The Effect of Multi-Session Prefrontal Cortical Stimulation on Aggression: A Randomized, Double-Blind, Parallel-Group Trial.

Findings from brain imaging studies investigating the neural underpinnings of antisocial behavior have implicated the prefrontal cortex in the regulation of aggressive reactions. However, relatively few studies have examined the role of the prefrontal cortex on aggression in an experimental way. This study examines whether upregulating the prefrontal cortex using repeated transcranial direct current stimulation (tDCS) reduces aggressive behavior. In a double-blind, parallel-group, randomized controlled trial, 88 healthy adults (42 males, 46 females) were assigned to one session of anodal tDCS over the ventromedial prefrontal cortex (n = 47) or sham stimulation (n = 41) per day for three consecutive days and assessed using a behavioral measure of aggression. Levels of aggressive responses post-intervention did not significantly differ between the active and sham stimulation groups. However, a significant interaction effect between the stimulation group and gender was observed, whereby males, but not females, exhibited reduced aggression after prefrontal stimulation. To the authors' knowledge, this is the first study to examine the effect of multi-session prefrontal tDCS on aggressive behavior in healthy adults. Results highlight that there are differences in responsivity to tDCS in modifying aggressive behavior.

Genicular nerve block for emergency department patient: a successful management of subacute osteoarthritic knee pain.

The genicular nerve block (GNB) performed under ultrasound is a common procedure in the perioperative and outpatient setting for the treatment of surgical knee pain and osteoarthritis. It provides motor-sparing analgesia to the knee, making it a potential alternative to other modes of pain management in the emergency department (ED). We present an elderly woman with acute-on-chronic osteoarthritic knee pain which was relieved for a week after a GNB during her ED visit. In patients with knee pain, the ultrasound guided GNB has the potential to provide short-term analgesia for patients with pain refractory to other modes of analgesia. The GNB shows promise as a reliable contribution to a multimodal approach to pain management in the ED setting.

Rectal MRI radiomics for predicting pathological complete response: Where we are.

Radiomics using rectal MRI radiomics has emerged as a promising approach in predicting pathological complete response. In this study, we present a typical pipeline of a radiomics analysis and review recent studies, exploring applications, development of radiomics methodologies and model construction in pCR prediction. Finally, we will offer our opinion about the future and discuss the next steps of rectal MRI radiomics for predicting pCR.

Roles for L o microdomains and ESCRT in ER stress-induced lipid droplet microautophagy in budding yeast.

Microlipophagy (µLP), degradation of lipid droplets (LDs) by microautophagy, occurs by autophagosome-independent direct uptake of LDs at lysosomes/vacuoles in response to nutrient limitations and ER stressors in Saccharomyces cerevisiae. In nutrient-limited yeast, liquid-ordered (Lo) microdomains, sterol-rich raftlike regions in vacuolar membranes, are sites of membrane invagination during LD uptake. The endosome sorting complex required for transport (ESCRT) is required for sterol transport during Lo formation under these conditions. However, ESCRT has been implicated in mediating membrane invagination during µLP induced by ER stressors or the diauxic shift from glycolysis- to respiration-driven growth. Here we report that ER stress induced by lipid imbalance and other stressors induces Lo microdomain formation. This process is ESCRT independent and dependent on Niemann-Pick type C sterol transfer proteins. Inhibition of ESCRT or Lo microdomain formation partially inhibits lipid imbalance-induced µLP, while inhibition of both blocks this µLP. Finally, although the ER stressors dithiothreitol or tunicamycin induce Lo microdomains, µLP in response to these stressors is ESCRT dependent and Lo microdomain independent. Our findings reveal that Lo microdomain formation is a yeast stress response, and stress-induced Lo microdomain formation occurs by stressor-specific mechanisms. Moreover, ESCRT and Lo microdomains play functionally distinct roles in LD uptake during stress-induced µLP.

Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.

Membrane dynamics and protein targets of lipid droplet microautophagy during ER stress-induced proteostasis in the budding yeast, Saccharomyces cerevisiae.

