Short Rest Between Flights Is Associated With Increased Serum Stress Hormone Levels in Airline Pilots: A Cross-Sectional Study.

BACKGROUND: Work-related stress is a critical area of research in civil aviation, given the potential for severe consequences when airline pilots (APs) are overwhelmed or unable to perform optimally. While pilots are traditionally considered to be exposed to various stressors, the impact of specific occupational characteristics on stress in the aviation industry remains inadequately understood. Considering that biomarkers are increasingly being utilized as objective measures of stress in human research, this cross-sectional study investigated the association between occupational variables and serum levels of cortisol and dehydroepiandrosterone sulfate (DHEAS) as stress biomarkers in commercial APs. METHODS: A total of 120 male APs completed a survey assessing the following work-related characteristics: position (captain vs. first officer), years of experience, total flight hours, flight hours in the preceding year, inter-flight rest duration, and flight route length. Serum cortisol and DHEAS concentrations were determined from venous blood samples obtained between 08:00 and 09:00 a.m., following a minimum eight-hour fasting period. The biomarker data were analyzed in relation to the aforementioned occupational characteristics. RESULTS: The mean serum cortisol and DHEAS concentrations in the entire cohort were 8.5±2.1 µg/dL and 214.6±96.4 µg/dL, respectively. There were no significant differences in the levels of the two stress hormones in relation to position, years of experience, total flight hours, flight hours in the preceding year, or flight route length. However, an inter-flight rest period of less than one hour was significantly associated with elevated serum cortisol (P<0.01) and reduced DHEAS levels (P<0.001) compared to longer rest durations. Notably, a stepwise decrease in DHEAS concentrations was observed for rest periods of <1 hour, 1-4 hours, 4-24 hours, and >24 hours. After adjustment for potential confounders in multivariable analyses, a rest period of <1 hour remained independently associated with both serum cortisol (odds ratio [OR]=1.09, 95% confidence interval [CI]=1.04-1.13, P<0.01) and DHEAS (OR=0.94, 95% CI=0.92-0.97, P<0.001). CONCLUSIONS: Serum stress hormones in APs are associated with short inter-flight rest periods. Optimization of rest durations may contribute to improved pilot well-being and performance. Further research is warranted to determine ideal rest period lengths and develop interventions to mitigate the potential adverse effects of abbreviated rest periods between flights.

Splice-switching antisense oligonucleotide controlling tumor suppressor REST is a novel therapeutic medicine for neuroendocrine cancer.

RNA splicing regulation has revolutionized the treatment of challenging diseases. Neuroendocrine cancers, including small cell lung cancer (SCLC) and neuroendocrine prostate cancer (PCa), are highly aggressive, with metastatic neuroendocrine phenotypes, leading to poor patient outcomes. We investigated amido-bridged nucleic acid (AmNA)-based splice-switching oligonucleotides (SSOs) targeting RE1-silencing transcription factor (REST) splicing as a novel therapy. We designed AmNA-based SSOs to alter REST splicing. Tumor xenografts were generated by subcutaneously implanting SCLC or PCa cells into mice. SSOs or saline were intraperitoneally administered and tumor growth was monitored. Blood samples were collected from mice after SSO administration, and serum alanine aminotransferase and aspartate aminotransferase levels were measured to assess hepatotoxicity using a biochemical analyser. In vitro, REST_SSO reduced cancer cell viability. In a tumor xenograft model, it exhibited significant antitumor effects. It repressed REST-controlled RE1-harboring genes and upregulated miR-4516, an SCLC biomarker. Our findings suggest that REST_SSO suppresses tumorigenesis in neuroendocrine cancers by restoring REST function. This novel therapeutic approach holds promise for intractable neuroendocrine cancers such as SCLC and neuroendocrine PCa.

EPO modified MSCs protects SH-SY5Y cells against ischemia/hypoxia-induced apoptosis via REST-dependent epigenetic remodeling.

