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Objective To assess the efficiency and the mechanism of fractional erbium:yttrium aluminum garnet (Er:YAG) laser for the treatment of morphea in mouse model. Background Morphea is a rare autoimmune disease characterized by excessive collagen deposition in skin. Fractional Er:YAG laser treatment is a promising treatment to improve morphea, despite limited studies about the therapeutic effect and underlying mechanism. Methods The mouse model of morphea was established by subcutaneously injecting with bleomycin (BLM). A total of 24 mice received fractional Er:YAG laser treatment once a week for 4 weeks. Objective measurement employed was ultrasonic imaging to measure dermal thickness. Subjective measures included scoring according to the adjusted Localized morphea Cutaneous Assessment Tool (LoSCAT); hematoxylin and eosin (H&E) staining to evaluate the histological grade of fibrosis; and quantitative morphometric studies to determine the expression of transforming growth factor‐β1 (TGF‐β1) and matrix metalloproteinase‐1 (MMP1) by immunohistochemistry. Results In this self‐controlled study, fractional Er:YAG laser treatment significantly ameliorate the severity of morphea, including lower clinical score (p < 0.01), decreased dermal thickness (p < 0.001), declined histological grade of fibrosis (p < 0.001), increased MMP1 (p < 0.001), and reduced TGF‐β1 (p < 0.01) expression. Conclusions We found that fractional Er:YAG laser treatment of morphea has good clinical, ultrasonic, and histopathologic efficacy, which may be a promising treatment in the future.

Background: Patients with diminished ovarian reserve (DOR) face challenges such as inadequate follicular recruitment and decreased oocyte quality when subjected to in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods: This retrospective self-controlled study included 130 patients with DOR who underwent IVF-ET using either the progestin-primed ovarian stimulation (PPOS) or luteal-phase ovarian stimulation (LPOS) protocol. In the PPOS protocol, ovarian stimulation was initiated in the early follicular phase with medroxyprogesterone acetate (MPA) combined with gonadotropins. In the LPOS protocol, ovarian stimulation began in the luteal phase with letrozole and gonadotropins, followed by dydrogesterone. Final oocyte triggering, retrieval, and embryo culture were performed using standardized procedures. The primary outcomes included gonadotropin consumption, oocyte maturation and fertilization rates, as well as pregnancy-related outcomes. Results: Compared to the LPOS group, the PPOS protocol was associated with a significantly shorter duration of gonadotropin stimulation and a lower total gonadotropin dose (p < 0.05). The LPOS group did not have significantly higher metaphase II (MII) oocyte and normal fertilization rates (p > 0.05). The abnormal fertilization rate was numerically lower in the LPOS group, but the difference was not statistically significant. Multivariate logistic regression analysis revealed that the LPOS protocol remained independently associated with a higher MII oocyte rate (adjusted odds ratio [aOR]: 1.42, 95% confidence interval [CI]: 1.07–1.91, p = 0.017), even after adjusting for age, body mass index (BMI), and antral follicle count (AFC). No significant association was observed between stimulation protocol and clinical pregnancy after adjustment. Conclusion: Both PPOS and LPOS protocols effectively prevent premature luteinizing hormone (LH) surges and support the development of viable embryos in patients with DOR. Multivariate analysis further confirmed LPOS as an independent predictor of improved oocyte maturity, suggesting its potential utility in individualized stimulation strategies for this patient population.

