognising and managing new side effects associated with these treatments. This article presents an overview of some of the newer and recently approved drugs and the important side effects that have been associated with them. Clinical nurse specialists and advanced nurse practitioners are at the forefront of patients' treatment journeys and play a central role in supporting patients and families to manage side effects. Through this support, patients can continue the treatments for as long as possible with the aim of maintaining a good quality of life.

PMID:37737854 | DOI:10.12968/bjon.2023.32.17.S4

Hum Vaccin Immunother. 2023 Aug;19(2):2260534. doi: 10.1080/21645515.2023.2260534. Epub 2023 Sep 22.

NO ABSTRACT

PMID:37737129 | DOI:10.1080/21645515.2023.2260534

BMC Anesthesiol. 2023 Sep 22;23(1):323. doi: 10.1186/s12871-023-02282-y.

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the effect of intravenous (IV) dexamethasone on the duration of hyperbaric bupivacaine spinal anesthesia.

METHODS: Two hundred patients between the ages of 18 and 60, of both sexes with ASA I- II classification scheduled for lower abdominal surgery under spinal anesthesia using hyperbaric bupivacaine 0.5% were randomly divided into two groups: the dexamethasone group (Dexa group) and the control group, with 100 patients in each group. Before the administration of spinal anesthesia, the Dexa group received an intravenous infusion of 8 mg dexamethasone in 500 mL normal saline, while the control group received 500 mL normal saline only. The primary outcome of this study was to assess the effect of IV dexamethasone on the regression of hyperbaric bupivacaine spinal anesthesia. Secondary outcome measures included the total duration of sensory and motor blocks, VAS score, time of first analgesic request, total analgesic consumption within the first 24 h, and the occurrence of any side effects.

RESULTS: The Dexa group had significantly delayed onset of 2 dermatomes regression (P < 0.001) compared to the control group. Additionally, the Dexa group had significantly longer duration of both sensory block (P = 0.01) and motor block (P < 0.001). The Dexa group had significantly longer duration until the first postoperative analgesic request (P < 0.001) and a lower incidence of side effects compared to the control group.

CONCLUSION: Although the intravenous administration of dexamethasone had a limited effect on the duration of hyperbaric bupivacaine spinal anesthesia, it improved postoperative VAS scores compared to the control group and decreased overall postoperative analgesic consumption. Therefore, it can be considered a valuable addition to postoperative multimodal analgesia strategies, aiming to minimize total analgesic consumption.

CLINICAL TRIAL REGISTRATION: ID: NCT04778189 (2/3/2021).

PMID:37736711 | PMC:PMC10515039 | DOI:10.1186/s12871-023-02282-y

Front Immunol. 2023 Sep 6;14:1248867. doi: 10.3389/fimmu.2023.1248867. eCollection 2023.

ABSTRACT

The treatment of cancer was revolutionized within the last two decades by utilizing the mechanism of the immune system against malignant tissue in so-called cancer immunotherapy. Two main developments boosted cancer immunotherapy: 1) the use of checkpoint inhibitors, which are characterized by a relatively high response rate mainly in solid tumors; however, at the cost of serious side effects, and 2) the use of chimeric antigen receptor (CAR)-T cells, which were shown to be very efficient in the treatment of hematologic malignancies, but failed to show high clinical effectiveness in solid tumors until now. In addition, active immunization against individual tumors is emerging, and the first products have reached clinical approval. These new treatment options are very cost-intensive and are not financially compensated by health insurance in many countries. Hence, strategies must be developed to make cancer immunotherapy affordable and to improve the cost-benefit ratio. In this review, we discuss the following strategies: 1) to leverage the antigenicity of "cold tumors" with affordable reagents, 2) to use microbiome-based products as markers or therapeutics, 3) to apply measures that make adoptive cell therapy (ACT) cheaper, e.g., the use of off-the-shelf products, 4) to use immunotherapies that offer cheaper platforms, such as RNA- or peptide-based vaccines and vaccines that use shared or common antigens instead of highly personal antigens, 5) to use a small set of predictive biomarkers instead of the "sequence everything" approach, and 6) to explore affordable immunohistochemistry markers that may direct individual therapies.

PMID:37736099 | PMC:PMC10509759 | DOI:10.3389/fimmu.2023.1248867

BMC Neurol. 2023 Sep 21;23(1):332. doi: 10.1186/s12883-023-03375-4.

ABSTRACT

BACKGROUND: Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia. Some studies reported MFS as an adverse effect of the COVID-19 vaccination. We aimed to have a detailed evaluation on demographic, clinical, and para-clinical characteristics of subjects with MFS after receiving COVID-19 vaccines.

MATERIALS AND METHODS: A thorough search strategy was designed, and PubMed, Web of Science, and Embase were searched to find relevant articles. Each screening step was done by twice, and in case of disagreement, another author was consulted. Data on different characteristics of the patients and types of the vaccines were extracted. The risk of bias of the studies was assessed using Joanna Briggs Institute (JBI) tools.

