The Modulation of Respiratory Epithelial Cell Differentiation by the Thickness of an Electrospun Poly-ε-Carprolactone Mesh Mimicking the Basement Membrane.

The topology of the basement membrane (BM) affects cell physiology and pathology, and BM thickening is associated with various chronic lung diseases. In addition, the topology of commercially available poly (ethylene terephthalate) (PET) membranes, which are used in preclinical in vitro models, differs from that of the human BM, which has a fibrous and elastic structure. In this study, we verified the effect of BM thickness on the differentiation of normal human bronchial epithelial (NHBE) cells. To evaluate whether the thickness of poly-ε-carprolactone (PCL) mesh affects the differentiation of NHBE cells, cells were grown on thin- (6-layer) and thick-layer (80-layer) meshes consisting of electrospun PCL nanofibers using an air-liquid interface (ALI) cell culture system. It was found that the NHBE cells formed a normal pseudostratified epithelium composed of ciliated, goblet, and basal cells on the thin-layer PCL mesh; however, goblet cell hyperplasia was observed on the thick-layer PCL mesh. Differentiated NHBE cells cultured on the thick-layer PCL mesh also demonstrated increased epithelial-mesenchymal transition (EMT) compared to those cultured on the thin-layer PCL mesh. In addition, expression of Sox9, nuclear factor (NF)-κB, and oxidative stress-related markers, which are also associated with goblet cell hyperplasia, was increased in the differentiated NHBE cells cultured on the thick-layer PCL mesh. Thus, the use of thick electrospun PCL mesh led to NHBE cells differentiating into hyperplastic goblet cells via EMT and the oxidative stress-related signaling pathway. Therefore, the topology of the BM, for example, thickness, may affect the differentiation direction of human bronchial epithelial cells.

Wearing a back-support exoskeleton alters lower-limb joint kinetics during single-step recovery following a forward loss of balance.

We assessed the effects of a passive, back-support exoskeleton (BSE) on lower-limb joint kinetics during the initiation and swing phases of recovery from a forward loss of balance. Sixteen (8M, 8F) young, healthy participants were released from static forward-leaning postures and attempted to recover their balance with a single-step while wearing a BSE (backXTM) with different levels of support torque and in a control condition. The BSE provided âˆ¼ 15-20 Nm of external hip extension torque on the stepping leg at the end of initiation and beginning of swing phases. Participants were unable to generate sufficient hip flexion torque, power, and work to counteract this external torque, although they sustained hip flexion torque for a more prolonged period, resulting in slightly increased hip contribution to positive leg work (compared to control). However, net positive leg work, and the net contribution of hip joint (human + BSE) to total leg work decreased with BSE use. While all participants had changes in hip joint kinetics, a significant compensatory increase in ankle contribution to positive leg work was observed only among females. Our results suggest that BSE use adversely affects reactive stepping by decreasing the stepping leg kinetic energy for forward propulsion, and that the relative contributions of lower-limb joints to total mechanical work done during balance recovery are altered by BSE use. BSEs may thus need to be implemented with caution for dynamic tasks in occupational settings, as they may impair balance recovery following a forward loss of balance.

Depression and Subclinical Coronary Atherosclerosis in Adults Without Clinical Coronary Artery Disease.

BACKGROUND: The relationship between depression and subclinical coronary atherosclerosis in asymptomatic individuals is not clear. We evaluated this relationship in a Korean population. METHODS AND RESULTS: We analyzed 3920 individuals (mean age 54.7±7.9 years and 2603 men [66.4%]) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography and screening for depression using the Beck Depression Inventory as part of a general health examination. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography, and ≥50% diameter stenosis was defined as significant. Participants were categorized into groups of those with or without depression using the Beck Depression Inventory scores ≥16 as a cutoff value. Of the study participants, 272 (6.9%) had a Beck Depression Inventory score of 16 or higher. After adjustment for cardiovascular risk factors, depression was not significantly associated with any coronary plaque (adjusted odds ratio [OR], 1.05 [95% CI, 0.78-1.41]; P=0.746), calcified plaque (OR, 0.95 [95% CI, 0.71-1.29]; P=0.758), noncalcified plaque (OR, 1.31 [95% CI, 0.79-2.17]; P=0.305), mixed plaque (OR, 1.16 [95% CI, 0.60-2.23]; P=0.659), or significant coronary artery stenosis (OR, 1.22 [95% CI, 0.73-2.03]; P=0.450). In the propensity score-matched population (n=1318) as well, none of the coronary artery disease measures of subclinical coronary atherosclerosis were statistically significantly associated with depression (all P>0.05). CONCLUSIONS: In this large cross-sectional study with asymptomatic individuals undergoing coronary computed tomographic angiography and Beck Depression Inventory evaluation, depression was not associated with an increased risk of subclinical coronary atherosclerosis.

