Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.

BACKGROUND: Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses. METHODS: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. RESULTS: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%. CONCLUSION: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

Lateralization of the 5-HT1A receptors in the basolateral amygdala in metabolic and anxiety responses to chronic restraint stress.

Behavioral and functional studies describe hemispheric asymmetry in anxiety and metabolic behaviors in responses to stress. However, no study has reported serotonergic receptor (the 5-HT1A receptor) lateralization in the basolateral amygdala (BLA) in vivo on anxiety and metabolic behaviors under stress. In the present study, the effect of unilateral and bilateral suppression of the 5-HT1A receptor in the BLA on anxiety, and metabolic responses to chronic restraint stress was assessed. Male Wistar rats 7 days after cannulation into the BLA received chronic restraint stress for 14 consecutive days. 20 minutes before induction of stress, WAY-100-635 (selective 5-HT1A antagonist) or sterile saline (vehicle) was administered either uni- or bi-laterally into the BLA. Behavioral (elevated plus maze; EPM, and open field test), and metabolic parameter studies were performed. Results showed that stress causes a significant increase in weight gain compared to control. In the non-stress condition, the left and bilaterally, and in the stress condition the right, left, and both sides, inhibition of 5-HT1A in the BLA reduced weight gain. In the restraint stress condition, only inhibition of the 5-HT1A receptor in the left BLA led to decreased food intake compared to the control group. In stress conditions, inhibition of the 5-HT1A receptor on the right, left, and bilateral BLA increased water intake compared to the stress group. Inhibition of the 5-HT1A receptor on the left side of the BLA by WAY-100-635 induced anxiety-like behaviors in stressed rats. Similarly, WAY-100-635 on the left BLA effectively caused anxiety-like behaviors in both EPM and open field tests in the control animals. In conclusion, it seems that 5-HT1A receptors in the left BLA are more responsible for anxiety-like behaviors and metabolic changes in responses to stress.

Counteracting mental fatigue for athletes: a systematic review of the interventions.

The deleterious effects of mental fatigue (MF) on athletes have been carefully studied in various sports, such as soccer, badminton, and swimming. Even though many researchers have sought ways to ameliorate the negative impact of MF, there is still a lack of studies that review the interventions used to counteract MF among athletes. This review aims to report the current evidence exploring the effects of interventions on MF and sport-specific performance, including sport-specific motor performance and perceptual-cognitive skills. Web of Science, Scopus, PubMed, and SPORTDicus (EBSCOhost) were combed through to find relevant publications. Additionally, the references and Google Scholar were searched for any grey literature. For the current review, we included only randomized controlled trials that involved athletes, a primary task to induce MF, interventions to counter MF with comparable protocols, and the outcomes of sport-specific motor performance and perceptual-cognitive skill. The selection criteria resulted in the inclusion of 10 articles. The manipulations of autonomous self-control exertion, person-fit, nature exposure, mindfulness, and transactional direct current stimulation showed that positive interventions counteract MF and improve sport-specific performance in different domains, including strength, speed, skill, stamina, and perceptual-cognitive skills. The selected interventions could significantly counteract MF and improve subsequent sport-specific performance. Moreover, self-regulation and attention resources showed the importance of the potential mechanisms behind the relevant interventions.

The counteractive effects of interventions addressing mental fatigue on sport-specific performance among athletes: A systematic review with a meta-analysis.

The deleterious consequences of mental fatigue (MF) on athletes in diverse sporting domains have been subject to extensive inquiry. However, the efficacy of interventions to counteract the effects of MF remains largely elusive. This review aims to evaluate the effects of counteractive interventions on the sport-specific performance of mentally fatigued athletes. Moreover, synthesizes the current evidence on which sports effectively counter the detrimental effects of MF with interventions, highlighting potential avenues for upcoming research. A systematic search was executed via Web of Science, Scopus, PubMed, and EBSCOhost, in addition to Google Scholar and references for grey literature. A meta-analysis was executed to compute effect sizes for different interventions with 13 qualified papers. Interventions include transcranial direct current stimulation, person-fit, mindfulness, glucose supplementation, caffeine mouth rinsing, and nature exposure showed potential to mitigate the detrimental effects on sport-specific performance, particularly in shooting accuracy (ES = 0.591; p = 0.001), decision-making accuracy (ES = 0.553; p = 0.006), and reaction time (ES = -0.871; p < 0.001), however, not in completion time (ES = -0.302; p = 0.182). This review underscores the unique roles of self-regulatory resources and directed attention. Nonetheless, a cautious interpretation of the findings is warranted given the paucity of investigations involving potential interventions in numerous other sports, such as volleyball, Australian football, cricket, and boxing.

