Spatial variations in aromatic hydrocarbon emission in a dust-rich galaxy.

Dust grains absorb half of the radiation emitted by stars throughout the history of the universe, re-emitting this energy at infrared wavelengths1-3. Polycyclic aromatic hydrocarbons (PAHs) are large organic molecules that trace millimetre-size dust grains and regulate the cooling of interstellar gas within galaxies4,5. Observations of PAH features in very distant galaxies have been difficult owing to the limited sensitivity and wavelength coverage of previous infrared telescopes6,7. Here we present James Webb Space Telescope observations that detect the 3.3 µm PAH feature in a galaxy observed less than 1.5 billion years after the Big Bang. The high equivalent width of the PAH feature indicates that star formation, rather than black hole accretion, dominates infrared emission throughout the galaxy. The light from PAH molecules, hot dust and large dust grains and stars are spatially distinct from one another, leading to order-of-magnitude variations in PAH equivalent width and ratio of PAH to total infrared luminosity across the galaxy. The spatial variations we observe suggest either a physical offset between PAHs and large dust grains or wide variations in the local ultraviolet radiation field. Our observations demonstrate that differences in emission from PAH molecules and large dust grains are a complex result of localized processes within early galaxies.

Better together: utilizing an interprofessional course and escape room to educate healthcare students about opioid use disorder.

BACKGROUND: The aim of the present study was to determine the impact of an innovative interprofessional educational activity on healthcare professional students' learning. The educational activity targeted student knowledge of opioid use disorder (OUD) and perceptions of working with an interprofessional team while caring for patients with OUD. METHODS: Students from nursing, pharmacy, physician assistant, dentistry, social work, and medicine programs were recruited to participate in the interprofessional educational activity. The educational experience included seven asynchronous modules and a virtual synchronous escape room. Prior to the educational programming, participants completed a pre-survey that assessed their knowledge and attitudes towards working on an interprofessional team and perceptions of patients with OUD. The asynchronous modules were required in order to participate in the escape room and each module contained its own pre/post quiz to assess student knowledge. RESULTS: A total of 402 students participated in the course. Prior to participating in the course, students disagreed that they had extensive educational experience with SUD (2.45 ± 0.79). The students displayed significant improvement in the knowledge based areas after completing the seven asynchronous modules. The largest significant area of knowledge-based improvement was seen in treatment of OUD where on the pre-quiz 65.54 ± 20.21% were answered correctly compared to 95.97 ± 9.61% on the post-quiz. Participation in the escape room significantly changed the students' perceptions of working in interprofessional teams while managing patients with OUD. Of the eleven perception variables assessed, seven showed a significant increase in the post-survey. Following the escape room, participants also strongly agreed that they now would refer patients to colleagues in other disciplines. CONCLUSIONS: An interprofessional educational experience including both an asynchronous course and virtual synchronous escape room can increase participant knowledge around OUD and may improve student perceptions of working with an interprofessional team and caring for patients with OUD.

Rapid Diagnostic Testing for Response to the Monkeypox Outbreak - Laboratory Response Network, United States, May 17-June 30, 2022.

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

Francisella tularensis Transmission by Solid Organ Transplantation, 20171.

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation.

Near-infrared background anisotropies from diffuse intrahalo light of galaxies.

Unresolved anisotropies of the cosmic near-infrared background radiation are expected to have contributions from the earliest galaxies during the epoch of reionization and from faint, dwarf galaxies at intermediate redshifts. Previous measurements were unable to pinpoint conclusively the dominant origin because they did not sample spatial scales that were sufficiently large to distinguish between these two possibilities. Here we report a measurement of the anisotropy power spectrum from subarcminute to one-degree angular scales, and find the clustering amplitude to be larger than predicted by the models based on the two existing explanations. As the shot-noise level of the power spectrum is consistent with that expected from faint galaxies, a new source population on the sky is not necessary to explain the observations. However, a physical mechanism that increases the clustering amplitude is needed. Motivated by recent results related to the extended stellar light profile in dark-matter haloes, we consider the possibility that the fluctuations originate from intrahalo stars of all galaxies. We find that the measured power spectrum can be explained by an intrahalo light fraction of 0.07 to 0.2 per cent relative to the total luminosity in dark-matter haloes of 10(9) to 10(12) solar masses at redshifts of about 1 to 4.