Surgery-related anxiety regarding arthroscopic meniscectomy under general anesthesia: a retrospective observational study.

BACKGROUND: The prevalence of anxiety among patients undergoing arthroscopic surgery and its association with postoperative function has been well documented; however, the level of anxiety and anxiety-related characteristics remain unclear. As such, the present study investigated the characteristics of state anxiety in patients undergoing arthroscopic meniscectomy. METHODS: Data from 75 patients, who underwent arthroscopic partial meniscectomy under general anesthesia and completed an anxiety status questionnaire between April 2021 and March 2022, were retrospectively collected and reviewed. The State-Trait Anxiety Inventory (STAI)-X was used to measure state anxiety; a total score ≥ 52 was defined as clinically meaningful state anxiety. STAI score, main cause of preoperative anxiety, most anxious period, and most helpful factors for reducing perioperative anxiety were investigated. Patients were divided into 2 groups according to the main cause of preoperative anxiety; surgery or anesthesia (group I [n = 47]); and postoperative pain or rehabilitation (group II [n = 28]) Characteristics of state-anxiety between the two groups were compared using independent t-tests. RESULTS: The mean STAI score of the total population was 39.1 points (range, 20-60 points). The mean STAI score was significantly higher in group I than in group II (41.9 vs. 34.4 points, respectively; P < 0.001). The proportion of patients with clinically meaningful state anxiety was significantly higher in group I than in group II (23.4% vs. 3.6%, respectively, P = 0.02). Most patients (66.0% in group I and 50.0% in group II) responded that trust in medical staff was the most helpful factor in overcoming preoperative anxiety. In group I, 63.8% reported that the surgeon's explanation was the most helpful factor in reducing postoperative anxiety, whereas in group II, 71.4% reported that the natural course after surgery was the most helpful factor. CONCLUSIONS: Surgeons should be aware that anxiety related to arthroscopic meniscectomy differs according to patient characteristics, and a preoperative explanation of the postoperative process with the surgeon is important for patients who experience preoperative anxiety regarding anesthesia or the surgery itself.

Influence of Intolerance of Uncertainty on Preoccupation With Coronavirus Disease 2019 Among Frontline Nursing Professionals: Mediating Role of Reassurance-Seeking Behavior and Adherence to Physical Distancing.

BACKGROUND: This study investigated the relationship between preoccupation with coronavirus disease 2019 (COVID-19), reassurance-seeking behavior, viral anxiety, intolerance of uncertainty, and adherence to physical distancing among frontline nursing professionals working in COVID-19 inpatient wards. Additionally, the study aimed to determine whether the commitment to physical distancing mediates the influence of intolerance of uncertainty on viral anxiety. METHODS: Frontline healthcare professionals working in the COVID-19 inpatient wards at three tertiary-level affiliated hospitals in Korea were surveyed between April 7 and 26, 2022. The survey included scales-such as the Obsession with COVID-19 Scale, Coronavirus Reassurance-Seeking Behaviors Scale, Fear of COVID-19 Scale, and Intolerance of Uncertainty Scale-12 and a questionnaire on adherence to physical distancing. A total of 256 responses were analyzed after excluding inappropriate or incomplete responses. RESULTS: Pearson's correlation analysis found that age was significantly associated with the Obsession with COVID-19 Scale (r = -0.12, P < 0.05) and adherence to physical distancing (r = 0.27, P < 0.01). Linear regression analysis ascertained that age (ß = -0.07, P = 0.002), Coronavirus Reassurance-Seeking Behaviors Scale (ß = 0.35, P < 0.001), and Fear of COVID-19 Scale (ß = 0.24, P < 0.001) were predictors of obsession with COVID-19 (Adjusted R² = 0.60, F = 78.1, P < 0.001). The indirect pathway by mediation analysis showed that reassurance-seeking and viral anxiety mediated the effect of intolerance of uncertainty on the preoccupation with COVID-19. CONCLUSION: During the pandemic, there may be a strong association between reassurance-seeking behavior, viral anxiety, and a heightened preoccupation with COVID-19 among frontline healthcare workers. Thus, from the early stages of infectious disease, a psychological support team for medical staff responding to the disease should be established, and periodic evaluations should be conducted to identify high-risk groups.

