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Cellular and extracellular vaginal changes following murine ovarian removal

Physiol Rep. 2023 Aug;11(15):e15762. doi: 10.14814/phy2.15762.

ABSTRACT

Loss of estrogen as a result of aging, pelvic cancer therapy, genetics, or eating disorders affects numerous body systems including the reproductive tract. Specifically, a chronic hypoestrogenic state fosters debilitating vaginal symptoms like atrophy, dryness, and dyspareunia. Current treatment options, including vaginal estrogen and hyaluronan (HA), anecdotally improve symptoms, but rectifying mechanisms are largely understudied. In order to study the hypoestrogenic vaginal environment, in particular the extracellular matrix (ECM), as well as understand the mechanisms behind current treatments and develop new therapies, we characterized a reliable and reproducible animal model. Bilateral ovariectomies (OVX) were performed on 9-week-old CD1 mice. After 1 month of estrogen loss due to ovarian removal, a phenotype that is similar to human vaginal tissue in an estrogen reduced state was noted in mice compared to sham-operated controls. The uterine to body weight ratio decreased by 80% and vaginal epithelium was significantly thinner in OVX compared to sham mice. Estrogen signaling was altered in OVX, but submucosal ERα localization did not reach statistical differences. HA localization in the submucosal area was altered and CD44 expression decreased in OVX mice. Collagen turn-over was altered following OVX. The inflammation profile was also disrupted, and submucosal vaginal CD45+ and F4/80+ cell populations were significantly reduced in the OVX mice. These results show altered cellular and molecular changes due to reduced estrogen levels. Developing new treatments for hypoestrogenic vaginal symptoms rely on better understanding of not only the cellular changes, but also the altered vaginal ECM environment. Further studies using this mouse model has the potential to advance women’s vaginal health treatments and aid in understanding the interplay between organ systems in both healthy, aged, and diseased states.

PMID:37549960 | DOI:10.14814/phy2.15762

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Distribution characteristics and results of allergens in patients with allergic rhinitis in Ningxia area

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2023 Jul;37(7):562-569. doi: 10.13201/j.issn.2096-7993.2023.07.010.

ABSTRACT

Objective:To investigate the distribution of allergens in patients with allergic rhinitis (AR) in Ningxia, and provide theoretical data for the prevention and treatment of AR in this region. Methods:A total of 1664 patients diagnosed with AR in the Otorhinolaryngology Head and Neck Surgery Department of Yinchuan First People’s Hospital Outpatient Clinic from January 2018 to December 2021 were retrospectively collected. Use the allergen sIgE antibody detection kit (immunoblotting method) to detect inhalation and ingestion allergens in patients.Results: ①Among all AR patients, 1 158 cases were detected positive, resulting in the detection rate was 69.59%; ②The detection rate of inhalation allergen was 65.87%, and the detection rate of ingestion allergen was 19.83%; ③Mugwort was the most sensitive allergen, and 76.32% of the patients having a positive grade ≥3; ④Out of the patients, 294 cases (25.39%) were allergic to only one allergen, 244 cases (21.07%) were allergic to two allergens, and 620 cases (53.54%) were allergic to three or more allergens; ⑤During different seasons, the highest number of positive allergens detected was in the summer, with 968 cases (83.59%). Mugwort was the main allergen during this season (69.01%). After the COVID-19 epidemic, the total positive rate of sIgE tests in AR patients decreased compared to before, and the difference was statistically significant (P<0.001); ⑥Mugwort, dog epithelium, mold combination, egg, peanut, soybean, Marine fish combination and fruit combination all showed statistically significant differences between different gender groups (P<0.05); ⑦Common ragweed, mugwort, dust mite combination, cockroach, egg, milk, Marine fish combination, shrimp, fruit combination and nut combination all showed statistically significant differences among different age groups (P<0.05); ⑧There were statistically significant differences in hay dust among different ethnic groups (P<0.05). Conclusion:Artemisia argyi is the main allergen in Ningxia, and the distribution characteristics of different allergens are influenced by treatment season, the COVID-19 epidemic, gender, age, ethnicity, and other factors, showing certain distribution patterns and rules.

