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Background Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes. Objective The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain. Methods To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations. Results Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity. Conclusion By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity.

It is vital to have accurate predictions of the gas exchange behavior of an engine in order to reliably study engine performance and emissions using engine simulation models. There are a multitude of factors, both upstream and downstream of the engine cylinder, which influence its gas exchange characteristics. Quite often these influences are interconnected in a non-linear manner that results in complicated feedback loops, which can introduce significant errors in the computed thermodynamic state of the post-breathing cylinder mixture. The effects of such bi-directional movement of pressure pulses are particularly pronounced in two-stroke engines. This study investigates the importance of exhaust system design on the scavenging characteristics of a piston-scavenged, cross-flow, two-stroke engine. A validated one-dimensional predictive model is used to study the effects of changing the exhaust port timing, exhaust system length, and exhaust port efficiency on the breathing performance of the engine, along with the consequent effects on the thermal efficiency and NOx emissions. Exhaust pressure waves and mass flows across ports are used to understand and explain the observed changes. The results show that while making design changes, thermodynamic efficiency considerations can act as a barrier to improving the scavenging efficiency of the engine; in addition, a trade-off between the two has to be considered in the design process to meet engine performance targets. The effects of such a trade-off on the NOx production are analyzed and two exhaust system modifications are discussed.

Background: Despite all efforts, spinal cord ischemia (SCI) is a relevant and feared complication after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Besides the established correlation of motor evoked potentials (MEPs) and SCI, the usage of biomarkers for early detection of SCI intraoperatively and postoperatively after TAAA surgery is scarcely described in literature.Methods: The methods include retrospective assessment of 33 patients (48.48% male) undergoing open and endovascular TAAA repair between January 2017 and January 2018. Levels of the biomarkers neurone-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100 B were correlated with a decrease of the amplitude of the MEPs of more than 50%, indicating SCI. Linear mixed models were applied to test for differences in the biomarker levels between open and endovascular surgery and between different times of measurement. Post hoc analyses were performed using Tukey's multiple comparisons test. Logistic regression models were used to investigate the association between GFAP, NSE, and S100 B levels at different times and a significant decrease in MEP or in-hospital mortality.Results: Altogether, 19 patients were treated by endovascular repair; 14 patients were treated by open repair; 5 patients were treated because of a type I TAAA; 7 received treatment because of a type II TAAA; 7, 10, and 4 patients received type III, IV, or V TAAA repair, respectively. In-hospital mortality was 18.18% (n = 6); 5 of these patients were treated because of symptomatic TAAA. MEP decrease could be observed in 18 cases (54.5%), with 16 (48.4%) recovering during the intervention. SCI could be observed in 9.09% (n = 3), 2 endovascular repairs leading to paraplegia and one open repair leading to paraparesis. All biomarkers showed increasing levels over time, with no statistically significant difference between open and endovascular repair. The difference in NSE and S100 B levels between the different times of measurements was statistically significant (P < 0.0001, P = 0.0017, respectively). In a univariable logistic regression analysis, no correlation with the end points "significant decrease in MEP'' or "in-hospital mortality'' was observed for any of the assessed biomarkers.Conclusions: SCI-related biomarkers, namely NSE and S100 B, show a relevant increase directly after open and endovascular TAAA surgery, while no clear association between these biomarker levels and an intraoperatively measurable indicator for SCI could be observed.

Background The New Zealand Ministry of Health provides funding for the delivery of health care across regions via 20 District Health Boards. Funding includes the subsidisation of therapeutic pharmaceutical agents/drugs. The distribution of optometrists and ophthalmologists across the regions was investigated to understand the accessibility of eye care in New Zealand. Changes made to the optometrists' scope of practice in 2005 and in 2014 increased the range of drugs that suitably qualified optometrists could prescribe. Therefore, the distribution of optometrists authorised to prescribe drugs and those not authorised to prescribe drugs was also investigated. Methods Information from the New Zealand Optometrists and Dispensing Opticians Board register and information from the Medical Council's website were used to create a database of ophthalmic practitioners and their locations. The χ2 goodness-of-fit test was carried out to determine whether the distribution of the number of practitioners across the regions was in proportion to the population of the regions. Results Ophthalmologists were distributed across the regions in proportion to the regional population size. However, optometrists were concentrated in Auckland and other regions with high populations. Optometrists authorised to prescribe drugs comprised over 74 per cent of optometrists and were the majority of optometrists in most regions. Many of the regions with populations less than 200,000 had high population-to-practitioner ratios, indicating that they may not have sufficient numbers of ophthalmic practitioners in order to provide for the ocular needs of the community. Conclusion Better distribution of the optometric workforce could make eye care more accessible in many regions of New Zealand.