Efficacy of ferric carboxymaltose in iron deficiency anemia patients scheduled for pancreaticoduodenectomy.

Purpose: Perioperative transfusion is reported to be an independent risk factor not only for postoperative complications but also for early recurrence of periampullary carcinoma after pancreaticoduodenectomy (PD). The purpose of this study was to evaluate the safety and efficacy of ferric carboxymaltose (FCM) in reducing the need for perioperative transfusion in iron deficiency anemia patients scheduled for PD. Methods: Twenty-two male patients (hemoglobin [Hb] 7 to <13 g/dL) and 18 female patients (Hb 7 to <12 g/dL) were enrolled in the study group and administered FCM 1-3 weeks before PD. The perioperative transfusion rate was the primary endpoint; morbidity, length of postoperative hospital stay, change in hematological parameters after FCM injection, and adverse effects of FCM were also investigated. Results: The perioperative transfusion rate of the study group was 22.5% (9 of 40). Hb level was significantly higher on the day of the operation compared to baseline (P < 0.001). Levels of Hb, transferrin saturation, and ferritin were higher at the follow-up compared to baseline (P = 0.008, P = 0.033, and P < 0.001, respectively). Conclusions: FCM administration was associated with a reduced need for perioperative transfusion and can safely stabilize hematological parameters.

Impact of Resilience and Viral Anxiety on Psychological Well-Being, Intrinsic Motivation, and Academic Stress in Medical Students During the COVID-19 Pandemic.

OBJECTIVE: We aimed to explore the association between academic stress or motivation and the psychological well-being of medical students during the coronavirus disease-2019 (COVID-19) pandemic. We also explored the effects of their resilience or viral anxiety on this association. METHODS: This online surveyed for medical students was done during October 20-28, 2021. Participants' age, sex, grades, and COVID-19-related experiences were collected. Their symptoms were measured with Stress and Anxiety to Viral Epidemics-6 items, Medical Stress Scale (MSS), intrinsic motivation using Academic Motivation Scale, Connor Davidson Resilience Scale-2 items (CD-RISC2), the 5-item World Health Organization Well-Being Index (WHO-5), and GRIT scale. RESULTS: Among 251 medical students, linear regression performed to explore the predicting factors for psychological well-being or medical stress showed that WHO-5 score was predicted by age (ß=0.16, p=0.02) and CD-RISC2 (ß=0.29, p<0.001) (F=15.5, p<0.001). In addition, the MSS score was predicted by age (ß=0.20, p=0.004), intrinsic motivation (ß=-0.31, p<0.001), GRIT (ß=0.21, p=0.003), and CD-RISC2 (ß=-0.31, p<0.001) (F=15.6, p<0.001). The resilience of medical students partially influenced their intrinsic motivation, affecting their psychological well-being or academic stress. However, no significant association was observed in the case of viral anxiety as a mediator, indicating that viral anxiety did not mediate the association. CONCLUSION: This study highlights the importance of resilience in mediating the relationship between intrinsic motivation and psychological well-being or academic stress. However, viral anxiety was not found to be a mediator in this relationship.

Validation of the healthcare workers' version of the Pandemic Grief Scale among frontline nursing professionals during the COVID-19 pandemic in Korea.

