Sub-wavelength scale characterization of on-chip coupling mirrors.

Miniature free-space optical beams, originating from on-chip microstructures, are usually measured and quoted without reference to a particular polarization state. We develop an automated platform to characterize tightly focused free-space optical beams in three dimensions. We present a detailed description of each subsystem including the calibration and test procedure. We demonstrate how amplitude and phase are measured at sub-wavelength resolution using a cleaved fiber with a heterodyne reference. Further analysis provides information about the phase and intensity profile of the beam with regards to its polarization content and spatial confinement. We perform a proof-of-concept experiment for a custom waveguide-coupled micro-mirror. The work opens new possibilities for rapid analysis of micro-mirrors in prototyping and optimization of integrated optical systems.

IL-17A disrupts the nasal mucosal epithelial barrier in patients with chronic rhinosinusitis by activating the ERK/STAT3 pathway.

BACKGROUND: The mucosal epithelial barrier, the first line of immune defense, is vulnerable to allergens, pathogens, and inflammatory cytokines, contributing to CRS development. Our previous studies found high interleukin-17A(IL-17A) expression correlated with CRS severity and low glucocorticoid efficacy. The role of IL-17A in disrupting the nasal mucosal epithelial barrier leading to CRS remains unclear. We aimed to investigate how IL-17A promoting epithelial barrier damage and identify new treatment targets for CRS. METHODOLOGY: Nasal tissue samples from 36 CRSwNP, 34 CRSsNP, and 39 controls were examined for the expression of IL-17A and tight junction (TJ) proteins using qRT-PCR, immunohistochemistry and immunofluorescence. The integrity of TJs and signaling pathways activation were observed using western blot, immunofluorescence, TEER and FITC-FD4, transmission electron microscopy before and after IL-17A stimulation in human primary nasal epithelial cells (hNECs). Concurrently, studies were also conducted in an CRS mouse model induced by anti-IL-17A neutralizing antibody administration. RESULTS: TJs expression in the nasal mucosa of CRS patients was lower than in controls. IL-17A stimulation reduced TJs expression and TEER while increasing hNECs permeability. Inhibition of the (ERK/STAT3) pathway reversed the downregulation of TJs and the disruption of the epithelial barrier induced by IL-17A stimulation. In the CRS mouse model, anti-IL-17A antibody treatment rescued the nasal mucosal epithelial barrier. CONCLUSIONS: IL-17A disrupts the nasal mucosal epithelial barrier by activating the ERK/STAT3 pathway in patients with CRS.

End-of-life practices in Hong Kong intensive care units: results from the Ethicus-2 study.

INTRODUCTION: The need for end-of-life care is common in intensive care units (ICUs). Although guidelines exist, little is known about actual end-of-life care practices in Hong Kong ICUs. The study aim was to provide a detailed description of these practices. METHODS: This prospective, multicentre observational sub-analysis of the Ethicus-2 study explored end-of-life practices in eight participating Hong Kong ICUs. Consecutive adult ICU patients admitted during a 6-month period with life-sustaining treatment (LST) limitation or death were included. Follow-up continued until death or 2 months from the initial decision to limit LST. RESULTS: Of 4922 screened patients, 548 (11.1%) had LST limitation (withholding or withdrawal) or died (failed cardiopulmonary resuscitation/brain death). Life-sustaining treatment limitation occurred in 455 (83.0%) patients: 353 (77.6%) had decisions to withhold LST and 102 (22.4%) had decisions to withdraw LST. Of those who died without LST limitation, 80 (86.0%) had failed cardiopulmonary resuscitation and 13 (14.0%) were declared brain dead. Discussions of LST limitation were initiated by ICU physicians in most (86.2%) cases. Shared decision-making between ICU physicians and families was the predominant model; only 6.0% of patients retained decision-making capacity. Primary medical reasons for LST limitation were unresponsiveness to maximal therapy (49.2%) and multiorgan failure (17.1%). The most important consideration for decision-making was the patient's best interest (81.5%). CONCLUSION: Life-sustaining treatment limitations are common in Hong Kong ICUs; shared decision-making between physicians and families in the patient's best interest is the predominant model. Loss of decision-making capacity is common at the end of life. Patients should be encouraged to communicate end-of-life treatment preferences to family members/surrogates, or through advance directives.

