Aerial maneuvering by plethodontid salamanders spanning an arboreality gradient.

Wandering salamanders (Aneides vagrans) inhabit the crowns of the world's tallest trees, taking refuge in epiphytic fern mats within these complex arboreal environments. These salamanders readily jump from the canopy when disturbed and maintain stable postures while falling via fine adjustments of the limbs and tail in lieu of dedicated aerodynamic control surfaces, thus reliably carrying out non-vertical descent. Here, we examined the aerial behavior and performance of A. vagrans and three other species of plethodontid salamander across a habitat gradient of arboreality by recording salamanders falling from short heights and moving within the jet of a vertical wind tunnel. Kinematic performance of aerial behavior in plethodontid salamanders was correlated with a gradient of arboreal habitats; moreover, salamanders from arboreal niches were more effective in slowing and redirecting descent compared with other salamanders. Aneides vagrans and the closely related Aneides lugubris consistently engaged in parachuting and gliding when falling; their trajectories were very steep, but were sufficiently angled to enable contact with either the home trunk or nearby branches during falls or jumps from great heights. Aerial maneuvering in arboreal salamanders is similar to that seen in other vertebrates capable of non-vertical and controlled descent, suggesting that the long limbs and active tail of these arboreal plethodontids (often cited as adaptations for climbing) may also contribute to parachuting and gliding when falling from trees. These aerial behaviors within the redwood canopy warrant further investigations into other canopy residents that lack conspicuous surfaces for aerodynamic control.

Will artificial intelligence eventually replace psychiatrists?

SUMMARY: The dystopian scenario of an 'artificial intelligence takeover' imagines artificial intelligence (AI) becoming the dominant form of intelligence on Earth, rendering humans redundant. As a society we have become increasingly familiar with AI and robots replacing humans in many tasks, certain jobs and even some areas of medicine, but surely this is not the fate of psychiatry?Here a computational neuroscientist (Janaina Mourão-Miranda) and psychiatrist (Justin Taylor Baker) suggest that psychiatry as a profession is relatively safe, whereas psychiatrists Christian Brown and Giles William Story predict that robots will be taking over the asylum.

Negative first follow-up prostate biopsy on active surveillance is associated with decreased risk of upgrading, suspicion of progression and converting to active treatment.

OBJECTIVE: To determine the risk of disease progression and conversion to active treatment following a negative biopsy while on active surveillance (AS) for prostate cancer (PCa). PATIENTS AND METHODS: Men on an AS programme at a single tertiary hospital (London, UK) between 2003 and 2018 with confirmed low-intermediate-risk PCa, Gleason Grade Group <3, clinical stage 30% positive cores, magnetic resonance imaging (MRI) Likert score >3/T3 or PSA level of >20 ng/mL. Conversion to treatment included radical or hormonal treatment. RESULTS: Among the 460 eligible patients, 23% had negative follow-up biopsy findings. The median follow-up was 62 months, with one to two repeat biopsies and two MRIs per patient during that period. Negative biopsy findings at first repeat biopsy were associated with decreased risk of converting to active treatment (hazard ration [HR] 0.18, 95% confidence interval [CI] 0.09-0.37; P < 0.001), suspicion of disease progression (HR 0.56, 95% CI: 0.34-0.94; P = 0.029), and upgrading (HR 0.48, 95% CI 0.23-0.99; P = 0.047). Data are limited by fewer men with multiple follow-up biopsies. CONCLUSION: A negative biopsy finding at the first scheduled follow-up biopsy among men on AS for PCa was strongly associated with decreased risk of subsequent upgrading, clinical or radiological suspicion of disease progression, and conversion to active treatment. A less intense surveillance protocol should be considered for this cohort of patients.

Expression and Purification of DGD2, a Chloroplast Outer Membrane-Associated Glycosyltransferase for Galactolipid Synthesis.

