Path Model Analysis of the Effects of Perceived Formalism, and Fear of COVID-19 on Police Officers' PTSD and Insomnia.

This study examines whether law enforcement officers' fear of COVID-19, job burnout, and job stress have increased their PTSD and insomnia during the epidemic. This article introduces the perceived formalism of police agencies into the causal model to explore whether perceived formalism increases the job burnout and job stress of police officers. The formalism of administrative agencies is rarely included in epidemic research. This study collected 306 Taiwanese police officers as research subjects. We used confirmatory factor analysis and SEM for hypothesis testing. The study found that perceived formalism positively affects the job burnout and job stress of police officers. Job stress, fear of COVID-19, and job burnout positively affect PTSD and insomnia.

Efficacy and Safety of Triptorelin 3-Month Formulation in Chinese Children with Central Precocious Puberty: A Phase 3, Open-Label, Single-Arm Study.

INTRODUCTION: Triptorelin is available as 1- and 3-month prolonged-release (PR) formulations; at the time of the study, only the former was approved for central precocious puberty (CPP) in China. This study assessed the efficacy and safety of the triptorelin 3-month PR formulation in Chinese children with CPP. METHODS: In this 12-month, prospective, open-label, multicentre, single-arm study (NCT04736602), Chinese children (mean age [standard deviation (SD)], 7.6 ± 0.8 years) with CPP received triptorelin pamoate 15 mg on day 1 and at months 3, 6 and 9. The primary endpoint was the proportion with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 3 IU/L after gonadotropin-releasing hormone [GnRH] stimulation) at month 3. Secondary endpoints included changes from baseline in hormone levels and clinical parameters, as well as safety assessments. RESULTS: Overall, 32 children were enrolled, including three boys. LH suppression to prepubertal levels (≤ 3 IU/L) after GnRH stimulation was observed in 100%, 93.5% and 93.5% of participants at months 3, 6 and 12, respectively. Basal and peak LH and follicle-stimulating hormone levels were substantially suppressed at months 3, 6 and 12, and most participants showed sex hormone suppression. At months 6 and 12 respectively 92.9% and 89.3% of girls had stable breast development, and all boys had stable genital development. There was a decrease in mean growth velocity from baseline (8.96 cm/year) to months 3, 6 and 12 (8.07, 5.24 and 6.94 cm/year, respectively). The mean difference between bone and chronological age decreased from baseline (2.85 years) to month 12 (2.39 years). In girls, uterine length was stable or reduced at month 12; in boys, testicular volume was reduced. Triptorelin was well tolerated. CONCLUSION: The triptorelin 3-month PR formulation demonstrated similar efficacy to that previously reported in non-Chinese patients with CPP and had an acceptable safety profile. This supports triptorelin 3-month PR as a viable option for Chinese children with CPP.

Central precocious puberty (CPP) occurs when the reproductive organs and secondary sexual characteristics develop too early in children (before 8 years old in girls or 9 years old in boys). It can cause significant psychological harm and may lead to health problems later in life. Triptorelin is a type of treatment designed to suppress the hormonal activity responsible for CPP and therefore slow down early pubertal development. Triptorelin can be given as an injection into muscle every month or every 3 months; the 3-monthly formulation is commonly used in many countries but at the time of this study it was not licensed for patients with CPP in China. Our trial assessed the effect of triptorelin treatment every 3 months for 1 year in 32 Chinese children with CPP. For all patients who had measurements available, 3-monthly triptorelin suppressed luteinizing hormone­a key hormone involved in CPP­to below typical prepubertal levels. Other hormones involved in puberty were also suppressed. Children experienced a slowing down of the development of secondary sexual characteristics (breasts, genitals and pubic hair), and stabilization or reduction in the size of internal sexual organs (uterine length in girls and testicular volume in boys). Their height also increased less rapidly than previously. There were no concerning side effects of triptorelin treatment, and the safety profile matched that seen in other countries where triptorelin is widely used for CPP. Overall, our study findings suggest that the 3-monthly triptorelin formulation may be a good option for Chinese children with CPP.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM. MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage. RESULTS: PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times. CONCLUSION: A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.

A critical role of RUNX1 in governing megakaryocyte-primed hematopoietic stem cell differentiation.

