Significant Adverse Effects Research Articles (Page 1)

On-street parking violations has significant adverse effects on both traffic efficiency and safety. Existing studies are constrained by data limitations, leading to an absence of a comprehensive analytical framework for examining the impact mechanisms of parking violations across temporal dimensions. This gap impedes a deeper understanding and effective management of parking violations. To uncover the temporal patterns and determinants of parking violations in urban areas, this study analyzed 10,396 electronic records of parking violations captured by law enforcement over a two-month period. Nineteen influencing factors were selected from three key domains: land use, parking supply, and road design. Hierarchical clustering and Pearson correlation analysis were employed to examine the temporal distribution of parking violations and to refine feature selection. Given the characteristics of the dependent variables, a Bayesian quantile regression model was developed to evaluate the relationship between parking violations and influencing factors during different peak hours. The key findings of this study are as follows. First, concerning the temporal distribution of parking violations, weekday violations occur at a significantly higher frequency than those on weekends, with the highest concentration observed in the middle of the week. Clustering analysis of weekday time intervals identified three distinct patterns: peak hours (8:00–10:00 and 17:00–19:00), periods of peak-hour convergence (10:00–11:00 and 15:00–17:00), and other time periods. Second, the Bayesian quantile regression results reveal that land use, parking supply, and road design exhibit nonlinear effects on parking violations. Therefore, parking violation management strategies should be tailored to specific temporal and spatial contexts.

Objective This study aimed to evaluate the effectiveness of Airofit PRO™, a mobile respiratory trainer device, on pulmonary function, chest expansion, and functional status in patients with ankylosing spondylitis (AS) compared to a conventional pursed-lip breathing (PLB) exercise program. Methods A randomized controlled trial was conducted with 70 patients with AS who were allocated into two groups: the mobile device exercise (MDE) group (n = 36), using Airofit PRO™, and the PLB control group (n = 34). The participants underwent a 12-week exercise regimen consisting of three 6-minute daily sessions. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25–75% (FEF25–75), peak expiratory flow (PEF), chest expansion, and the Bath Ankylosing Spondylitis Functional Index (BASFI) scores, were measured pre- and post-intervention. Results Significant improvements were observed in the MDE group compared to the PLB group. Male patients in the MDE group exhibited statistically significant improvements in FEV1, FVC, FEF25–75, and PEF (p < 0.05). Female patients in the MDE group demonstrated significant improvements in PFT parameters and chest expansion (p < 0.05). No significant improvement was observed in the PLB group. The compliance rates were similar between the groups, and no significant adverse effects were reported. Conclusion The Airofit PRO™ respiratory trainer significantly improved pulmonary function parameters and chest expansion in AS patients , demonstrating greater effectiveness compared to conventional PLB exercises. These findings suggest that mobile respiratory trainers may provide a promising adjunctive therapeutic option for the pulmonary rehabilitation of patients with AS.

Candida auris is an emerging multidrug-resistant fungal pathogen associated with severe nosocomial outbreaks and high mortality rates worldwide. The increasing incidence of antifungal resistance underscores the urgent need for agents with novel mechanisms of action. APC6 is a zinc-chelating cyclic alkyl polyamine compound that selectively disrupts zinc homeostasis in fungal cells. We have previously reported that APC6 has antifungal activity against Candida spp., including Candida auris, and low cytotoxicity to human cells. In this study, we evaluated the in vivo efficacy and safety of APC6 using a neutropenic murine model of disseminated C. auris infection. APC6 significantly improved survival and reduced fungal burden in the liver, kidneys, and brain. At a therapeutic dose of 15 mg/kg, APC6 had similar or superior antifungal activity to that of amphotericin B. Histopathological analysis revealed a decreased number of fungal microabscesses in APC6-treated tissues. No significant adverse effects were observed following 28-day repeated intraperitoneal administration, and the Ames assay revealed no mutagenic activity. To our knowledge, this is the first study to demonstrate that a zinc-chelating compound can improve survival and reduce organ fungal burden in a mammalian model of drug-resistant C. auris infection. These results highlight APC6 as a promising lead compound targeting fungal zinc homeostasis and support its further development as a novel antifungal agent.