Galactolipids are characteristic lipids of the photosynthetic membranes. They are highly enriched in the chloroplast and are present in photosystem structures. There are two major types of galactolipids, i.e., monogalactosyldiacylglycerol and digalactosyldiacylglycerol (DGDG) in chloroplastic membranes, which amount to ∼50 and ∼20 mol % of the total chloroplast lipids, respectively. Under phosphate-limiting conditions, the amount of DGDG increases dramatically for rescuing phosphate from phospholipids. In Arabidopsis thaliana, the gene digalactosyldiacylglycerol synthase 2 (DGD2) encodes a membrane-associated glycosyltransferase. The gene expression is highly responsive to phosphate starvation and is significantly upregulated in this case. To understand the molecular mechanism of DGD2, we established a protocol for DGD2 expression and purification in an Escherichia coli-based system. The work involved optimization of the expression condition and the purification protocol and a careful selection of buffer additives. It was found that a removal of around 70 C-terminal residues was necessary to produce a homogeneous monomeric protein sample with high purity, which was highly active. The purified sample was characterized by an activity assay for enzyme kinetics in which a range of membrane mimetics with different lipid compositions were used. The results demonstrate that DGD2 activity is stimulated by the presence of negatively charged lipids, which highlight the importance of the membrane environment in modulating the enzyme's activity. The study also paves way for future biophysical and structural studies of the enzyme.

The management impact of 68gallium-tris(hydroxypyridinone) prostate-specific membrane antigen (68Ga-THP-PSMA) PET-CT imaging for high-risk and biochemically recurrent prostate cancer.

PURPOSE: To determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of 68Ga-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT). METHODS: One hundred eighteen consecutive patients (50 HR, 68 BCR) had management plans documented at a multidisciplinary meeting before 68Ga-THP-PSMA PET-CT. Patients underwent PET-CT scans 60-min post-injection of 68Ga-THP-PSMA (mean 159 ± 21.2 MBq). Post-scan management plans, Gleason score, prostate-specific antigen (PSA) and PSA doubling time (PSAdt) were recorded. RESULTS: HR group: 12/50 (24%) patients had management changed (9 inter-modality, 3 intra-modality). Patients with PSA < 20 µg/L had more frequent management changes (9/26, 34.6%) compared with PSA > 20 µg/L (3/24, 12.5%). Gleason scores > 8 were associated with detection of more nodal (4/16, 25% vs 5/31, 16.1%) and bone (2/16, 12.5% vs 2/31, 6.5%) metastases. BCR group: Clinical management changed in 23/68 (34%) patients (17 inter-modality, 6 intra-modality). Forty out of 68 (59%) scans were positive. Positivity rate increased with PSA level (PSA < 0.5 µg/L, 0%; PSA 0.5-1.0 µg/L, 35%; PSA 1.0-5.0 µg/L, 69%; PSA 5.0-10.0 µg/L, 91%), PSAdt of < 6 months (56% vs 45.7%) and Gleason score > 8 (78.9% vs 51.2%). CONCLUSIONS: 68Ga-THP-PSMA PET-CT influences clinical management in significant numbers of patient with HR prostate cancer pre-radical treatment and is associated with PSA. Management change also occurs in patients with BCR and is associated with PSA and Gleason score, despite lower scan positivity rates at low PSA levels < 0.5 µg/L.

Community-based outreach associated with increased health utilization among Navajo individuals living with diabetes: a matched cohort study.

BACKGROUND: Navajo community members face high rates of diabetes mellitus and other chronic diseases. The Navajo Community Health Representative Outreach Program collaborated with healthcare providers and academic partners to implement structured and coordinated outreach to patients living with diabetes. The intervention, called Community Outreach and Patient Empowerment or COPE, provides home-based health coaching and community-clinic linkages to promote self-management and engagement in healthcare services among patients living with diabetes. The purpose of this study was to evaluate how outreach by Navajo Community Health Representatives ("COPE Program") affected utilization of health care services among patients living with diabetes. METHODS: De-identified data from 2010 to 2014 were abstracted from electronic health records at participating health facilities. In this observational cohort study, 173 cases were matched to 2880 controls. Healthcare utilization was measured as the number of times per quarter services were accessed by the patient. Changes in utilization over 4 years were modeled using a difference-in-differences approach, comparing the trajectory of COPE patients' utilization before versus after enrollment with that of the control group. The model was estimated using generalized linear mixed models for count outcomes, controlling for clustering at the patient level and the service unit level. RESULTS: COPE enrollees showed a 2.5% per patient per quarter (pppq) greater increase in total utilization (p = 0.001) of healthcare services than non-COPE enrollees; a 3.2% greater increase in primary care visits (p = 0.024); a 6.3% greater increase in utilization of counseling and behavioral health services (p = 0.013); and a 9.0% greater increase in pharmacy visits (p <  0.001). We found no statistically significant differences in utilization trends of inpatient, emergency room, specialty outpatient, dental, laboratory, radiology, or community encounter services among COPE participants versus control. CONCLUSIONS: A structured intervention consisting of Community Health Representative outreach and coordination with clinic-based providers was associated with a modest increase in health care utilization, including primary care and counseling services, among Navajo patients living with diabetes. Community health workers may provide an important linkage to enable patients to access and engage in clinic-based health care. TRIAL REGISTRATION: NCT03326206, registered 10/31/2017, retrospectively registered.