Our previous studies reveal a mechanism for lipid droplet (LD)-mediated proteostasis in the endoplasmic reticulum (ER) whereby unfolded proteins that accumulate in the ER in response to lipid imbalance-induced ER stress are removed by LDs and degraded by microlipophagy (µLP), autophagosome-independent LD uptake into the vacuole (the yeast lysosome). Here, we show that dithiothreitol- or tunicamycin-induced ER stress also induces µLP and identify an unexpected role for vacuolar membrane dynamics in this process. All stressors studied induce vacuolar fragmentation prior to µLP. Moreover, during µLP, fragmented vacuoles fuse to form cup-shaped structures that encapsulate and ultimately take up LDs. Our studies also indicate that proteins of the endosome sorting complexes required for transport (ESCRT) are upregulated, required for µLP, and recruited to LDs, vacuolar membranes, and sites of vacuolar membrane scission during µLP. We identify possible target proteins for LD-mediated ER proteostasis. Our live-cell imaging studies reveal that one potential target (Nup159) localizes to punctate structures that colocalizes with LDs 1) during movement from ER membranes to the cytosol, 2) during microautophagic uptake into vacuoles, and 3) within the vacuolar lumen. Finally, we find that mutations that inhibit LD biogenesis, homotypic vacuolar membrane fusion or ESCRT function inhibit stress-induced autophagy of Nup159 and other ER proteins. Thus, we have obtained the first direct evidence that LDs and µLP can mediate ER stress-induced ER proteostasis, and identified direct roles for ESCRT and vacuolar membrane fusion in that process.

Feasibility of Mynxgrip®-Assisted Percutaneous Transhepatic Portal Venous Access Closure.

PURPOSE: Life-threatening bleeding may occur following percutaneous portal venous access procedures. Various embolic agents have been utilised to minimise this risk, each with their own disadvantages, including inadvertent embolization of the portal vein and inadequate tract embolization. We aim to assess the feasibility of a novel approach to percutaneous portal venous access closure by utilising the MYNXGRIP® vascular closure device (Cardinal Health, USA). MATERIALS AND METHODS: This retrospective study analysed 20 patients who underwent interventional radiological procedures with closure of the percutaneous transhepatic portal venous access tract using the MYNXGRIP® closure device with either N-butyl cyanoacrylate or thick gelatin paste. RESULTS: None of these patients demonstrated clinical evidence of post-procedural haemorrhage, which was further confirmed on abdominal imaging in 15 of these patients. CONCLUSION: MYNXGRIP®-assisted percutaneous transhepatic portal venous access closure is feasible and able to achieve haemostasis with minimal embolization risk.

Biofilm and Infectious Agents Present at the Time of Penile Prosthesis Revision Surgery: Times Are a Changing.

INTRODUCTION: Although infection rates have decreased with the use of antibiotic-coated implants and other enhancements, the risk of infection is still considered a serious concern in penile implant revision surgeries. AIM: To review the literature for advances made in inflatable penile prosthesis (IPP) revision surgery and organisms found at the time of revision, the significance of biofilm in prosthetic infection, and the bacteriology of infection. METHODS: PubMed was reviewed for articles spanning the past three decades that discussed micro-organisms and biofilm in relation to penile implant revision surgery. MAIN OUTCOME MEASURES: All articles were reviewed for evidence of bacteria found at revision IPP surgeries and any improvements made in surgical techniques and prosthesis enhancements. RESULTS: During the period examined, several improvements have lowered the rate of infection in penile implant surgery: notably, antibiotic-coated IPPs, revision washout, and alcohol-based skin preparations. The biofilm composition on clinically uninfected and infected IPPs appears to have changed over time. The abundance of staphylococcal species-particularly coagulase-negative organisms-in positive cultures has decreased in infected implants, and clinically uninfected implants also have shown a decrease in the proportion of staphylococcal species. Conversely, other isolates such as fungi, Escherichia coli, and Enterococcus species have increased in clinically uninfected and infected implants, and there has been an overall increase in unique isolates that form the biofilm. CONCLUSION: A multitude of enhancements has decreased the presence of micro-organisms and the subsequent formation of biofilm. Nevertheless, the formation of biofilm on penile implants has been noted more frequently in the past decade, and the microbial composition of biofilms seems to be changing. Dawn LE, Henry GD, Tan GK, Wilson SK. Biofilm and Infectious Agents Present at the Time of Penile Prosthesis Revision Surgery: Times Are a Changing. Sex Med Rev 2017;5:236-243.

Causes of hepatic capsular retraction: a pictorial essay.

Hepatic capsular retraction refers to the loss of the normal convex hepatic contour, with the formation of an area of flattening or concavity. This can result from myriad causes, including intrinsic hepatic conditions such as cirrhosis, biliary obstruction, benign tumours, malignancy and infections, as well as extrahepatic causes such as trauma. This article aims to provide familiarity with this wide spectrum of conditions, including mimics of hepatic capsular retraction, by highlighting the anatomic, pathologic and imaging features that help distinguish these entities from one another. TEACHING POINTS: • Hepatic capsular retraction can occur due to various intrinsic or extrinsic hepatic causes. • Hepatic capsular retraction is observed in both benign and malignant conditions. • Recognising associated imaging features can help elicit causes of hepatic capsular retraction.