Plasma proteins are covalently modified in vivo by the high-glucose conditions in the bloodstreams of people with diabetes, resulting in changes to both structure and function. Human Serum Albumin (HSA) functions as a carrier-protein in the bloodstream, binding various ligands and tightly regulating their bioavailability. HSA is known to react with glucose via the Maillard reaction, causing adverse effects on its ability to bind and deliver certain ligands, such as metals. Here, the binding between in vivo glycated HSA and zinc (Zn2+) was determined using a novel centrifugal ultrafiltration method that was developed using a 3D-printed device. This method is rapid (90 minutes), capable of high-throughput measurements (24 samples), low-cost (

PURPOSE To investigate the association of postdiagnosis body mass index (BMI) and weight change with prostate cancer–specific mortality (PCSM), cardiovascular disease–related mortality (CVDM), and all-cause mortality among survivors of nonmetastatic prostate cancer. METHODS Men in the Cancer Prevention Study II Nutrition Cohort diagnosed with nonmetastatic prostate cancer between 1992 and 2013 were followed for mortality through December 2016. Current weight was self-reported on follow-up questionnaires approximately every 2 years. Postdiagnosis BMI was obtained from the first survey completed 1 to < 6 years after diagnosis. Weight change was the difference in weight between the first and second postdiagnosis surveys. Deaths occurring within 4 years of the follow-up were excluded to reduce bias from reverse causation. Analyses of BMI and weight change included 8,330 and 6,942 participants, respectively. RESULTS Postdiagnosis BMI analyses included 3,855 deaths from all causes (PCSM, n = 500; CVDM, n = 1,155). Using Cox proportional hazards models, hazard ratios (HRs) associated with postdiagnosis obesity (BMI ≥ 30 kg/m2) compared with healthy weight (BMI 18.5 to < 25.0 kg/m2) were 1.28 for PCSM (95% CI, 0.96 to 1.67), 1.24 for CVDM (95% CI, 1.03 to 1.49), and 1.23 for all-cause mortality (95% CI, 1.11 to 1.35). Weight gain analyses included 2,973 deaths (PCSM, n = 375; CVDM, n = 881). Postdiagnosis weight gain (> 5% of body weight), compared with stable weight (± < 3%), was associated with a higher risk of PCSM (HR, 1.65; 95% CI, 1.21 to 2.25) and all-cause mortality (HR, 1.27; 95% CI, 1.12 to 1.45) but not CVDM. CONCLUSION Results suggest that among survivors of nonmetastatic prostate cancer with largely localized disease, postdiagnosis obesity is associated with higher CVDM and all-cause mortality, and possibly higher PCSM, and that postdiagnosis weight gain may be associated with a higher mortality as a result of all causes and prostate cancer.

In all areas related to protein adsorption, from medicine to biotechnology to heterogeneous nucleation, the question about its dominant forces and control arises. In this study, we used ellipsometry and quartz-crystal microbalance with dissipation (QCM-D), as well as density-functional theory (DFT) to obtain insight into the mechanism behind a wetting transition of a protein solution. We established that using multivalent ions in a net negatively charged globular protein solution (BSA) can either cause simple adsorption on a negatively charged interface, or a (diverging) wetting layer when approaching liquid-liquid phase separation (LLPS) by changing protein concentration (c p ) or temperature (T). We observed that the water to protein ratio in the wetting layer is substantially larger compared to simple adsorption. In the corresponding theoretical model, we treated the proteins as limited-valence (patchy) particles and identified a wetting transition for this complex system. This wetting is driven by a bulk instability introduced by metastable LLPS exposed to an ion-activated attractive substrate.

The COVID-19 pandemic has disrupted every aspect of society in a way never previously experienced by our nation's orthopaedic surgeons. In response to the challenges the American Board of Orthopaedic Surgery has taken steps to adapt our Board Certification and Continuous Certification processes. These changes were made to provide flexibility for as many Candidates and Diplomates as possible to participate while maintaining our high standards. The American Board of Orthopaedic Surgery is first and foremost committed to the safety and well-being of our patients, physicians, and families while striving to remain responsive to the changing circumstances affecting our Candidates and Diplomates.

Adverse local tissue reactions (ALTRs) were first associated with patients with failed metal-on-metal surface replacements and total hip arthroplasty (THA). However, an increasing number of cases of ALTR in metal-on-polyethylene (MOP) THA patients is being reported. Clinically, ALTR appears as benign, aseptic masses or bursae in the periprosthetic tissues. Histopathologically, ALTRs are distinguished by an intense lymphocyte infiltrate, destruction of the synovial surfaces, widespread necrosis, and fibrin exudate. Tribocorrosion of modular junctions appears to be the cause of ALTR in MOP patients. The various tribocorrosion damage modes occurring at modular junctions produce metal ions and a diversity of particulates in relation to size, chemical composition, and structure. The mechanisms by which these various products of tribocorrosion lead to ALTR are still a matter of considerable research. This review clarifies what constitutes ALTR, its relationship to implant factors, and highlights current methods for diagnosis and management of patients with ALTR in the setting of MOP THA.