PMID:37549949 | DOI:10.13201/j.issn.2096-7993.2023.07.010

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A Ground-State Dual-Descriptor Strategy for Screening Efficient Singlet Fission Systems

J Phys Chem Lett. 2023 Aug 7:7198-7207. doi: 10.1021/acs.jpclett.3c01554. Online ahead of print.

ABSTRACT

Exploration of singlet fission (SF) materials is vital for enhancing the photoelectric conversion efficiency of photovoltaic devices, and the development of an effective screening means is in great demand. In this work, we for the first time propose a promising dual-descriptor strategy to predict the SF energetics (ΔESF) from ground-state electronic properties, the gap (GapHL) and exchange energy (KHL) between the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO), where GapHL plays a dominant role and KHL acts as a correction. This strategy is statistically verified through exploring the effect of N-doping on the electronic/energetic properties of the N-doped tetracene derivatives and isomers. Several rules of thumb are suggested, and the reliability of this strategy is validated by comparison with experiments. This work proposes a novel strategy for exploring SF chromophores with insights into the SF energetics from ground-state properties and certainly has fundamental interest and generality in exploring efficient SF-capable materials.

PMID:37549938 | DOI:10.1021/acs.jpclett.3c01554

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Dexamethasone solution and dexamethasone in Mucolox™ for the treatment of oral inflammatory ulcerative diseases: A phase II randomized clinical trial

J Oral Pathol Med. 2023 Aug 7. doi: 10.1111/jop.13471. Online ahead of print.

ABSTRACT

BACKGROUND: Mucolox™ is a mucosal drug delivery system that prolongs the contact time between the oral mucosa and topical corticosteroids, potentially reducing the need for multiple applications daily. This study aimed to assess the clinical efficacy and tolerability of dexamethasone 0.5 mg/5 mL solution in Mucolox™ for the management of oral inflammatory ulcerative diseases.

METHODS: Participants were randomly assigned to receive dexamethasone 0.5 mg/5 mL in Mucolox™ (Mucolox™ arm) or dexamethasone 0.5 mg/5 mL solution (standard arm) and instructed to swish/gargle for 5 min three times daily. Changes from pre- to posttreatment patient’s sensitivity score (0-10 on a visual analog scale), reticulation/erythema/ulceration score, and oral health-related quality of life were evaluated at baseline and at the end of the study period.

RESULTS: Twenty nine patients (75% females) with a median age of 58 years (range 18-79) were enrolled and randomly allocated to the Mucolox™ or standard arm. One subject was excluded. Although statistically significant in both arms, the pre- to posttreatment sensitivity score reduction was higher in the Mucolox™ arm (6.3 vs. 4.4-point reduction). Both arms showed a decrease in the reticulation/erythema/ulceration score between the two visits (7.2 vs. 4.7 [Mucolox™ arm]; 8.0 vs. 4.8 [standard arm]; p > 0.05). Mucolox™ in dexamethasone 0.5 mg/5 mL solution was better tolerated when taste and level of comfort were considered.

CONCLUSIONS: Both treatments were effective in the management of oral inflammatory ulcerative diseases. Dexamethasone 0.5 mg/5 mL in Mucolox™ was better tolerated and was slightly better in controlling patients’ oral sensitivity. Larger studies are needed to confirm these findings in oral inflammatory ulcerative diseases patients.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04540133.

PMID:37549933 | DOI:10.1111/jop.13471

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Findings from a pilot randomized trial of spinal decompression alone or spinal decompression plus instrumented fusion

Bone Jt Open. 2023 Aug 8;4(8):573-579. doi: 10.1302/2633-1462.48.BJO-2023-0049.

ABSTRACT

AIMS: Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted.

METHODS: As part of the SpInOuT-F study, a pilot randomized trial was carried out across five NHS hospitals. Patients were randomized to either spinal decompression alone or spinal decompression plus instrumented fusion. Patient-reported outcome measures were collected at baseline and three months. The intended sample size was 60 patients.

RESULTS: Of the 90 patients screened, 77 passed the initial screening criteria. A total of 27 patients had a PI-LL mismatch and 23 had a dynamic spondylolisthesis. Following secondary inclusion and exclusion criteria, 31 patients were eligible for the study. Six patients were randomized and one underwent surgery during the study period. Given the low number of patients recruited and randomized, it was not possible to assess completion rates, quality of life, imaging, or health economic outcomes as intended.