Hypoxic-ischemic encephalopathy (HIE) is a diffuse brain tissue injury caused by acute ischemia and hypoxia, and it is most commonly found in newborn infants but can also occur in adults. Mesenchymal stem cell (MSC) therapies have showed improved outcomes for treating HIE-induced neuronal defects. However, many key issues associated with poor cell viability and tolerance of grafted MSCs after HIE remain to be resolved. Genetic engineering could endow MSCs with more robust regenerative capacities. Our research, along with that of other scientists, has found that the expression of intracellular erythropoietin (EPO) in human umbilical cord MSCs (hUC-MSCs) increases proportionally with the duration of hypoxia exposure. Furthermore, we observed that EPO, when introduced into the EPO gene-modified hUC-MSCs, can be secreted into the extracellular space. However, the underlying mechanisms that support the neuroprotective effects of EPO-MSCs remain unclear. EPO-MSCs, hUC-MSCs, and NC-MSCs were identified by flow cytometry, osteogenic, and adipogenic differentiation assays. The oxygen-glucose deprivation (OGD)-induced SH-SY5Y cell-line was established, and five groups were set up: control, 24-h ischemia-hypoxia, co-cultured with hUC-MSCs, NC-MSCs, and EPO-MSCs after hypoxia. LEGENDplex™ multi-factor flow cytometry was used to detect the secretion of inflammatory factors in cell supernatants and cerebrospinal fluid. Chromosome-targeted excision and tagging (CUT&Tag) sequencing was applied to detect genomic H3K4me2 modifications, and conjoint analysis with transcriptome sequencing (RNA-seq) was performed. Lentiviral vector infection was used to construct SH-SY5Y cells with stable knockdown of RE1-silencing transcription factor (REST), and flow cytometry was used to detect alterations in apoptosis. Finally, the molecular mechanism underlying the neuroprotective and anti-apoptotic effects of EPO-MSCs was investigated using RNA sequencing, qRT-PCR, and western blot assays. Our results suggest that EPO-MSCs are genetically engineered to secrete significantly more EPO. EPO-MSCs treatment has anti-apoptotic properties and offers neuronal protection during ischemic-hypoxic injury. Furthermore, RNA-seq results suggest that multiple inflammation-related genes were down-regulated after EPO-MSCs treatment. Application of RNA-seq and CUT&Tag combined analysis found that the expressions of REST were significantly up-regulated. Lentiviral vector infection to construct REST knockdown SH-SY5Y failed to rescue apoptosis after hypoxia and co-culture with EPO-MSCs, and SETD2-mediated H3K36me3 protein level expression was reduced. EPO-MSCs may promote neuronal survival by affecting H3K4me2 and thus activating the expression of REST and TET3. EPO-MSCs also upregulated the modification level of SETD2-mediated H3K36me3 and regulated the expression of inflammation-related genes such as PLCG2, as well as apoptosis genes BCL2A1. To investigate the neuroprotective effects of EPO-modified hUC-MSCs and the underlying epigenetic regulatory mechanisms, this study aims to provide a theoretical foundation for the potential application of EPO gene-modified hUC-MSCs in the treatment of HIE.

Cognitive correlates of circadian rhythm and sleep-wake behaviour in chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) patients often experience reduced physical activity, sleep disturbances, and cognitive impairment. However, reports on measurement of rest-activity rhythm and sleep-wake behavior and their impact on cognitive functions in COPD patients are limited. This study aimed to objectively measure circadian rhythms (rest-activity and ambient illuminance) and sleep behaviors in clinically stable COPD patients and their relationship with cognitive functions. The study involved 65 male COPD patients and 50 age-matched controls, monitored over 3-7 days using actigraphy. Cognitive status was assessed using the Montreal Cognitive Assessment (MoCA) followed by short interbal time estimation via time production and reproduction with reaction time measurement using TimeProd software. Findings indicated significant disruptions in circadian rhythms in COPD patients, characterized by lower mesor, amplitude, and autocorrelation coefficients compared to controls. Patients also reported poorer sleep quality and higher sleep fragmentation, with 85.7% displaying cognitive impairment. Notably, longer time estimations, increased variability in task performance, and slower reaction times suggested cognitive deterioration. Positive correlations emerged between rhythm parameters (amplitude and circadian quotient) and cognitive performance metrics. This highlights the relevance of circadian and sleep disturbances in COPD, suggesting that addressing these rhythms could help mitigate cognitive decline, potentially through chronotherapeutic strategies.