Background Chronic pain afflicts approximately 20% of the global adult population and is frequently undertreated, with available pharmacologic options often associated with significant long-term adverse effects. Although omega-3 fatty acids are known for their anti-inflammatory and immunomodulatory effects, current clinical evidence regarding their efficacy in pain management remains inconclusive. Objective To determine how well omega-3 fatty acids reduce chronic pain, and to investigate how factors like disease type, dosage, treatment duration, and study design influence their effectiveness. Methods We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) from inception to 14 February 2025 with no language restrictions. Forty-one randomised controlled trials (RCTs; n = 3,759) met predefined criteria. Risk of bias was assessed with RoB 2. Pooled standardised mean differences (SMDs) for pain intensity were obtained through random-effects meta-analyses. Subgroup, sensitivity, and publication-bias analyses were also conducted. Results Omega-3 fatty acids showed a moderate, statistically and clinically significant reduction in pain intensity with a standardized mean difference (SMD) of −0.55 (95% CI –0.76 to −0.34; I 2 = 87%). The relief was noticeable at 1 month (SMD = −0.27) and improved by 6 months (SMD = −0.83). Lower doses (≤1.35 g/day) were more effective (SMD = −0.60) compared to higher doses (&amp;gt;1.35 g; SMD = −0.53). The benefits were significant for rheumatoid arthritis, migraine, and other mixed chronic pain conditions, but not for osteoarthritis or mastalgia. There was minimal publication bias according to trim-and-fill adjustment, and leave-one-out tests confirmed robust results. Conclusion Omega-3 fatty acid supplementation offers a clinically meaningful and time-dependent reduction in chronic pain, particularly at moderate doses and in certain disease contexts. Standardization of outcome measures, dose optimization, and long-term trials are needed to better define its role in pain management. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251035960 , Identifier CRD420251035960.

Hypothyroidism (HypoTH) is an independent and major risk factor for myocardial infarction (MI). However, long noncoding RNA (lncRNA; ncRNAs&gt;200 bp) mechanisms in the cardiac thyroid hormone (TH) pathway are unclear. An array of in vitro, in vivo, computational, and statistical methods was employed. Paigen high-fat (PHF)-fed homozygous HypoE mice died rapidly (median survival [ms] 26 days) with severe MI, cardiac fibrosis, hypertrophy, inflammation, lipid deposition, and heart failure. So, we used cholate-free PHF diet, which showed more gradual mortality (ms: 41.5 days) with serum HypoTH, cardiac hypertrophy, splenomegaly, and alterations in real-time differential expression of multiple inflammatory/immune left ventricular (LV) lncRNAs, especially the lncRNA, XRik (&gt;2-fold; p&lt;0.05). Oral T3 therapy restored LV contractility, atrial refractory period, expression levels of LV epigenetic enzymes and lncRNAs, especially XRik, without increases in heart rate or hypertrophy. We genetically manipulated XRik using siRNAs, overexpression, and CRISPRa (dCas9)-based activation strategies in HL1 adult mouse myocytes, primary adult mouse ventricular myocytes, and/or primary adult mouse ventricular nonmyocytes (fibroblasts). XRik overexpression improved cell viability against Doxorubicin or H2O2 injury (p&lt;0.05). While XRik siRNA inhibited cardiac cell viability following low-iodine diet-induced HypoTH in control mice, both overexpression and CRISPRa-activation improved cell viability. siRNA-induced increase in proapoptotic Cytochrome C levels was attenuated by T3 (and CRISPRa; p&lt;0.05). Our LV lncRNA-seq-based prediction of XRik ’s interaction with an miRNA was mediated by T3 via dual-luciferase assays. In vivo lentiviral CRISPRa XRik delivery improved LV fractional shortening in cholate-free PHF homozygous HypoE mice without significant adverse effects on hypertrophy or heart rate (p&lt;0.05). LV mRNA-sequencing identified alterations in several genes/transcripts in these mice, which were improved following in vivo XRik CRISPRa. Enrichment analyses showed improvements in genes/transcripts related to pathways including TH synthesis, cardiac contraction, lipid metabolism, ATP/Ca++ binding, inflammation, apoptosis, etc. CRISPRa in vivo also significantly reduced the levels of multiple proinflammatory cytokines (p&lt;0.05). In conclusion, we uncovered a novel mechanism by which T3 regulates XRik in mediating cardioprotection in high-fat-diet-induced atherosclerosis-driven MI.

