Menstrual abnormalities effects on clinical features and in vitro fertilization pregnancy outcomes in women with polycystic ovarian syndrome.

BACKGROUND: The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. OBJECTIVE: This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. STUDY DESIGN: Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. RESULTS: Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25-39.50] vs 28.00 [range, 24.00-36.00]; P<.001), an elevated level of antimüllerian hormone (7.02 ng/mL [range, 3.60-11.47] vs 5.66 ng/mL [range, 3.65-8.92]; P=.024), a higher level of baseline luteinizing hormone (10.01±5.93 vs 8.51±5.53 IU/l; P<.001) and luteinizing hormone-to-follicle-stimulating hormone ratio (1.51 [range, 1.00-2.32] vs 1.45 [range, 0.92-2.13]; P<.001), lower levels of fasting glucose (5.47 mmol/L [range, 5.11-5.73] vs 5.50 mmol/L [range, 5.17-5.76]; P<.001), and insulin at 2 hours after 75-g oral glucose tolerance test (56.85 µU/mL [range, 34.63-94.54] vs 59.82 µU/mL [range, 33.56-94.67]; P=.027), a higher level of high-density lipoprotein (1.26 mmol/L [range, 1.04-1.37] vs 1.21 mmol/L [range, 1.07-1.45]; P=.006). During in vitro fertilization, the early group had a higher level of peak estradiol (4596.50 pg/mL [range, 2639.25-6321.00] vs 3954.00 pg/mL [range, 2378.75-6113.50]; P=.013), and luteinizing hormone (2.52 IU/L [range, 1.40-4.21] vs 1.93 IU/L [range, 0.91-3.32]; P=.010) on the day of human chorionic gonadotropin trigger. There was no statistically significant difference observed in the number of oocytes and embryos, the rates of pregnancy and live birth, and the risks of obstetrical and neonatal between the 2 groups. CONCLUSION: An early onset of menstrual disturbance in patients with polycystic ovary syndrome may be associated with slightly more severe reproductive features and slightly milder metabolic features. Nonetheless, the outcomes of in vitro fertilization and the initial cycle of embryo transfer were comparable between the 2 groups.

The difference in early trimester fetal growth between singletons after frozen embryo transfer and fresh embryo transfer.

BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight. STUDY DESIGN: This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer between January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11-13 weeks gestation. The secondary outcomes were perinatal outcomes, including birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. RESULTS: A total of 6742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53 cm vs 5.57±0.48 cm, P<.001) and an increased risk of larger-than-expected crown-rump length (13.5% vs11.2%, P=.013) than the fresh embryo transfer group. After adjusting for confounders in multivariable linear regression models, frozen embryo transfer was still associated with a larger crown-rump length (regression coefficient, 3.809 [95% confidence intervals, 3.621-3.997], P<.001). When subgrouped by fetal gender, the crown-rump length of the frozen embryo transfer group was larger than the fresh embryo transfer group in both male and female fetuses. In addition, the crown-rump length was consistently larger in the frozen embryo transfer group than the fresh embryo transfer group in subgroups of the peak estradiol levels. The comparisons among different crown-rump length groups showed that smaller-than-expected crown-rump length was associated with increased risks of small for gestational age (6.3% vs 3.0%, P<.001) and preterm delivery (9.6% vs 6.7%, P=.004) than normal crown-rump length. CONCLUSION: Frozen embryo transfer was associated with a larger crown-rump length than fresh embryo transfer, suggesting that the effect of frozen embryo transfer on fetal growth may begin in the early trimester. Suboptimal fetal growth in the first trimester may be associated with low birthweight and premature delivery.

Association between time to colonoscopy after positive fecal testing and colorectal cancer outcomes in Alberta, Canada.