Early outcomes of robotic-assisted inguinal hernia repair in obese patients: a multi-institutional, retrospective study.

BACKGROUND: Minimally invasive inguinal hernia repair (IHR) in general and particularly in obese patients has not been widely adopted, potentially due to the perceived technical challenges and the well-documented learning curve associated with laparoscopic repair. Outcomes in robotic-assisted IHR in obese (BMI ≥ 30 kg/m2) patients have not been described and warrant study. METHODS: Seven surgeons conducted a multicenter retrospective chart review of their early robotic-assisted IHR (RHR) cases and compared them with their open IHR (OHR) cases. Demographics, operative characteristics, and perioperative morbidity were compared for unadjusted and propensity-matched populations. RESULTS: 651 robotic-assisted cases and 593 open cases were collected. The outcomes of 148 RHRs to 113 OHRs in obese patients were compared. For obese populations-whether unadjusted (robotic-assisted, n = 148; open, n = 113) or matched (1:1) (robotic-assisted, n = 95; open, n = 93)-the robotic-assisted and open cohorts were comparable in terms of demographics and baseline characteristics. Significantly higher percentages of OHR patients experienced postoperative complications post-discharge (unadjusted: 11.5% vs. 2.7%, p = 0.005; and matched: 10.8% vs. 3.2%, p = 0.047). More concomitant procedures and bilateral repairs were conducted in obese RHR patients than in obese OHR patients (unadjusted 29.7% vs. 16.8%, p = 0.019; and unadjusted 35.1% vs. 11.5%, p < 0.0001-respectively). Prior laparoscopic IHR experience did not affect 30-day outcomes. CONCLUSIONS: Obese patients who undergo RHR have a lower rate of postoperative complications compared to obese patients who undergo OHR. Previous laparoscopic IHR experience, more bilateral repairs, and more concomitant procedures were not associated with increased complications in RHR patients. These outcomes may facilitate increased adoption of minimally invasive IHR approaches in the obese population.

Cosmesis, patient satisfaction, and quality of life after da Vinci Single-Site cholecystectomy and multiport laparoscopic cholecystectomy: short-term results from a prospective, multicenter, randomized, controlled trial.

BACKGROUND: Single-incision laparoscopic cholecystectomy evolved from the traditional multiport laparoscopic technique. Prior trials have demonstrated improved cosmesis with the single-incision technique. Robotic single-site surgery minimizes the technical difficulties associated with laparoscopic single-incision approach. This is the first prospective, randomized, controlled study comparing robotic single-site cholecystectomy (RSSC) and multiport laparoscopic cholecystectomy (MPLC) in terms of cosmesis and patient satisfaction. METHODS: Patients with symptomatic benign gallbladder disease were randomized to RSSC or MPLC. Data included perioperative variables such as operative time, conversion and complications and cosmesis satisfaction, body image perception, quality of life using validated questionnaires, at postoperative visits of 2, 6 weeks and 3 months. RESULTS: One hundred thirty-six patients were randomized to RSSC (N = 83) and MPLC (N = 53) at 8 institutions. Both cohorts were dominated by higher enrollment of females (RSSC = 78%, MPLC = 92%). The RSSC and MPLC cohorts were otherwise statistically matched. Operative time was longer for RSSC (61 min vs. 44 min, P < 0.0001). There were no differences in complication rates. RSSC demonstrated a significant superiority in cosmesis satisfaction and body image perception (P value < 0.05 at every follow-up). There was no statistically significant difference in patient-reported quality of life. Multivariate analysis of female patients demonstrated significantly higher preference for RSSC over MPLC in cosmesis satisfaction and body image perception with no difference seen in overall quality of life. CONCLUSIONS: Results from this trial show that RSSC is associated with improved cosmesis satisfaction and body image perception without a difference in observed complication rate. The uncompromised safety and the improved cosmesis satisfaction and body image perception provided by RSSC for female patients support consideration of the robotic single-site approach. ClinicalTrials.gov identifier NCT01932216.

Robotic-assisted ventral hernia repair: a multicenter evaluation of clinical outcomes.