The purpose of this retrieval study was to determine the effect of implant positioning on wear, taking patient-related factors into account. Therefore, the volumetric material loss of 59 retrieved tibial liners was quantitatively determined using a coordinate measuring-machine. All retrievals were made of the same polyethylene and design by a single manufacturer. Using time in-situ and linear regression, a wear rate for each liner was determined and corrected for bedding-in. Backside damage was qualitatively scored. The following implant positioning parameters were obtained from radiographs: anatomical lateral-distal femoral angle, anatomical medial-proximal tibial angle, femoral tilt angle and posterior tibial slope. The patella position was assessed by the Blackburne-Peel Index and the Insall-Salvati Ratio. Unlike the Insall-Salvati Ratio, the Blackburne-Peel Index is known to detect surgical joint line elevation. Using general linear modeling the most impactful factors on wear rate and backside damage was determined, thereby taking patient demographic factors into account. The mean volumetric wear rate was 11.6 mm(3)/yr. Wear decreased with older age (p=0.021) and female sex (p=0.001). The wear rate increased with joint line elevation as indicated from a decreased Blackburne-Peel Index (p=0.019), and increased with increased posterior tibial slope (p = 0.026). The backside damage score also increased with joint line elevation (p=0.036). A Blackburne-Peel Index decrease of 0.1, signifying joint line elevation, was found to increase the wear rate by 1.8 mm(3)/yr and increase back-sided wear. A high tibial slope (>7°) led to a 9.3 mm(3)/yr increase in wear rate compared with a low tibial slope (

The aim of this study was to determine the effect of two in-vivo-determined gait patterns, one with low and one with high anteroposterior (AP) motion, on total and backside polyethylene insert wear in comparison with the ISO (International Organization for Standardization) standard 14243-3. In order to differentiate and accurately quantify topside and backside wear, a novel technique was employed where different lanthanide tracers were incorporated into the polyethylene during manufacture. Wear particle analysis was conducted following established protocols. For all tested liners and motion protocols, the chemically calculated wear rates correlated closely with gravimetrically determined wear. Both in vivo motion groups displayed higher wear rates than the ISO group following the order of the AP motion amplitudes. Backside wear for ISO constituted 2.76% ± 0.90% (mean ± SE) of the total wear, increasing significantly to 15.8% ± 3.2% for the low AP and further increasing to 19.3% ± 0.95% for the high AP motion protocol. The mean wear particle sizes were under 200 nm for all three motion patterns, being largest for the protocol with high AP motion. Particle release from the low and high AP gait patterns was 1.9 to 2.8 times that from the ISO protocol. Testing for the proportion of backside wear across various activities of daily living should be an important consideration in evaluating knee prostheses wear.

Backgrounds/aims Distal pancreatic resections are intricate operations with potential for significant morbidity; there is controversy surrounding the appropriate setting regarding surgeon/hospital volume. We report our distal pancreatectomy experience from a community-based teaching hospital. Methods This study includes all patients who underwent laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) for benign and malignant lesions between June 2004 and October 2017. Both groups were compared for perioperative characteristics, parenchymal resection technique, and outcomes. Results 138 patients underwent distal pancreatectomy during this time. The distribution of LDP and ODP was 68 and 70 respectively. Operative time (146 vs. 174 min), blood loss (139 vs. 395 ml) and mean length of stay (4.8 vs. 8.0 days) were significantly lower in the laparoscopic group. The 30-day Clavien Grade 2/3 morbidity rate was 13.7% (19/138) and the incidence of Grade B/C pancreatic fistula was 6.5% (9/138), with no difference between ODP and LDP. 30-day mortality was 0.7% (1/138). 61/138 resections had a malignancy on final pathology. ODP mean tumor diameter was greater (6.4 cm vs. 2.9 cm), but there was no significant difference in the mean number of harvested nodes (8.6 vs. 7.4). The cost of hospitalization, including readmissions and surgery was significantly lower for LDP ($7558 vs. $11610). Conclusions This series of distal pancreatectomies indicates a shorter hospital stay, less operative blood loss and reduced cost in the LDP group, and comparable morbidity and oncologic outcomes between LDP and ODP. It highlights the feasibility and safety of these complex surgeries in a community setting.

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4–10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta’s function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior–posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes., We show that the human hippocampus exhibits two distinct theta oscillations during spatial navigation with the faster oscillation in posterior regions showing movement modulation. This result suggests a distinct feature of the human hippocampus compared to rodents, which generally show a single 8 Hz rhythm.