OBJECTIVE: To quantify the associations between time to colonoscopy after a positive fecal immunochemical test (FIT+) and colorectal cancer (CRC)-related outcomes in the context of a provincial, population-based CRC screening program. SETTING: Population-based, retrospective cohort study in Alberta, Canada, including Albertans aged 50-74 with at least one FIT+ in 2014-2017. METHODS: Study outcomes were CRC diagnosis after a FIT+ and a diagnostic follow-up colonoscopy in 2014-2019 and CRC stage at diagnosis. Multivariable logistic regression models were used to evaluate the relative risk of any CRC or advanced-stage CRC. Results were presented as crude odds ratio (OR) and adjusted OR (aOR) with 95% confidence intervals (CIs). RESULTS: Of the 787,967 participants who had a FIT, 63,232 (8%) had a FIT+ and met the study's eligibility criteria. The risk of any CRC or advanced-stage CRC stayed high and was relatively consistent for follow-up colonoscopies performed within 1-12 months of the FIT+. After 12 months, the risk of CRC was considerably higher, particularly for advanced-stage CRC. The OR and aOR for any CRC were 1.40 (95% CI: 1.13-1.73; p < 0.05) and 1.20 (95% CI: 0.96-1.49), respectively, and the OR and aOR for advanced-stage CRC were 1.42 (95% CI: 0.98-2.08) and 0.88 (95% CI: 0.59-1.32), respectively, for colonoscopy follow-up within 12-18 months versus 1-2 months. CONCLUSIONS: For Albertans who used FIT for CRC screening, a longer time interval between a FIT+ and follow-up colonoscopy, particularly over 12 months, increases the risk of having CRC and decreases the effectiveness of CRC screening programs.

The impact of early nutritional support on postoperative wound healing in patients with complex fractures: A meta-analysis review.

Complex fractures present significant challenges in orthopaedic surgery, particularly in terms of postoperative wound healing. Nutritional status plays a crucial role in the recovery process, with early nutritional support potentially influencing wound healing outcomes. This meta-analysis aimed to assess the impact of early nutritional interventions on postoperative wound healing and scar formation in patients with complex fractures. From an initial pool of 1742 articles, 7 studies were selected for analysis. The results revealed that preoperative nutritional support significantly improved early wound healing, as indicated by lower REEDA scores (SMD = -14.06, 95% CI: [-16.79, -11.32], p < 0.01) 1 week post-surgery. Furthermore, there was a notable reduction in scar formation, as demonstrated by lower Manchester Scar Scale scores (SMD = -25.03, 95% CI: [-30.32, -19.74], p < 0.01) 3 months post-surgery. These findings highlight the importance of incorporating nutritional strategies into the management of complex fractures to optimize postoperative recovery.

Selection of a Surgical Approach for Middle Ear Cholesteatoma Based on the Fusion Images of Non-Echo Planar Diffusion-Weighted MRI and CT.

PURPOSE: This study aimed to explore the ability of fusion images of non-echo planar diffusion-weighted magnetic resonance imaging (non-EPI-DWI MRI) and computed tomography (CT) to accurately locate cholesteatoma and plan the surgical approach. METHODS: In the first part, 41 patients were included. Their CT images and non-EPI DWMRI images were fused. The scope of cholesteatoma in the fusion image was compared with that in the surgical video to evaluate the capability to locate cholesteatoma. A total of 229 patients were included in the second part, and they were divided into 2 groups. We chose the surgical approach for the CT group and the fusion group, and compared the accuracy of surgical approaches in the CT group and the fusion group using the surgical records. RESULTS: The location of cholesteatoma shown in the fusion images was almost identical to that observed during the operation (kappa = .862). The overall specificity and sensitivity of the fusion images in locating cholesteatoma were 94.12% and 93.06%, respectively. The accuracy of surgical approach selection based on the fusion images (99.02%) was higher than that of surgical approach selection based on the CT images (85.83%). CONCLUSION: It is recommended that the fusion images be used to locate the range of the cholesteatoma before operation.

Effect of wound drainage on the wound infection and healing in patients undergoing spinal surgery: A meta-analysis.

A meta-analysis was conducted to comprehensively evaluate the impact of wound drainage on postoperative wound infection and healing in patients undergoing spinal surgery. Computer searches were performed, from database inception to October 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for studies related to the application of wound drainage in spinal surgery. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 11 articles involving 2102 spinal surgery patients were included. The analysis showed that, compared to other treatment methods, the use of wound drainage in spinal surgery patients significantly shortened the wound healing time (standardized mean difference [SMD]: -1.35, 95% confidence intervals [CI]: -1.91 to -0.79, p < 0.001). However, there was no statistical difference in the incidence of wound infection (odds ratio: 1.35, 95% CI: 0.83-2.19, p = 0.226). This study indicates that wound drainage in patients undergoing spinal surgery is effective, can accelerate wound healing and is worth promoting in clinical practice.