Developing and Evaluating a School-Based Tobacco and E-Cigarette Prevention Program for Deaf and Hard-of-Hearing Youth.

School-based programs are an important tobacco prevention tool. Yet, existing programs are not suitable for Deaf and Hard-of-Hearing (DHH) youth. Moreover, little research has examined the use of the full range of tobacco products and related knowledge in this group. To address this gap and inform development of a school-based tobacco prevention program for this population, we conducted a pilot study among DHH middle school (MS) and high school (HS) students attending Schools for the Deaf and mainstream schools in California (n = 114). American Sign Language (ASL) administered surveys, before and after receipt of a draft curriculum delivered by health or physical education teachers, assessed product use and tobacco knowledge. Thirty-five percent of students reported exposure to tobacco products at home, including cigarettes (19%) and e-cigarettes (15%). Tobacco knowledge at baseline was limited; 35% of students knew e-cigarettes contain nicotine, and 56% were aware vaping is prohibited on school grounds. Current product use was reported by 16% of students, most commonly e-cigarettes (12%) and cigarettes (10%); overall, 7% of students reported dual use. Use was greater among HS versus MS students. Changes in student knowledge following program delivery included increased understanding of harmful chemicals in tobacco products, including nicotine in e-cigarettes. Post-program debriefings with teachers yielded specific recommendations for modifications to better meet the educational needs of DHH students. Findings based on student and teacher feedback will guide curriculum development and inform next steps in our program of research aimed to prevent tobacco use in this vulnerable and heretofore understudied population group.

Tissue oxidative stress and expression of chicken UCP and ANT mRNA in laying hens exposed to acute cold stress.

1. Exposure to stress alters normal homoeostasis and, hence, the antioxidant defence system. The aim of this study was to examine the effect of acute cold temperature on the antioxidant defence system in hens.2. Hy-line grey commercial layers (80 40-week-old) were randomly assigned to one of eight groups. In groups 1 to 5, hens were exposed to low temperature at -8.68°C (cool stressed) for 2, 4, 6, 8 and 10 h, respectively. In groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C to recovery for 2 h and 4h, respectively. In treatment groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C for 2 h and 4 h, respectively. Group 8 was the control, where hens were housed under regular condition at 21°C as controls.3. Antioxidant enzymes (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA), in skeletal muscle, the kidney, liver and pancreas were measured. The transcription of avUCP and ANT mRNA was tested by RT-PCR.4. The T-AOC activity was increased in the skeletal muscle of hens cold stressed for 2, 4, 6, 8 and 10 h and the 2 h recovery groups compared with control hens (p < 0.05). The GPx activity was increased in the liver and skeletal muscle after cold stress 4 h and in the pancreas of cold stress 2 h compared with the control group (p < 0.05). Antioxidant SOD activity was increased in the kidney after cold stress 6 h and in the liver after cold stress 10 h compared to the control group (p < 0.05). Measured MDA activity was increased in the pancreas after 2 h cold stress (p < 0.05).5. UCP mRNA expression level was increased in the pectoral muscle for 2 h and 4 h recovery groups compared with the control hens (p < 0.05) and avian uncoupling protein (UPC), adenine nucleotide translocator (ANT) expression level was increased in the leg muscle of hens cold stress for 2, 6, 8 h and recovery 2 and 4 h.6. The observed changes in the antioxidant defence system were tissue specific. Increments in levels of ANT (leg muscle) and UCP (pectoral and leg muscle) mRNA expression may be involved in the regulation of thermogenesis in skeletal muscle.

[The non-bacterial pathogenic and clinical characteristics of acute respiratory tract infection in children in a hospital of pediatric in Sichuan Province from 2019 to 2021].

Objective: To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province. Methods: Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ2 Inspection. Results: A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old (χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) (χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath (χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old (χ2=9.74, P<0.001), while RSV is more common in children under 1 year old (χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old (χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak (χ2=252.68, P<0.001). Conclusion: The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

[HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases].

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

[A case of hypereosinophilia with diffuse pulmonary nodules].

We reported a case of a 36-year-old woman who presented with cough, dyspnea, hypereosinophilia, multiple pulmonary nodules and mediastinal lymphadenopathy. The percentage of eosinophils in bronchoalveolar lavage fluid (BALF) was as high as 65%. Pathogenic tests and cytologic examination of BALF were negative. Transbronchial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration revealed only eosinophil infiltration. As the patient responded poorly to high-dose corticosteroids, a surgical lung biopsy was performed. The pathological diagnosis was angioimmunoblastic T-cell lymphoma. The patient received chemotherapy and achieved a partial response. Her eosinophil count returned to the normal range, and the pulmonary nodules on chest CT partially resolved.