CONCLUSION: This study provides a unique insight into the prevalence of dynamic spondylolisthesis and PI-LL mismatch in patients with symptomatic spinal stenosis, and demonstrates that there is a need for a definitive RCT which stratifies for these groups in order to inform surgical decision-making. Nonetheless a definitive study would need further refinement in design and implementation in order to be feasible.

PMID:37549931 | DOI:10.1302/2633-1462.48.BJO-2023-0049

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Diabetes Mellitus in the Elderly Adults in Korea: Based on Data from the Korea National Health and Nutrition Examination Survey 2019 to 2020

Diabetes Metab J. 2023 Aug 7. doi: 10.4093/dmj.2023.0041. Online ahead of print.

ABSTRACT

BACKGROUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES).

METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured.

RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. Conclusion: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.

PMID:37549924 | DOI:10.4093/dmj.2023.0041

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Deep-learning based classification of a tumor marker for prognosis on Hodgkin’s disease

Eur J Haematol. 2023 Aug 7. doi: 10.1111/ejh.14066. Online ahead of print.

ABSTRACT

PURPOSE: Hodgkin’s disease is a common malignant disorder in adolescent patients. Although most patients are cured, approximately 10%-15% of patients experience a relapse or have resistant disease. Furthermore, there are no definitive molecular predictors for early identification of patients at high risk of treatment failure to first line therapy. The aim of this study was to evaluate the deep learning-based classifier model of medical image classification to predict clinical outcome that may help in appropriate therapeutic decisions.

METHODS: Eighty-three FFPE biopsy specimens from patients with Hodgkin’s disease were stratified according to the patient’s qPET scores, stained with picrosirius red dye and digitalized by whole slide image scanning. The resulting whole slide images were cut into tiles and annotated by two classes based on the collagen fibers’ degree of coloring with picrosirius red. The neural network (YOLOv4) was then trained with the annotated data. Training was performed with 30 cases. Prognostic power of the weakly stained picrosirius red fibers was evaluated with 53 cases. The same neural network was trained with MMP9 stained tissue slides from the same cases and the quantification results were compared with the variant from the picrosirius red cases.

RESULTS: There was a weak monotonically increasing relationship by parametric ANOVA between the qPET groups and the percentages of weakly stained fibers (p = .0185). The qPET-positive cases showed an average of 18% of weakly stained fibers, and the qPET-negative cases 10%-14%. Detection performance showed an AUC of 0.79.

CONCLUSIONS: Picrosirius red shows distinct associations as a prognostic metric candidate of disease progression in Hodgkin’s disease cases using whole slide images but not sufficiently as a prognostic device.

PMID:37549921 | DOI:10.1111/ejh.14066

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Compound Kushen Injection Reduces Severe Toxicity and Symptom Burden Associated With Curative Radiotherapy in Patients With Lung Cancer

J Natl Compr Canc Netw. 2023 Aug;21(8):821-830.e3. doi: 10.6004/jnccn.2023.7036.

ABSTRACT

BACKGROUND: Radiotherapy (RT) causes adverse events for which there are no effective treatments. This study investigated the clinical benefits of compound Kushen injection (CKI) in managing radiation injury in patients with lung cancer.

METHODS: A multicenter, open-label, randomized clinical trial randomly assigned patients with lung cancer to receive either CKI (20 mL/d for at least 4 weeks) integrated with curative RT (RT + CKI group; n=130) or RT alone (control group; n=130). The primary outcome was the incidence of grade ≥2 radiation-induced lung injury (RILI) in the lungs, esophagus, or heart. Secondary outcomes included patient-reported symptoms, quality of life, objective response rate (ORR), and toxic effects.

RESULTS: During the 16-week trial, the RT + CKI group had a significantly lower incidence of grade ≥2 RT-related injury than the control group (12.3% [n=16] vs 23.1% [n=30]; P=.02). Compared with the control group, the RT + CKI group experienced a significant decrease in moderate-to-severe symptoms of fatigue, cough, and pain (P<.001 for the treatment and time interaction term); significantly less physical symptom interference (P=.01); and significantly better quality of life by the end of the trial (P<.05). No statistically significant difference in ORR was found. Adverse reactions associated with CKI were rare.