Background Gastric cancer remains a major health burden in China, with low early screening rates and limited access to endoscopic services. Gastric ultrasound offers a noninvasive, low-cost alternative but is underutilized due to the lack of effective training models. This study aimed to evaluate a novel standardized patient (SP)-based drinking simulation for teaching gastric ultrasound to residents. Methods In a self-controlled design, 32 ultrasound residents underwent a structured training program comprising a 90-minute theoretical lecture and a 2-hour hands-on workshop. Trainees acted as mutual SPs after ingesting warm water to simulate gastric filling. Outcomes included theoretical test scores, Direct Observation of Procedural Skills (DOPS) assessments, and Likert-scale self-assessment questionnaires. DOPS was conducted immediately after training and at one-month follow-up to assess skill retention. Statistical analyses were performed using SPSS v30.0. Results Theoretical scores significantly improved from 5.09 ± 0.89 to 8.28 ± 0.58 ( P  < 0.05, Pearson’s r  = 0.87). Post-training DOPS scores averaged 41.03 ± 2.72, with 81.25% of residents achieving the passing threshold. However, scores declined at one month (32.78 ± 3.69, P  < 0.05), highlighting the need for reinforcement. Self-assessment scores increased from 34.27% to 80.75% ( P  < 0.05), with marked gains in confidence, procedural readiness, and satisfaction. No correlation was observed between theoretical and procedural scores ( R ² = 0.001). Conclusion SP-based drinking simulation is a practical, low-cost, and educationally impactful method for teaching gastric ultrasound. It effectively improves residents’ theoretical knowledge, procedural ability, and self-confidence, while addressing the current gap in gastric-specific simulation training and supporting broader implementation in resource-limited settings. However, the observed short-term skill attrition highlights the need for continuous reinforcement and integration of interactive or computer-based theoretical modules. Future multicenter studies should validate its long-term effectiveness and clinical applicability.

Objective Adverse Social Determinants of Health (SDoH) are considered major obstacles to effective management of type-2 diabetes. This study aims to quantify the impact of SDoH factors on diabetes management outcomes. Materials and Methods We quantified the joint impact of multiple SDoH by applying a self-control case series method—which accounts for confounding by using individuals as their own control—to electronic health record data from an academic health system in Maryland. Results We found a consistent increase in HbA1c levels associated with SDoH across alternative study designs. The estimated total contributions of SDoH ranged 0.014–0.065 across the alternative designs. Transportation issues demonstrated particularly significant contributions, with estimates of 0.077–0.144. When assuming SDoH’s risk window to be ±45 days, for example, the total contribution was estimated to be 0.065 (95% CI [0.010, 0.120]) increase in HbA1c and the transportation issues’ contribution 0.134 (95% CI [0.020, 0.249]). Discussion and Conclusion Our result suggests that reducing transportation barriers may be an effective SDoH intervention strategy for diabetes management; however, the clinical impact of such interventions warrants further investigation. Lay Summary Did you know where you live impacts your life expectancy more than your genetic makeup? It affects your access to healthy food, healthcare services, exercise facilities, economic opportunities, and so forth. The  Centers for Disease Control and Prevention (CDC) defines these non-medical factors affecting health as Social Determinants of Health (SDoH). Many with diabetes struggle to manage their disease, despite the availability of effective treatments, due to SDoH-related difficulties. Our study attempts to quantify the impact of SDoH on poor diabetes management by using electronic health records (EHRs) and examining how an individual’s blood sugar levels change over time as he/she encounters adverse SDoH. Our analysis shows the lack of reliable transportation to be a significant contributor to worse diabetes control, manifested by higher levels of hemoglobin A1c. While our study identifies no other SDoH factors as significant contributors, this finding could simply be an artifact of the poor recording of SDoH issues in EHRs despite their sizable roles in individuals’ health. More careful documentation of SDoH by healthcare providers will help us quantify their true health impacts and thus identify the most effective interventions.

IntroductionAlthough topical use of moisturisers is slightly effective for the prevention and avoiding the aggravation of hand–foot syndrome induced by multikinase inhibitors, there is still room for improvement. Hydrocolloid dressing is a type of wound dressing often used for wounds such as decubitus ulcers. The purpose of this study is to verify the usefulness of application of hydrocolloid dressings as prophylaxis against development of hand–foot syndrome induced by multikinase inhibitors by comparing the effects of this dressing and standard supportive care (moisturising care alone) within the same individuals.MethodsThis study is a phase 3 randomised, self-controlled study to compare prophylactic moisturising care with or without hydrocolloid dressing for hand–foot syndrome induced by multikinase inhibitors. Patients with radically unresectable advanced or recurrent colorectal carcinoma, gastrointestinal stromal tumour and hepatocellular carcinoma who scheduled to receive regorafenib or sorafenib therapy are eligible for enrolment.Supportive care for hand–foot syndrome will consist of basic moisturising care with or without hydrocolloid dressing. If hand–foot syndrome occurs, a steroid ointment will be applied two times per day at the affected sites. The primary endpoint is an incidence rate of grade 2 or more severe hand–foot syndrome (soles of the feet only) assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events V.4.0. Grading of hand–foot syndrome will be performed by central review using photographs taken weekly by blinded trained physicians. The ethical approval was obtained from National Cancer Center Hospital. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conference.DiscussionIf the positive results are found in this study, it is shown that hydrocolloid dressing is effective not only as a symptom management but also as a prevention in hand–foot syndrome induced by multikinase.Trial statusThe enrolment was started in January 2019, and planned to closed in January 2021. As of February 2020, 26 patients enrolled in this study.Trial registration numberUMIN Clinical Trial Registry (UMIN000034853).Protocol versionV.1.4, 9 January 2020.