BACKGROUND: The open approach continues to be widely performed for ventral hernia repair, while the minimally invasive laparoscopic approach has grown adoption over the last decade. Recently, robotic operation was described as a new modality due to the ease for performing intracorporeal closure of the hernia defect. This study is one of the first multi-institutional case series evaluating robotic-assisted laparoscopic ventral hernia repairs, with the goal of describing robotic-assisted surgical techniques for ventral and incisional hernia repair and the outcomes in teaching and community hospital settings. METHODS: Medical records of consecutive patients (including surgeon's learning curve cases) who underwent ventral or incisional hernia repair utilizing the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale CA) were retrospectively reviewed. Data collected included preoperative history and perioperative outcomes. RESULTS: Data for a total of 368 patients from four institutions involving five surgeons were analyzed. They were predominantly females (60.3 %), and the mean age was 51 years. The majority of the patients were obese or morbidly obese (47.8 and 20.9 %), and 83.2 % of the patients had a history of prior abdominal operation. Conversion rate was 0.8 %, and mean length of stay was 1 day. Total postoperative complications rate up to 30 days was 8.4 %, of which incidence of paralytic ileus was 2.4 %. CONCLUSION: This large case series of 368 patients demonstrates reproducibility of safety and performance associated with robotic-assisted ventral hernia repairs performed by five surgeons at four institutions. In addition, the results of short term perioperative outcomes for surgeons during their early experience for robotic-assisted cases are in the range of what is reported in the existing published data on laparoscopic and open ventral hernia repairs. Further comparative evidence initiatives are being pursued to determine the benefits of robotic-assisted technique and technology for long-term and patient-reported outcomes.

Multicenter Evaluation of Clinical Diagnostic Methods for Detection and Isolation of Campylobacter spp. from Stool.

The use of culture-independent diagnostic tests (CIDTs), such as stool antigen tests, as standalone tests for the detection of Campylobacter in stool is increasing. We conducted a prospective, multicenter study to evaluate the performance of stool antigen CIDTs compared to culture and PCR for Campylobacter detection. Between July and October 2010, we tested 2,767 stool specimens from patients with gastrointestinal illness with the following methods: four types of Campylobacter selective media, four commercial stool antigen assays, and a commercial PCR assay. Illnesses from which specimens were positive by one or more culture media or at least one CIDT and PCR were designated "cases." A total of 95 specimens (3.4%) met the case definition. The stool antigen CIDTs ranged from 79.6% to 87.6% in sensitivity, 95.9 to 99.5% in specificity, and 41.3 to 84.3% in positive predictive value. Culture alone detected 80/89 (89.9% sensitivity) Campylobacter jejuni/Campylobacter coli-positive cases. Of the 209 noncases that were positive by at least one CIDT, only one (0.48%) was positive by all four stool antigen tests, and 73% were positive by just one stool antigen test. The questionable relevance of unconfirmed positive stool antigen CIDT results was supported by the finding that noncases were less likely than cases to have gastrointestinal symptoms. Thus, while the tests were convenient to use, the sensitivity, specificity, and positive predictive value of Campylobacter stool antigen tests were highly variable. Given the relatively low incidence of Campylobacter disease and the generally poor diagnostic test characteristics, this study calls into question the use of commercially available stool antigen CIDTs as standalone tests for direct detection of Campylobacter in stool.

Feasibility of robotic inguinal hernia repair, a single-institution experience.