Introduction: Nurses have been repeatedly exposed to unexpected death and grief during COVID-19 pandemic, and it is necessary to provide grief support for the nurses who have experienced the loss of patients to COVID-19. We aimed to explore the reliability and validity of the Pandemic Grief Scale (PGS) for Healthcare Workers among frontline nursing professionals working in COVID-19 inpatient wards whose patients may have died. Methods: An anonymous online survey was performed among frontline nursing professionals working in COVID-19 wards in three tertiary-level general hospitals in Korea between April 7 and 26, 2021. In total, 229 from participants who confirmed they had witnessed death of patients were employed for the statistical analysis. The survey included demographic characteristics and rating scales, including the Korean version of the PGS for Healthcare Workers, the Fear of COVID-19 scale, the Generalized Anxiety Disorder-7 items, and the Patient Health Questionnaire-9 items. Results: The single-factor structure of the Korean version of the PGS for Healthcare Workers showed good fits for the model. The scale had good internal consistency and convergent validity with other anxiety and depression scales. Conclusion: The Korean version of the PGS of Healthcare Workers was valid and reliable for measuring grief reactions among nursing professionals facing the pandemic. It will be helpful in evaluating the grief reaction of the healthcare workers and providing them with a psychological support system.

Grief Response of Nursing Professionals Is Associated With Their Depression, Loneliness, Insomnia, and Work-Related Stress While Working in COVID-19 Inpatients Wards.

OBJECTIVE: We aimed to explore whether nursing professionals' psychological states affect their grief response for a patient's death in the coronavirus disease-2019 (COVID-19) inpatients' ward. METHODS: Survey was conducted among frontline nursing professionals working in COVID-19 inpatients wards at three tertiary-level affiliated hospitals of the University of Ulsan during April 7-26, 2022. Participants' information such as age, years of employment, or marital status were collected, and their responses to rating scales including Pandemic Grief Scale (PGS) for healthcare workers, Stress and Anxiety to Viral Epidemics-9 items (SAVE-9), Patient Health Questionnaire-9 (PHQ-9), Loneliness and Social Isolation Scale, and Insomnia Severity Scale (ISI) were collected. RESULTS: All 251 responses were analyzed. We observed that 34% reportedly suffered from depression. The linear regression analysis showed that a high PGS score was expected by high SAVE-9 (ß=0.12, p=0.040), high PHQ-9 (ß=0.25, p<0.001), high loneliness (ß=0.17, p=0.006), and high ISI score (ß=0.16, p=0.006, F=20.05, p<0.001). The mediation analysis showed that the depression of nursing professionals directly influenced their pandemic grief reaction, and their work-related stress and viral anxiety, insomnia severity, and loneliness partially mediated the association. CONCLUSION: We confirm that frontline nursing professionals' depression directly influenced their grief reaction, and their work-related stress and viral anxiety, insomnia severity, and loneliness partially mediated the association. We hope to establish a psychological and social support system for the mental health of nurses working in the COVID-19 wards.

Surgery-related anxiety on geriatric patients undergoing total knee arthroplasty: a retrospective observational study.