Feasibility Evaluation of Online Classification-based Control for Gross Movement in a 2-DoF Prosthetic Arm.

Regression and classification models have been extensively studied to exploit the myoelectric and kinematic input information from the residual limb for the control of multiple degree-of-freedom (DoF) powered prostheses. The gross movement control of above-elbow prostheses is mainly based on regression models which map the available inputs to continuous prosthetic poses. However, the regression output is sensitive to the variation in the input signal. The myoelectric signal variation is usually large due to unintentional muscle contractions, which can deteriorate the user-in-the-loop performance with respect to the offline analysis. Alternatively, the classification models offer the advantage of being more robust to the input signal variation, but they were predominantly used for fine motor functions such as grasping. For gross motor functions, the discrete output may cause issues. Therefore, this work attempts to investigate the feasibility of utilising the classification model to control a 2-DoF transhumeral prosthesis for gross movement. The performance of 6 able-bodied subjects was evaluated in performing reaching and orientation matching tasks with a prosthetic arm in a virtual reality environment. The results were compared with the case of using their intact arms and existing results using the regression model. Our findings indicate that the classification-based method provides comparable performance to the regression model, making it a potential alternative for gross arm movement in multi-DoF prosthetic arms.

Effects of the suppression of 5-HT1A receptors in the left, right, or bilateral basolateral amygdala on memory consolidation in chronic stress in male rats.

The serotonin-1A receptors (5-HT1A) in the two cerebral hemispheres are differentially involved in memory. The distribution of 5-HT1A receptors in the left and right amygdala is different. Furthermore, evidence shows that the 5-HT1A receptors in the left and right amygdala work differently in memory function. The basolateral amygdala (BLA) also regulates hippocampal long-term potentiation (LTP) during stress. However, which BLA structure in each hemisphere underlies such lateralized function is unclear. The present research investigated the possible involvement of 5-HT1A lateralization in the BLA on stress-induced memory impairment. 5-HT1A receptor antagonist (Way-100-635) was injected into the left, right, or bilateral BLA twenty minutes before chronic restraint stress (CRS) for 14 consecutive days. Results indicated that suppression of 5HT1A-receptors in the BLA plays an essential role in reducing the acquisition of passive avoidance in the shuttle box test and spatial memory in the Barnes maze test in the stress animals. This decrease was significant in the CRS animals with left and bilateral suppressed 5HT1A-receptors in the BLA. Field potential recording results showed that the left, right, and bilateral injection of Way-100-635 into the BLA significantly reduced the slope and amplitude of fEPSP in the CA1 area of the hippocampus in stressed rats. No significant difference was observed in neuronal arborization in the CA1 area of the hippocampus. In conclusion, the 5-HT1A receptor in the left and right sides of BLA nuclei play a different role in memory consolidation in the hippocampus under stress.

Correction: Identifying connectivity for two sympatric carnivores in human-dominated landscapes in central Iran.

[This corrects the article DOI: 10.1371/journal.pone.0269179.].

The impact of opioid administration for post gamma knife radiosurgery frame removal: a prospective quality-improvement study.

PURPOSE: In our center, five Gamma Knife proceduralists differed in opioid administration practices prior to Leksell frame removal, providing the opportunity to improve the care of patients with brain metastases by studying whether opioid medications improve pain scores and patient satisfaction during Gamma Knife treatment in a prospective, pseudorandomized fashion. METHODS: We prospectively administered a questionnaire to patients undergoing Gamma Knife Radiosurgery for metastases between November, 2017 and July, 2018. Using multivariable methods, we assessed whether opioid pain medication administration influenced the change in pain scores after frame removal, and whether they influenced patient satisfaction on how often their pain was controlled, and their overall satisfaction. RESULTS: We included 142 patients. Mean age was 65.2 ± 10.8 years and 52.7% were female. Morphine was the most commonly administered medication. Pain increases were greater around frame removal than placement. Opioids were not associated with any difference in the change in pain scores before and after frame removal, or patient satisfaction. Patients with higher pre-removal pain scores had smaller increases in pain scores after removal; they also had worse pain control and overall satisfaction with their treatment. CONCLUSION: Morphine administration prior to frame removal did not improve pain scores or pain control satisfaction. Absence of efficacy may be related to delayed onset of action, and stronger and faster-acting agents should be explored. Pre-removal pain scores were associated with decreased pain control and overall satisfaction, further identifying earlier and stronger pain treatment as a potential area for improvement.

Where to place emergency ambulance vehicles: use of a capacitated maximum covering location model with real call data.