Effectiveness and feasibility of three types of parent reminders to increase adolescent human papillomavirus (HPV) vaccination.

Parent reminders have produced modest improvements in human papillomavirus (HPV) vaccination among adolescents. However, little prior research has compared the effectiveness and feasibility of different HPV reminder types in resource-limited settings. We conducted a quasi-experimental study (2016-2017) to evaluate the effectiveness of three parent reminder types (mailed letters, robocalls, text messages) on next-dose HPV vaccine receipt among 12-year-olds in a large Federally Qualified Health Center in Los Angeles County. Six clinics were matched into three pairs: randomly assigning one clinic within each pair to intervention and control. Intervention clinics were randomly assigned to deliver one of the three parent reminder types. We calculated rates of next-dose vaccine receipt and assessed intervention effects using logistic regression models. We calculated the proportion of each type of reminder successfully delivered as a feasibility measure. The study sample comprised 877 12-year-olds due for an HPV vaccine dose (47% female, >85% Latino). At 4-month follow-up, 23% of intervention patients received an HPV vaccine dose compared to only 12% of control patients. Overall, receipt of any reminder increased rates of the next-needed HPV vaccine compared to usual care (p = 0.046). Significant improvements were observed for text reminders (p = 0.036) and boys (p = 0.006). Robocalls were the least feasible reminder type. Text message reminders are feasible and effective for promoting HPV vaccination. Future research is needed to assess the effectiveness and feasibility of reminders compared to other vaccine promotion strategies.

[Correlation between fluid parameter and cardiovascular events in hemodialysis patients based on repeated body composition analyses].

Objective: To explore the correlation between fluid load index and cardiovascular events in hemodialysis patients based on repeated body composition analyses. Methods: A prospective cohort study was conducted to collect the clinical data of patients undergoing maintenance hemodialysis (MHD) in the Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine from July to September 2020. The pre-dialysis fluid overload (FO) index-overhydration (OH) was measured by bioelectrical impedance method, and the follow-up monitoring was conducted every 6 months. According to the baseline OH value, patients were divided into non-FO group (OH≤2.5 L) and FO group (OH>2.5 L). Moreover, according to the repeated measurements, the patients were divided into continuous non-FO group, continuous FO group and intermittent FO group. All patients were followed up until October 1, 2022, and the outcomes were recorded. The end point of follow-up was cardiovascular events. The cumulative incidence of cardiovascular events was calculated by the Kaplan-Meier method, and the risk factors of cardiovascular events were analyzed by Cox proportional hazards regression model. Results: A total of 289 patients were included, including 88 patients (30.4%) with FO and 201 patients (69.6%) with non-FO. There were 168 males (58.1%) and 121 (41.9%) females, with an average age of (58±13) years and an average follow-up time of (22.0±6.5) months. Kaplan-Meier analysis showed that the incidence of cardiovascular events in the baseline FO group was higher than that in the non-FO group (log-rank χ2=14.44, P<0.001). The incidence of cardiovascular events in both the continuous FO group and the intermittent FO group was higher than that in the continuous non-FO group (log-rank χ2=41.47, P<0.001; log-rank χ2=18.36, P<0.001). After adjustment for gender, age, comorbidities, and biochemical indicators, the incidence of cardiovascular events in the baseline FO group was 1.850 times of the non-FO group (95%CI: 1.046-3.271, P=0.034). The incidence of cardiovascular events in the continuous FO group was 4.679 times of the continuous non-FO group (95%CI: 2.189-10.002, P<0.001). The incidence of cardiovascular events in the intermittent FO group was 3.410 times of the continuous non-FO group (95%CI: 1.696-6.857, P=0.001). Conclusions: OH value measured by bioelectrical impedance can be used as an important reference index for clinical monitoring of cardiovascular events in MHD patients. Continuous chronic and intermittent exposures to FO are risk factors for cardiovascular events in hemodialysis patients.

An investigation of the PM2.5 concentrations and cumulative inhaled dose during subway commutes in Changchun, China.