BACKGROUND: With the growth of the discipline of laparoscopic surgery, technology has been further developed to facilitate the performance of minimally invasive hernia repair. Most of the published literature regarding robotic inguinal hernia repair has been performed by urologists who have dealt with this entity in a concomitant way during radical prostatectomies. General surgeons, who perform the vast majority of inguinal herniorrhaphies worldwide, have yet to describe the role of robotic inguinal hernia repair. Here, we describe our initial experience and create the foundation for future research questions regarding robotic inguinal hernia repair. METHODS: A retrospective chart review was performed in 78 patients who underwent robotic transabdominal preperitoneal TAPP inguinal hernia repair with a prosthetic mesh using the da Vinci platform (Intuitive Surgical Inc). Data collected included patient demographics, past medical history, previous surgeries, details related to the surgical procedure, perioperative outcomes and complications. RESULTS: A total of 123 hernias were repaired. Forty-five patients had bilateral robotic inguinal herniorrhaphies, and the mean age was 55.1 years (SD 15.1), with a mean BMI of 27.6 (SD 6.1). There were 71 male and 7 female patients. Surgical complications included hematoma in three patients (3.9 %), two seromas (2.6 %) and one superficial surgical site infection at a trocar site (1.3 %), which resolved with oral antibiotics. Chronic postoperative complications (>30 days post-surgery) included the persistence of hematomas in two patients (2.6 %). Same day discharge was achieved in 60 patients (76.9 %) with a mean length of stay of 8 h (SD 2.65). Neither mortality nor conversion to open surgery occurred. CONCLUSION: Our early experience has demonstrated that the robotic transabdominal preperitoneal (TAPP) inguinal hernia repair is a safe and versatile approach that allows the general surgeon to perform this procedure in more complex cases such as those involving incarcerated and/or recurrent hernias.

A multicenter study of initial experience with single-incision robotic cholecystectomies (SIRC) demonstrating a high success rate in 465 cases.

BACKGROUND: Recently, the robotic single-site platform has been used to ameliorate the difficulties seen in single-incision laparoscopic surgery (SILC) while preserving the benefits of standard laparoscopic cholecystectomy. The purpose of this study is to describe the clinical outcomes of a large series of single-incision robotic cholecystectomy (SIRC). METHODS: Medical records of consecutive patients who underwent SIRC were retrospectively reviewed. All procedures were performed by six surgeons at five different North American centers involved in the study. All patients included in the study underwent a cholecystectomy attempted through single site at the umbilicus, using the da Vinci(®) Surgical System (Intuitive Surgical Inc. Sunnyvale, CA). RESULTS: A total of 465 patients met study criteria. Median age was 48 years (range 18-89); 351 (75.5 %) were female and 304 (66.4 %) were overweight or obese. Except for gender, case characteristics differed significantly by surgeon/site. Previous abdominal surgery was reported for 226 (48.6 %) cases. SIRC was successfully completed in 455 (97.8 %) cases, and there were no conversions to open surgery. Median surgical time was 52 min with a decreasing trend after 55-85 cases. Male gender, obesity and diagnoses other than biliary dyskinesia were independent predictors of longer surgical times. The complication rate was 2.6 %. CONCLUSIONS: Our large, multicenter study demonstrates that robotic single-site cholecystectomy is safe and feasible in a wide range of patients.

Intravenous acetaminophen in bariatric surgery: effects on opioid requirements.

BACKGROUND: Opioids are commonly used after bariatric surgery for pain control because of their potent analgesic effects. Nevertheless, the morbidly obese patient has increased risk for developing adverse effects produced by opioids (such as sedation, apnea, hypoxemia, ileus, and vomiting). Intravenous acetaminophen (IVA) has been evaluated in some specialties showing a reduction in opioid consumption. The purpose of this study was to evaluate the effect on opioid consumption when IVA is administered in bariatric surgery patients. MATERIAL AND METHODS: A retrospective study was performed in patients who underwent bariatric surgery. Group A included those patients who received IVA perioperatively and group B those who did not. The amount of opioids administered was calculated and compared for each group. RESULTS: Group A included 38 cases (44.7%) and group B included 47 cases (55.3%). A comparison was performed in terms of age (P = 0.349), body mass index (P = 0.311), gender (P = 0.890), American Society of Anesthesiologist score (P = 0.438), total surgical time (P = 0.497), perioperative complications (P = 0.786), number of procedures per surgeon (P = 0.08), and type of surgical procedure (P ≤ 0.01). Group A had a mean 24-h total opioid dose of 99.5 mg, whereas group B of 164.6 mg (P = 0.018). Group A received 39.5% less opioids than group B. A post hoc analysis determined a statistical power of 0.74. CONCLUSIONS: IVA used perioperatively can decrease opioid consumption in patients after bariatric surgery. Randomized trials are needed to corroborate these results.

Description of robotic single site cholecystectomy and a review of outcomes.