This study integrates geographical information systems (GIS) with a mathematical optimization technique to enhance emergency medical services (EMS) coverage in a county in the northeast of Iran. EMS demand locations were determined through one-year EMS call data analysis. We formulated a maximal covering location problem (MCLP) as a mixed-integer linear programming model with a capacity threshold for vehicles using the CPLEX optimizer, an optimization software package from IBM. To ensure applicability to the EMS setting, we incorporated a constraint that maintains an acceptable level of service for all EMS calls. Specifically, we implemented two scenarios: a relocation model for existing ambulances and an allocation model for new ambulances, both using a list of candidate locations. The relocation model increased the proportion of calls within the 5-minute coverage standard from 69% to 75%. With the allocation model, we found that the coverage proportion could rise to 84% of total calls by adding ten vehicles and eight new stations. The incorporation of GIS techniques into optimization modelling holds promise for the efficient management of scarce healthcare resources, particularly in situations where time is of the essence.

A bioinspired 3D-printable flexure joint with cellular mechanical metamaterial architecture for soft robotic hands.

Compliant flexure joints have been widely used for cable-driven soft robotic hands and grippers due to their safe interaction with humans and objects. This paper presents a soft and compliant revolute flexure joint based on the auxetic cellular mechanical metamaterials with a heterogeneous structure. The heterogeneous architecture of the proposed metamaterial flexure joint (MFJ), which is inspired by the human finger joints, provides mechanically tunable multi-stiffness bending motion and large range of bending angle in comparison to conventional flexure joints. The multi-level variation of the joint stiffness over the range of bending motion can be tuned through the geometrical parameters of the cellular mechanical metamaterial unit cells. The proposed flexure joints are 3D printed with single flexible material in monolithic fashion using a standard benchtop 3D printer. The application of the MFJ is demonstrated in robotic in-hand manipulation and grasping thin and deformable objects such as wires and cables. The results show the capability and advantages of the proposed MFJ in soft robotic grippers and highly functional bionic hands.

18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

High-risk spatiotemporal patterns of cutaneous leishmaniasis: a nationwide study in Iran from 2011 to 2020.

BACKGROUND: Cutaneous leishmaniasis (CL) is a wide-reaching infection of major public health concern. Iran is one of the six most endemic countries in the world. This study aims to provide a spatiotemporal visualization of CL cases in Iran at the county level from 2011 to 2020, detecting high-risk zones, while also noting the movement of high-risk clusters. METHODS: On the basis of clinical observations and parasitological tests, data of 154,378 diagnosed patients were obtained from the Iran Ministry of Health and Medical Education. Utilizing spatial scan statistics, we investigated the disease's purely temporal, purely spatial, spatial variation in temporal trends and spatiotemporal patterns. At P = 0.05 level, the null hypothesis was rejected in every instance. RESULTS: In general, the number of new CL cases decreased over the course of the 9-year research period. From 2011 to 2020, a regular seasonal pattern, with peaks in the fall and troughs in the spring, was found. The period of September-February of 2014-2015 was found to hold the highest risk in terms of CL incidence rate in the whole country [relative risk (RR) = 2.24, P < 0.001)]. In terms of location, six significant high-risk CL clusters covering 40.6% of the total area of the country were observed, with the RR ranging from 1.87 to 9.69. In addition, spatial variation in the temporal trend analysis found 11 clusters as potential high-risk areas that highlighted certain regions with an increasing tendency. Finally, five space-time clusters were found. The geographical displacement and spread of the disease followed a moving pattern over the 9-year study period affecting many regions of the country. CONCLUSIONS: Our study has revealed significant regional, temporal, and spatiotemporal patterns of CL distribution in Iran. Over the years, there have been multiple shifts in spatiotemporal clusters, encompassing many different parts of the country from 2011 to 2020. The results reveal the formation of clusters across counties that cover certain parts of provinces, indicating the importance of conducting spatiotemporal analyses at the county level for studies that encompass entire countries. Such analyses, at a finer geographical scale, such as county level, might provide more precise results than analyses at the scale of the province.

Sensor Selection with Composite Features in Identifying User-Intended Poses for Human-Prosthetic Interfaces.