Persistent severe obstructive sleep apnea (OSA) after adenotonsillectomy (AT) is not uncommon in children with genetic syndromes and/or obesity. Although continuous positive airway pressure (CPAP) is the standard treatment, adherence in pediatric patients is often low, limiting its effectiveness. We report three cases of children with persistent OSA and failure to continue CPAP therapy, in whom an alternative pharmacological approach was explored. In agreement with their families, a 4-week trial of combined atomoxetine and oxybutynin was initiated. Of note, the first patient was concurrently treated with lisdexamfetamine for attention deficit hyperactivity disorder, while the second had morbid obesity under treatment with liraglutide. Both patients demonstrated a great improvement in their apnea-hypopnea index (AHI), with reductions &amp;gt;50% measured by polysomnography. The combination therapy was well tolerated, with no significant adverse effects or interactions with ongoing medications. The third patient did not adhere to the drug therapy, and the effect of a single night of treatment before the follow-up polysomnography was evaluated, showing no change in AHI. These cases suggest a potential role for atomoxetine and oxybutynin as alternative therapeutic options for pediatric OSA in complex scenarios where severe OSA persists despite AT and failed CPAP therapy, warranting further evaluation in large pediatric clinical trials. Nevertheless, the final case underscores that even pharmacological treatments, although seemingly straightforward to administer, may encounter adherence challenges.

Background and Aims: Cardiovascular disease is a global health concern requiring effective prevention. Colchicine has gained interest for reducing cardiovascular events in high-risk patients. This study evaluates the efficacy and safety of colchicine in preventing these events. Methods: A systematic search was conducted in PubMed, CENTRAL, and Embase databases according to PRISMA guidelines, including studies up to August 26, 2024. Measures of effect included relative risk (RR) and mean differences. Meta-regressions and sensitivity analyses were performed to explore heterogeneity, which was quantified using the I 2 statistic. The certainty of evidence was assessed using the GRADE approach. Results: Analysis of 37,812 patients showed colchicine significantly reduced the risk of acute myocardial infarction (moderate certainty) (RR=0.81 [95% CI: 0.71-0.92], p=0.002), pericarditis (high certainty) (RR=0.48 [95% CI: 0.39-0.59], p&lt;0.00001), atrial fibrillation (high certainty) (RR=0.74 [95% CI: 0.66-0.84], p&lt;0.00001), acute coronary syndrome (high certainty) (RR=0.39 [95% CI: 0.23-0.65], p=0.0004) and hospitalization (high certainty) (RR=0.52 [95% CI: 0.38-0.70], p&lt;0.0001). Outcomes such as cardiovascular mortality (moderate certainty), total mortality (moderate certainty), non-cardiovascular mortality (low certainty), length of hospital stay (low certainty), and cardiac tamponade (very low certainty) did not show statistically significant differences. Significant adverse effects included gastrointestinal disorders such as diarrhea, flatulence, nausea, and elevated ALT or AST levels. Conclusions: Colchicine effectively reduces cardiovascular event risk but may cause gastrointestinal side effects. Its benefit in cardiovascular prevention is clear, yet safety should be evaluated prudently.