Association between rest-activity rhythm and diabetic retinopathy among US middle-age and older diabetic adults.

Background: The disruption of circadian rhythm has been reported to aggravate the progression of diabetic retinopathy (DR). Rest-activity rhythm (RAR) is a widely used method for measuring individual circadian time influencing behavior. In this study, we sought to explore the potential association between RAR and the risk of DR. Methods: Diabetic participants aged over 40 from 2011-2014 National Health and Nutrition Examination Survey (NHANES) were enrolled. Data from the wearable device ActiGraph GT3X was used to generate RAR metrics, including interdaily stability (IS), intradaily variability (IV), most active 10-hour period (M10), least active 5-hour period (L5), and Relative amplitude (RA). Weighted multivariable logistic regression analysis and restricted cubic spline analysis were conducted to examine the association between RAR metrics and DR risk. Sensitivity analysis was also conducted to examine the robustness of the findings. An unsupervised K-means clustering analysis was conducted to identify patterns in IV and M10. Results: A total of 1,096 diabetic participants were enrolled, with a DR prevalence of 20.53%. The mean age of participants was 62.3 years, with 49.57% being male. After adjusting covariates, IV was positively associated with DR (ß: 3.527, 95%CI: 1.371-9.073). Compared with the lowest quintile of IV, the highest quintile of IV had 136% higher odds of DR. In contrast, M10 was negatively associated with DR (ß: 0.902, 95%CI: 0.828-0.982), with participants in the highest M10 quintile showing 48.8% lower odds of DR. Restricted cubic spline analysis confirmed that these associations were linear. Meanwhile, sensitivity analysis confirmed the robustness. K-means clustering identified three distinct clusters, with participants in Cluster C (high-IV, low-M10) had a significantly higher risk of DR comparing with Cluster A (low-IV, high-M10). Conclusion: A more fragmented rhythm and lower peak activity level might be associated with an increased risk of DR. These findings indicate that maintaining a more rhythmic sleep-activity behavior might mitigate the development of DR. Further research is necessary to establish causality and understand the underlying mechanisms, and focus on whether interventions designed to enhance daily rhythm stability and increase diurnal activity level can effectively mitigate the risk of progression of DR.

Threshold and Standard Error of Measurement for Relative Rest Time of Pericervical Muscles During Prolonged Computer-Typing Tasks in Individuals With Neck Symptoms.