A Human-Prosthetic Interface (HPI) serves to estimate and realise the limb pose intended by the human user, using the information obtained from sensors worn by the user. In recent studies, the HPI maps multi-joint limb poses (i.e. coordinated movement of the body and limbs) to the inputs of multiple sensors. This is in contrast to the conventional methods where each degree of freedom of the powered prosthesis is mapped to the input of one/a pair of sensors. In this approach, it is necessary to systematically select sensors that carry the most information for the intended set of poses, to improve system accuracy and/or minimise the number of sensors, thus the complexity, in the prosthetic system. In this paper, sensor selection process is systematically formulated to maximise the information contained in the input features for a given number of sensors. Most importantly, it accounts for composite features, which are features requiring information from multiple sensors. Such composite features exist and are important in HPIs as we seek to capture coordinated motion involving movements of multiple limb and body segments. A non-convex optimisation problem is formulated which accounts for the constraint introduced by the composite features. A projection matrix is utilised as the optimisation variable to select intended features for evaluation. The problem is solved by the proposed Sensor Selection with Composite Features (SS-CF) algorithm which adapts convex-relaxation techniques. The SS-CF is benchmarked against HPI with expert-selected sensors in the literature and against a greedy heuristic method. The outcome demonstrated the efficacy of the SS-CF algorithm.

Efficacy of laser interstitial thermal therapy for biopsy-proven radiation necrosis in radiographically recurrent brain metastases.

Background: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies. Methods: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival. Results: Ninety patients met the inclusion criteria. Four patients underwent 2 ablations on the same day. Median hospitalization time was 32.5 hours. The median time to corticosteroid cessation after LITT was 13.0 days (0.0, 1229.0) and cumulative incidence of lesional progression was 19% at 1 year. Median post-procedure overall survival was 2.55 years [1.66, infinity] and 77.1% at one year as estimated by KaplanMeier. Median KPS remained at 80 through 2-year follow-up. Seizure prevalence was 12% within 1-month post-LITT and 7.9% at 3 months; down from 34.4% within 60-day prior to procedure. Conclusions: LITT for RN was not only again found to be safe with low patient morbidity but was also a highly effective treatment for RN for both local control and symptom management (including seizures). In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the rapid cessation of steroids, thereby facilitating maximal possible survival for these patients.

The effects of mental fatigue on sport-specific motor performance among team sport athletes: A systematic scoping review.

Background: The psychobiological state known as mental fatigue (MF) is by engaging in mentally taxing activities for an extended period, which is typically found in team sports, of the high cognitive demand and unpredictable environment. It increases the perception of effort and influences executive functions, impairing sport-specific performance in athletes. However, the consequences of MF on sport-specific motor performance (SSMP) among athletes in team sports remain unclear. Objective: This scoping review seeks to find and map research publications that investigate the effect of MF on SSMP in team sports. Methods: Web of Science, Scopus, and PubMed were searched as the main databases, and CENTRAL, Psychology, and Behavioral Sciences Collection, SPORTDicus obtained from EBSCOhost, as well as gray literature was searched for relevant literature and Google Scholar. Cognitive tasks before the SSMP exam are the focus of the selected literature on mental exhaustion. Only experiments testing mental and non-mental exhaustion were chosen. Results: Twelve studies fulfill the requirement of selection criteria. SSMP in team sports, including soccer, basketball, cricket, and Australian football mainly is examined as physical and technical performance. More specifically, MF significantly influenced physical performance measured as intermittent endurance and total distance (P < 0.05), while data was inclusive when assess in an ecological setting (e.g., small-sided game) (P > 0.05). Technical performance was mainly measured as ball loss, errors in passing and shooting, interception, and successful tackle and showed a dramatic impairment (P < 0.05). The decline of physical activity is relevant with higher level PRE, while decreased technical performance is related to impaired attention resources shown as visual perceptual. Conclusion: MF adversely influences SSMP in team sports. The most relevant theory for future study to examine the impacts of MF on team-sport athletes could be the psychological model of exercise and its potential extension on attention resources, rather than the traditional "catastrophe" theory.

Temporal and spatial characteristics of bone conduction as non-invasive haptic sensory feedback for upper-limb prosthesis.

Bone conduction is a promising haptic feedback modality for upper-limb prosthesis users, however, its potential and characteristics as a non-invasive feedback modality have not been thoroughly investigated. This study aimed to establish the temporal and spatial characteristics of non-invasive bone conduction as a sensory feedback interface for upper-limb prostheses. Psychometric human-subject experiments were conducted on three bony landmarks of the elbow, with a vibrotactile transducer affixed to each to provide the stimulus. The study characterized the temporal domain by testing perception threshold and resolution in amplitude and frequency. The spatial domain was evaluated by assessing the ability of subjects to detect the number of simultaneous active stimulation sites. The experiment was conducted with ten able-bodied subjects and compared to two subjects with trans-radial amputation. The psychometric evaluation of the proposed non-invasive bone conduction feedback showed results comparable to invasive methods. The experimental results demonstrated similar amplitude and frequency resolution of the interface for all three stimulation sites for both able-bodied subjects and subjects with trans-radial amputation, highlighting its potential as a non-invasive feedback modality for upper-limb prostheses.