Purpose: To analyze the changes in target vessel (TV) anatomy after fenestrated endovascular aneurysm repair (fEVAR) during midterm follow-up. Materials and Methods: A retrospective single-center study analyzed 56 patients (mean age 71±7 years; 49 men) who underwent fEVAR using custom-made stent-grafts (22 Zenith and 34 Anaconda) between June 2010 and July 2016. Advanta V12 (V12; 74, 53%) and BeGraft (BeG; 66, 47%) stent-grafts were used to bridge to the 140 TVs. Measurements of the TV deviation at the aortic origin, the vessel shift distal to the bridging stent-graft (BSG), and the outer and inner BSG curve lengths were performed after 3-dimensional reconstruction of the serial computed tomography angiography scans. The results of the measurements for the main devices, the TVs, and the bridging stent-grafts were compared using univariable and multivariable analysis. Results: Of the 140 BSGs examined (74 V12s and 66 BeGs), 393 measurements (38 celiac trunks, 102 superior mesenteric arteries, 121 left renal arteries, and 132 right renal arteries) were analyzed. The outer/inner BSG curve length ratio was larger after implantation of Zenith devices compared with Anaconda (p

OBJECTIVE: The aim of this pilot study was to evaluate intraoperative contrast-enhanced ultrasound (iCEUS) examination for endoleak (EL) detection after complex endovascular aortic repairs (EVAR) in comparison with the standard angiographic completion control.METHODS: Twenty-one patients (16 male; median age, 73 years [range, 54-81 years]) who underwent single-stage EVARs at our center between October 2016 and October 2018 were included prospectively. The procedures comprised fenestrated and/or branched EVAR (n = 14; 66%), infrarenal EVAR (n = 5; 24%), infrarenal EVAR with bilateral iliac side branch implantation (n = 1; 5%), and infrarenal EVAR with occluder implantation into the internal iliac artery (n = 1; 5%). The used endografts included 14 custom made devices (Cook, Australia Pty Ltd, Brisbane, Australia, n = 6; Vascutek Terumo, Glasgow, Scotland, n = 8) and seven standard infrarenal endografts (Medtronic Inc, Santa Rosa, Calif, n = 5; Vascutek Terumo, Glasgow, Scotland, n = 1; Cook, n = 1). All patients underwent an angiographic completion control for EL detection followed by iCEUS examination. The iCEUS examination was performed by the same examiner who was blinded to the angiography result. In addition to the comparison of the angiographic results to iCEUS examination, iCEUS examination was also compared with the computed tomography angiography (CTA) before discharge (median time to CTA, 5 days [range, 1-7 days]).RESULTS: Angiography detected eight type II EL, defining the EL origin in four cases. In addition to detecting all of those eight EL, iCEUS examination revealed eight more type II EL not seen on angiography (P = .002) and allowed a definition of the EL origin in all cases. CTA before discharge showed a persistence of only 5 of the 16 type II EL detected by iCEUS examination (31%, P = .002).CONCLUSIONS: An iCEUS examination can be used as another adjunct to decrease exposure to contrast agent and radiation during EVAR, including complex procedures. A replacement of the completion angiography by iCEUS examination is conceivable for infrarenal EVAR, but also for endovascular type IV or type V repairs. Future studies with larger patient numbers will help to further validate iCEUS examination during complex EVAR.

Recognizing and adopting standardized terms for adverse local tissue reaction associated with tribocorrosion in total hip arthroplasty are essential for clear scientific discourse and clinical communication. Our goal was to develop terms that can be broadly applied to characterize the local tissue response to tribocorrosion debris, based on current evidence regarding the etiology of this failure mode and its consequences. The proposed standardized terms will improve the understanding and interpretation of analytical tests, advance diagnostic and treatment algorithms, and reduce confusion in research by maintaining consistent nomenclature.

Perceived illness stigma is associated with increased depressive symptoms in youth with inflammatory bowel disease (IBD), but the mechanisms by which stigma influences emotional adjustment remain unclear. It is possible that youth with IBD who are more present-focused and better able to come to terms with aspects of their disease that are less controllable (i.e. are mindful) may develop more adaptive strategies when facing illness uncertainty, resulting in more positive emotional adjustment. The present study examined the indirect association between illness stigma, illness uncertainty, depressive symptoms, and the potential moderating effect of mindfulness on this process. One hundred and seven youth (56 female, 51 male; M