Introduction The most common work-related musculoskeletal disorder worldwide is neck pain, especially among individuals who extensively use computers in a seated position. One biomedical cause of this neck pain is the prolonged activity of the muscles around the neck. Electromyography (EMG) has been used to evaluate the frequency and intensity of muscle activity. "Relative rest time (RRT)" is an index derived indicating the proportion of time below a certain threshold to the total task time. This study aimed to investigate the measurement errors and minimum detectable change (MDC) of RRT of the pericervical muscles during prolonged typing tasks in individuals with neck symptoms and to examine the differences in measurement errors at 3 µV and 6 µV thresholds. Methods This test-retest reliability study was conducted twice with a one-week interval to examine measurement errors of the RRT using surface EMG. The number of participants was set to 30 subjects who had neck symptoms with a Neck Disability Index of 16% or higher. The primary outcome measure was RRT of the following: the pericervical muscles of the right side during a 60-minute typing task; the splenius capitis muscle, upper trapezius (UT) muscle, middle trapezius muscle, sternocleidomastoid muscle, serratus anterior muscle, longissimus muscle, and pectoralis major muscle. RRT was calculated as the percentage of time that muscle activity was below the threshold for more than 0.250 seconds continuously during a 60-minute typing task. The standard error of measurement (SEM) and MDC were calculated with the two thresholds of 3 µV and 6 µV. The SEMs of the two thresholds were compared using a paired method. Results Ultimately, the data of 26 participants were analyzed. The SEM (MDC) values of the RRT at the 3 µV and 6 µV thresholds were 19.22 (53.27) and 9.52 (26.39) for the splenius capitis muscle, 3.24 (8.97) and 0.38 (1.05) for the sternocleidomastoid muscle, 15.47 (42.88) and 18.79 (52.08) for the UT muscle, 21.28 (58.99) and 2.28 (6.32) for the middle trapezius muscle, 13.67 (37.90) and 11.64 (32.27) for the serratus anterior muscle, 16.81 (46.60) and 3.32 (9.20) for the longissimus muscle, and 8.97 (24.87) and 4.24 (11.74) for the pectoralis major muscle, respectively. The SEMs of the RRT with the 6 µV threshold were statistically significantly lower than those with the 3 µV threshold in all pericervical muscles, except for the UT muscle. Conclusion This study identified the SEM and MDC of the RRT for the pericervical muscles during prolonged typing tasks in individuals with neck symptoms. Except for the UT muscle, the SEMs of the RRT with the 6 µV threshold were statistically smaller than those with the 3 µV threshold. Therefore, when using the RRT in intervention studies that aim to reduce muscle activity during typing in those with neck symptoms, the 6 µV threshold measurement would be recommended for the RRT of the pericervical muscles except for the UT muscle.

Brain-first forms of Parkinson's disease are over-represented in patients with non-responsive resting tremor.

Motor subtypes in Parkinson's Disease (PD) are unstable over time, limiting mechanistic insights and biomarker discovery. We focused on Rest Tremor (RT) as a symptom to test for phenotype stability and link it to specific circuits and disease mechanisms. Using the PPMI cohort data over 5 years we found that RT is more stable than classical Tremor-Dominant definitions, a stability also seen for RT response to therapy. At time of diagnosis, the population of therapy-resistant RT patients was enriched with a brain-first PD profile as predicted by a-Synuclein origin site and connectome (SOC) model. Resistant-RT patients have lower gastrointestinal and cardiovascular symptoms, lower prevalence of probable REM-Sleep behaviour disorder, and higher dopaminergic asymmetry compared to therapy-responsive or no tremor patients. Treating RT as a distinct phenomenon revealed a relative phenotypic stability with treatment response being linked to different patterns of disease progression.

Experiences of a controlled early exercise intervention following a sport-related concussion: A qualitative study of rugby union student-athletes.

BACKGROUND: Early aerobic exercise is associated with improved outcomes following recovery from sport-related concussion (SRC) and is now recommended in guidance for clinicians managing athletes return-to-play. OBJECTIVES: To explore student-athlete experiences of a novel early aerobic exercise intervention. DESIGN: Qualitative study using semi-structured interviews. SETTING: Loughborough University, UK. PARTICIPANTS: Ten rugby union university aged student-athletes (6 men) that had been medically diagnosed with an SRC sustained playing rugby. RESULTS: Three themes divided into eight supporting subthemes were generated. Main findings were: 1) Experience: despite some apprehension over the novel approach, most had a positive experience, 2) Adherence: Participants suggested reasonably good overall adherence to the prescribed exercises but intrinsic and extrinsic factors for non-adherence were identified, 3) Outcomes: the intervention was perceived to help rehabilitation, improve confidence, support retention of athletic identity and, for some, influenced more cautious attitudes toward brain health. CONCLUSIONS: The novel early exercise intervention was reasonably well received and adhered to. Unintended benefits included supporting retainment of athletic identity and encouraging precautious health behaviours. As early exercise protocols are refined, these findings will help inform the design and delivery of future interventions, particularly in relation to intensity and diversity of exercises and supporting education.

Acute Effect of Fixed vs. Self-Selected Rest Interval Between Sets on Physiological and Performance-Related Responses.