Background Human epidermal growth factor receptor 2 (HER2) gene amplification in lung adenocarcinoma is associated with aggressive tumor behavior and poor prognosis. Currently, there is no standard targeted therapy for HER2-amplified lung cancer. Case summary A 60-year-old male presented with a mass in the right cervical spine area. Imaging and pathological examinations confirmed stage IV (T4N3M1) lung adenocarcinoma with metastases to both lungs, multiple lymph nodes, the pleura, the left adrenal gland, and the meninges. Genetic testing revealed HER2 gene amplification and low programmed death-ligand 1 (PD-L1) expression (tumor proportion score &amp;lt;1%). The patient declined conventional chemotherapy due to concerns about side effects. With his informed consent, he was treated with a combination of cadonilimab (a PD-1/cytotoxic T-lymphocyte antigen 4 bispecific antibody) and disitamab vedotin (an anti-HER2 antibody–drug conjugate), administered intravenously every 3 weeks. After nine treatment cycles over 6 months, imaging assessments showed complete disappearance of the pulmonary lesions, and the achieved complete response (CR) persisted for at least 7 months. The treatment was well-tolerated, and the patient maintained an excellent performance status (Eastern Cooperative Oncology Group score of 0) without significant adverse effects. Conclusion Treatment with cadonilimab and disitamab vedotin induced a sustained complete response in a patient with advanced HER2-amplified lung adenocarcinoma who declined chemotherapy. Thus, this combination therapy may offer a promising, effective, and well-tolerated treatment alternative for similar patients. Further clinical trials are warranted to validate these findings and potentially establish a new standard of care for this subset of lung cancer patients.

Hypofractionated radiation therapy (Hypo-RT) schedules may offer radiobiological, patient convenience, and healthcare resource advantages over standard fractionated radiation therapy (S-RT) for glioblastoma (GBM). Additionally, simulated integrated boost (SIB) Hypo-RT is proven to be an effective and safe treatment. We report on our experience regarding progression-free survival (PFS), overall survival (OS), and RT-related toxicities in GBM patients treated with Hypo-RT and S-RT. Patients with IDH-wild-type GBM received either Hypo-RT (40.05-52.5Gy/15 fractions) or S-RT (60-70Gy/30 fractions). Volumetric modulated arc therapy was performed for all patients. Concomitant temozolomide (75mg/m2/day) and adjuvant chemotherapy (TMZ 150-200mg/m2 for 5days every 28days) were administered. OS and PFS were estimated using the Kaplan-Meier method. Ninety-five patients were treated (Hypo-RT: 52, S-RT: 43). With a median follow-up of 25months (range 9-63), the median age was 65 and 54years for the Hypo-RT and S-RT groups, respectively. All patients tolerated the treatment well; no significant adverse effects were observed in either group. No acute or late neurological side effects of grade ≥ 2 were reported during RT. Grade 3-4 hematologic toxicity occurred in five cases, all of which interrupted concomitant TMZ (all happening in the S-RT arm). The time to progression for the S-RT and Hypo-RT groups was 13.7 and 11.1months, respectively (p = 0.243). Regarding OS, the S-RT group had a median OS of 28.8months compared to 17.5months in the Hypo-RT group (p = 0.007). Although further investigations are ongoing, a statistically significant difference exists between Hypo-RT and S-RT in OS. Hypo-RT could potentially become the standard of care not only for elderly patients but also for those with poor prognosis. Further investigation with additional data is necessary to determine the most effective standard approach.

This study aimed to evaluate the efficacy of posterior subtenon injection of interferon alfa-2B (PSII) as a therapeutic option for managing recurrent inflammatory macular edema (IME). A retrospective study was conducted at a tertiary care eye center in South India. Patients receiving PSII for recurrent infectious or non-infectious IME were included in the study. Recurrent IME was defined as less than 50 µm improvement in central macular thickness (CMT) on spectral-domain optical coherence tomography within 1 month or relapse of IME within 3 months of previous treatment. Patients received a single PSII (1 MIU/mL) under topical anesthesia. Follow-up visits included clinical examinations and CMT measurement, best-corrected visual acuity (BCVA), and intraocular pressure (IOP). The study included 13 patients with a mean age of 46.2 years. Diagnosis varied, including pseudophakic IME, post-endophthalmitis IME, and various forms of uveitis. Mean CMT significantly reduced from 639.0 µm at baseline to 427.45 µm at one week ( P < 0.001). But further increased to 500.62 µm at 1-2 months follow-up ( P < 0.05). Mean BCVA improved from 20/70 (0.57 logMAR) to 20/40 (0.33 logMAR) at 1-month follow-up. No significant adverse effects were observed, although one patient with post-endophthalmitis IME developed granulomatous anterior uveitis 40 days after the injection. The study demonstrates the potential short-term efficacy of PSII in reducing CMT and improving BCVA in patients with recurrent IME. Further research is needed to optimize dosing protocols and explore long-term efficacy.