Olive mills produce pomace as a by-product of olive oil production process, which has a negative environmental impact. In this study, the dry extract of pomace (OG2), rich in polyphenols, was used for cosmetic purposes. The polyphenolic extract was encapsulated together with sh-oligopeptide-1 using cellulose fibres by spray-drying technology. Cytotoxicity and antistress cell studies were carried out using a modified cell line (THP1). Based on the results, a single, randomised, self-controlled study was conducted to evaluate the cream in thirty healthy volunteers. Statistical analysis was performed using a paired samples t-test. Skin moisture increased in the treated forearm (p-value < 0.000). There was an increase in elasticity in the treated forearm (p-value 0.042). TEWL decreased after one week of cream application (p-value 0.099). The results of this clinical study showed that the cream improved barrier function after one week of application on healthy skin.

Background: Following radioiodine (131I) therapy of differentiated thyroid cancer, the salivary glands may become inflamed, leading to dysfunctions and decreases in patients’ nutritional status and quality of life. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define at-risk patients, which would allow the delivered activity to be adapted to the expected risk of salivary dysfunctions. Objective: The aims of this study are to estimate the incidence of salivary dysfunctions, and consequences on the quality of life and nutritional status for patients after 131I-therapy; to characterize at-risk patients of developing posttreatment dysfunctions using clinical, biomolecular, and biochemical factors; and to validate a dosimetric method to calculate the dose received at the salivary gland level for analyzing the dose-response relationship between absorbed doses to salivary glands and salivary dysfunctions. Methods: This prospective study aims to include patients for whom 131I-therapy is indicated as part of the treatment for differentiated thyroid cancer in a Paris hospital (40 and 80 patients in the 1.1 GBq and 3.7 GBq groups, respectively). The follow-up is based on three scheduled visits: at inclusion (T0, immediately before 131I-therapy), and at 6 months (T6) and 18 months (T18) posttreatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (Hospital Anxiety and Depression scale, Medical Outcomes Study 36-Item Short Form Survey), and nutritional status (visual analog scale) are administered by a trained clinical research associate. At T0 and T6, saliva samples and individual measurements of the salivary flow, without and with salivary glands stimulation, are performed. External thermoluminescent dosimeters are positioned on the skin opposite the salivary glands and at the sternal fork immediately before 131I administration and removed after 5 days. From the doses recorded by the dosimeters, an estimation of the dose received at the salivary glands will be carried out using physical and computational phantoms. Genetic and epigenetic analyses will be performed to search for potential biomarkers of the predisposition to develop salivary dysfunctions after 131I-therapy. Results: A total of 139 patients (99 women, 71.2%; mean age 47.4, SD 14.3 years) were enrolled in the study between September 2020 and April 2021 (45 and 94 patients in the 1.1 GBq and 3.7G Bq groups, respectively). T6 follow-up is complete and T18 follow-up is currently underway. Statistical analyses will assess the links between salivary dysfunctions and absorbed doses to the salivary glands, accounting for associated factors. Moreover, impacts on the patients’ quality of life will be analyzed. Conclusions: To our knowledge, this study is the first to investigate the risk of salivary dysfunctions (using both objective and subjective indicators) in relation to organ (salivary glands) doses, based on individual dosimeter records and dose reconstructions. The results will allow the identification of patients at risk of salivary dysfunctions and will permit clinicians to propose a more adapted follow-up and/or countermeasures to adverse effects. Trial Registration: ClinicalTrials.gov NCT04876287; https://clinicaltrials.gov/ct2/show/NCT04876287 International Registered Report Identifier (IRRID): DERR1-10.2196/35565