The impact of physiotherapy interventions on enhancing wound healing post knee osteoarthritis surgery: A meta-analysis.

In knee osteoarthritis surgery, managing postoperative wound healing and minimizing scar formation are pivotal for patient recovery and satisfaction. These aspects are particularly challenging due to the nature of the surgical procedure and patient demographics. Physiotherapy interventions are increasingly recognized for their role in improving these postoperative outcomes. This meta-analysis sought to evaluate the efficacy of physiotherapy in enhancing wound healing, as measured by REEDA scores, and reducing scar formation, as indicated by Manchester Scar Scale (MSS) scores, following knee osteoarthritis surgery. Analysing data from eight studies, we found that physiotherapy significantly improved wound healing, evidenced by lower REEDA scores (SMD = -19.58, 95% CI: [-22.49, -16.66], p < 0.01), and reduced scar formation, reflected in lower MSS scores (SMD = -24.79, 95% CI: [-30.03, -19.55], p < 0.01). These findings highlight the crucial role of physiotherapy in postoperative care for knee osteoarthritis patients, emphasizing its impact on enhancing recovery and improving surgical outcomes.

Assessing Breast Cancer Screening and Outcomes Among First Nations Women in Alberta.

BACKGROUND: Breast cancer (BC) incidence rates for First Nations (FN) women in Canada have been steadily increasing and are often diagnosed at a later stage. Despite efforts to expand the reach of BC screening programs for FN populations in Alberta (AB), gaps in screening and outcomes exist. METHODS: Existing population-based administrative databases including the AB BC Screening Program, the AB Cancer Registry, and an AB-specific FN registry data were linked to evaluate BC screening participation, detection, and timeliness of outcomes in this retrospective study. Tests of proportions and trends compared the findings between FN and non-FN women, aged 50-74 years, beginning in 2008. Incorporation of FN principles of ownership, control, access, and possession (OCAP®) managed respectful sharing and utilization of FN data and findings. RESULTS: The average age-standardized participation (2013-8) and retention rates (2015-6) for FN women compared to non-FN women in AB were 23.8% (P < .0001) and 10.3% (P = .059) lower per year, respectively. FN women were diagnosed with an invasive cancer more often in Stage II (P-value = .02). Following 90% completion of diagnostic assessments, it took 2-4 weeks longer for FN women to receive their first diagnosis as well as definitive diagnoses than non-FN women. CONCLUSION: Collectively, these findings suggest that access to and provision of screening services for FN women may not be equitable and may contribute to higher BC incidence and mortality rates. Collaborations between FN groups and screening programs are needed to eliminate these inequities to prevent more cancers in FN women.

Health Care Utilization and Costs in Lung Cancer Screening Participants-A Propensity-Matched Economic Analysis.

Introduction: Lung cancer screening (LCS) for high-risk populations has been firmly established to reduce lung cancer mortality, but concerns exist regarding unintended downstream costs. Methods: Mean health care utilization and costs were compared in the Alberta Lung Cancer Screening Study in a cohort undergoing LCS versus a propensity-matched control group who did not. Results: A cohort of 651 LCS participants was matched to 336 unscreened controls. Over the study period (mean 3.6 y), a modest increase in the number of claims (22.4 versus 21.9 per person-year [PY]; Δ 0.50 [95% confidence interval: 0.15-0.86], p = 0.006) and outpatient visits (4.01 versus 3.50 per PY; Δ 0.51 [0.37-0.65], p <0.0001), but not in inpatient admissions, was noted in the screened cohort. Claims payments, inpatient costs, and cancer care costs were similar in the screening arm versus the unscreened. Outpatient encounter costs per participant were higher in the screened group ($2662.18 versus $2040.67 per PY; Δ -$621.51 [-1118.05 to -124.97], p = 0.014). Removing the additional computed tomography screening examinations rendered differences not significant. Mean total costs were not significantly different at $6461.10 per PY in the screening group and $6125.31 in the unscreened group (Δ -$335.79 [-2009.65 to 1338.07], p = 0.69). Conclusions: Modest increases in outpatient costs are noted in individuals undergoing LCS, in part attributable to the screening examinations, without differences in overall health care costs. Health care costs and utilization seem otherwise similar in individuals participating in LCS and those who do not.