Air quality in subway systems is crucial as it affects the health of passengers and staff. Although most tests of PM2.5 concentrations in subway stations have taken place in public areas, PM2.5 is less understood in workplaces. Few studies have estimated the cumulative inhaled dose of passengers based on real-time changes in PM2.5 concentrations as they commute. To clarify the above issues, this study first measured PM2.5 concentrations in four subway stations in Changchun, China, where measuring points included five workrooms. Then, passengers' exposure to PM2.5 during the whole subway commute (20-30 min) was measured and segmented inhalation was calculated. The results showed that PM2.5 concentration in public places ranged from 50 to 180 µg/m3, and was strongly correlated with outdoors. While the PM2.5 average concentration in workplaces was 60 µg/m3, and it was less affected by outdoor PM2.5 concentration. Passenger's cumulative inhalations in single commuting were about 42 µg and 100 µg when the outdoor PM2.5 concentrations were 20-30 µg/m3 and 120-180 µg/m3, respectively. The PM2.5 inhalation in carriages accounted for the largest proportion of the entire commuting, about 25-40%, because of the longer exposure time and higher PM2.5 concentrations. It is recommended to improve the tightness of the carriage and filter the fresh air to improve the air quality inside. The average daily PM2.5 inhaled by staff was 513.53 µg, which was 5-12 times higher than that of passengers. Installing air purification devices in workplaces and reminding staff to take personal protection can positively protect their health.

Utilization of Monitored Beds for Children Admitted With Unintentional Poisonings.

OBJECTIVES: Children with unintentional poisonings (UPs) are frequently admitted to monitored beds (MBs), though most require minimal interventions. We aimed to (1) describe clinical factors and outcomes for children admitted for UPs and (2) identify clinical factors associated with MB placement. METHODS: In this single-center retrospective cohort study, we studied patients younger than 6 years admitted from the emergency department (ED) for UPs over a 5-year period to a quaternary-care children's hospital. Primary outcome was disposition (MB vs non-MB). Secondary outcomes included length of stay, escalation of inpatient care, 7-day readmission, and death. Covariates included age, certainty of ingestion, altered mental status, and ED provider training level. Subanalysis of drug class effect on disposition was also studied. Associations of clinical factors with MB placement were tested with multivariable logistic regression. RESULTS: Of 401 patients screened, 345 subjects met inclusion criteria. Most subjects (308 of 345 [89%]) were admitted to MBs. Children with high certainty of ingestion (adjusted odds ratio [aOR], 4.2; 95% confidence interval [CI], 1.52-11.58), altered mental status (aOR, 5.82; 95% CI, 2.45-13.79), and a fellow (vs faculty) ED provider (aOR, 2.34; 95% CI, 1.04-5.24) were more likely to be admitted to MBs. No escalations of care, readmissions, or deaths occurred. Exposures to cardiac drugs had increased MB placement (aOR, 6.74; 95% CI, 1.93-23.59). CONCLUSIONS: The majority of children admitted for UPs were placed in MBs. Regardless of inpatient placement, no adverse events were observed, suggesting opportunities for optimized resource utilization. Future research may focus on direct costs, inpatient interventions, or prospective outcomes to validate these findings.

[Prognostic value of translocation t(11;14) in primary light-chain amyloidosis treated with bortezomib-based regimen].

Objective: To investigate the prognostic value of translocation t(11;14) in newly-diagnosed primary light-chain (AL) amyloidosis patients treated with bortezomib-based regimen. Method: Clinical information of newly-diagnosed AL amyloidosis patients in Peking Union Medical College Hospital who had baseline t(11;14) data and accepted bortezomib-combined therapies from September, 2015 to September, 2021 was collected. The relationships between t(11;14) status and baseline characteristics, hematological response, organ response and prognosis were analyzed. Results: A total of 152 patients were included, aged (59.5±9.1) years and 93 cases were male (61.2%). Forty-six patients carried t(11;14) (30.3%). There was no statistical difference in the proportion of organ involved, distribution of Mayo 2004 and 2012 stages and laboratory indexes between patients with and without t(11;14) (all P>0.05). For hematological response, the difference in the rates of ≥very good partial response (VGPR) between those with t(11;14) and without after the first cycle [28.2%(11/39) vs 37.4%(34/91), P>0.05] was not statistically significant. After 3 cycles, the difference in the rates of ≥VGPR between two groups was not statistically significant [35.9%(14/39) vs 51.1%(46/90), P>0.05]. The difference in the ratio of the best hematological response reaching ≥VGPR between two groups during the first-line treatment was not statistically significant [52.2%(24/46) vs 64.2%(68/106), P>0.05]. But patients with t(11;14) had lower cardiac response rate at 3 months [15.2%(5/33) vs 34.6%(28/81), P=0.038] and 6 months [19.4%(6/31) vs 50.6%(42/83),P=0.003] than those without, but the difference in cardiac response rates at 12 months was not statistically significant [41.7%(10/24) vs 53.5%(38/71),P>0.05]. For survival, the differences in overall survival (not reached vs 50.1 months, P>0.05) and hematological event-free survival (36.2 months vs 39.9 months, P>0.05) between patients carrying t(11;14) and those without were not statistically significant. Conclusion: Patients with t(11;14) had lower cardiac response rate than those without, but their hematological response and survival are not significantly different from those free from t(11;14).