CONCLUSIONS: This study demonstrated low toxicity of CKI and its effectiveness in patients with lung cancer in reducing the incidence of grade ≥2 RILI and symptom burden, improving patients’ quality of life.

PMID:37549911 | DOI:10.6004/jnccn.2023.7036

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Hematologic Malignancy: Who Cares in the End? A Retrospective Cohort Study of Markers of Quality End-of-Life Care

J Natl Compr Canc Netw. 2023 Aug;21(8):813-820.e1. doi: 10.6004/jnccn.2023.7033.

ABSTRACT

BACKGROUND: Early palliative care is increasingly used in solid organ malignancy but is less established in patients with hematologic malignancy. Disease-related factors increase the demand for hospitalization, treatment, and supportive care in patients with hematologic malignancy. The terminal phase of illness in patients with hematologic malignancy can be difficult to predict, resulting in complexities in establishing a standard for quality end-of-life care.

METHODS: This is a retrospective single-center cohort study of adult patients with hematologic malignancy who died between October 2019 and July 2022. Patients were identified, and disease characteristics, therapy, and outcomes were extracted from medical records. Descriptive statistics are reported and univariate analyses were performed across a range of factors to assess for associations.

RESULTS: A total of 229 patients were identified, with a median age of 77 years and 35% female. In the final 30 days of life, 65% presented to the emergency department, 22% had an ICU admission, 22% had an invasive procedure, 48% received cytotoxic therapy, 61% received a RBC transfusion, and 46% received a platelet transfusion. Use of intensive chemotherapy was particularly associated with hospitalization and ICU admission. A total of 74% referred to palliative care, with a median time from referral to death of 13 days. Of these patients, one-third were referred within the last 5 days of life. In terms of place of death, 54% died in the acute hospital setting and 30% in hospice, with a median hospice length of stay of 4 days.

CONCLUSIONS: These findings highlight the need for further research into quality indicators for end of life in hematologic malignancy and earlier integration of specialist supportive and palliative care in both inpatient and outpatient settings.

PMID:37549908 | DOI:10.6004/jnccn.2023.7033

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Effect and Process Evaluation of an Intervention to Improve Hand Hygiene Compliance in Long-Term Care Facilities

J Am Med Dir Assoc. 2023 Aug 4:S1525-8610(23)00610-2. doi: 10.1016/j.jamda.2023.06.020. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the effect of a tailored, multifaceted improvement strategy on hand hygiene compliance in long-term care facilities (LTCFs). We also performed a process evaluation to explore the mechanisms through which our strategy brought about change.

DESIGN: We conducted a stepped-wedge cluster-randomized controlled trial with a sequential rollout of the improvement strategy to all participating LTCFs. The strategy consisted of education, training, reminders, observation sessions (including feedback), and team meetings (including feedback).

SETTING AND PARTICIPANTS: The study included nursing professionals from 14 LTCFs (23 wards) in the Netherlands.

METHODS: Hand hygiene compliance was observed during 5 measurement periods using WHO’s “Five Moments for Hand Hygiene.” Multilevel analyses and corresponding tests were completed on an intention-to-treat basis.

RESULTS: The absolute intervention effect of overall hand hygiene compliance (primary outcome measure) was 13% (95% CI 9.3-16.7, P < .001), adjusted for time and clustering. The adjusted absolute effect was 23% (95% CI 7-39, P < .002) before a clean and aseptic procedure, 18% (95% CI 10-26, P < .001) after touching a resident, 14% (95% CI 7-22, P < .003) before touching a resident, 10% (95% CI 5-15, P < .001) after contact with body fluid, and 1% (95% CI -11 to 13, P = .8) after touching a resident’s surroundings. With the exception of leadership, participants at LTCFs with more exposure to the intervention components showed statistically significantly more improvement than those at facilities with lower exposure scores.

CONCLUSIONS AND IMPLICATIONS: Our strategy was successful in improving hand hygiene compliance. LTCFs with more team members exposed to the different intervention components, demonstrated a greater effect from the intervention. To strengthen the impact of our intervention, we recommend that future improvement strategies provide more support to managers to ensure they are better equipped to take on their leadership roles and enable their teams to improve and maintain hand hygiene compliance.

PMID:37549888 | DOI:10.1016/j.jamda.2023.06.020