New technologies have been developed to make laparoscopic cholecystectomy less invasive through single incision laparoscopic surgery (SILS), however this approach has its own limitations. Single incision robotic surgery (SIRC) is designed to overcome them. The concerns that limit adoption of this technology are attributed increases in costs, prolonged learning curves and surgical times. Here, we provide a literature review as well as our own experience with SIRC, with the intent to clarify these important concerns.

Robotic inguinal hernia repair.

Inguinal hernias have been described throughout the history of medicine with many efforts to achieve the cure. Currently, with the advantages of minimally invasive surgery, new questions arise: what is going to be the best approach for inguinal hernia repair? Is there a real benefit with the robotic approach? Should minimally invasive hernia surgery be the standard of care? In this report we address these questions by describing our experience with robotic inguinal hernia repair.

Use of abdominal thrusts is associated with improved rates of successful emesis induction in dogs.

OBJECTIVE: To evaluate the effect of abdominal thrusts as a synergistic procedure to IV apomorphine administration on the occurrence and rate of onset of successful induction of emesis in dogs. ANIMALS: 31 client-owned dogs. METHODS: Dogs in which induction of emesis via IV apomorphine was prescribed by the attending clinician were prospectively randomized to either receive abdominal thrusts performed by a nurse or clinician or to have no physical interventions performed following IV apomorphine administration. Data collected included signalment, weight, reason for emesis, time from suspected ingestion to presentation, time from the dog's last meal to presentation, dose of apomorphine administered in milligrams, and time from apomorphine administration to emesis. RESULTS: Emesis induction was successful in 14 of 14 (100%) of the dogs in the abdominal thrust group and 13 of 17 (76.5%) in the control group (P = .02). In dogs with successful emesis, median time to emesis was 90.5 seconds (range, 36 to 348 seconds) in the abdominal thrust group and 106 seconds (range, 37 to 360 seconds) in the control group (P = .29). CLINICAL RELEVANCE: Abdominal thrusts were associated with an increased frequency of successful emesis in dogs following IV apomorphine, but did not shorten the rate of onset of emesis in dogs that vomited. Application of abdominal thrusts may be beneficial in dogs in which emesis is indicated and that do not have a clear contraindication.

Single-incision cholecystectomy: a comparative study of standard laparoscopic, robotic, and SPIDER platforms.

BACKGROUND: Many series have shown the feasibility and safety of single-incision laparoscopic cholecystectomy (SILC), but this technique still has limitations such as instrument collisions and lack of triangulation. Recently, two single-incision platforms, robotic and SPIDER, have attempted to ameliorate such problems. This study aimed to compare three different techniques of single-incision cholecystectomy: standard laparoscopic, robotic, and SPIDER approaches. METHODS: The authors retrospectively collected data from their first 166 single-incision robotic cholecystectomies (SIRCs) and compared the findings with the data from their first 166 SILCs and the first 166 s-generation SPIDER procedures. All the SILCs were performed with three trocars placed in one umbilical incision and with gallbladder retraction using a Prolene stitch on the right upper quadrant. All the robotic cases were managed using the da Vinci Single-Site Surgical System, and all the SPIDER procedures were performed using the SPIDER Surgical System. RESULTS: The SILC, SIRC, and SPIDER groups consisted respectively of 129 (76.3%), 131 (78.9%), and 136 (81.9%) women with the respective mean ages of 44.5 ± 14.3, 51.6 ± 15.9, and 46.4 ± 15.2 years. The mean body mass indexes (BMIs) were respectively 29.1 ± 5.6, 29.4 ± 6.2, and 27.5 ± 4.8 kg/m(2), and the mean surgical times were 37.1 ± 13.3, 63.0 ± 25.2, and 52.8 ± 18.7 min. The total hospital stays were respectively 1.3 ± 5.3, 1.2 ± 2.2, and 1.5 ± 2.6 days, and complications were seen respectively in three SILC cases (1.8%), three SIRC cases (1.8%), and two SPIDER cases (1.2%). CONCLUSIONS: The results of this study demonstrate similar results among the three platforms for most of the parameters measured. The SILC procedure appears to be superior to SIRC and SPIDER in terms of surgical time, but selection bias could be the cause. The SILS, SIRC, and SPIDER procedures all are similar in terms of complication profile. It can be concluded that SILC, SIRC, and SPIDER all are feasible and safe alternatives when used for single-incision cholecystectomy.