Background: Although the comparison between self-managed rest and fixed rest periods in subjects experienced in lower-limb strength training has been investigated, the results remain unclear due to controversies among some studies. Therefore, the present study aimed to analyze the role of self-managed rest versus fixed rest in athletic performance, mean propulsive velocity, velocity loss, muscle oxygen saturation, and rest time in trained subjects; Methods: Thirteen subjects with a minimum of one year of training experience (age (years): 26.31 ± 3.84; height (cm): 175.46 ± 5.61; weight (kg): 79.24 ± 6.83) were randomly assigned to two groups (self-selected rest group [SR] = 7 and fixed rest group [FR] = 6). The subjects underwent a session for evaluation (one maximum repetition (1RM) estimation, familiarization, and data collection) and another day for a traditional strength training session for the back squat, consisting of five sets of four repetitions at 80% of 1RM. One group took a fixed 2 min break, while the other group managed their breaks autonomously (resuming when they felt ready to perform the next set at maximum velocity). Mean propulsive velocity (MPV) was monitored using a linear position transducer, and muscle oxygen saturation (SmO2) was measured with a near-infrared spectroscopy device; Results: Significant differences between the groups were found for the rest time between the first and second sets (SR 97.29 ± 23.70 seg vs. FR 120 ± 0.00 seg). However, no differences were found for MPV, velocity loss, or SmO2; Conclusions: Given the similarities in performance and physiological outcomes between fixed and self-selected rest conditions, both can be used equally depending on the preferences and training goals of coaches and athletes.

Disrupted rest-activity circadian rhythms are associated with all-cause mortality in patients with chronic kidney diseases.

Circadian rhythms are important biological contributors to health. Rest activity rhythms (RAR) are emerging as biomarkers of circadian behavior that are associated with chronic disease when abnormal. RAR have not yet been characterized in chronic kidney diseases (CKD). Leveraging the National Health and Nutrition Examination Survey (2011-2014), patients with CKD (n = 1114; Mean [95% CI]: Age, 50 [58-61] y; 52% female) were compared with non-CKD individuals (n = 5885; Age, 47 [46-48] y; 52% female). Actigraphy data were processed for RAR parameters including rhythmic strength (amplitude), the rhythm adjusted mean (mesor), the timing of peak activity (acrophase), activity regularity (inter-daily stability), and activity fragmentation (intra-daily variability). Cox regression was performed to assess RAR parameters for the prediction of all-cause mortality. Compared to non-CKD adults, patients with CKD had a lower rhythmic amplitude and mesor, and exhibited greater fragmentation and less day-to-day stability in RAR (ps < 0.001). Among CKD patients, a lower rhythmic amplitude (HR [95% CI]: 0.88 [0.82-0.96]; p < 0.001), a lower rhythm adjusted mean (0.87 [0.81-0.95]; p = 0.002), and a higher daily activity fragmentation (1.87 [1.10-3.18]; p = 0.023) were associated with an increased risk of all-cause mortality. Patients with CKD showed dampened rhythmic amplitudes and greater fragmentation of activity that were associated with a higher risk of all-cause mortality. These findings demonstrate a relationship between circadian disruption and prognosis in patients with CKD.

KIF15 promotes human glioblastoma progression under the synergistic transactivation of REST and P300.

Glioblastoma (GBM) is highly invasive and lethal. The failure to cure GBM highlights the necessity of developing more effective targeted therapeutic strategies. KIF15 is a motor protein to be involved in cell mitosis promotion, cell structure assembly and cell signal transduction. The precise biological function and the potential upstream regulatory mechanisms of KIF15 in GBM remain elusive. Here, we demonstrated that KIF15 was abnormally up-regulated in GBM and predicted poor prognosis of GBM patients. KIF15 promotes GBM cell proliferation, metastasis and cell cycle progression. REST could bind to KIF15 promoter and transactivate KIF15. Furthermore, REST interacts with P300 and depends on its histone acetyltransferase (HAT) activity to co-regulate KIF15 expression. Both REST and P300 were highly expressed in GBM and predicted poor prognosis of GBM patients alone or in combination with KIF15. The tumorigenic function of KIF15 in GBM was regulated by REST in vitro and in vivo and the combinational treatment of cell cycle inhibitor Palbociclib with P300 HAT inhibitor inhibited GBM xenografts survival more significantly. Our findings indicate that KIF15 promotes GBM progression under the synergistic transactivation of REST and P300. P300/REST/KIF15 signaling axis is expected to be served as a cascade of candidate therapeutic targets in anti-GBM.