As a transcription factor in the RUNT domain core-binding factor family, RUNX1 is crucial in multiple stages of hematopoiesis, and its mutation can cause familial platelet disorder with a predisposition to acute myeloid leukemia. Previous work has established that RUNX1 is involved in the maturation of megakaryocytes (MKs) and the production of platelets. Recent studies have shown that there exists a subpopulation of hematopoietic stem cells (HSCs) with relatively high expression of von Willebrand factor and CD41 at the apex of the HSC hierarchy, termed MK-HSCs, which can give rise to MKs without going through the traditional differentiation trajectory from HSC via MPP (multipotent progenitors) and MEP (megakaryocyte-erythroid progenitor). Here, by using Runx1F/FMx1-Cre mouse model, we discovered that the MK-HSC to MK direct differentiation can occur within 1 cell division, and RUNX1 is an important regulator in the process. Runx1 knockout results in a drastic decrease in platelet counts and a severe defect in the differentiation from MK-HSCs to MKs. Single cell RNA sequencing (RNAseq) analysis shows that MK-HSCs have a distinct gene expression signature compared with non-MK-HSCs, and Runx1 deletion alters the platelet and MK-related gene expression in MK-HSCs. Furthermore, bulk RNAseq and Cut&Run analyses show that RUNX1 binds to multiple essential MK or platelet developmental genes, such as Spi1, Selp, and Itga2b and regulates their expressions in MK-HSCs. Thus, by modulating the expression of MK-related genes, RUNX1 governs the direct differentiation from MK-HSCs to MKs and platelets.

Identifying the needs of our older community-based patients in the COVID era: A telephone survey.

Background: Older people's vulnerability during a pandemic may extend to social connectedness, access to healthcare, and information delivery. We sought to identify whether and how older community-based patients are maintaining connections and accessing information during COVID-19. Methods: We administered a telephone questionnaire to all patients (or carer/proxy answering 'on patient's behalf') who previously attended our Geriatric Medicine clinic, May-December 2019. Results: Response rate was 58.8% (151/257), carer respondents comprising 23.8% (36/151). Mean patient age was 81.8 years (SD 8.6); 59.6% were female, 15.2% lived alone. English was the preferred language for 72.9% (110/151). Almost half (46.4%, 70/151) felt COVID-related restrictions had impacted them. Thirty-eight percent (58/151) reported feelings of social isolation, most (38/58) reporting this new since COVID. Nonetheless, 92.1% (139/151) reported maintaining social connections, all with family (139/139), less often with friends (69.8%, 97/139). COVID-related information sources included television 68.9% (104/151), family/friends (54.3%), healthcare providers (24.5%), and written sources (21.2%, 32/151); 12.6% used online resources. Increasing age lowered likelihood of accessing online information, while having smartphone/computer increased. Most (82.6%) believed their healthcare needs were being met, and 76.1% had accessed their GP, 87% (100/115) in-person. Only 33.1% (50/151) agreed telehealth acceptable, more often those with smartphone/computer (OR 2.15, p=0.04). Conclusions: Interventions to reduce isolation and optimize connectedness and healthcare- despite physical distancing- are important during COVID-19. During a rapidly evolving pandemic, healthcare delivery and information provision to our older population is likely best served by a multifaceted approach which acknowledges identified preferences, practices and barriers.

Neutrophil transit time and localization within the megakaryocyte define morphologically distinct forms of emperipolesis.

Neutrophils transit through megakaryocytes in a process termed emperipolesis, but it is unknown whether this interaction is a single type of cell-in-cell interaction or a set of distinct processes. Using a murine in vitro model, we characterized emperipolesis by live-cell spinning disk microscopy and electron microscopy. Approximately half of neutrophils exited the megakaryocyte rapidly, typically in 10 minutes or less, displaying ameboid morphology as they passed through the host cell (fast emperipolesis). The remaining neutrophils assumed a sessile morphology, most remaining within the megakaryocyte for at least 60 minutes (slow emperipolesis). These neutrophils typically localized near the megakaryocyte nucleus. By ultrastructural assessment, all internalized neutrophils remained morphologically intact. Most neutrophils resided within emperisomes, but some could be visualized exiting the emperisome to enter the cell cytoplasm. Neutrophils in the cytoplasm assumed close contact with the platelet-forming demarcation membrane system or the perinuclear endoplasmic reticulum. These findings reveal that megakaryocyte emperipolesis reflects at least 2 distinct processes differing in transit time and morphology, fast and slow emperipolesis, suggesting divergent physiologic functions.

Patient-Reported Outcomes for Quality of Life in SLE: Essential in Clinical Trials and Ready for Routine Care.