Efficacy and safety of the Plook-Fire-Thatu recipe on breast milk volume and breast milk macronutrient composition in postpartum women: A randomised controlled trial.

Sedatives, a class of psychotropic medications widely prescribed to hospitalized patients, offer various therapeutic benefits. However, inappropriate use can result in significant adverse effects. This study aims to investigate potential breakpoints of sedative use, hospital stays, and associated costs. Data were extracted from a hospital information system, including 13 822 eligible hospitalizations involving chronic disease treatment with sedative prescriptions from 2016 to 2023. Sedative dosages were standardized to diazepam equivalents using defined daily dosages (DDDs). Generalized additive models (GAMs) were used to examine nonlinear associations of sedative DDDs with length of stay (LOS) and hospital costs. Breakpoints in these associations were further estimated using segmented regressions. In the total sample, the median DDD of sedatives was 1.00 (interquartile range: 0.62, 1.69). Segmented regressions estimated breakpoints at 0.83 DDD (95% CI: 0.82, 0.84) for LOS and 0.81 DDD (95% CI: 0.80, 0.83) for hospital costs. Below these DDD breakpoints, GAMs results estimated that an increase of 0.1 units in DDD was associated with a 5.5% decrease in LOS and a 6% decrease in hospital costs, respectively. It was predicted that reaching these breakpoints was associated with a 7.8% reduction in LOS and a 6.8% reduction in hospital costs for DDD values below these thresholds. Our findings suggest that the rational use of sedatives below specific cutoff values was associated with a significant reduction in hospitalization burden among patients with chronic diseases.

Artemisia keiskeana Miq. alleviates oxidative stress and ferroptosis in APAP-induced liver injury by mediating Nrf2/GPX4/NF-κB signaling pathway through ESR1.

Background: Neuropathic pain (NP) presents a significant actual public health challenge. Traditional treatments primarily involve medications, but these approaches frequently yield unsatisfactory results, highlighting the need to explore alternative therapies, such as platelet-rich plasma (PRP), an autologous plasma derivative enriched with platelets. Objective: This article aims to systematically review the literature and provide an updated assessment of the efficacy and safety of PRP treatment for NP. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched databases, including Web of Science, Embase, PubMed, Scopus, and Cochrane Library. We assessed bias risk using the Cochrane Risk of Bias 2 tool (RoB2). Results: Among 1230 studies identified, 12 randomized trials meeting eligibility criteria were included. Due to substantial heterogeneity, pairwise meta-analysis and intervention ranking were found to be unfeasible. Most trials suggest PRP is effective in relieving NP, with no reported serious complications or significant PRP-related adverse effects. However, these findings were compromised by methodological heterogeneity and study inconsistency. Conclusion: PRP has shown to be promising as a safe therapeutic option for managing NP. Future studies should prioritize improved rigor and reproducibility for more stringent conclusions.

Pulmonary delivery of small circular RNA vaccines for influenza prevention.