MARCHF1 promotes breast cancer through accelerating REST ubiquitylation and following TFAM transcription.

Breast cancer has become the leading cause of death in women. Membrane associated ring-CH-type finger 1 (MARCHF1) is associated with the development of various types of cancer, but the exact role of MARCHF1 in breast cancer remains unclear. In our study, the higher MARCHF1 expression was observed in tumor samples of patients with breast cancer and then the role of MARCHF1 in breast cancer was further evaluated. Overexpression of MARCHF1 contributed to proliferation of cancer cells and inhibition of oxidative stress. Knockdown of MARCHF1 reduced breast cancer cell proliferation, increased mitochondrial dysfunction induced by oxidative stress, eventually aggravating cell death. In vivo, MARCHF1 promoted the tumor growth and oppositely, MARCHF1 silencing suppressed the tumor development. Moreover, MARCHF1 interacted with repressor Element-1 silencing transcription factor (REST) and facilitated its ubiquitylation and degradation. Subsequently, REST negatively regulated the transcription of mitochondrial transcription factor A (TFAM). The subcutaneous tumor formation assay in nude mice also supported these conclusions. In details, knockdown of MARCHF1 upregulated the protein expression of REST and downregulated the mRNA level of TFAM. On the contrary, MARCHF1 overexpression exhibited opposite effects. Thus, MARCHF1 is conducive to the progression of breast cancer via promoting the ubiquitylation and degradation of RSET and then the transcription of TFAM. Downregulating MARCHF1 could provide a novel direction for treating breast cancer.

Acute effects of resistance exercise on the muscle architecture and tissue organization of the maximal isometrically contracted and uncontracted gastrocnemius medialis muscle.

This study aimed to investigate the acute effects of resistance exercise on muscle architecture and tissue organization at rest and during isometric maximum voluntary contraction (iMVC) of the gastrocnemius medialis muscle. In 16 healthy adults (25 ± 3 y), ultrasound scans were captured before (pre), immediately after (post), and 15 min after (post_15) single-leg calf raises during rest and iMVCs. Measurements included muscle thickness (MT), pennation angle (PA), and fascicle length (FL). Spatial frequency analysis (SFA) assessed tissue organization (e.g. peak spatial frequency radius (PSFR), quality factor (Q6)). MT increased significantly from pre to post (+5.7%) and post_15 (+5.6%) at rest. During iMVC, MT and FL increased significantly from pre to post (MT: +8.1%, FL: +14.9%) and post_15 (MT: +5.2%, FL: +10.5%), while PA decreased significantly from pre to post_15 (-10.2%). PSFR and Q6 decreased significantly from pre to post (-7.0-8.2%) and increased from post to post_15 (+10.3-10.6%) at rest, with no significant changes during iMVC. Resistance exercise led to altered muscle architecture for more than 15 min, while SFA parameters reverted to baseline within 15 min. Thus, SFA potentially enables early differentiation of potential physiological alterations in muscle micro-morphology.

Laparoscopic resection for a case preoperatively diagnosed as adrenal rest tumor in the liver: A case report.

