Impact of high MELD scores on CMV viremia following liver transplantation.

INTRODUCTION: Advanced liver disease or cirrhosis is associated with an increased risk of infections; however, the impact of high pretransplant model for end-stage liver disease (MELD) score on cytomegalovirus (CMV) viremia after liver transplantation is unknown. METHODS: This single-center, retrospective, cohort study evaluated CMV high-risk (CMV immunoglobulin G D+/R-) liver transplant recipients who received valganciclovir prophylaxis for 3 months between 2009 and 2019. Patients were stratified by pretransplant MELD score of <35 (low MELD) and ≥35 (high MELD). The primary outcome was 12-month CMV viremia, and secondary outcomes included CMV resistance and tissue invasive disease, mortality, biopsy-proven acute rejection (BPAR), leukopenia, and thrombocytopenia. Multivariable Cox proportional-hazards modeling was used to assess the association of MELD score with the time to CMV viremia. RESULTS: There were 162 and 79 patients in the low and high MELD groups, respectively. Pretransplant MELD score ≥35 was associated with an increased risk of CMV viremia (hazard ratio [HR] 1.73; confidence interval 1.06-2.82, p = .03). CMV viremia occurred at 162 ± 61 days in the low MELD group and 139 ± 62 days in the high MELD group. Although BPAR occurred early at 30 days (13-59) in the low-MELD group and at 18 days (11-66) in the high-MELD group (p = .56), BPAR was not associated with an increased risk of CMV viremia (HR 1.55 [0.93-2.60], p = .1). DISCUSSION: MELD scores ≥35 were associated with an increased hazards of CMV viremia. In liver transplant recipients with MELD scores ≥35 who are CMV high-risk, additional CMV intervention may be warranted.

A Narrative Review of the Evaluation and Management of Liver Transplant Complications in the Emergency Department.

BACKGROUND: Liver transplant recipients are prone to both short-term and long-term complications and may present to any emergency department. OBJECTIVE: This narrative review summarized key aspects of liver transplantation and reviewed the major complications that may result in emergency department presentation. DISCUSSION: Liver transplantation is the only curative therapy for end-stage liver disease and the liver is the second most commonly transplanted solid organ. With nearly 100,000 living liver transplant recipients in the United States, these patients no longer present exclusively to transplantation centers. Critical complications may manifest with a variety of subtle signs and symptoms that must be considered by the emergency physician. Appropriate evaluation often includes laboratory analysis and imaging. Treatment may be time-sensitive and is variable depending on the specific complication. CONCLUSIONS: Emergency physicians in all settings must be prepared to evaluate and treat liver transplant recipients who present with potential graft- and life-threatening complications.

EFFECTIVENESS OF UNILATERAL ADRENALECTOMY IN BILATERAL ADRENAL INCIDENTALOMA PATIENTS WITH SUBCLINICAL HYPERCORTISOLEMIA.

Objective: Unilateral adrenalectomy (UA) is an alternative for treatment in bilateral adrenal incidentaloma (AI) to avoid possible long-term risks of bilateral adrenalectomy. In this study, we aimed to evaluate the effectiveness of UA in bilateral AI patients with subclinical hypercortisolemia (SH). Method: A total of 35 patients were included in this study. The patients were divided into two groups; those who underwent UA (n=27) and patients without adrenalectomy (PWA) (n=8). Hormone tests related to cortisol mechanism were reviewed to analyze results at the time of diagnosis compared to the latest available results to figure out any changes in cortisol mechanism and determine whether SH has recovered or not. Results: Median age of PWA group were higher compared to UA group (p=0.03). Median duration of follow-up in groups were similar (p=0.3). In the PWA group, none of the patients recovered from hypercortisolemia during their follow-up. In UA group 92.6% of the patients went into remission, whereas during follow-up 3.3% had recurred and another 3.3% were found to have post-adrenalectomy persistent SH. Patients in UA group had lower final cortisol level following dexamethasone suppression (p=0.003) and higher final adrenocorticotrophic hormone (ACTH) levels (p=0.001) than patients in PWA group. In UA group, final basal cortisol level (p=0.009) and final cortisol level after 1 mg dexamethasone suppression test (DST) (p=0.004) were lower than corresponding levels at the time of diagnosis. Discussion: Our study demonstrates unilateral adrenalectomy targeting the side with the larger lesion is an effective approach to reduce excess cortisol levels in bilateral AI patients with SH.