Patient-reported outcome (PRO) instruments are widely used to assess quality of life in Systemic Lupus Erythematosus (SLE) research, and there is growing evidence for their use in clinical care. In this review, we evaluate the current evidence for their use in assessing quality of life in SLE in both research and clinical settings and examine the different characteristics of the commonly used PRO tools. There are now several well-validated generic and SLE-specific tools that have demonstrated utility in clinical trials and several tools that complement activity and damage measures in the clinical setting. PRO tools may help overcome physician-patient discordance in SLE and are valuable in the assessment of fibromyalgia and type 2 symptoms such as widespread pain and fatigue. Future work will identify optimal PRO tools for different settings but, despite current limitations, they are ready to be incorporated into patient care.

Identifying co-morbid fibromyalgia in patients with systemic lupus erythematosus using the Multi-Dimensional Health Assessment Questionnaire.

OBJECTIVE: Fibromyalgia (FM) is prevalent but often under-recognized in patients with systemic lupus erythematosus (SLE). Patient-reported outcomes (PROs) from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) can identify co-morbid FM in patients with rheumatic diseases. The present study examined the utility of the MDHAQ in recognizing FM in patients with SLE during routine consultations. METHODS: Patients with SLE completed an MDHAQ. FM status was determined by the validated 2016 revision of the ACR 2010/2011 preliminary FM criteria. Individual PROs from the MDHAQ and composite Fibromyalgia Assessment Tool (FAST) indices of the discriminatory PROs were compared between patients with and without FM using Student's unpaired t-test and receiver operating characteristic curve analysis to determine the area under the curve (AUC). The physician's clinical impression of FM was recorded, and the SLE Disease Activity Index was used to assess disease activity. RESULTS: Of 88 patients with SLE, 23 (26%) satisfied the 2016 FM criteria. The FAST3 composite measure of two out of three of pain (≥6/10), joint count (≥16/48) and symptom checklist (≥16/60) correctly classified 89% of patients (AUC=0.90, kappa=0.71). Physician diagnosis demonstrated moderate agreement with the 2016 FM criteria (kappa=0.43) but missed 43% of patients with FM. In the presence of active disease, the FAST3 correctly classified 91% of patients. CONCLUSIONS: Co-morbid FM is prevalent in SLE yet often underdiagnosed by physicians. The simple FAST3 index of the MDHAQ provides an easy-to-use self-reported tool to improve identification of FM in patients with SLE.

Performance Comparison between Polyvinylidene Fluoride and Polytetrafluoroethylene Hollow Fiber Membranes for Direct Contact Membrane Distillation.

Increasing water demand coupled with projected climate change puts the Southwestern United States at the highest risk of water sustainability by 2050. Membrane distillation offers a unique opportunity to utilize the substantial, but largely untapped geothermal brackish groundwater for desalination to lessen the stress. Two types of hydrophobic, microporous hollow fiber membranes (HFMs), including polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF), were evaluated for their effectiveness in direct contact membrane distillation (DCMD). Water flux and salt rejection were measured as a function of module packing density and length in lab-scale systems. The PVDF HFMs generally exhibited higher water flux than the PTFE HFMs possibly due to thinner membrane wall and higher porosity. As the packing density or module length increased, water flux declined. The water production rate per module, however, increased due to the larger membrane surface area. A pilot-scale DCMD system was deployed to the 2nd largest geothermally-heated greenhouse in the United States for field testing over a duration of about 22 days. The results demonstrated the robustness of the DCMD system in the face of environmental fluctuation at the facility.

A smart medication recommendation model for the electronic prescription.

BACKGROUND: The report from the Institute of Medicine, To Err Is Human: Building a Safer Health System in 1999 drew a special attention towards preventable medical errors and patient safety. The American Reinvestment and Recovery Act of 2009 and federal criteria of 'Meaningful use' stage 1 mandated e-prescribing to be used by eligible providers in order to access Medicaid and Medicare incentive payments. Inappropriate prescribing has been identified as a preventable cause of at least 20% of drug-related adverse events. A few studies reported system-related errors and have offered targeted recommendations on improving and enhancing e-prescribing system. OBJECTIVE: This study aims to enhance efficiency of the e-prescribing system by shortening the medication list, reducing the risk of inappropriate selection of medication, as well as in reducing the prescribing time of physicians. METHOD: 103.48 million prescriptions from Taiwan's national health insurance claim data were used to compute Diagnosis-Medication association. Furthermore, 100,000 prescriptions were randomly selected to develop a smart medication recommendation model by using association rules of data mining. RESULTS AND CONCLUSION: The important contribution of this model is to introduce a new concept called Mean Prescription Rank (MPR) of prescriptions and Coverage Rate (CR) of prescriptions. A proactive medication list (PML) was computed using MPR and CR. With this model the medication drop-down menu is significantly shortened, thereby reducing medication selection errors and prescription times. The physicians will still select relevant medications even in the case of inappropriate (unintentional) selection.