BACKGROUND: The prevalence of anxiety in patients undergoing total knee arthroplasty (TKA) and its association with postoperative functions are well known; however, the levels of anxiety or anxiety-related characteristics are unknown. This study aimed to investigate the prevalence of clinically significant state anxiety in geriatric patients undergoing TKA for osteoarthritis (OA) of the knee and to evaluate the anxiety-related characteristics experienced by these patients pre- and post-operatively. METHODS: This retrospective observational study recruited patients who had undergone TKA for knee OA using general anesthesia between February 2020 and August 2021. The study participants were geriatric patients older than 65 years who had moderate or severe OA. We evaluated patient characteristics including age, sex, body mass index, smoking status, hypertension, diabetes, and cancer. We assessed their levels of anxiety status using the STAI-X which comprises 20-item scales. Clinically meaningful state anxiety was defined as a total score of 52 or higher. An independent Student's t-test was used to determine differences of STAI score between subgroups in terms of patient characteristics. And patients were asked to complete questionnaires, which assessed four areas: (1) the main cause of anxiety; (2) the most helpful factor in overcoming anxiety before surgery; (3) the most helpful factor in reducing anxiety after surgery; and (4) the most anxious moment during the entire process. RESULTS: The mean STAI score of patients who underwent TKA was 43.0 points and 16.4% of patients experienced clinically significant state anxiety. The current smoking status affect STAI score and the proportion of patients with clinically meaningful state anxiety. The most common cause of preoperative anxiety was the surgery itself. Overall, 38% of patients reported that they experienced the greatest level of anxiety when the surgeon had recommended TKA in the outpatient clinic. The trust in the medical staff before surgery and the surgeon's explanations after surgery helped the most in reducing anxiety. CONCLUSIONS: One in six patients before TKA experience clinically meaningful state anxiety, and about 40% of patients experience anxiety from the time they are recommended for surgery. Patients tended to overcome anxiety before TKA through trust in the medical staff, and the surgeon's explanations after surgery was found to be helpful in reducing anxiety.

MYC Overexpression Drives Immune Evasion in Hepatocellular Carcinoma That Is Reversible through Restoration of Proinflammatory Macrophages.

Cancers evade immune surveillance, which can be reversed through immune-checkpoint therapy in a small subset of cases. Here, we report that the MYC oncogene suppresses innate immune surveillance and drives resistance to immunotherapy. In 33 different human cancers, MYC genomic amplification and overexpression increased immune-checkpoint expression, predicted nonresponsiveness to immune-checkpoint blockade, and was associated with both Th2-like immune profile and reduced CD8 T-cell infiltration. MYC transcriptionally suppressed innate immunity and MHCI-mediated antigen presentation, which in turn impeded T-cell response. Combined, but not individual, blockade of PDL1 and CTLA4 could reverse MYC-driven immune suppression by leading to the recruitment of proinflammatory antigen-presenting macrophages with increased CD40 and MHCII expression. Depletion of macrophages abrogated the antineoplastic effects of PDL1 and CTLA4 blockade in MYC-driven hepatocellular carcinoma (HCC). Hence, MYC is a predictor of immune-checkpoint responsiveness and a key driver of immune evasion through the suppression of proinflammatory macrophages. The immune evasion induced by MYC in HCC can be overcome by combined PDL1 and CTLA4 blockade. SIGNIFICANCE: Macrophage-mediated immune evasion is a therapeutic vulnerability of MYC-driven cancers, which has implications for prioritizing MYC-driven hepatocellular carcinoma for combination immunotherapy.

Impact of single-nucleotide polymorphisms on tacrolimus pharmacokinetics in liver transplant patients after switching to once-daily dosing.

BACKGROUND: The effects of multidrug resistance-1 (MDR1), ABCC2, and P450 oxidoreductase (POR)*28 gene polymorphisms on tacrolimus metabolism following a switch to once-daily dosing have not been elucidated. We investigated the effects of recipient and donor CYP3A5, MDR1, ABCC2, and POR*28 polymorphisms on tacrolimus pharmacokinetics following a switch to once-daily tacrolimus dosing. METHODS: Eighty-seven liver transplant recipients who were switched from twice- to once-daily tacrolimus dosing following living-donor liver transplantation and 81 matched donors were genotyped for CYP3A5, MDR1 (1236C>T, 2677G>T/A, and 3435C>T), ABCC2 (-24C>T, 1249G>A, and 3972C>T), and POR*28. Tacrolimus dose-adjusted trough levels (C0/dose) before and after the switch were determined and calculated based on past medical records. Recipients were divided into two groups, one group constituted of 38 patients with a C0/dose decrease of less than 30% following conversion (group 1) and the other constituted of 49 patients with a C0/dose decrease of ≥ 30% (group 2). RESULTS: CYP3A5 *1/*3 and *3/*3 were more frequent in recipients in group 1 (60.5% vs. 36.8%), while CYP3A5 *1/*1 was more frequent in group 2 (59.2% vs. 32.7%) (p = 0.016). The proportions of donor ABCC2 1249G>A genotypes AA and AG were higher in group 2 than in group 1 (20.4% vs. 5.3%; p = 0.042). CONCLUSION: Recipient CYP3A5 polymorphism and donor ABCC2 1249G>A polymorphism affected tacrolimus pharmacokinetics following the switch to once-daily dosing. Dose adjustment to maintain therapeutic tacrolimus levels following the switch to once-daily dosing should be considered based on polymorphisms in both the recipient and donor.