Preoperative Therapeutic Plasma Exchange and Surgical Treatment in Thyrotoxicosis Patients: A Single-Centre Retrospective Cohort Study.

Context: Therapeutic plasma exchange (TPE) provides time for thyroidectomy in thyrotoxic patients. Objective: TPE is indicated in cases where antithyroid medications cannot be used due to the side effects or attain no adequate hormonal suppression response at the highest dosage and in cases of rapid onset of clinical symptoms. This study presents the treatment results of patients who underwent TPE and were subsequently operated for thyrotoxicosis. Design: The patients who underwent thyroidectomy and TPE between January 1999 and February 2019 were retrospectively analyzed. Subjects and Methods: The files of 27 patients with thyrotoxicosis who performed TPE prior to surgery were analyzed in relation to the demographic and clinical features. Results: We included 15 (55.6%) females, 12 (44.4%) males with a mean age of 44 (23-82) years. The pre-TPE mean free thyroxine (fT4) level was 12 (5-46) pmol/L while free tri-iodothyronine (fT3) level was 34 (17-141) pmol/L. The post-TPE fT4 level was 6 (3-10) pmol/L while the fT3 level was 21 (12-41). There was one case of an allergic reaction during the procedure. In the postoperative follow-up, there was transient hypocalcemia in 8 (29%) patients, permanent hypocalcemia in 1 (3.7%) patient, and surgical site infection in 1 (3.7%) patient. Conclusion: Preoperative TPE is an alternative treatment option for thyrotoxic patients. This is an especially effective treatment for patients with inadequate response or adverse reaction to antithyroid drugs or patients who need urgent surgery for thyroid storm.

Pericardial Type 1 Parathyromatosis: A very rare cause of primary hyperparathyroidism.

BACKGROUND: Parathyromatosis is a rare clinical condition where hyperfunctioning parathyroid tissue is scattered in the neck and the mediastinum. It is difficult to diagnose and manage due to recurrent or persistent hyperparathyroidism. CASE REPORT: We present a peculiar case of hyperparathyroidism as the parathyroid tissue was in unusual location. Scintigraphy done revealed a lesion suspicious for ectopic parathyroid tissue in the retrosternum in a 58 years old female patient with primary hyperparathyroidism. No pathologic lesions were found on neck exploration, subsequently, sternotomy was performed and suspicious lesion removed but microscopic evaluation of the frozen section found no parathyroid tissue in the resected specimen. A decision to perform thymectomy and total resection of pericardial fatty tissue was made. Final histopathology revealed parathyromatosis and confirmed the first case of pericardial type 1 parathyromatosis. CONCLUSION: Long-term remission is rare in these patients, sometimes needing medical treatment and multiple surgeries. In this patient, there was no recurrence during the four years follow-up. In patients with no history of neck surgery, primary parathyromatosis should be considered in the differential diagnosis of hyperparathyroidism.

Clinical outcomes of valganciclovir prophylaxis in high-risk (D+/R-) renal transplant recipients experiencing delayed graft function.

BACKGROUND: Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear. METHODS: This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n = 72) versus those with immediate graft function (IGF; n = 66). RESULTS: Cytomegalovirus viremia by 12 months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P = 0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P = 0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P = 0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P = 0.62) or patient survival (98.5% vs 95.8%, P = 0.62) at 1 year between the IGF and DGF groups, respectively. CONCLUSION: Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.

Can N-terminal pro B-type natriuretic peptide, neutrophil-to-lymphocyte ratio, C-reactive protein help to predict short and long term mortality?

BACKGROUND: There is limited data about ICU, short and long-term mortality prediction of severe CAP with neutrophil-to-lymphocyte ratio (NLR): N-terminal proB- type natriuretic peptide (NT-proBNP): C-reactive protein (CRP). AIM: Besides the known severity indexes of ICU, can NLR, NT-proBNP, CRP predict ICU, short and long term mortality? METHODS: A retrospective cohort study was carried out in a level III ICU of a tertiary training hospital for chest diseases and thoracic surgery. RESULTS: Over the study period, a total of 143 patients were enrolled in the study. The APACHE II scoring showed a significantly higher predicting performance for ICU mortality (p = 0.002). The performance for predicting short term mortality NLR (p = 0.039) and long term mortality NTproBNP (p = 0.002) had a significantly higher performance. The survival analysis revealed that mortality was significantly higher in patients with CURB65 score ≥ 4 (p = 0.047). CONCLUSION: NLR, NTproBNP > 2000pg/mL can be used to predict pneumonia severity in ICU alike CURB65 and PSI. Higher NLR, APACHE II and atrial fibrillation can cause an important mortality factor in long term. Consequently, clinicians should take an attention for good cardiac evaluation and cardiac follow-up of patients with CAP (Tab. 4, Fig. 3, Ref. 36).