Qualitative evaluation of a community health representative program on patient experiences in Navajo Nation.

BACKGROUND: Community Health Representatives (CHRs) overcome health disparities in Native communities by delivering home care, health education, and community health promotion. The Navajo CHR Program partners with the non-profit Community Outreach and Patient Empowerment (COPE), to provide home-based outreach to Navajo clients living with diabetes. COPE has created an intervention (COPE intervention) focusing on multiple levels of improved care including trainings for CHRs on Motivational Interviewing and providing CHRs with culturally-appropriate education materials. The objective of this research is to understand the participant perspective of the CHR-COPE collaborative outreach through exploring patient-reported outcomes (PROs) of clients who consent to receiving the COPE intervention (COPE clients) using a qualitative methods evaluation. METHODS: Seven COPE clients were selected to participate in semi-structured interviews one year after finishing COPE to explore their perspective and experiences. Qualitative interviews were recorded, transcribed, and coded to identify themes. RESULTS: Clients revealed that health education delivered by CHRs facilitated lifestyle changes by helping them understand key health indicators and setting achievable goals through the use of accessible material and encouragement. Clients felt comfortable with CHRs who respected traditional practices and made regular visits. Clients also appreciated when CHRs educated their family members, who in turn were better able to support the client in their health management. Finally, CHRs who implemented the COPE intervention helped patients who were unable to regularly see a primary care doctor for critical care and support in their disease management. CONCLUSION: The COPE-CHR collaboration facilitated trusting client-CHR relationships and allowed clients to better understand their diagnoses. Further investment in materials that respect traditional practices and aim to educate clients' families may foster these relationships and improve health outcomes. TRIAL REGISTRATION: clinicaltrials.gov: NCT03326206. Registered 9/26/2017 (retrospectively registered).

Community Outreach for Navajo People Living with Diabetes: Who Benefits Most?

INTRODUCTION: The Community Outreach and Patient Empowerment (COPE) intervention provides integrated outreach through community health representatives (CHRs) to people living with diabetes in Navajo Nation. The aim of this study was to identify groups for whom the intervention had the greatest effect on glycated hemoglobin A1c (HbA1c). METHODS: We analyzed de-identified data extracted from routine health records dated from December 1, 2010, through August 31, 2014, to compare net change in HbA1c among COPE patients and non-COPE patients. We used linear mixed models to assess whether the intervention was modified by age, sex, preferred language, having a primary care provider, baseline HbA1c, or having a mental health condition. RESULTS: Age, having a primary care provider, and baseline HbA1c significantly modified HbA1c levels. Among patients aged 64 or younger, COPE participation was associated with a net decrease in HbA1c of 0.77%; among patients aged 65 or older, the net decrease was 0.49% (P = .03). COPE participation was associated with a steeper decrease in HbA1c among patients without a primary care physician (net decrease, 0.99%) than among patients with a primary care provider (net decrease, 0.57%) (P = .03). COPE patients with a baseline HbA1c >9% had a net decrease of 0.70%, while those with a baseline HbA1c ≤9% had a net decrease of 0.34% (P = .01). We found no significant differences based on sex, preferred language, or having a mental health condition. CONCLUSION: Findings suggest that the COPE intervention was robust and equitable, benefiting all groups living with diabetes in Navajo Nation, but conferring the greatest benefit on the most vulnerable.

Integrating community health representatives with health care systems: clinical outcomes among individuals with diabetes in Navajo Nation.