RESULTS: In this study, 15 patients were identified from 15 case studies. The median age of the patients was 64, ranging from 24 to 84 years. Ten patients (66.6%) were men and Pfizer made up 46.7% of the injected vaccines. The median time from vaccination to symptoms onset was 14 days and varied from 7 to 35 days. Furthermore,14 patients had ocular signs, and 78.3% (11/14) of ocular manifestations were bilateral. Among neurological conditions, other than MFS triad, facial weakness or facial nerve palsy was the most frequently reported side effect that was in seven (46.7%) subjects. Intravenous immunoglobulin (IVIg) was the most frequently used treatment (13/15, 86.7%). Six patients received 0.4 g/kg and the four had 2 g/kg. Patients stayed at the hospital from five to 51 days. No fatal outcomes were reported. Finally, 40.0% (4/15) of patients completely recovered, and the rest experienced improvement.

CONCLUSION: MFS after COVID-19 immunization has favorable outcomes and good prognosis. However, long interval from disease presentation to treatment in some studies indicates that more attention should be paid to MFS as the adverse effect of the vaccination. Due to the challenging diagnosis, MFS must be considered in list of the differential diagnosis in patients with a history of recent COVID-19 vaccination and any of the ocular complaints, ataxia, or loss of reflexes, specially for male patients in their 60s and 70s.

PMID:37735648 | PMC:PMC10512542 | DOI:10.1186/s12883-023-03375-4

BMC Psychiatry. 2023 Sep 21;23(1):686. doi: 10.1186/s12888-023-05189-7.

ABSTRACT

BACKGROUND: As 40-60% of the patients with obsessive-compulsive disorder (OCD) do not adequately respond to the first-line treatment, finding an effective second-line treatment is required. Our aim was to assess the efficacy and safety of agomelatine (a selective melatonin receptor agonist and a 5-hydroxytryptamine (HT)2 C antagonist) augmentation of sertraline in the treatment of patients with moderate to severe OCD.

METHODS: In this 12-week randomized, double-blinded, placebo-controlled, parallel-group clinical trial, 65 patients with moderate to severe OCD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5) criteria and a Yale-Brown obsessive compulsive scale (Y-BOCS) score of over 21, were included. They were assigned with sertraline (100 mg/day for the first 4 weeks and 200 mg/day for the next 8 weeks) and either agomelatine (25 mg/day) or placebo. The primary outcome was OCD symptoms measured by the Y-BOCS.

RESULTS: Fifty patients (24 in agomelatine group and 26 in placebo group) completed the trial. The Y-BOCS scores in total (MD (95% CI) = 12.25 (11.00, 13.49) (P < 0.001) vs. MD (95% CI) = 12.46 (6.65, 15.74) (P < 0.001)), the obsession subscale (MD (95% CI) = 5.04 (4.19, 5.88) (P < 0.001) vs. MD (95% CI) = 5.00 (3.84, 6.16) (P = 0.0001)), and compulsion subscale (MD (95% CI) = 7.21 (6.34, 8.07) (P < 0.001) vs. MD (95% CI) = 7.460 (6.50, 8.42) (P < 0.001)) significantly decreased in both groups. Although, at the end of the trial, no significant difference was observed between the scores of the two groups in total (MD (95% CI) = 0.480 (-1.23, 2.19) (P = 0.78)), the obsession subscale (MD (95% CI) = 1.020 (-0.15, 2.19) (P = 0.38)), and the compulsion subscale (MD (95% CI) = 0.540 (-0.34, 1.42) (P = 0.54)). No major adverse effects were recorded, and the frequency of side effects was not significantly different between the groups.

CONCLUSION: Agomelatine in augmentation with sertraline is safe and tolerable in patients with moderate to severe OCD. However, our study does not support its efficacy in improving OCD symptoms, compared to placebo.

TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials on 14/07/2020 ( www.irct.ir ; IRCT ID: IRCT20170123032145N5).

PMID:37735631 | PMC:PMC10512611 | DOI:10.1186/s12888-023-05189-7

Sci Rep. 2023 Sep 21;13(1):15701. doi: 10.1038/s41598-023-42508-0.

ABSTRACT

NeuMANTA is a new generation boron neutron capture therapy (BNCT)-specific treatment planning system developed by the Neuboron Medical Group and upgraded to an important feature, a Hounsfield unit (HU)-based material conversion algorithm. The range of HU values was refined to 96 specific groups and established corresponding to tissue information. The elemental compositions and mass densities have an important effect on the calculated dose distribution. The region of interest defined in the treatment plan can be converted into multiple material compositions based on HU values or assigned specified single material composition in NeuMANTA. Different material compositions may cause normal tissue maximum dose rates to differ by more than 10% in biologically equivalent doses and to differ by up to 6% in physically absorbed doses. Although the tumor has a lower proportion of BNCT background dose, the material composition difference may affect the minimum dose of biologically equivalent dose and physically absorbed dose by more than 3%. In addition, the difference in material composition could lead to a change in neutron moderation as well as scattering. Therefore, the material composition has a significant impact on the assessment of normal tissue side effects and tumor control probability. It is essential for accurate dose estimation in BNCT.