A novel approach to quantify the assistive torque profiles generated by passive back-support exoskeletons.

Industrial exoskeletons are a promising ergonomic intervention to reduce the risk of work-related musculoskeletal disorders by providing external physical support to workers. Passive exoskeletons, having no power supplies, are of particular interest given their predominance in the commercial market. Understanding the mechanical behavior of the torque generation mechanisms embedded in passive exoskeletons is, however, essential to determine the efficacy of these devices in reducing physical loads (e.g., in manual material handling tasks). We introduce a novel approach using a computerized dynamometer to quantify the assistive torque profiles of two passive back-support exoskeletons (BSEs) at different support settings and in both static and dynamic conditions. The feasibility of this approach was examined using both human subjects and a mannequin. Clear differences in assistive torque magnitudes were evident between the two BSEs, and both devices generated more assistive torques during trunk/hip flexion than extension. Assistive torques obtained from human subjects were often within similar ranges as those from the mannequin, though values were more comparable over a narrow range of flexion/extension angles due to practical limitations with the dynamometer and human subjects. Characterizing exoskeleton assistive torque profiles can help in better understanding how to select a torque profile for given task requirements and user anthropometry, and aid in predicting the potential impacts of exoskeleton use by incorporating measured torque profiles in a musculoskeletal modeling system. Future work is recommended to assess this approach for other occupational exoskeletons.

Wearing a back-support exoskeleton impairs single-step balance recovery performance following a forward loss of balance - An exploratory study.

Back-support exoskeletons (BSEs) are a promising ergonomic intervention for reducing physical demands on the low-back, but little is known regarding whether BSE use alters balance recovery following external perturbations. Hence, we investigated the effects of wearing a BSE on single-step balance recovery following a forward loss of balance. Sixteen (8 M, 8F) young, healthy participants were released from static forward-leaning postures and attempted to recover their balance with a single step while wearing a BSE (backXTM) with three different levels of support torque (i.e., no torque, low, and high) and in a control condition (no exoskeleton). Lean angle was increased until they failed in two consecutive trials to recover their balance with a single step. The maximum lean angle from which individuals could successfully recover was not significantly altered when wearing the BSE. However, wearing the BSE under all torque conditions increased reaction times. The BSE also impeded hip flexion (i.e., decrease in both peak hip flexion angle and angular velocity), resulting in decreased peak knee flexion velocity, knee range of motion, and step length. Measures of the margin of stability decreased significantly in the high-torque BSE condition. Overall, our results suggest that use of a BSE that provides external hip extension torque impairs balance recovery responses. Future work extending kinetic analyses to recovery responses, as well as a study of recovery when responding to slips and trips while walking, would offer a more complete picture of how a BSE may impact balance recovery following a loss of balance.

The Mediating Effect of Reassurance-Seeking Behavior on the Influence of Viral Anxiety and Depression on COVID-19 Obsession Among Medical Students.

Objectives: Healthcare workers experienced great psychological burden due to the continuation of the COVID-19 pandemic. During the pandemic, medical healthcare workers experienced greater instances of insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms than the general population. This study aimed to explore the association between viral anxiety and obsession with COVID-19 among medical students with reassurance-seeking behavior as a mediator. Methods: In October 2021, an online survey was conducted among medical students at the University of Ulsan College of Medicine. The clinical characteristics of 162 participants and their responses to rating scales, including stress and anxiety to viral Epidemics-6 items (SAVE-6), Coronavirus Reassurance-Seeking Behaviors Scale (CRBS), Patient Health Questionnaire-9 items (PHQ-9), and Obsession with COVID-19 scale were collected. Results: Medical students' obsession with COVID-19 was based on the PHQ-9 (ß = 0.15, p = 0.01), SAVE-6 (ß = 0.43, p < 0.001), and CRBS (ß = 0.38, p < 0.001) scores (adjusted R2 = 0.49, F = 39.9, p < 0.001). Mediation analysis showed that medical students' viral anxiety and depression directly influenced their obsession with COVID-19, and their reassurance-seeking behavior partially mediated the effects of depression or viral anxiety on obsession with COVID-19. Conclusions: Medical students' viral anxiety and depression may affect their obsession with COVID-19, and reassurance-seeking behaviors may mediate this. Therefore, medical students should adopt adaptive coping strategies to prevent high levels of viral anxiety and recurrent reassurance-seeking behavior.