[Analysis of epidemiological characteristics of pulmonary tuberculosis patients in Fengtai District, Beijing City from 2011 to 2021].

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Fengtai District from 2011 to 2021. Methods: A retrospective study was conducted, the data of PTB patients in Fengtai District from 2011 to 2021 were collected in Chinese disease prevention and Control Information System, which included etiological classification, gender, age, occupation, onset time, demographic information etc. the epidemiological characteristics of reported PTB patients was analysis. Results: A total of 10 342 cases of PTB were reported from 2011 to 2021 in Fengtai District, with an average annual reported incidence rate of 42.87/ 100 000. The incidence rate was the highest in 2012(75.89/100 000), and significantly declined from 2013, which declined to 29.70/100 000 in 2017. It showed a slow rise from 2018 to 2021. The difference was statistically significant (χ2=1 471.77,P<0.001).There were 2 975 cases of etiologic positive PTB from 2011 to 2021, and 76 cases of Rifampicin-resistant PTB from 2017 to 2021. The ratio of male cases to female was 1.75, the average annual incidence rate of male (53.94/100 000) was higher, than female(31.57/100 000).(χ2=704.01,P<0.001). Among all age groups, 25-29 years group, 20-24 years group and 30-34 years group had the highest proportion, which were 1 506 cases (14.56%) , 1 292 cases (12.49%) and 1 024 cases (9.90%) respectively. The average annual incidence rate was the lowest in the group less than 10 years old (1.43/100 000), and the highest in the group 85 years old and over (195.20/100 000), the difference was statistically significant(χ2=3164.24, P<0.001). The top occupations from high to low were housework and unemployment (2 917 cases, 28.21%), retirees (2 308 cases, 22.32%), workers (1 047 cases, 10.12%), cadres and staff (950 cases, 9.19%), farmers (860 cases, 8.32%), business services (698 cases, 6.75%), teachers and students (455 cases, 4.40%). Conclusion: From 2011 to 2021, the incidence rate of PTB was decreased from 2012 to 2017, and slowly increased lately in Fengtai District. The epidemiological characteristics of PTB vary in different age and gender.

Response to Lynch et al: On measuring head motion and effects of head molds during fMRI.

We recently presented evidence indicating limited efficacy of custom-molded headcases in reducing head motion in two naturalistic experimental contexts - passive movie watching, and speaking in the scanner (Jolly et al., 2020). In a commentary on this work, Lynch et al (2020) present additional data that support the original findings of (Power et al., 2019) and raise several potential issues with our recent work. We appreciate the opportunity to address these criticisms and raise additional points that should be considered when interpreting these conflicting findings. We do not believe that their criticisms diminish the value of our work, but instead, along with this reply, help better elucidate the key factors researchers should consider to make the most informed choice about their own research protocols.