Geospatial analysis and participant characteristics associated with colorectal cancer screening participation in Alberta, Canada: a population-based cross-sectional study.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in Canada and early detection can prevent deaths through screening. However, CRC screening in Alberta, Canada remains suboptimal and varies by sociodemographic and health system characteristics, as well as geographic location. This study aimed to further the understanding of these participant and health system characteristics associated with CRC screening in Alberta and identify clusters of regions with higher rates of overdue or unscreened individuals. METHODS: We included Albertans aged 52 to 74 as of December 31, 2019 (index date) and we used data from administrative health data sources and linked to the Alberta Colorectal Cancer Screening Program database to determine colorectal cancer screening rates. We used multivariable multinomial logistic regression analysis to investigate the relationship between sociodemographic, health system characteristics and participation in CRC screening. We used optimized Getis-Ord Gi* hot-spot analysis to identify hot and cold-spots in overdue for and no record of CRC screening. RESULTS: We included 919,939 Albertans, of which 65% were currently up to date on their CRC screening, 21% were overdue, and 14% had no record of CRC screening. Compared to Albertans who were currently up to date, those who were in older age groups, those without a usual provider of care, those who were health system non-users, and those living in more deprived areas were more likely to have no record of screening. Areas with high number of Albertans with no record of screening were concentrated in the North and Central zones. CONCLUSIONS: Our study showed important variation in colorectal cancer screening participation across sociodemographic, health system and geographical characteristics and identified areas with higher proportions of individuals who have no record of screening or are under-screened in Alberta, Canada.

Creation of a Métis-Specific Instrument for Cancer Screening: A Scoping Review of Cancer-Screening Programs and Instruments.

Understanding the barriers to and facilitators of cancer screening programs among Indigenous populations remains limited. In the spirit of mutual respect, this co-led, collaborative project was carried out between the Métis Nation of Alberta and Screening Programs from Alberta Health Services (AHS). This scoping review assessed the cancer screening literature for available questionnaires and then identified themes and suitable questions for a Métis-specific cancer screening questionnaire. Literature searches on cervical, breast, and colorectal cancer screening programs and related concepts were conducted in electronic databases, including the Native Health Database, MEDLINE (Ovid), PsycINFO, PubMed, PubMed Central, CINAHL, MEDLINE (Ebsco), Psychology & Behavioral Sciences Collection, and Web of Science. Grey literature was collected from AHS Insite, Open Archives Initiative repository, American Society of Clinical Oncology, European Society of Medical Oncology, Google, and Google Scholar. 135 articles were screened based on the eligibility criteria with 114 articles selected, including 14 Indigenous-specific ones. Knowledge, attitude, belief, behaviour, barrier, and facilitator themes emerged from the review, but no Métis-specific cancer screening instruments were found. Thus, one was developed using existing cancer screening instruments, with additional questions created by the project team. A survey of the Métis population in Alberta will use this questionnaire and provide data to address the burden of cancer among Métis people.

Interpregnancy Interval After Clinical Pregnancy Loss and Outcomes of the Next Frozen Embryo Transfer.