IntroductionZinc is well known for its anti-inflammatory effects, including regulation of migration and activity of polymorphonuclear neutrophils (PMN). Zinc deficiency is associated with inflammatory diseases such as acute lung injury (ALI). As deregulated neutrophil recruitment and their hyper-activation are hallmarks of ALI, benefits of zinc supplementation on the development of lipopolysaccharides (LPS)-induced ALI were tested.Methods64 C57Bl/6 mice, split into eight groups, were injected with 30 µg zinc 24 hours before exposure to aerosolised LPS for 4 hours. Zinc homoeostasis was characterised measuring serum and lung zinc concentrations as well as metallothionein-1 expression. Recruitment of neutrophils to alveolar, interstitial and intravascular space was assessed using flow cytometry. To determine the extent of lung damage, permeability and histological changes and the influx of protein into the bronchoalveolar lavage fluid were measured. Inflammatory status and PMN activity were evaluated via tumour necrosis factor α levels and formation of neutrophil extracellular traps. The effects of zinc supplementation prior to LPS stimulation on activation of primary human granulocytes and integrity of human lung cell monolayers were assessed as well.ResultsInjecting zinc 24 hours prior to LPS-induced ALI indeed significantly decreased the recruitment of neutrophils to the lungs and prevented their hyperactivity and thus lung damage was decreased. Results from in vitro investigations using human cells suggest the transferability of the finding to human disease, which remains to be tested in more detail.ConclusionZinc supplementation attenuated LPS-induced lung injury in a murine ALI model. Thus, the usage of zinc-based strategies should be considered to prevent detrimental consequences of respiratory infection and lung damage in risk groups.

Sub-lethal effects, such as oxidative stress, can be linked to various breeding and thermophysiological strategies, which themselves can be linked to seasonal variability in abiotic factors. In this study, we investigated the subterranean, social living Natal mole-rat (Cryptomys hottentotus natalensis), which, unlike other social mole-rat species, implements heterothermy seasonally in an attempt to avoid exercise-induced hyperthermia and relies solely on behavioural reproductive suppression to maintain reproductive skew in colonies. Subsequently, we investigated how oxidative stress varied between season, sex and breeding status in Natal mole-rats. Oxidative markers included total oxidant status (TOS measure of total peroxides present), total antioxidant capacity (TAC), OSI (oxidative stress index) and malondialdehyde (MDA) to measure oxidative stress. Breeding and non-breeding mole-rats of both sexes were captured during the summer (wet season) and winter (dry season). Seasonal environmental variables (air temperature, soil temperature and soil moisture) had a significant effect on TOS, OSI and MDA, where season affected each sex differently. Unlike other social mole-rat species that use both physiological and behavioural means of reproductive suppression, no oxidative costs to reproduction were present in the Natal mole-rats. Males had significantly higher MDA than females, which was most apparent in summer (wet season). We conclude that the significant oxidative damage in males is a consequence of exercise-induced oxidative stress, exacerbated by increased burrow humidities and poorer heat dissipation abilities as a function of body mass. This study highlights the importance of both breeding and thermophysiological strategies in affecting oxidative stress.

Disseminated intravascular coagulation (DIC) is a serious syndrome characterized by the systemic activation of blood coagulation resulting in the thrombosis of vessels leading to organ dysfunction and severe bleeding. When physicians try to treat DIC, it is imperative to diagnose and treat the underlying conditions. Anyone can be affected by DIC, but vulnerable groups such as pediatric populations, pregnant women and the elderly may be at higher risk. In this review, the current literature on DIC in pregnancy, the pediatric population, and the elderly is reported. This review also highlights the similarities and differences in the etiology, clinical presentation, diagnosis, and management of DIC in the aforementioned groups (i.e., pediatrics, pregnant women, and the elderly). Findings from this study may help increase awareness about various presentations of DIC in these groups to facilitate rapid recognition of symptoms leading to correct diagnoses.

Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, is commonly used as an anesthetic and analgesic but has recently shown promising research in treating certain psychiatric conditions such as depression, post-traumatic stress disorder (PTSD), suicidal ideation, and substance use disorder. Due to its euphoric, dissociative, and hallucinogenic properties, ketamine has been abused as a recreational drug, which has led to rigid regulation of medication. The COVID-19 pandemic has been an unprecedented challenge for the American population which was reflected in increased reports of problems regarding their mental health. Mood disorders have dramatically increased in the past two years. Approximately one in ten people stated that they had started or increased substance use because of the COVID-19 pandemic. Furthermore, rates of suicidal ideation have significantly increased when compared to pre-pandemic levels, with more than twice the number of adults surveyed in 2018 indicating suicidal thoughts "within the last 30 days" at the time they were surveyed. Moreover, many responders indicated they had symptoms of PTSD. The PubMed database was searched using the keyword "ketamine," in conjunction with "depression," "suicidal ideation," "substance use disorder," and "post-traumatic stress disorder." The inclusion criteria encompassed articles from 2017 to 2022 published in the English language that addressed the relationship between ketamine and mental health disorders. With this sharp increase in the prevalence of psychiatric disorders and an increased public interest in mental health combined with the promise of the therapeutic value of ketamine for certain mental health conditions, including suicidal ideation, this narrative review sought to identify recently published studies that describe the therapeutic uses of ketamine for mental health. Results of this review indicate that ketamine's therapeutic effects offer a potential alternative treatment for depression, suicidal ideation, substance use disorders, and PTSD.