ObjectivesTo provide population-level insights into COVID-19 testing behaviour and test results among all pregnant women in the Netherlands and to assess the effects of SARS-CoV-2 infection during pregnancy on maternal and neonatal health outcomes.DesignRetrospective population-based cohort study.SettingDutch registry data on maternal and neonatal health outcomes linked with COVID-19 testing and sociodemographic data for the study period 2020 and 2021.ParticipantsTo study testing behaviour, all pregnant women who gave birth in the Netherlands during 2020 and 2021 were included (N=322 720). To study the effects of maternal infection, women who gave birth between June 2020 and September 2021 and who were tested for COVID-19 were included (N=68 059).Primary and secondary outcome measuresFor testing behaviour: number of COVID-19 tests performed and COVID-19 test results. For neonatal health outcomes: preterm birth, low birth weight for gestational age (small for gestational age (SGA)), BIG2 (preterm birth and/or SGA), Apgar score at 5 min below seven (low Apgar), Apgar score at 5 min below four (very low Apgar), neonatal intensive care unit admission, congenital anomalies and mortality. For maternal health outcomes: major postpartum haemorrhage (>1000 mL), severe ruptures (third or fourth degree), type of delivery and episiotomy.ResultsCompared with the reference group (women aged 30–34), women under 20 had the lowest probability of being tested (16.5% vs 31.3%; OR 0.43, 95% CI 0.38 to 0.49), but when tested, they had significantly higher odds of testing positive (19.3% vs 12.9%; OR 1.62, 95% CI 1.21 to 2.14). Women originating from ‘other African’ countries were least likely to be tested (15.1%; OR 0.37, 95% CI 0.35 to 0.39), while women whose country of origin was ‘Morocco’ were most likely to test positive when tested (33.4%; OR 3.63, 95% CI 3.35 to 3.93). While over all trimesters a SARS-CoV-2 infection during pregnancy did not show significant effects, an infection during the first trimester was associated with an increased risk of preterm birth (5.2% vs 6.4%; OR 1.25, 95% CI 1.03 to 1.52) and a low 5-min Apgar score (1.9% vs 2.9%; OR 1.50, 95% CI 1.12 to 2.02). No significant adverse maternal health effects were observed.ConclusionThere were significant differences in testing behaviour and the probability of testing positive for COVID-19 among pregnant women from different age groups, countries of origin and socioeconomic backgrounds. SARS-CoV-2 infection during pregnancy was not associated with significant effects on maternal health outcomes, and only limited effects on neonatal health were observed. Only infections occurring in the first trimester were linked to an increased risk of preterm births and low 5-min Apgar scores.

This systematic review aimed to update a 2016 review and answer two questions: (1) Among breastfeeding women, does the use of progestogen-only contraception (POC) (ie, pills, injectables, implants, hormonal intrauterine devices) increase the risk of poor breastfeeding or infant outcomes compared with those not using POC? (2) Among breastfeeding women, does the initiation of POC before 6 weeks postpartum increase the risk of poor breastfeeding or infant outcomes compared with the initiation of POC at 6 weeks or later? We searched multiple databases (MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov and CINAHL) from inception to 6 September 2023. We extracted data and assessed risk of bias (RoB) for each study and certainty of evidence for each outcome. Sixty-one articles met the inclusion criteria; 11 were newly identified since the previous review, most with high RoB. Nine new randomised and non-randomised studies assessing breastfeeding and/or infant outcomes met the inclusion criteria for Question 1. Two new randomised studies assessing breastfeeding and/or infant outcomes met the inclusion criteria for Question 2, examining early versus late initiation of the implant. One new article for each objective included preterm infants. For both questions, studies continue to find no significant adverse effects on breastfeeding (eg, continuation, supplementation, duration) or infant (eg, growth, illness) outcomes. The certainty of evidence ranged from very low to moderate across outcomes. This updated systematic review provides additional evidence for the safety of POC use during breastfeeding. Newly identified studies are consistent with the prior review in suggesting no consistent findings of adverse effects, while adding evidence for preterm infants.

In silico multiscale computational modelling of botulinum toxin a diffusion for glabellar wrinkle treatment: Optimizing injection volumes across formulations.

Toxicological mechanisms of gold nanoclusters in zebrafish embryos.

Psilocybin use in bipolar disorder: A comprehensive review.