PMID:37735580 | PMC:PMC10514297 | DOI:10.1038/s41598-023-42508-0

J Aerosol Med Pulm Drug Deliv. 2023 Sep 22. doi: 10.1089/jamp.2023.0014. Online ahead of print.

ABSTRACT

Purpose: TRK-250 is a novel single-stranded oligonucleotide carrying a human Transforming growth factor-beta 1-targeting siRNA motif tethered by two proline linkers. Nonclinical studies have shown that TRK-250 may have potency to prevent the progression of pulmonary fibrosis. Herein, a phase I study was conducted to investigate the safety and pharmacokinetics (PKs) of TRK-250 in patients with idiopathic pulmonary fibrosis (IPF). Method: In the phase I study, 34 IPF patients were partially randomized to receive a placebo or TRK-250 in 4 single doses of 2, 10, 30, and 60 mg or multiple rising doses of 10, 30, and 60 mg once per week for 4 weeks by oral inhalation. For both the single- and multiple-dose studies, the primary endpoint was safety, and the secondary endpoint was PKs. Result: In all IPF patients who orally inhaled TRK-250, no significant drug-related adverse events (AEs) were observed. The AEs were mild or moderate, except for one severe case with acute exacerbation. One of the more common AEs was coughing. One patient discontinued treatment before the last dose because of coughing. There were no medically important findings related to safety endpoints based on clinical laboratory data (clinical chemistry, hematology, or urinalysis), vital signs data, electrocardiogram data, physical examination findings, pulse oximetry data, spirometry data, or diffusing capacity of the lung for carbon monoxide data. All the bioanalytical results of PKs in the blood were below the lower limit of quantification. Conclusions: Both the single and multiple doses of TRK-250 were safe and well tolerated in this first study done in IPF patients. Furthermore, TRK-250 was not detected in the systemic circulation following inhalation, indicating low or virtually nonexistent systemic exposure. This study is registered at ClinicalTrials.gov with identifier number NCT03727802.

PMID:37738329 | DOI:10.1089/jamp.2023.0014

S D Med. 2023 Jul;76(7):311-313.

ABSTRACT

INTRODUCTION: Increasing and easy availability of so-called natural/herbal supplements pose the unique challenge of identifying associated side effects, including arrhythmias in otherwise-healthy individuals.

CASE PRESENTATION: A 25-year-old female patient presented to the emergency department with fatigue and lightheadedness. The electrocardiogram showed complete AV block with a junctional escape rhythm at 55 beats per minute with QT prolongation (542ms). One week ago, she started to use a herbal medication (Muscle Eze Advanced) for muscle cramps after workouts. Extensive cardiac testing, including complete blood count, complete metabolic panel, TSH, transthoracic echocardiography, urine drug analysis, Lyme antibody were negative. Normal sinus rhythm was restored spontaneously within 1 day of discontinuing the herbal medication. PR and corrected QT intervals returned to baseline over the next two weeks.

CONCLUSION: Muscle Eze Advanced consists of seven ingredients, including Melissa officinalis and Valeriana officinalis that have negative chronotropic, negative dromotrophic and QT prolonging effects. Recognizing the association between certain over-the-counter supplements and brady-arrhythmias may circumvent need for permanent pacemakers - an important consideration especially in the young.

PMID:37733962

S D Med. 2023 Jul;76(7):305-308.

ABSTRACT

Cytochrome P450 polymorphisms have gathered much attention regarding personalized psychopharmacological care. It is well documented that these drug metabolizing enzymes lead to interpatient variability in pharmacokinetic profiles. It appears that less functional genotype may increase of risk of higher side-effect burden. Here we highlight the importance of genetic polymorphisms to potentially predict a toxicity related phenotype after an intentional overdose. Genotyping may have a role in predicting serious side effects to help clinicians educate patients and their families, and implement more intensive monitoring and institute prophylactic treatment as needed.

PMID:37733961

Science. 2023 Sep 22;381(6664):1316-1323. doi: 10.1126/science.abq1053. Epub 2023 Sep 21.

ABSTRACT

Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of complex I (CI) and complex II (CII), the gatekeepers for initiating electron flow, remains unclear. In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell-mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex-antigen processing and presentation (MHC-APP) genes independent of interferon signaling. Furthermore, knockout of methylation-controlled J protein (MCJ), to promote electron entry preferentially through CI, provides proof of concept of ETC rewiring to achieve antitumor responses without side effects associated with an overall reduction in mitochondrial respiration in noncancer cells. Our results may hold therapeutic potential for tumors that have reduced MHC-APP expression, a common mechanism of cancer immunoevasion.

PMID:37733872 | DOI:10.1126/science.abq1053