Importance: The optimal interpregnancy interval (IPI) after a clinical pregnancy loss (CPL) remains controversial. Few studies have addressed the role of the IPI after a preceding CPL during in vitro fertilization (IVF) treatment. Objective: To evaluate the association between different IPI lengths after a preceding CPL and pregnancy outcomes of the next frozen embryo transfer (FET). Design, Setting, and Participants: This retrospective cohort study was conducted using data from the Center for Reproductive Medicine of Shandong University in China. The study included women who underwent frozen-thawed blastocyst transfer between July 1, 2017, and June 30, 2022, within 1 year after a preceding CPL during IVF treatment. Follow-up for pregnancy outcomes was completed for all participants on March 31, 2023. Data analysis was performed from April to May 2023. Exposures: Interpregnancy interval length was classified as less than 3 months, 3 to less than 6 months, or 6 to 12 months. Main Outcomes and Measures: Outcomes included live birth, conception, clinical pregnancy, pregnancy loss, preterm birth, small or large for gestational age, and low birth weight. Multivariable logistic regression analysis was conducted to evaluate the association between IPI and pregnancy outcomes by adjusted odds ratios (AORs). Results: This study included 2433 women (mean [SD] age, 31.8 [4.6] years) who received IVF treatment. There were 338 women (13.9%) with an IPI of less than 3 months, 1347 (55.4%) with an IPI of 3 to less than 6 months, and 748 (30.7%) with an IPI of 6 to 12 months. The median (IQR) IPI lengths for the 3 groups were 77 (65-85), 128 (109-152), and 234 (202-288) days, respectively. Compared with an IPI of 6 to 12 months, shorter IPIs (<3 and 3 to <6 months) were associated with decreased odds of clinical pregnancy (AOR, 0.70 [95% CI, 0.53-0.92] and 0.79 [0.65-0.95]), live birth (AOR, 0.64 [95% CI, 0.48-0.85] and 0.74 [0.61-0.90]), and healthy live birth (AOR, 0.63 [95% CI, 0.46-0.87] and 0.79 [0.64-0.98]). Compared with women with an IPI of 6 to 12 months, women with shorter IPIs (<3 and 3 to <6 months) had a higher risk of total pregnancy loss (AOR, 1.87 [95% CI, 1.31-2.67] and 1.29 [1.00-1.66], respectively). Conclusions and Relevance: The results of this study suggest that delaying the next FET for at least 6 months after a preceding CPL was associated with beneficial pregnancy outcomes, considering that a decreased likelihood of achieving clinical pregnancy and live birth was observed among women with shorter IPIs. Further prospective studies are needed to confirm these findings.

FAM134B-induced endoplasmic reticulum (ER)-phagy exacerbates cisplatin-insulted hair cell apoptosis ：Possible relation to excessive ER stress.

AIMS: FAM134B, the initial endoplasmic reticulum (ER)-phagy receptor identified, facilitates ER-phagy during ER stress. The malfunction of FAM134B has been demonstrated to have a crucial role in the pathological mechanisms of diverse human ailments. However, the role of FAM134B-mediated ER-phagy in ototoxicity, particularly in cisplatin-induced ototoxicity, remains unclear. The present study endeavors to investigate whether FAM134B is expressed in House Ear Institute-Organ of Corti 1 (HEI-OC1) and C57BL/6 murine cochlear hair cells (HCs), and to explore its potential function in cisplatin-mediated ototoxicity, with the aim of discovering new insights that can mitigate or forestall the irreversible adverse effect of cisplatin. METHODS: Immunofluorescence (IF) staining was used to test the expression pattern of FAM134B, levels of C/EBP-homologous protein (CHOP), autophagy, and co-localization ratio of lysosomes and ER. Western blotting was employed to measure changes in expression levels of FAM134B, LC3B, ER stress-related proteins, LAMP1 and apoptotic mediators. Cell apoptosis was examined using transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. RESULTS: In the present investigation, it was observed that FAM134B exhibited a diffuse expression pattern in the cytoplasm and nuclei of control HEI-OC1 cells. Following cisplatin administration, FAM134B was found to accumulate and form distinct dots around the nuclei, concomitant with increased levels of ER-phagy, ER stress, unfolded protein response (UPR), and cell apoptosis. Additionally, knockdown of FAM134B resulted in reduced ER-phagy, mitigated ER stress and UPR, and decreased apoptotic activity in HEI-OC1 cells following cisplatin exposure. CONCLUSIONS: Collectively, the findings of this study demonstrate that FAM134B-mediated ER-phagy enhances the susceptibility of HCs to ER stress and apoptosis in response to cisplatin-induced stress. This suggests a sequential progression of ER-phagy, ER stress and apoptosis following cisplatin stimulus, and implies the potential therapeutic benefit of inhibiting of FAM134B-mediated ER-phagy in the prevention of cisplatin-related ototoxicity.

The impact on clinical outcomes and healthcare resources from discontinuing colonoscopy surveillance subsequent to low-risk adenoma removal: A simulation study using the OncoSim-Colorectal model.

OBJECTIVE: To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1-2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. METHODS: The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1-2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. RESULTS: Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. CONCLUSIONS: Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs.

Creating Health Equity in Cancer Screening: Developing Outreach Strategies for Under-Screened Populations through Community Engagement.