SERUM 25-HYDROXYVITAMIN D(3) LEVELS IN TYPE 2 DIABETIC PATIENTS WITH NORMO-, MICRO-, AND MACROALBUMINURIA.

BACKGROUND: The aim of this study was to observe the differences in serum 25-hydroxyvitamin D(3) levels in nondiabetic healthy control subject and type 2 diabetic patients, and to investigate the differences in serum 25-hydroxyvitamin D(3) levels in type 2 diabetic patients with normo-, micro- and macroalbuminuria. PATIENTS AND METHODS: Total 140 nondiabetic healthy controls and 384 type 2 diabetic patients (156 normoalbuminuric, 152 microalbuminuric and 76 macroalbuminuric) were included in the study. 25-hydroxyvitamin D(3) levels were measured in sera with the method of electrochemiluminescence using modular immunoassay analyzer. RESULTS: Vitamin D deficiency was detected in 70.85% and 22.9% of type 2 diabetic patients and nondiabetic healthy controls, respectively. Serum 25-hydroxyvitamin D(3) levels were significantly lower in type 2 diabetic patients compared to nondiabetic healthy controls (16.4 ± 9.5 ng/mL vs. 28.2 ± 11.6 ng/mL, p=0.0001). Serum 25-hydroxyvitamin D(3) levels were lower in albuminuric and nonalbuminuric diabetic patients (14.3 ± 7.9 ng/mL vs. 19.6±10.9 ng/mL, respectively, p=0.013). Serum 25-hydroxyvitamin D(3) levels were 19.6 ± 10.9 ng/mL in normoalbuminuric, 14.9 ± 8.8 ng/mL in microalbuminuric and 12.9 ± 5.8 ng/mL in macroalbuminuric diabetic patients. While lower serum 25-hydroxyvitamin D(3) levels were detected both in microalbuminuric (p=0.028) and macroalbuminuric diabetic patients (p=0.014) compared to normoalbuminuric diabetic patients, 25-hydroxyvitamin D(3) levels did not change significantly between microalbuminuric and macroalbuminuric diabetic patients (p=0.67). Serum 25-hydroxyvitamin D(3) levels correlated negatively with urinary albumin excretion (r=-0.24, p=0.016) in patients with diabetes mellitus. CONCLUSION: Findings of the present study demonstrated reduced serum 25-hydroxyvitamin D(3) levels which were significantly related with albuminuria in type 2 diabetic patients.

A single sub-kilometre Kuiper belt object from a stellar occultation in archival data.

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects. Small, sub-kilometre-sized, Kuiper belt objects elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied abundances are inconsistent with each other and far exceed theoretical expectations. Here we report an analysis of archival data that reveals an occultation by a body with an approximately 500-metre radius at a distance of 45 astronomical units. The probability of this event arising from random statistical fluctuations within our data set is about two per cent. Our survey yields a surface density of Kuiper belt objects with radii exceeding 250 metres of 2.1(-1.7)(+4.8) x 10(7) deg(-2), ruling out inferred surface densities from previous claimed detections by more than 5sigma. The detection of only one event reveals a deficit of sub-kilometre-sized Kuiper belt objects compared to a population extrapolated from objects with radii exceeding 50 kilometres. This implies that sub-kilometre-sized objects are undergoing collisional erosion, just like debris disks observed around other stars.

Effectiveness study of recrystallisation method in pharmaceutical salt production from processed salt with zero waste concept.