Before COVID-19, preclinical medical students traditionally attended didactic lectures in in-person settings. Due to social distancing, students were required to switch to online meeting platforms, such as Zoom. For medical students accustomed to in-person interactions, these changes may add more stress to the already stressful medical school experience. Furthermore, it was unclear if students' stress levels were related to their preference for one learning modality over another. The purpose of this study was thus to explore associations between lecture modality (synchronous Zoom lectures versus live, in-person lectures) and stress in second-year medical students after they transitioned from a face-to-face learning experience to a fully online lecture platform.Cross-sectional data were collected from 112 second-year medical students enrolled in a large U.S. medical school using an anonymous questionnaire delivered electronically via social media and emails. The survey contained items pertaining to students' attitudes towards different types of lecture modalities and how they relate to personal stress. Descriptive data and Spearman's rank correlation tests were conducted using IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp.This study examined correlations between preclinical medical school lecture delivery and personality type, stress levels, attendance, and burnout. Overall, no significance was found between mode of delivery and personality type. On the other hand, the mode of delivery significantly affected stress levels, attendance, and burnout. Moderate to strong correlations were found between the item "Zoom lectures have reduced stress compared to in-person lectures" and preference for Zoom, quality of education using Zoom compared to the in-person lectures, belief that Zoom lectures should continue as part of the curriculum delivery method, staying motivated with lectures fully online with Zoom, and liking that Zoom lectures save commute time to campus.Findings suggest that a fully online curriculum may play a role in reducing stress in medical students without compromising the quality of education.

While the primary goal of focal therapy for prostate cancer (PCa) is conserving patient quality of life by reducing oncological burden, available modalities use thermal energy or whole-gland radiation which can damage critical neurovascular structures within the prostate and increase risk of genitourinary dysfunction. High-frequency irreversible electroporation (H-FIRE) is a promising alternative ablation modality that utilizes bursts of pulsed electric fields (PEFs) to destroy aberrant cells via targeted membrane damage. Due to its nonthermal mechanism, H-FIRE offers several advantages over state-of-the-art treatments, but waveforms have not been optimized for treatment of PCa. In this study, we characterize lethal electric field thresholds (EFTs) for H-FIRE waveforms with three different pulse widths as well as three interpulse delays in vitro and compare them to conventional irreversible electroporation (IRE). Experiments were performed in non-neoplastic and malignant prostate cells to determine the effect of waveforms on both targeted (malignant) and adjacent (non-neoplastic) tissue. A numerical modeling approach was developed to estimate the clinical effects of each waveform including extent of nonthermal ablation, undesired thermal damage, and nerve excitation. Our findings indicate that H-FIRE waveforms with pulse durations of 5 and 10 μs provide large ablations comparable to IRE with tolerable levels of thermal damage and minimized muscle contractions. Lower duration (2 μs) H-FIRE waveforms exhibit the least amount of muscle contractions but require increased voltages which may be accompanied by unwanted thermal damage.

Water storage plays an important role in mitigating heat and flooding in urban areas. Assessment of the water storage capacity of cities remains challenging due to the inherent heterogeneity of the urban surface. Traditionally, effective storage has been estimated from runoff. Here, we present a novel approach to estimate effective water storage capacity from recession rates of observed evaporation during precipitation-free periods. We test this approach for cities at neighborhood scale with eddy-covariance based latent heat flux observations from 14 contrasting sites with different local climate zones, vegetation cover and characteristics, and climates. Based on analysis of 583 drydowns, we find storage capacities to vary between 1.3 and 28.4 mm, corresponding to e-folding timescales of 1.8-20.1 days. This makes the urban storage capacity at least five times smaller than all the observed values for natural ecosystems, reflecting an evaporation regime characterized by extreme water limitation.

Brain function depends on neural communication, but the mechanisms of this communication are not well understood. Recent studies suggest that one form of neural communication is through traveling waves (TWs)—patterns of neural oscillations that propagate within and between areas. We show that TWs appear robustly in microarray recordings in monkey frontal and parietal cortex and encode memory for recent rewards. While making saccades to obtain probabilistic rewards, monkeys were sensitive to the (statistically irrelevant) prior reward, which is consistent with behavioral biases produced by reward history. TWs in frontal and parietal areas were stronger in trials following a prior reward versus a lack of reward and, in the frontal lobe, correlated with the monkeys’ sensitivity to the prior reward. The findings suggest that neural communication across fronto-parietal areas, reflected by TWs, maintains default reward memories, while communication within the frontal lobe mediates the read out of the memories for prospective expectations.