Incidental Finding of a Lipoleiomyoma During Robotic Inguinal Hernia Repair: A Case Report.

Lipoleiomyomas are rare, fatty variants of leiomyomas (commonly referred to as fibroid), which are frequently found in the uterine corpus and cervix. Here, we present a case of a robotic inguinal hernia repair with resection of an incidental lipoleiomyoma. A 74-year-old woman presented to the office with complaints of pain and a palpable mass in the right inguinal region. Physical examination revealed tender, moderate-to-large bilateral inguinal hernias. Robotic bilateral inguinal hernia repair with mesh was performed. Intraoperatively, a mass measuring 4 × 3 cm was noted near the round ligament of the uterus. The mass was encapsulated without invading any surrounding structures. The mass was resected and sent to the histopathology department. The pathological evaluation identified a leiomyoma filled with mature adipocytes, compatible with the diagnosis of an extrauterine lipoleiomyoma. Lipoleiomyoma incidentally found in the inguinal canal is extremely rare. The medical literature regarding this incidental finding is limited. Resection of the mass was easily performed using the same robotic instruments as used for the inguinal hernia repair.

Engineered Synthetic STxB for Enhanced Cytosolic Delivery.

Many molecular targets for cancer therapy are located in the cytosol. Therapeutic macromolecules are generally not able to spontaneously translocate across membranes to reach these cytosolic targets. Therefore a strong need exists for tools that enhance cytosolic delivery. Shiga toxin B-subunit (STxB) is used to deliver therapeutic principles to disease-relevant cells that express its receptor, the glycolipid Gb3. Based on its naturally existing membrane translocation capacity, STxB delivers antigens to the cytosol of Gb3-positive dendritic cells, leading to the induction of CD8+ T cells. Here, we have explored the possibility of further increasing the membrane translocation of STxB to enable other therapeutic applications. For this, our capacity to synthesize STxB chemically was exploited to introduce unnatural amino acids at different positions of the protein. These were then functionalized with hydrophobic entities to locally destabilize endosomal membranes. Intracellular trafficking of these functionalized STxB was measured by confocal microscopy and their cytosolic arrival with a recently developed highly robust, sensitive, and quantitative translocation assay. From different types of hydrophobic moieties that were linked to STxB, the most efficient configuration was determined. STxB translocation was increased by a factor of 2.5, paving the path for new biomedical opportunities.

Dopamine facilitates the translation of physical exertion into assessments of effort.

Our assessments of effort are critically shaped by experiences of exertion. However, it is unclear how the nervous system transforms physical exertion into assessments of effort. Availability of the neuromodulator dopamine influences features of motor performance and effort-based decision-making. To test dopamine's role in the translation of effortful exertion into assessments of effort, we had participants with Parkinson's disease, in dopamine depleted (OFF dopaminergic medication) and elevated (ON dopaminergic medication) states, exert levels of physical exertion and retrospectively assess how much effort they exerted. In a dopamine-depleted state, participants exhibited increased exertion variability and over-reported their levels of exertion, compared to the dopamine-supplemented state. Increased exertion variability was associated with less accurate effort assessment and dopamine had a protective influence on this effect, reducing the extent to which exertion variability corrupted assessments of effort. Our findings provide an account of dopamine's role in the translation of features of motor performance into judgments of effort, and a potential therapeutic target for the increased sense of effort observed across a range of neurologic and psychiatric conditions.

A synthetic delivery vector for mucosal vaccination.

The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8+ T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB. Here, we describe the highly efficient chemical synthesis of the protein, and its in vitro folding. This straightforward preparation led to a synthetic delivery tool whose biophysical and intracellular trafficking characteristics were largely indistinguishable from recombinant STxB. The chemical approach allowed for the generation of new variants with bioorthogonal handles. Selected variants were chemically coupled to several types of antigens derived from the mucosal viruses SARS-CoV-2 and type 16 human papillomavirus. Upon intranasal administration in mice, mucosal immunity, including resident memory CD8+ T cells and IgA antibodies was induced against these antigens. Our study thereby identifies a novel synthetic antigen delivery tool for mucosal vaccination with an unmatched potential to respond to an urgent medical need.