Indonesia's vast archipelago offers abundant seawater resources, holding the potential for salt production. Salt, a vital commodity in human life, typically contains sodium chloride and impurities like Ca2+, Mg2+, SO42-, and K+. Pharmaceutical salt is an industrial category adhering to pharmacopoeial standards regarding sodium chloride levels and impurity content, ensuring quality for drug preparations in Indonesia. Prior research indicates that recrystallisation, specifically evaporation crystallisation, enhances salt quality by increasing NaCl content. Chemical precipitating agents like NaOH and Na2CO3 can be introduced to improve salt purity further. This study aims to identify optimal conditions for pharmaceutical salt production from processed salt raw materials, considering crystallisation time, stirring speed, chemical additives (NaOH and Na2CO3), and double crystallisation stages. The method commences with pre-treatment, involving salt dissolution in distilled water to saturation, with the addition of precipitating agents as per designated variables. Precipitates formed from precipitating agents (NaOH and Na2CO3) are isolated through filtration. The filtrate undergoes evaporation crystallisation at 103 °C, varying between single and double crystallisation. Salt crystals are separated, dried, and weighed to calculate yield. Pharmaceutical salt is analysed for water content, NaCl, and impurities (Ca2+, Mg2+, SO42-, and K+). The optimal conditions for pharmaceutical salt production were double crystallisation with a 20 % excess of chemicals (NaOH and Na2CO3), 100 min of crystallisation time, and a stirring speed of 600 rpm. This yielded a 15 % NaCl content of 99.87 %, Mg2+ at 0 ppm, Ca2+ at 69.6 ppm, SO42- at 366 ppm, K+ at 370 ppm, and water content at 0.166 %. Notably, the pharmaceutical salt production process generates no waste, as byproducts like Mg(OH)2 and CaCO3 can be recycled and hold commercial value. However, it is essential to re-evaluate raw materials and technologies to address the market's high cost and competitiveness issues.

Disclosure of genetic diversity of mackerel fish (Scomberomorus spp.) in Indonesian waters based on the mitochondrial cytochrome oxidase subunit II (COII) gene.

Mackerel fish (Scomberomorus spp.) represents a significant marine fisheries commodity in Indonesia, characterized by its high commercial value and nutritional content. To understand the intraspecific interactions and genetic variability of Scomberomorus spp., a more extensive research of Scomberomorus spp. populations, including both cultivated and wild specimens, is required. This study aimed to explore the genetic diversity of mackerel fish in Indonesian waters, focusing on the mitochondrial DNA (mtDNA) cytochrome oxidase subunit II (COII) gene, which encodes the second subunit of cytochrome c oxidase (complex IV), is essential for aerobic respiration and energy transformation. Muscle tissue samples from 18 individual mackerel fish collected from various regions in Indonesia, including Palembang, Cilacap, Rembang, Banjarmasin, Ambon, and Fak-Fak Regencies, were utilized. The genomic DNA was isolated and amplified using specific primers: CO2TF (5'-ACCGCTCTGTCACTTTCTTC-3') and CO2TR (5'-ATGTCACTAAGGGTGGTTGG-3'). Subsequently, the obtained amplicons were subjected to sequencing. The sequence data were then analyzed using the MEGA11 and DnaSP 6 software. Our findings revealed 120 variable sites within the 691 base pairs of mtDNA COII sequences, resulting in a nucleotide diversity (Pi) of 0.07169. Furthermore, we identified eight haplotypes, demonstrating a haplotype diversity (Hd) of 0.8889. Remarkably, all mackerel samples from Palembang and Cilacap clustered into discrete haplotypes, specifically haplotype 1 and haplotype 2, respectively. Our phylogenetic analysis delineated three distinct clades. Clade I, closely related to Scomberomorus cavalla, encompassed all individuals from Ambon, Palembang, Rembang, and one from Banjarmasin. Clade II, associated with Scomberomorus niphonius, included individuals from Cilacap and two from Banjarmasin. Clade III, linked to Scomberomorus semifasciatus, exclusively consisted of individuals from Fak-Fak (Papua). In conclusion, Indonesian waters harbor diverse genetic variations within Scomberomorus spp., and population relationships based on the mtDNA COII gene exhibit notable complexities. Future research endeavors should focus on further elucidating the diversity and relationships among Scomberomorus spp. in diverse Indonesian populations.

Exploring Relationships of Heart Rate Variability, Neurological Function, and Clinical Factors with Mortality and Behavioral Functional Outcome in Patients with Ischemic Stroke.