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Diplopia is a common non-motor symptom in patients with Parkinson’s disease (PD) affecting 1/3rd of patients. We used high-resolution video-oculography to demonstrate that diplopia in PD arises from disruption of binocular co-ordination of eye movements. Using video-oculography we measured fixation eye movements, the angle and control of eye alignment and its correlation to convergence insufficiency in 13 PD patients and 6 healthy controls. We found that all PD patients had larger amplitude of fixational saccades with increased inter-saccadic drifts particularly of the non-fixing or non-viewing eye. Eye movement recordings suggest that the extent of eye alignment varies across PD subjects, 38% had good eye alignment and control under monocular and binocular viewing similar to controls (Group1). 62% of PD patients had increase in eye position difference, which was outside the threshold window of good alignment under monocular and binocular viewing (Group2 PD). PD subjects with good eye alignment were less likely to exhibit saccadic responses to disparity-driven vergence whereas those with poor control and worse eye alignment were more likely to exhibit saccadic responses with staircase saccades. A cohort of PD patients (Group2) exhibited pure vergence or combined vergence/saccade responses; they had deficits of both fusion initiating (prolonged latencies, reduced gain and peak vergence velocities) and fusion sustaining components (increased eye position variance). The results demonstrate that the vergence abnormalities in PD subjects systematically correlate with both the angle and control of eye alignment. Further, our data suggests an interaction between the vergence and saccade subsystems in PD patients. Abnormalities of vergence in PD may be the result of direct effects of the disease on vergence motor control, coupled with disturbances in the saccadic pathway indirectly leading to effects on vergence.

Background The advent of the coronavirus disease 2019 (COVID-19) has generated varying opinions toward adhering to safety protocols among public health experts. With decreasing restrictions on public gatherings, lax protective behaviors, distortion of facts, and increasing availability of COVID-19 vaccines, response to public health guidelines vary greatly. Personal experiences with COVID-19, education, and work environment may influence decisions on safety recommendations and vaccination protocols among the public and healthcare professionals alike. To better understand how individuals process and make decisions regarding COVID-19 safety measures, this study investigated the attitudes among clinical and non-clinical healthcare workers and non-healthcare workers toward COVID-19 safety protocols. Methodology Cross-sectional data were collected from Florida residents using an online, 20-item anonymous questionnaire. Participants were recruited using the Florida Department of Health database for physician emails, social media, and snowball sampling strategies. The survey consisted of demographic items and questions regarding patient attitudes toward safety protocols for COVID-19 (e.g., likeliness to wear a mask in public despite state regulations being lifted, maintaining a distance of at least 6 feet between close friends and family, dining at restaurants/bars, gathering in groups larger than 10 people, getting a COVID-19 vaccine if one becomes available). Data were analyzed using one-way analysis of variance and chi-square test using SPSS version 27 (IBM Corp., Armonk, NY, USA). Results Of the 373 participants who completed the survey, 183 (49.1%) worked in the healthcare field, with 100 (28.6%) providing direct patient care. The rest (n = 190; 50.9%) reported that they do not work in the healthcare industry. Findings suggest that those working in healthcare with direct involvement in patient care were more likely to get the COVID-19 vaccine than those not working in healthcare. Additionally, those working in healthcare and providing direct patient care were more likely to think that masks were effective in reducing the spread of COVID-19 compared to those who worked in healthcare but did not provide direct patient care. Conclusions This study provides new insights into the attitudes of front-line clinicians, non-clinical healthcare workers, and the general population. Increasing health promotion efforts and debunking myths about COVID-19 may prove useful in mitigating the spread of the disease.

Background Medical students' confidence in their ability to conduct research has been speculated to be a significant factor influencing the engagement of research, yet their confidence may remain low. Moreover, it is unclear what barriers exist to high engagement in research before graduation. Hence, the objective of this study was to investigate medical students' attitudes, confidence, and perceived barriers regarding conducting research. Methodology A cross-sectional study was conducted using quantitative and qualitative methods to investigate medical students' attitudes, confidence, and perceived barriers regarding doing research. Quantitative data were collected from 141 first-year medical students via an online questionnaire in September 2020 asking about their perceptions toward participating in research while in school. Linear regression was performed to determine if certain perceptions and self-reported abilities would significantly contribute to research confidence. Additionally, focus groups were conducted with 30 students to assess student perceptions toward engaging in research. For qualitative data, an inductive thematic analysis was performed to allow for the patterns, themes, and categories to emerge. Results Regression modeling successfully explained 71% of the variance in predicting research confidence [F(3,137) = 116.91, p0.01] with an R