Excessive daytime sleepiness and obstructive sleep apnea in patients with sarcoidosis.

BACKGROUND: Systemic symptoms are common in sarcoidosis and are associated with a decreased quality of life. Excessive daytime sleepiness (EDS) often is associated with obstructive sleep apnea (OSA) but may be a systemic symptom independently associated with sarcoidosis. The aim of this study was to assess the relationship between sarcoidosis and EDS. METHODS: In a retrospective analysis, we used Epworth Sleepiness Scale scores to compare sleepiness in 62 patients with sarcoidosis with 1,005 adults without sarcoidosis referred for polysomnography for suspicion of OSA. Linear regression models controlled for covariates. In a subgroup analysis of patients with sarcoidosis, sleepiness scores and polysomnograms were compared between those with normal and those with abnormal pulmonary function based on total lung capacity. RESULTS: EDS was more common in patients with sarcoidosis than in those without, and sarcoidosis remained an independent predictor of increased sleepiness after controlling for covariates. Compared with control patients referred for polysomnography, fewer patients with sarcoidosis had clinically significant OSA. However, among patients with sarcoidosis, OSA was more severe in those with abnormal lung function. CONCLUSIONS: Sarcoidosis is independently associated with EDS. Sleepiness may contribute to the morbidity of sarcoidosis and should be followed even after treating for potentially coexisting OSA or depression. Abnormal lung function in sarcoidosis may contribute to OSA, although the mechanisms for this are not known.

Confirmatory spirometry for adults hospitalized with a diagnosis of asthma or chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD. During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear. Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts. This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation. METHODS: Multi-center study of four academic healthcare institutions. Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation. Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data. Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations. RESULTS: There was an almost perfect agreement for acceptability (κ = 0.92) and reproducibility (κ =0.93) of spirometry tracings. Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality. Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease. Obese patients (BMI ≥30 kg/m2) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007). CONCLUSIONS: Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation. Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese patients.

CT emphysema predicts thoracic aortic calcification in smokers with and without COPD.

COPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects' demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD.

Prostaglandin E2 induces glutamate release from subventricular zone astrocytes.

It was recently reported that in one of the adult neurogenetic zones, the subventricular zone (SVZ), astrocyte-like cells release glutamate upon intracellular Ca2+ increases. However, the signals that control Ca2+ activity and glutamate release from SVZ astrocytes are not known. Here, we examined whether prostaglandin E2 (PGE2), which induces glutamate release from mature astrocytes, is such a signal. Using the gramicidin-perforated patch-clamp technique, we show that the activity of N-Methyl-D-Aspartate receptor (NMDAR) channel in neuroblasts is a high fidelity sensor of ambient glutamate levels. Using such sensors, we found that application of PGE2 led to increased ambient glutamate levels in the SVZ. In parallel experiments, PGE2 induced an increase in intracellular Ca2+ levels in SVZ cells, in particular astrocyte-like cells, as shown using Ca2+ imaging. Finally, a PGE2 enzyme immunoassay showed that the choroid plexus of the lateral ventricle and to a lesser extent the SVZ (ten-fold less) released PGE2. These findings suggest that PGE2 is a physiological signal for inducing glutamate release from SVZ astrocytes that is important for controlling neuroblast survival and proliferation. This signal may be accentuated following ischemia or injury-induced PGE2 release and may contribute to the injury-associated increased neurogenesis.

Recent advances in selective estrogen receptor modulators for breast cancer.

Estrogen has important physiological effects on the growth and function of hormone-dependent tissues, and the link between estrogen and breast cancer has been deciphered at the end of the 20(th) century. Tamoxifen, one of the first generation selective estrogen receptor modulators (SERMs), has been the gold standard of first-line therapeutic drugs for all stages of estrogen-dependent breast cancer and has been found to reduce the incidence of breast cancer in high-risk pre- and postmenopausal women. Raloxifene, a second-generation SERM, was recently approved by FDA to decrease the risk of invasive breast cancer in postmenopausal women. During these years, many other novel types of SERAMs are being studied. This review highlights their recent advances. The discovery of selective estrogen receptor alpha modulators (SERAMs) and the latest information about their clinical and preclinical trials will be introduced intensively.