TDP-43 maintains chondrocyte homeostasis and alleviates cartilage degradation in osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is the most prevalent age-related disorder due to cartilage degradation. Previous studies have identified aberrant chondrocyte homeostasis under extracellular stress as a key pathological mechanism behind cartilage degradation in OA. TDP-43, a DNA/RNA-binding protein has been demonstrated to participate in processing many extracellular stress responses; however, understanding of the role of TDP-43 in OA is limited. This study aims to investigate the role of TDP-43 in chondrocyte homeostasis and cartilage degradation in OA. METHODS: The role of TDP-43 during degradation of cartilage is examined by experimental posttraumatic OA animal models and human cartilage specimens. Cartilage degradation is assessed by histological analysis, qPCR, and Western blot. The molecular mechanisms are investigated in vitro using human primary chondrocytes. RESULTS: TDP-43 decreases significantly in degenerated cartilage. TDP-43 concentration is positively correlated with IL-1ß concentration in synovial fluid derived from OA patients (Pearson r = 0.95, CI (95%) [0.80, 0.99], P < 0.0001). Intra-articular injection of recombinant TDP-43 significantly alleviates cartilage degradation and subchondral bone remodeling in vivo. In vitro mechanistic analyses show that TDP-43 maintains chondrocyte homeostasis under oxidative stress through regulating stress granule dynamics via G3BP1. CONCLUSION: The present study indicates that TDP-43 maintains chondrocyte homeostasis under oxidative stress and alleviates cartilage degeneration in osteoarthritis, identifying TDP-43 as a potential target for the diagnosis and treatment of knee OA.

Mode-splitting in a microring resonator for self-referenced biosensing.

Self-referenced biosensing based on mode-splitting on a microring resonator is experimentally demonstrated. A Bragg grating integrated on the surface of the ring provides coupling between the clockwise and counterclockwise travelling modes of the pristine ring resonator lifting their degeneracy. The amount of mode-splitting is directly related to the reflectivity of the grating and it is only affected by structurally modifying the grating. Environmental perturbations to the surroundings of the gratings, such as temperature and bulk refractive index variations, have a minor effect on the amount of mode-splitting. This principle allows the realization of a self-referenced sensing scheme based on the detection of variations of the mode-splitting induced by structural changes to the grating. In this work, a polymethyl methacrylate (PMMA) Bragg grating is integrated onto a ring resonator in Al2O3. It is shown both theoretically and experimentally that the amount of splitting of a resonance varies minimally under temperature or bulk refractive index perturbations. However, the structural change of attaching a layer of biomolecules inside the grating does affect its reflectivity and the amount of mode splitting present. This result represents the first proof-of-concept demonstration of an integrated mode-splitting biosensor insensitive to temperature and refractive index variations of the liquid matrix where the molecules to be detected are embedded. The reported results pave the road towards the realization of truly self-referenced biosensors.

One-year outcomes of an osteoporosis liaison services program initiated within a healthcare system.

Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. INTRODUCTION: A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. METHODS: Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. RESULTS: Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. CONCLUSIONS: The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

[Quantitative analysis of myelofibrosis and its prognostic significance in patients with myelodysplastic syndrome].

Objective: To quantitatively analyze the reticulin fiber intensity density (RFD) in patients with myelodysplastic syndrome (MDS) by using the computer-aided grid point method, and preliminarily explore its correlation with the prognosis of MDS patients. Methods: Bone marrow (BM) slices from 32 primary MDS patients treated in Tongren Hospital Shanghai Jiao Tong University School of Medicine from February 2017 to December 2019 were observed. Images were taken by the optical microscope imaging system after the Gomori staining. The computer grid marking software was developed according to the principle of the mesh micrometer to assess RFD, meanwhile, the artificial semi-quantitative were used to assess the fibrosis of bone marrow. The co-relation between the above two methods was evaluated, and the relationship between RFD and prognosis of MDS patients were further investigated with Cox regression analysis. Results: Of the patients, there were 17 males and 15 females with a median age of 69 years (32-91 years). The RFD quantitatively analyzed by the computer-based method was positively correlated with the myelofibrosis grade by the artificial semi-quantitative analysis (r=0.497, P=0.004). The RFD in patients diagnosed with MDS complicated with excess blasts (MDS-EB) was significantly higher than that in the non-MDS-EB group((9.55%±0.75%) vs (1.71%±0.23%), P<0.001). Cox regression model analysis showed that the RFD of MDS patients had better prognostic value when compared with the artificial semi-quantitative analysis, which was also a poor prognostic factor (RR=1.337, 95%CI: 1.085-1.648, P=0.006). The overall survival (OS) of patients with RFD>5.54% was significantly shorter than that with RFD≤5.54% (P=0.001). The OS of MDS-EB patients with RFD>9.81% was significantly shorter than that in patients with RFD≤9.81% (P=0.003). Conclusion: Abnormal proliferative fibrosis of bone marrow is a potential high-risk factor for poor prognosis of MDS patients.