Studies of the immune response at the site of disease in extra-pulmonary tuberculosis (EPTB) disease are scarce. In this study, we compared the cellular profile of Mycobacterium tuberculosis (Mtb)-specific T cells in pericardial fluid and peripheral blood in patients with pericardial TB (PCTB). Whole blood and pericardial fluid (PCF) samples were collected at the time of diagnostic sampling, with repeat blood sampling after completion of anti-tubercular treatment (ATT) in 16 PCTB patients, most of them being HIV-1 infected (n=14). These samples were stimulated ex vivo and the phenotypic and functional cellular profile of PCF and blood was assessed by flow cytometry. We found that lymphocytes were the predominant cell type in PCF in PCTB, with a preferential influx of CD4 T cells. The frequencies of TNF-α producing Mtb-specific granulocytes and Mtb-specific CD4 T cells were significantly higher in PCF compared to blood. Mtb-specific CD4 T cells in PCF exhibited a distinct phenotype compared to those in blood, with greater GrB expression and lower CD27 and KLRG1 expression. We observed no difference in the production IFNγ, TNF or IL-2 by Mtb-specific CD4 T cells between the two compartments, but MIP-1β production was lower in the PCF T cells. Bacterial loads were not associated with alterations in the phenotype or function of Mtb-specific CD4 T cells. Upon ATT completion, HLA-DR, Ki-67 and GrB expression was significantly decreased, and relative IL-2 production was increased in peripheral Mtb-specific CD4 T cells. Overall, using an ex vivo assay to compare the immune response towards Mtb in PCF and in blood, we identified significant difference in the phenotypic profile of Mtb-specific CD4 T response between these two compartments. Moreover, we show that the activation profile of peripheral Mtb-specific CD4 T cells could be used to monitor treatment response in PCTB.

Innovation - the ability to solve problems in a novel way - is not only associated with cognitive abilities and relative brain size, but also by noncognitive traits, such as personality and motivation. We used a novel foraging task with three access options to determine how neophobia, exploration, and persistence influence innovation in 12 habituated bat-eared foxes (Otocyon megalotis) in the Kalahari Desert. Bat-eared foxes offer a unique system to understand cognition as they have the smallest relative brain size of measured canids and a specialized, termite-based diet, yet have displayed foraging innovations. Interestingly, most of our individuals solved the task at least once and six individuals solved the task in every trial. Neophobia did not influence success on the first trial, but both exploration and persistence influenced success across all trials. Those individuals that solved the puzzle over multiple trials became faster over time, suggesting that they learned how to open the box more efficiently. We found some variation in the method to open the puzzle box with six individuals solving the puzzle using two methods and one individual using all three methods. This is the first study to show innovation in a novel foraging task in wild bat-eared foxes.

Medicina 58(11), 1594 (2022). doi:10.3390/medicina58111594 special issue: "Special Issue "Modern Endovascular Therapy for Peripheral Arterial Disease" / Special Issue Editors: Dr. Florian Enzmann, Guest Editor; Prof. Dr. Sabine Helena Wipper, Guest Editor", Published by Kaunas Univ. of Medicine, Kaunas

ObjectivesTo reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes.SettingHospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems.Participants425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set.Primary and secondary outcomesWe measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host–response biomarkers, SARS-CoV-2 RNA load and clinical outcomes.ResultsInter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). In the discovery cohort, the required level of respiratory support at the time of CXR acquisition (supplemental oxygen or non-invasive ventilation (n=178); invasive-mechanical ventilation (n=234), extracorporeal membrane oxygenation (n=13)) was significantly associated with RALE scores (median (IQR): 20.0 (14.1–26.7), 26.0 (20.5–34.0) and 44.5 (34.5–48.0), respectively, pConclusionsWith a reproducible method to measure radiographic severity in COVID-19, we found significant associations with clinical and physiologic severity, host inflammation and clinical outcomes. The incorporation of radiographic severity assessments in clinical decision-making may provide important guidance for prognostication and treatment allocation in COVID-19.

Ti6Al4V is the most common titanium alloy within the biomaterial field. While material standards for different variations of this alloy exist, there are only minimal requirements with respect to its microstructure which is directly related to the alloy's properties. Thus, a better understanding of the Ti6Al4V microstructure of common contemporary implant components and its effect on the electrochemical behavior is needed; including additively manufactured (AM) devices. Therefore, this study aimed at characterizing the microstructures of conventional and AM total joint replacement components, and to identify the effect of microstructure on the electrochemical behavior. Thus, 22 components from conventional (surgically retrieved cast and wrought implants) and AM implants (not previously implanted) were analysed to characterize microstructure by means of electron backscatter diffraction (EBSD) and energy dispersive X-Ray spectroscopy (EDS), and tested to determine its electrochemical behavior (potentiodynamic polarization and EIS). The microstructure of the conventional implants varied broadly but could be categorized into four groups as to their grain size and shape: fine equiaxed, coarse equiaxed, bimodal, and lamellar. The AM components exhibited a fifth category: lath-type. The AM components had a network of β-phase along the α-phase grain boundaries, prior β-grains, and manufacturing voids. Finally, the electrochemical study showed that the equiaxed coarse grains and lath-type grains (AM components) had inferior electrochemical behavior, whereas cast alloys had superior electrochemical behaviour; fine-grained wrought alloys likely provide the best compromise between electrochemical and mechanical properties.