Inequities in cancer screening were identified in Calgary, AB, by correlating low screening participation with higher material deprivation. This initiative sought to understand awareness of and barriers to breast, cervical and colorectal cancer screening to inform the co-design and implementation of an outreach strategy to increase screening awareness. Online focus groups with community members (n = 69) identified five themes, and interviews with community health workers (n = 21) identified four themes. The engagement phase led to a multi-component outreach strategy including a multilingual video series, a media campaign leveraging partner channels and a health worker information package with resources to assist with hosting community-based education sessions.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) protects hair cells from cisplatin-induced ototoxicity in vitro: possible relation to the activities of p38 MAPK signaling pathway.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) gene encodes rate-limiting enzyme in cholesterol biosynthesis, which is related to cell proliferation and mitochondrial function. The present study was designed to explore the expression of HMGCR in murine cochlear hair cells and HEI-OC1 cells and the possible mechanisms underpinning the actions of HMGCR in cisplatin-induced ototoxicity, with special attention given to p38 mitogen-activated protein kinase (MAPK) activities in vitro. The expressions of HMGCR, p-p38, cleaved caspase-3 and LC3B was measured by immunofluorescence and western blot. JC-1 staining and MitoSOX Red were used to detect mitochondria membrane potential (MMP) and reactive oxygen species (ROS) levels respectively. The apoptosis of auditory cells was assessed by TUNEL staining and flow cytometry. Protein levels of bcl2/bax and beclin1 were examined by western blot. We found that HMGCR was widely expressed in the auditory cells, of both neonatal mice and 2-month-old mice, in cytoplasm, nucleus and stereocilia. Moreover, 30 µM cisplatin elicited the formation of ROS, which, in turn, led to HMGCR reduction, activating p38 kinase-related apoptosis and autophagy in auditory cells. Meanwhile, co-treatment with ROS scavenger at a concentration of 2 mM, N-acetyl-L-cysteine (NAC), could alleviate the aforementioned changes. In addition, HMGCR silencing resulted in higher p38 MAPK-mediated apoptosis and autophagy under cisplatin injury. Taken together, we demonstrate that, for the first time, that HMGCR is expressed in the cochlear. Furthermore, HMGCR exerts protective benefit on auditory cells against cisplatin-mediated injury stimulated by ROS, culminating in regulation of p38 MAPK-dependent apoptosis and autophagy.

Biomechanical analysis of a novel bone cement bridging screw system combined with percutaneous vertebroplasty for treating Kummell's disease.

Kummell's Disease (KD) was originally proposed by Dr. Hermann Kummell in 1891 as a type of delayed posttraumatic vertebral collapse, which is a clinical phenomenon. The purpose of this experiment is to compare the strength of bone cement and the novel bone cement bridging screw in the treatment of thoracolumbar Kummell disease (KD) with other treatment methods. Thirty sheep spine specimens were selected. T12 to L2 segments were selected, and a KD intravertebral vacuum cleft model was made at the L1 segment. According to the ways of cement filling, the specimens were divided into percutaneous vertebroplasty (PVP), PVP combined with unilateral percutaneous pediculoplasty (PPP), PVP combined with bilateral PPP, unilateral novel bone cement bridging screw system combined with PVP, and bilateral cement bridging screw system combined with PVP groups. There were two experiments: three-dimensional biomechanical strength test and axial compression test. In the three-dimensional biomechanical strength test, we measured the strength of bone cement in specimens under six motion states, including flexion, extension, left bending, right bending, and left and right axial rotations. In the axial compression test, we detected the maximum axial pressure that the bone cement could withstand when it was under pressure until the bone cement was displaced. The unilateral or bilateral novel bone cement bridging screw with PVP groups had the best strength under flexion, extension, left bending, right bending, and had better biomechanical strength, with a significant difference from the other three groups (p < 0.05). There was no significant difference between the unilateral or bilateral novel bone cement bridging screw with PVP groups (p > 0.05). Unilateral and bilateral novel bone cement bridging screw could achieve similar bone cement strength. Compared with the other three groups, the unilateral or bilateral novel bone cement bridging screw with PVP groups are higher 136.35%, 152.43%; 41.93%, 51.58%; 34.37%, 43.50% respectively. The bilateral novel bone cement bridging screw with PVP could bear the largest pressure under vertical force. To conclude, the novel bone cement bridging screw can increase the strength of bone cement and avoid the loosening and displacement of bone cement in the treatment of KD of the thoracolumbar spine.