Ischemic stroke is a leading cause of mortality and disability. The relationships of heart rate variability (HRV) and stroke-related factors with mortality and functional outcome are complex and not fully understood. Understanding these relationships is crucial for providing better insights regarding ischemic stroke prognosis. The objective of this study is to examine the relationship between HRV, neurological function, and clinical factors with mortality and 3-month behavioral functional outcome in ischemic stroke. We prospectively collected the HRV data and monitored the behavioral functional outcome of patients with ischemic stroke. The behavioral functional outcome was represented by a modified Rankin Scale (mRS) score. This study population consisted of 58 ischemic stroke patients (56.9% male; mean age 70) with favorable (mRS score ≤ 2) and unfavorable (mRS score ≥ 3) outcome. The analysis indicated that the median of the mean RR interval (RR mean) showed no statistical difference between mortality groups. Conversely, the median of the RR mean had significant association with unfavorable outcome (OR = 0.989, p = 0.007). Lower hemoglobin levels had significant association with unfavorable outcome (OR = 0.411, p = 0.010). Higher National Institute of Health Stroke Scale (NIHSS) score at admission had significant association with unfavorable outcome (OR = 1.396, p = 0.002). In contrast, age, stroke history, NIHSS score at admission, and hemoglobin showed no significant association with mortality in ischemic stroke. These results imply that HRV, as indicated by the median of RR mean, alongside specific clinical factors and neurological function at admission (measured by NIHSS score), may serve as potential prognostic indicators for 3-month behavioral functional outcome in ischemic stroke.

Applying persuasive messages to reduce public outdoor smoking: A pseudo-randomized controlled trial.

Despite efforts to create dedicated smoking areas and no-smoking signs, many smokers continue to light their cigarettes in front of public building entrances-leading to concerns over health consequences for non-smokers passing by. To increase compliance with no-smoking requests, behavioral interventions that tap into habitual and automatic processes seem promising. A pseudo-randomized controlled trial was conducted to assess the differential impact of seven behavioral interventions based on Cialdini's principles of persuasion. Over a period of 9 weeks, the number of smokers was counted (total n = 17,930 observations) in front of a German University Medical Center. Relative to a baseline and a control condition, interventions based on the principles of reciprocity, scarcity, and authority were most effective in reducing the number of observed smokers in front of the building entrance (41.5%, 45.7%, and 52.1% reduction rates, respectively). Having observed smokers' behavior in vivo, this study provides substantial evidence for the impact of persuasive strategies on outdoor smoking. In the future, this knowledge should be used to protect non-smokers from second-hand smoke by increasing the use of designated smoking areas, leave to another place to smoke, or not smoke at all.

A novel explosive process is required for the gamma-ray burst GRB 060614.

Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.

Relativistic ejecta from X-ray flash XRF 060218 and the rate of cosmic explosions.

Over the past decade, long-duration gamma-ray bursts (GRBs)--including the subclass of X-ray flashes (XRFs)--have been revealed to be a rare variety of type Ibc supernova. Although all these events result from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated with supernova SN 2006aj), the second-nearest GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 10(48) erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.

Hepatitis C viral clearance with coadministration of crushed sofosbuvir/velpatasvir and high-dose pantoprazole after liver transplantation.

PURPOSE: Direct-acting antivirals (DAAs) allow for successful transplantation of livers from hepatitis C nucleic acid test (NAT)-positive donors to negative recipients. However, limited data exist to support crushing DAAs in patients with multiple absorption concerns or significant drug interactions. SUMMARY: Crushed sofosbuvir/velpatasvir has been successfully used in nontransplant patients with dysphagia, but data in transplant patients with absorption concerns are limited. A 31-year-old hepatitis C-negative female underwent liver transplantation from a hepatitis C NAT-positive donor. Her postoperative course was complicated by a mucormycosis infection, gastrointestinal bleed, and necrotizing pancreatitis requiring treatment with liposomal amphotericin B and pantoprazole 80 mg twice daily. Surgical interventions included an above-the-knee amputation and ileostomy. Hepatitis C treatment was initially delayed because of concern for reduced absorption with crushed DAA administration through the nasogastric (NG) tube, high ileostomy output, gastrointestinal bleed, pancreatitis, and a known drug interaction with pantoprazole. One month after transplantation, the patient's bilirubin level remained elevated and hepatitis C treatment was initiated with sofosbuvir/velpatasvir. Crushed sofosbuvir/velpatasvir was mixed with 30 mL of water and administered through the NG tube daily. Hepatitis C viral loads were obtained weekly during treatment to monitor efficacy. Although the patient died before evaluation of sustained virological response at 12 weeks, hepatitis C viral clearance was observed within 4 weeks of initiating treatment. CONCLUSION: A liver transplant patient exhibited viral clearance of hepatitis C following administration of crushed sofosbuvir/velpatasvir in the setting of multiple absorption concerns.

Role of Clathrin and Dynamin in Clathrin Mediated Endocytosis/Synaptic Vesicle Recycling and Implications in Neurological Diseases.