INTRODUCTION AND IMPORTANCE: Adrenal rest tumors (ARTs) are frequently found in the abdominal axis and testis and are often detected incidentally during surgery or autopsy. The standard treatment is complete resection due to their malignant potential; however, precise preoperative diagnosis is difficult due to the similarity of the radiological findings of this disease with those of hepatocellular carcinoma (HCC) and angiomyolipoma. CASE PRESENTATION: A 58-year-old woman was diagnosed with a tumor through a physical examination and came to our clinic for a close examination. Dynamic computed tomography showed a tumor with a diameter of 27 mm that occupied segment 7 (S7) of the liver. The tumor was slightly enhanced in the arterial phase and washed out in the portal phase. Magnetic resonance imaging (MRI) demonstrated that this round tumor protruded from the liver surface and had high signal intensity on T2-weighted imaging. The tumor showed a high signal intensity on diffusion-weighted imaging. Chemical shift imaging revealed the markedly low intensity of the tumor. The preoperative diagnosis was suspected hepatic ART. Laparoscopic S7 partial resection was performed. The operative duration was 147 min, and the blood loss was 10 mL. The patient was discharged from the hospital on postoperative day 5. The pathological diagnosis was ART. CLINICAL DISCUSSION: Hepatic ART (HART) is diagnosed preoperatively as HCC in most cases, and resection is rarely reported. The most standard treatment for HART is surgery for possible malignancy. Recent advances in radiological imaging have made it possible to distinguish HART from HCC using MRI chemical shift images. In the case of a highly vascular and fatty tumor such as the present case, HART diagnosis can be made preoperatively using MRI chemical shift imaging. This case is the first reported preoperative diagnosis of HART using chemical shift imaging. CONCLUSIONS: We report a case of laparoscopic radical resection in a patient preoperatively diagnosed with hepatic ART. Chemical shift imaging in MRI is essential for distinguishing ART from HCC.

A Comprehensive Review on a Prosthetic Finger Fabrication Approach: Clinical Rest Position (CRP) vs Palms and Fingers Extended (PFE).

Creating effective prosthetic fingers involves precise treatment planning and skilled fabrication to restore aesthetic appearance and passive function. Successful outcomes depend significantly on retention and how closely the prosthesis mimics natural finger contours. We analyzed techniques for fabricating finger prostheses with palms and fingers in clinical rest position (CRP) versus palms and fingers extended (PFE) straight out. The aesthetics and function (passive) were also examined when fabricated in these two physiological conditions. We reviewed 20 articles from national and international journals over 20 years. Most literature focuses on extended posture fabrication, with few addressing CRP. This review article compares the CRP and PFE prosthetic finger fabrication approaches and explains how a prosthetic finger fabricated in a CRP offers superior aesthetic and partial functional outcomes and emerges as a promising alternative to the PFE. The potential impact of these findings on prosthodontics is significant, emphasizing the need for further research to validate these results and the ongoing development in the field.

The Level of Markers Stimulating Growth Factor 2 (ST2), N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP), and D-Dimer in Healthy Volunteer Testers in 21-Day Head-Down -6° Tilt Bed Rest as a Model of Hypodynamia.

The paper presents an analysis of the proteomic composition in relation to both the risk of thrombosis and changes in the state of cardiomyocytes associated with the risk of cardiac fibrosis and heart failure. We examined 12 practically healthy male volunteers exposed to head-down -6° tilt bed rest (HDBR) for 21 days. The revealed decrease in the level of stimulating growth factor 2 (ST2) on days 10 and 21 relative to the initial values (background; 5 days before HDBR) indicated a decrease in the myocardial load and cardiomyocyte extensibility. The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) increased on day 2, decreased on days 10 and 21 of HDBR relative to the background levels, and returned to baseline values after the recovery period (5 days after HDBR). The revealed changes in the level of NT-proBNP reflected the increase in circulating blood volume corresponding to HDBR duration and the role of the gravity component in increasing the functional load on the myocardium. Unchanged blood level of D-dimer at all points of the study indicates that there is no risk of thrombosis under the conditions of this study.

Functional Analysis of RE1 Silencing Transcription Factor as a Putative Tumor Suppressor in Human Endometrial Cancer.