Mediating Effect of Viral Anxiety and Perceived Benefits of Physical Distancing on Adherence to Distancing Among High School Students Amid COVID-19.

BACKGROUND: The aim of this study is to explore whether high school students' adherence to physical distancing was associated with health beliefs, social norms, and psychological factors during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Overall, 300 high school students participated in this anonymous online survey conducted from October 18-24, 2021. The survey included rating scales such as attitude toward physical distancing during the pandemic, Stress and Anxiety to Viral Epidemics-6 items (SAVE-6), Patient Health Questionnaire-9 items, Satisfaction with Life Scale, and Connor Davidson Resilience Scale 2-items. RESULTS: The results revealed that perceived susceptibility or severity (ß = -0.13, P = 0.038), perceived benefit (ß = 0.32, P < 0.001), descriptive social norms (ß = 0.10, P = 0.041), social injunctive norms (ß = 0.19, P < 0.001), and SAVE-6 (ß = 0.24, P < 0.001) predicted students' adherence to physical distancing (adjusted R² = 0.42, F = 19.2, P < 0.001). Social injunctive norms and personal injunctive norms directly influenced adherence to physical distancing. Viral anxiety, measured by SAVE-6, mediated the association between social injunctive norms and adherence to physical distancing, and perceived benefits mediated the relationship between personal injunctive norms and adherence to physical distancing. The influence of perceived susceptibility or severity on adherence to physical distancing was entirely mediated by perceived benefits or viral anxiety. CONCLUSION: Explaining the rationale or benefits of physical distancing may be important in increasing adherence to physical distancing among high school students.

Effect of perioperative fluid volume restriction on the incidence of complications following pancreaticoduodenectomy.

BACKGROUND: Perioperative fluid restriction has been suggested to reduce morbidity and length of stay. The purpose of this study was to compare the morbidity following pancreaticoduodenectomy (PD) between fluid restriction group and conventional management group. METHODS: Seventy-two patients were enrolled for perioperative fluid restriction of PD. During the operation, main fluid was infused at a rate of less than 8 mL/kg/hr. Until POD#3, 10% dextrose and Hartmann's solution were administered at rates of 40 mL/h and {(1.5*body weight) - 42} mL/h, respectively. The historical control group consisted of 139 patients. We compared the rates of major complication (Clavien-Dindo grade III to V) and clinically relevant postoperative pancreatic fistula (CR-POPF), length of hospital stays (LOS), amount of urine output, and the rate of acute kidney injury (AKI). RESULTS: The rates of major complication (19.0% versus 18.7%; p > 0.999), CR-POPF (15.5% versus 15.1%; p > 0.999), and LOS (19 days [range: 10-52] versus 19 days [range: 11-75]; p = 0.514) were comparable in the study and the control group, respectively. Amount of urine output during the operation and from POD#1 to POD#3 was more than minimal amount (0.5 mL/kg/hr) in the both groups. Incidence rate of AKI in the study group was not higher than the control group (Stage I: 1.7% versus 2.9%, p > 0.999; stage II: 0% versus 1.4%, p > 0.999). CONCLUSION: There was no decrease in incidence of morbidity including POPF following PD with perioperative fluid restriction. Fluid restriction was feasible because it did not reduce urine output and did not increase incidence of AKI.

Effects of Back-Support Exoskeleton Use on Lower Limb Joint Kinematics and Kinetics During Level Walking.