BACKGROUND: We studied the impact of Community Outreach and Patient Empowerment (COPE) intervention to support Community Health Representatives (CHR) on the clinical outcomes of patients living with diabetes in the Navajo Nation extending into the States of Arizona, Utah, and New Mexico. The COPE intervention integrated CHRs into healthcare teams by providing a structured approach to referrals and home visits. METHODS: We abstracted routine clinical data from the Indian Health Service's information system on individuals with diabetes mellitus seen at participating clinical sites from 2010 to 2014. We matched 173 COPE participants to 2880 patients with similar demographic and clinical characteristics who had not participated in COPE. We compared the changes in clinical outcomes between the two groups using linear mixed models. RESULTS: Over the four years of the study, COPE patients had greater improvements in glycosylated hemoglobin (- 0.56%) than non-COPE participants (+ 0.07%) for a difference in differences of 0.63% (95% confidence interval (CI): 0.50, 0.76). Low-density lipoprotein fell more steeply in the COPE group (- 10.58 mg/dl) compared to the non-COPE group (- 3.18 mg/dl) for a difference in differences of 7.40 mg/dl (95%CI: 2.00, 12.80). Systolic blood pressure increased slightly more among COPE (2.06 mmHg) than non-COPE patients (0.61 mmHg). We noted no significant change for body mass index in either group. CONCLUSION: Structured outreach by Community Health Representatives as part of an integrated care team was associated with improved glycemic and lipid levels in the target Navajo population. TRIAL REGISTRATION: Trial registration: NCT03326206. Registered 31 October 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT03326206.

New insights into the membrane association mechanism of the glycosyltransferase WaaG from Escherichia coli.

Monotopic glycosyltransferases (GTs) interact with membranes via electrostatic interactions. The N-terminal domain is permanently anchored to the membrane while the membrane interaction of the C-terminal domain is believed to be weaker so that it undergoes a functionally relevant conformational change upon donor or acceptor binding. Here, we studied the applicability of this model to the glycosyltransferase WaaG. WaaG is involved in the synthesis of lipopolysaccharides (LPS) in Gram-negative bacteria and was previously categorized as a monotopic GT. We analyzed the binding of WaaG to membranes by stopped-flow fluorescence and NMR diffusion experiments. We find that electrostatic interactions are required to bind WaaG to membranes while mere hydrophobic interactions are not sufficient. WaaG senses the membrane's surface charge density but there is no preferential binding to specific anionic lipids. However, the binding is weaker than expected for monotopic GTs but similar to peripheral GTs. Therefore, WaaG may be a peripheral GT and this could be of functional relevance in vivo since LPS synthesis occurs only when WaaG is membrane-bound. We could not observe a C-terminal domain movement under our experimental conditions.

Managing penetrating renal trauma: experience from two major trauma centres in the UK.

OBJECTIVES: To present our series of patients with penetrating renal trauma treated at two urban major trauma centres and to discuss the contemporary management of such injuries. METHODS: We reviewed prospective urological trauma databases for all patients presenting with penetrating renal trauma between January 2005 and October 2016. Patient demographics, clinical characteristics, imaging, management and follow-up data were analysed. RESULTS: Over the 11-year period, 63 patients presented with penetrating renal injuries. The vast majority of patients were male (n = 61; 96.8%), with a mean (range) age of 27.4 (14-71) years. Injuries were equally common on either side (31 left, 32 right). The most common mechanism of injury was stabbing (n = 55; 87.3%), followed by gunshot (n = 7; 11.1%) and crossbow injuries (n = 1; 1.6%). All patients underwent contrast-enhanced computed tomography. Using the American Association for the Surgery of Trauma renal injury grading system, 11 (17.5%) had grade II, 26 (41.3%) had grade III and 26 (41.3%) had grade IV injury. The most common associated injuries were thoracic (n = 23; 36.5%), liver (n = 11; 17.5%), splenic (n = 10; 15.9%), gastrointestinal tract (n = 8; 12.7%) and musculoskeletal (n = 6; 9.5%). At presentation, 16 patients (25.4%) were haemodynamically unstable. The majority of patients did not require blood transfusion (n = 56; 88.9%), while transfusion of >5 units was rare (n = 4; 6.3%). Fifty-two patients (82.5%) were managed by observation alone, while 10 (15.9%) underwent emergency angiography and embolization. Patients with grade IV injury were more likely to require embolization than those with grade III injury; however, the difference was not significant (26.9% vs 15.4%; P = 0.29). One patient (1.6%) underwent retroperitoneal exploration of their renal injury and was managed conservatively. Eight patients underwent laparotomy for other visceral injuries while their renal injury was managed conservatively. Renal artery pseudoaneurysm developed in five patients (7.9%) and one patient (1.6%) developed renal arteriovenous malformation. No patients underwent nephrectomy and no mortality was reported. CONCLUSIONS: The vast majority of patients with penetrating renal injuries can be safely managed non-operatively in this setting. Selective renal artery embolization is an effective option for patients in an unstable condition, with excellent outcomes. Associated thoracic or visceral injuries requiring operative management are common in penetrating renal trauma, while urologists should limit or have a high threshold for surgical intervention.