Background:Psychotropic polypharmacy is common in clinical practice although supporting evidence is limited. Extrapyramidal syndromes (EPS) are adverse events associated with use of psychotropic drugs, especially antipsychotics. There are quite a few reports that suggest association between each psychotropic drug and EPS; however, the risk of EPS associated with their polypharmacy has not been fully evaluated. This study aimed at examining the influence of psychotropic polypharmacy on EPS occurrence by drug category (anxiolytics, hypnotics, antidepressants, and antipsychotics).Methods:Sequence symmetry analyses were conducted using a large-scale Japanese health insurance claims database. This method assessed asymmetry in the distribution of EPS occurrence defined as both a diagnosis of EPS and a prescription for antiparkinsonian drugs before and after initiation of psychotropic drugs. The adjusted sequence ratio (ASR) and its 95% confidence interval (CI) were calculated. Results:All categories of psychotropic drugs (anxiolytics, hypnotics, antidepressants, and antipsychotics) were significantly associated with EPS, and the tendency was stronger in polypharmacy associated with them. A clearer association between polypharmacy of BZs and EPS was indicated. In the analyses by subclasses of drugs, BZs, tetracyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, typical and atypical antipsychotics were significantly associated with EPS. The ASR of atypical antipsychotics (ASR 11.3, 95% CI 7.95-16.4) was higher than that of typical ones (ASR 2.96, 95% CI 2.06-4.33).Conclusions:The association between psychotropic polypharmacy and EPS was indicated. Further investigation is needed to confirm these findings because of the pharmacoepidemiologic nature of this study.

Background. Herpes zoster is common and vaccine preventable. Stroke risk may be increased following zoster, but evidence is sparse and could be explained by differences between people with and without zoster. Our objective was to determine if stroke risk is increased following zoster. Methods. Within-person comparisons were undertaken using the self-controlled case-series method and data from the UK Clinical Practice Research Datalink (1987–2012). Participants had a first-ever diagnosis of zoster and stroke within the study period. Stroke incidence in periods following zoster was compared with incidence in other time periods. Age-adjusted incidence ratios (IRs) and 95% confidence intervals (CIs) were calculated. Results. A total of 6584 individuals were included. Stroke rate was increased following zoster compared with the baseline unexposed period, then gradually reduced over 6 months: weeks 1–4 (age-adjusted IR, 1.63; 95% CI, 1.32– 2.02), weeks 5–12 (IR, 1.42; 95% CI, 1.21–1.68), and weeks 13–26 (IR, 1.23; 95% CI, 1.07–1.42), with no increase thereafter. A stronger effect was observed for individuals with zoster ophthalmicus, rising to a >3-fold rate 5–12 weeks after zoster. Oral antivirals were given to 55% of individuals: IRs for stroke were lower among those receiving antivirals compared with those not treated, suggesting a protective effect. Conclusions. We have established an increased stroke rate within 6 months following zoster. Findings have implications for zoster vaccination programs, which may reduce stroke risk following zoster. The low antiviral prescribing rate needs to be improved; our data suggest that antiviral therapy may lead to a reduced stroke risk following zoster.

Concurrent use of Danshen (a Chinese herbal medicine) and anticoagulants may increase bleeding risk Danshen, also known as Salvia miltiorrhiza, is a traditional Chinese medicine that is commonly used for heart and circulation problems. In Taiwan, Danshen is frequently prescribed together with modern Western medications. One group of these medicines, called anticoagulants, are commonly used to prevent blood clots in people with conditions such as atrial fibrillation or heart disease. While anticoagulants are effective, they can increase the risk of bleeding. It has been uncertain whether using Danshen at the same time might make this risk even greater. In this study, we used a large medical records database to investigate the real-world safety of taking Danshen together with anticoagulants. We included 525 adults who were prescribed both treatments and 146 of them had records of bleeding events. To minimize differences between individuals, we applied a self-controlled case series (SCCS) study design, where each patient served as their own control. We found that the risk of bleeding was significantly higher during the first 28 days after patients started taking Danshen with an anticoagulant. The risk was especially high for gastrointestinal and intracranial bleeding. On average, the first bleeding event happened about 16 days after starting combined treatment. Importantly, most patients in our study already had a high baseline risk of bleeding, but even after adjusting for other factors, the increased risk remained clear. These findings suggest that patients who take Danshen alongside anticoagulants should be monitored carefully, particularly during the first few weeks of combined use. This study highlights the need for careful communication about herbal and conventional medicine use.