Endocytosis is a process essential to the health and well-being of cell. It is required for the internalisation and sorting of "cargo"-the macromolecules, proteins, receptors and lipids of cell signalling. Clathrin mediated endocytosis (CME) is one of the key processes required for cellular well-being and signalling pathway activation. CME is key role to the recycling of synaptic vesicles [synaptic vesicle recycling (SVR)] in the brain, it is pivotal to signalling across synapses enabling intracellular communication in the sensory and nervous systems. In this review we provide an overview of the general process of CME with a particular focus on two key proteins: clathrin and dynamin that have a central role to play in ensuing successful completion of CME. We examine these two proteins as they are the two endocytotic proteins for which small molecule inhibitors, often of known mechanism of action, have been identified. Inhibition of CME offers the potential to develop therapeutic interventions into conditions involving defects in CME. This review will discuss the roles and the current scope of inhibitors of clathrin and dynamin, providing an insight into how further developments could affect neurological disease treatments.

Does agency matter? Neural processing of robotic movements in 4- and 8-year olds.

Despite the increase in interactions between children and robots, our understanding of children's neural processing of robotic movements is limited. The current study theorized that motor resonance hinges on the agency of an actor: its ability to perform actions volitionally. As one of the first studies with a cross-sectional sample of preschoolers and older children and with a specific focus on robotic action (rather than abstract non-human action), the current study investigated whether the perceived agency of a robot moderated children's motor resonance for robotic movements, and whether this changed with age. Motor resonance was measured using electroencephalography (EEG) by assessing mu power while 4 and 8-year-olds observed actions performed by agentic versus non-agentic robots and humans. Results show that older children resonated more strongly with non-agentic than agentic robotic or human movement, while no such differences were found for preschoolers. This outcome is discussed in terms of a predictive coding account of motor resonance. Importantly, these findings contribute to the existing set of studies on this topic by showing that, while keeping all kinematic information constant, there is a clear developmental difference in how children process robotic movement depending on the level of agency of a robot.

Do We Take a Robot's Needs into Account? The Effect of Humanization on Prosocial Considerations Toward Other Human Beings and Robots.

Robots are becoming an integral part of society, yet the extent to which we are prosocial toward these nonliving objects is unclear. While previous research shows that we tend to take care of robots in high-risk, high-consequence situations, this has not been investigated in more day-to-day, low-consequence situations. Thus, we utilized an experimental paradigm (the Social Mindfulness "SoMi" paradigm) that involved a trade-off between participants' own interests and their willingness to take their task partner's needs into account. In two experiments, we investigated whether participants would take the needs of a robotic task partner into account to the same extent as when the task partner was a human (Study I), and whether this was modulated by participant's anthropomorphic attributions to said robot (Study II). In Study I, participants were presented with a social decision-making task, which they performed once by themselves (solo context) and once with a task partner (either a human or a robot). Subsequently, in Study II, participants performed the same task, but this time with both a human and a robotic task partner. The task partners were introduced via neutral or anthropomorphic priming stories. Results indicate that the effect of humanizing a task partner indeed increases our tendency to take someone else's needs into account in a social decision-making task. However, this effect was only found for a human task partner, not for a robot. Thus, while anthropomorphizing a robot may lead us to save it when it is about to perish, it does not make us more socially considerate of it in day-to-day situations.

A common origin for cosmic explosions inferred from calorimetry of GRB030329.

Past studies have suggested that long-duration gamma-ray bursts have a 'standard' energy of E(gamma) approximately 10(51) erg in the ultra-relativistic ejecta, after correcting for asymmetries in the explosion ('jets'). But a group of sub-energetic bursts, including the peculiar GRB980425 associated with the supernova SN1998bw (E(gamma) approximately 10(48) erg), has recently been identified. Here we report radio observations of GRB030329 that allow us to undertake calorimetry of the explosion. Our data require a two-component explosion: a narrow (5 degrees opening angle) ultra-relativistic component responsible for the gamma-rays and early afterglow, and a wide, mildly relativistic component that produces the radio and optical afterglow more than 1.5 days after the explosion. The total energy release, which is dominated by the wide component, is similar to that of other gamma-ray bursts, but the contribution of the gamma-rays is energetically minor. Given the firm link of GRB030329 with SN2003dh, our result indicates a common origin for cosmic explosions in which, for reasons not yet understood, the energy in the highest-velocity ejecta is extremely variable.