We assessed the effects of using a passive back-support exoskeleton (BSE) on lower limb joint kinematics and kinetics during level walking. Twenty young, healthy participants completed level walking trials while wearing a BSE (backXTM) with three different levels of hip-extension support torque (i.e., no torque, low, and high) and in a control condition (no-BSE). When hip extension torques were required for gait-initial 0-10% and final 75-100% of the gait cycle-the BSE with high supportive torque provided ~ 10 Nm of external hip extension torque at each hip, resulting in beneficial changes in participants' gait patterns. Specifically, there was a ~ 10% reduction in muscle-generated hip extension torque and ~ 15-20% reduction in extensor power. During the stance-swing transition, however, BSE use produced undesirable changes in lower limb kinematics (e.g., 5-20% increase in ankle joint velocity) and kinetics (e.g., ~ 10% increase in hip flexor, knee extensor, and ankle plantarflexor powers). These latter changes likely stemmed from the need to increase mechanical energy for propelling the leg into the swing phase. BSE use may thus increase the metabolic cost of walking. Whether such use also leads to muscle fatigue and/or postural instability in long-distance walking needs to be confirmed in future work.

Fate of Surgical Patients with Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An International Study Using Multi-Institutional Registries.

Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aims to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. The median age was 56 (range 16-80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (>1.5 cm; HR 4.28, 95% CI 1.80-10.18, p = 0.001) and nodal metastasis (HR 3.32, 95% CI 1.29-8.50, p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (HR 4.36, 95% CI 1.48-12.87, p = 0.008) and high Ki-67 index (≥3%; HR 9.06, 95% CI 3.01-27.30, p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5 cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs.

Anti-PD-L1 F(ab) Conjugated PEG-PLGA Nanoparticle Enhances Immune Checkpoint Therapy.

Background: Immune checkpoint therapies are effective in the treatment of a subset of patients in many different cancers. Immunotherapy offers limited efficacy in part because of rapid drug clearance and off-target associated toxicity. PEG-PLGA is a FDA approved, safe, biodegradable polymer with flexible size control. The delivery of immune checkpoint inhibitors such as anti-PD-L1 (α-PD-L1) via PEG-PLGA polymer has the potential to increase bioavailability and reduce immune clearance to enhance clinical efficacy and reduce toxicity. Methods: The Fc truncated F(ab) portion of α-PD-L1 monoclonal antibody (α-PD-L1 mAb) was attached to a PEG-PLGA polymer. α-PD-L1 F(ab)-PEG-PLGA polymers were incubated in oil-in-water emulsion to form a α-PD-L1 F(ab)-PEG-PLGA nanoparticle (α-PD-L1 NP). α-PD-L1 NP was characterized for size, polarity, toxicity and stability. The relative efficacy of α-PD-L1 NP to α-PD-L1 mAb was measured when delivered either intraperitoneally (IP) or intravenously (IV) in a subcutaneous mouse colon cancer model (MC38). Antibody retention was measured using fluorescence imaging. Immune profile in mice was examined by flow cytometry and immunohistochemistry. Results: Engineered α-PD-L1 NP was found to have pharmacological properties that are potentially advantageous compared to α-PD-L1 mAb. The surface charge of α-PD-L1 NP was optimal for both tumor cell uptake and reduced self-aggregation. The modified size of α-PD-L1 NP reduced renal excretion and mononuclear phagocyte uptake, which allowed the NP to be retained in the host system longer. α-PD-L1 NP was non-toxic in vitro and in vivo. α-PD-L1 NP comparably suppressed MC38 tumor growth. α-PD-L1 NP appeared to elicit an increased immune response as measured by increase in germinal center area in the spleen and in innate immune cell activation in the tumor. Finally, we observed that generally, for both α-PD-L1 NP and α-PD-L1 mAb, the IP route was more effective than IV route for tumor reduction. Conclusion: α-PD-L1 NP is a non-toxic, biocompatible synthetic polymer that can extend α-PD-L1 antibody circulation and reduce renal clearance while retaining anti-cancer activity and potentially enhancing immune activation.