Is Testicular Macrocalcification a Risk for Malignancy?: Tumor Development on Ultrasonographic Follow-up of Preexisting Intratesticular Macrocalcification.

Testicular macrocalcification is an uncommon finding when imaging the scrotum with ultrasonography (US). It is not normally a recognized risk factor for development of testicular malignancy, and patients are not usually offered follow-up US examinations or counseled for self-examination. This aspect is in distinction to patients with testicular microlithiasis (usually with an additional risk factor), who are offered follow-up on the assumption that microlithiasis is associated with malignancy. We report a series of 6 patients with predetermined testicular macrocalcification, with development of a malignancy on follow-up US. We encourage US follow-up examinations for patients with macrocalcification, potentially in a similar manner as for those with testicular microlithiasis.

Pre-biopsy 3-Tesla MRI and targeted biopsy of the index prostate cancer: correlation with robot-assisted radical prostatectomy.

OBJECTIVE: To study whether pre-biopsy 3-Tesla prostate magnetic resonance imaging (MRI) with targeted biopsy allows accurate anatomical and oncological characterization of the index prostate tumour, and whether this translates into improved positive surgical margin (PSM) rates after radical prostatectomy. PATIENTS AND METHODS: We conducted a retrospective analysis of all men (n = 201) who underwent robot-assisted radical prostatectomy (RARP) between July 2012 and July 2014. Patients were divided into a study group (n = 63) who had undergone pre-biopsy 3-Tesla MRI, followed by visual targeted and systematic prostate biopsy, and a control group (n = 138) who had undergone systematic biopsy alone. The two groups were well matched regarding patient and cancer characteristics. The primary study objective was to assess the accuracy of pre-biopsy MRI for localizing the index tumour. Secondary study objectives were to assess the accuracy of MRI in assessing the maximum tumour diameter (MTD) of the index tumour focus and accuracy of the targeted biopsy in determining the Gleason score and primary Gleason grade of the index tumour focus and whether PSMs were improved after RARP. The reference standard was whole-gland pathology of the resected prostate gland. Continuous variables and proportions were compared using the t-test and Mann-Whitney test or contingency tables, respectively. Pearson's correlation coefficient and Bland-Altman plots were used to compare measurement of MTD. RESULTS: The MRI accurately located the index tumour focus in 73% of patients. Accuracies, stratified according to use of the Prostate Imaging Reporting and Data System (PI-RADS) categories 5, 4 and 3, were 94, 75 and 60% respectively. Accuracies stratified according to MTD of ≤0.7, ≤1 and >1 cm were 50, 57 and 79%, respectively. There was a positive linear correlation between MRI and histological MTD (r = 0.42, 95% confidence interval [CI] 0.16-0.63; P = 0.002), but MRI generally underestimated the MTD: the mean MRI-measured MTD was 1.51 cm (95% CI 1.29-1.72) vs a mean pathological MTD of 2.15 cm (95% CI 1.86-2.43). Targeted biopsy identified 37% more cancer per core than non-targeted biopsy. The mean maximum core length was 8.9 mm (95% CI 7.8-10) vs 6.5 mm (95% CI 5.8-7.2) for the study vs the control group (P = 0.0002; non-paired t-test). Gleason scoring was significantly more predictive after targeted biopsies, with unchanged scores in 40/63 men (63%) vs 62/138 men (45%) in the study and control groups, respectively (P = 0.001; Fisher's test). The odds of Gleason upgrading were 2.5 times greater (P = 0.028) in the control group. The primary Gleason grade was not significantly different in the two groups [45/63 men (71%) vs 91/138 men (66%); study vs control group respectively (P = 0.51, Fisher's test)]. Overall PSMs were nonsignificantly lower in the study group (15.8 vs 18.8%; P = 0.84, Fisher's test); and the MRI location of the index tumour focus correlated with the site of PSM in 70% of men in the study group. CONCLUSIONS: Pre-biopsy MRI can accurately identify the index prostate tumour, especially in those with higher PI-RADS grades and tumour diameter. Targeted biopsy of this focus retrieves significantly more cancerous tissue per core, and is more accurate regarding Gleason scores, but not primary Gleason grade. MRI underestimated the MTD, and PSMs were not significantly improved in the present study.