Are we fearful of tubeless percutaneous nephrolithotomy? Assessing the need for tube drainage following percutaneous nephrolithotomy.

OBJECTIVE: The objective was to demonstrate that percutaneous nephrolithotomy (PCNL) can be safely performed with a tubeless or totally tubeless drainage technique. INTRODUCTION: Standard PCNL includes nephrostomy tube placement designed to drain the kidney and operative tract at the conclusion of the procedure. Modern technique trend is tubeless PCNL and totally tubeless PCNL, which are performed without standard nephrostomy drainage. We aim to reinforce current literature in demonstrating that PCNL can be safely performed using a tubeless technique. With compounded supportive data, we can help generate a trend toward a more cost-effective procedure with improved pain profiles and patient satisfaction, as previously shown with the tubeless technique. METHODS: Retrospective analysis of 165 patients who underwent PCNL treatment was performed. Of this group, 127 patients underwent traditional nephrostomy drainage following PCNL. A tubeless procedure was performed in the remaining 38 patients. Patient's postoperative stone size and burden as well as complication profiles were analyzed. Largest stone size and total stone burden was similar between the groups. RESULTS: Patient characteristics and demographic information were compared and no significant statistical difference was identified between the groups. Complication rates between the groups were compared and no statistical difference was noted. A total of 23 patients had at least one postoperative complication. CONCLUSION: Tubeless and totally tubeless PCNL demonstrates equivalent outcomes in the properly selected patient group when compared to PCNL performed with a nephrostomy tube. Although this is not the first study to demonstrate this, a large majority of urologists continue standard nephrostomy placement after PCNL. More studies are needed that demonstrate safety of this practice to shift the pendulum of care. Thus, tubeless and totally tubeless PCNL can be performed safely and effectively, which has previously been shown to improve cost, patient pain profiles, and length of hospitalization.

Adrenal congestion preceding adrenal hemorrhage on CT imaging: a case series.

INTRODUCTION: Adrenal hemorrhage is an uncommon but potentially life-threatening condition, particularly in cases of bilateral adrenal hemorrhage causing primary adrenal insufficiency. It is difficult to diagnose clinically, particularly in critically ill patients, given its non-specific symptoms and signs, which include abdominal pain, vomiting, fever, weakness, hypotension, and altered conscious state. Non-traumatic adrenal hemorrhage has been observed to occur in times of physiological stress, such as post-surgery, sepsis, burns, and hypotension. This is hypothesized to be due to a combination of increased arterial blood flow to the adrenal glands, the paucity of draining adrenal venules and adrenal vein thrombosis, leading to intra-glandular vascular congestion and subsequent hemorrhage. CASE SERIES: We present four cases of non-traumatic adrenal hemorrhage, which demonstrated features of preceding adrenal congestion (adrenal gland thickening and peri-adrenal fat stranding) on computed tomography (CT) imaging. Comparison was made with 12 randomly selected intensive care patients to observe if these findings were prevalent in this subgroup of patients. CONCLUSION: Non-traumatic adrenal hemorrhage is an uncommon condition that is difficult to diagnose clinically. As such, it may be useful to recognize CT features of adrenal congestion as a sign for potential adrenal dysfunction and subsequent adrenal hemorrhage, so early steroid replacement therapy can be commenced to prevent death from adrenal insufficiency.

Intraocular pressure lowering is associated with an increase in the photopic negative response (PhNR) amplitude in glaucoma and ocular hypertensive eyes.

PURPOSE: The aim of our study was to determine whether IOP lowering in glaucomatous and ocular hypertensive (OHT) eyes leads to an improvement in the full-field photopic negative response (PhNR) of the electroretinogram. METHODS: A prospective nonrandomized interventional cohort study was conducted. Patients with OHT or glaucomatous optic neuropathy were recruited, and photopic full-field electroretinograms (ERG) were performed at baseline and then repeated 1 to 2 months later. The change in PhNR amplitude was compared between those eyes that had a significant lowering in IOP (defined as >25% decrease from baseline or to a predetermined target IOP) during follow-up and those that did not. RESULTS: From a cohort of 30 eyes, 18 eyes had a significant reduction in IOP during follow-up (n = 18) and 12 eyes had no significant change in IOP (<25% reduction in IOP, n = 12). A significant increase in PhNR amplitude and the PhNR/b-wave amplitude ratios was observed in the reduced IOP group, but not in the IOP stable group for the two flash intensities used (2.25 and 3.00 cd.s/m(2)). CONCLUSIONS: The full-field PhNR amplitude provides a potentially reversible measure of inner retinal function that improves after IOP lowering. Further study now is required to assess its use as a measure of optic nerve health in glaucoma patients.