Uterine cancer is the most common gynecologic malignancy in the United States, with endometrioid endometrial adenocarcinoma (EC) being the most common histologic sub-type. Considering the molecular classifications of EC, efforts have been made to identify additional biomarkers that can assist in diagnosis, prognosis, and individualized therapy. We sought to explore the relationship of Repressor Element 1 (RE1) silencing transcription factor (REST), which downregulates neuronal genes in non-neuronal tissue, along with matrix metalloproteinase-24 (MMP24) and EC. We analyzed the expression of REST and MMP24 in 31 cases of endometrial cancer and 16 controls. We then explored the baseline expression of REST and MMP24 in two EC cell lines (Ishikawa and HEC-1-A) compared to a benign cell line (t-HESC) and subsequently evaluated proliferation, migration, and invasion in the setting of loss of REST gene expression. REST and MMP24 expression were significantly lower in human EC samples compared to control samples. REST was highly expressed in EC cell lines, but decreasing REST gene expression increased proliferation (FC: 1.13X, p < 0.0001), migration (1.72X, p < 0.0001), and invasion (FC: 7.77X, p < 0.05) in Ishikawa cells, which are hallmarks of cancer progression and metastasis. These findings elicit a potential role for REST as a putative tumor suppressor in EC.

Effects of intermittent seating upright, lower body negative pressure, and exercise on functional tasks performance after head-down tilt bed rest.

Introduction: Bed rest can be used as a ground-based analog of the body unloading associated with spaceflight. In this study, we determined how strict head-down tilt bed rest affects subjects' performance of functional tests (sit-to-stand, tandem walk, walk-and-turn, dynamic posturography) that challenge astronauts' balance control systems immediately after they return from space. Methods: Forty-seven participants were assessed before and a few hours after 30 days of 6° head down tilt bed rest at the DLR:envihab facility. During this bed rest study, called SANS-CM, the participants were divided into 4 groups that either a) were positioned in head-down tilt continuously throughout the 30 days; b) sat upright for 6 h a day; c) were exposed to lower body negative pressure (LBNP) for 6 h a day; or d) exercised for 60 min and then wore venous-occlusive cuffs for 6 h a day. Results: Results showed that strict head-down tilt bed rest caused deficits in performance of functional tasks that were similar to those observed in astronauts after spaceflight. Seated upright posture mitigated these deficits, whereas exercise or LBNP and cuffs partly mitigated them. Discussion: These data suggest that more direct, active sensorimotor-based countermeasures may be necessary to maintain preflight levels of functional performance after a long period of body unloading.

Rest Tremor in Parkinson's Disease Is Associated with Ipsilateral Striatal Dopamine Transporter Binding.

BACKGROUND: The cardinal motor symptoms of Parkinson's disease (PD) include rigidity, bradykinesia, and rest tremor. Rigidity and bradykinesia correlate with contralateral nigrostriatal degeneration and striatal dopamine deficit, but association between striatal dopamine function and rest tremor has remained unclear. OBJECTIVE: The aim of this study was to investigate the possible link between dopamine function and rest tremor using Parkinson's Progression Markers Initiative dataset, the largest prospective neuroimaging cohort of patients with PD. METHODS: Clinical, [123I]N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT), and structural magnetic resonance imaging data from 354 early PD patients and 166 healthy controls were included in this study. We employed a novel approach allowing nonlinear registration of individual scans accurately to a standard space and voxelwise analyses of the association between motor symptoms and striatal dopamine transporter (DAT) binding. RESULTS: Severity of both rigidity and bradykinesia was negatively associated with contralateral striatal DAT binding (PFWE < 0.05 [FWE, family-wise error corrected]). However, rest tremor amplitude was positively associated with increased ipsilateral DAT binding (PFWE < 0.05). The association between rest tremor and binding remained the same controlling for Hoehn & Yahr stage, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, bradykinesia-rigidity score, or motor phenotype. The association between rest tremor and binding was independent of bradykinesia-rigidity and replicated using 2-year follow-up data (PFWE < 0.05). CONCLUSION: In agreement with the existing literature, we did not find a consistent association between rest tremor and contralateral dopamine defect. However, our results demonstrate a link between rest tremor and increased or less decreased ipsilateral DAT binding. Our findings provide novel information about the association between dopaminergic function and parkinsonian rest tremor. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.