The likelihood of a healthy live birth after frozen embryo transfer with endometrium prepared by natural ovulation regimen vs programmed regimen: a propensity-score matching study.

BACKGROUND: The number of frozen embryo transfer cycles is increasing, but the optimal method of endometrial preparation for frozen embryo transfer remains controversial. Few studies have investigated the healthy live birth outcome after the natural ovulation regimen vs the programmed regimen. OBJECTIVE: This study aimed to explore whether the likelihood of a healthy live birth after frozen embryo transfer differs between the natural ovulation regimen and the programmed regimen. STUDY DESIGN: We conducted a retrospective cohort study including 7824 ovulatory women who underwent the first frozen embryo transfer cycle of single-blastocyst transfer with endometrial preparation by natural ovulation regimen vs programmed regimen, between June 2017 and June 2021. Propensity score matching was used to control for confounding variables in a 1:1 ratio. The primary outcome was healthy live birth, defined as birth of a live, singleton infant born at term, with an appropriate birthweight for gestational age. RESULTS: The natural ovulation regimen resulted in a higher probability of achieving healthy live birth compared with the programmed regimen (35.8% vs 30.6%; P<.0001). In addition, a higher rate of singleton live birth was observed after the natural ovulation regimen relative to the programmed regimen (49.6% vs 45.7%; P=.003). Women with the natural ovulation regimen were also less likely to experience clinical pregnancy loss (16.0% vs 19.7%; P=.005) and hypertensive disorders of pregnancy (3.9% vs 6.0%; P=.004) compared with women with the programmed regimen. Singletons born after the programmed regimen had greater mean birthweight (3441.50±539.97 vs 3394.96±503.87; P=.020) and higher risk of being large for gestational age (23.3% vs 18.7%; P=.003) than those conceived after the natural ovulation regimen. CONCLUSION: The natural ovulation regimen may be superior to the programmed regimen with regard to higher likelihood of healthy live birth and lower risk of pregnancy loss and maternal hypertensive disorders of pregnancy.

A microfluidic lung-on-a-chip based on biomimetic hydrogel membrane.

Lung-on-chips have showed great promise as a tool to recapitulate the respiratory system for investigation of lung diseases in the past decade. However, the commonly applied artificial elastic membrane (e.g., polydimethylsiloxane, PDMS) in the chip failed to mimic the alveolar basal membrane in the composition and mechanical properties. Here we replaced the PDMS film by a thin, biocompatible, soft, and stretchable membrane based on F127-DA hydrogel that well approached to the composition and stiffness of extracellular matrix in human alveoli for construction of lung-on-a-chip. This chip well reconstructed the mechanical microenvironments in alveoli so that the epithelial/endothelial functions were highly expressed with a well established alveolar-capillary barrier. In opposite to the unexpectedly accelerated fibrotic process on the PDMS-based lung-on-a-chip, HPAEpiCs on hydrogel-based chip only presented fibrosis under nonphysiologically high strain, well reflecting the features of pulmonary fibrosis in vivo. This physiologically relevant lung-on-a-chip would be an ideal model in investigation of lung diseases and for development of antifibrosis drugs.

Otomastoiditis Caused by Nocardia Farcinica: A Case Report and Literature Review.

Nocardia farcinica usually infects people with impaired immune status and usually manifests in the lungs. Otomastoiditis caused by Nocardia infection is extremely rare, with only 4 cases reported to date. This report describes a case of otomastoid N. farcinica infection in an immunocompetent patient. The case was a 10-month-old immunocompetent infant who presented with an approximately 3-month history of right ear discharge for which treatment with various antibiotics had not resulted in significant improvement. Multiple cultures of secretions and pathologic examination failed to identify the causative organism. The patient then underwent right mastoidectomy. Finally, metagenomic next-generation sequencing identified the pathogen to be N. farcinica. The patient was infection-free at the 6-month follow-up but had developed labyrinthitis ossificans. Otomastoid Nocardia infection has characteristic clinical features, namely, formation of a large amount of granulation tissue and coexistence of bone destruction and new bone formation. Traditionally, Nocardia is challenging to diagnose. Metagenomic next-generation sequencing of lesions is helpful. Complete local debridement and free drainage are key to treatment.