Strengthening the role of Community Health Representatives in the Navajo Nation.

BACKGROUND: Strengthening Community Health Worker systems has been recognized to improve access to chronic disease prevention and management efforts in low-resource communities. The Community Outreach and Patient Empowerment (COPE) Program is a Native non-profit organization with formal partnerships with both the Navajo Nation Community Health Representative (CHR) Program and the clinical facilities serving the Navajo Nation. COPE works to better integrate CHRs into the local health care system through training, strengthening care coordination, and a standardized culturally appropriate suite of health promotion materials for CHRs to deliver to high-risk individuals in their homes. METHODS: The objective of this mixed methods, cross sectional evaluation of a longitudinal cohort study was to explore how the COPE Program has effected CHR teams over the past 6 years. COPE staff surveyed CHRs in concurrent years (2014 and 2015) about their perceptions of and experience working with COPE, including potential effects COPE may have had on communication among patients, CHRs, and hospital-based providers. COPE staff also conducted focus groups with all eight Navajo Nation CHR teams. RESULTS: CHRs and other stakeholders who viewed our results agree that COPE has improved clinic-community linkages, primarily through strengthened collaborations between Public Health Nurses and CHRs, and access to the Electronic Health Records. CHRs perceived that COPE's programmatic support has strengthened their validity and reputation with providers and clients, and has enhanced their ability to positively effect health outcomes among their clients. CHRs report an improved ability to deliver health coaching to their clients. Survey results show that 80. 2% of CHRs feel strongly positive that COPE trainings are useful, while 44.6% of CHRs felt that communication and teamwork had improved because of COPE. CONCLUSIONS: These findings suggest that CHRs have experienced positive benefits from COPE through training. COPE may provide a useful programmatic model on how best to support other Community Health Workers through strengthening clinic-community linkages, standardizing competencies and training support, and structuring home-based interventions for high-risk individuals.

Pathological Concordance between Prostate Biopsies and Radical Prostatectomy Using Transperineal Sector Mapping Biopsies: Validation and Comparison with Transrectal Biopsies.

Background/Aims/Objectives: Our aim was to evaluate the accuracy of systematic transperineal sector mapping biopsy (TPSMB) in predicting Gleason score (GS) at radical prostatectomy (RP), to compare its accuracy with standard transrectal ultrasound-guided biopsies (TRUS) and to establish the clinical impact of discordance between biopsies and RP on subsequent surgical management. METHODS: Two hundred fifty-five patients from 2008 to 2013 who underwent RP following TPSMB (n = 204) or TRUS (n = 51), were included in this retrospective multi-institutional study. Concordance between biopsies and RPs GS was assessed both as percentages and with Cohen's Kappa coefficient. All mismatches between biopsies and RP were assessed for significance by 3 urologists using the Delphi method. RESULTS: No differences were present among the groups. Concordance between biopsy and RP GS was 75.49% for TPSMB and 64.70% for TRUS. Kappa coefficient was 0.42 and 0.39 respectively. The Delphi method showed lower clinical impact of GS discordances for TPSMB with 7.8% of patients having significant change, thus being potentially more suitable for other treatment modalities, compared to TRUS (13.7%). CONCLUSIONS: TPSMB had a higher accuracy for predicting the GS grade at RP showing superior GS concordance compared with standard TRUS. TPSMB provides an effective technique for systematic prostate biopsy to evaluate overall prostate cancer GS.

Insight into the adsorption profiles of the Saprolegnia monoica chitin synthase MIT domain on POPA and POPC membranes by molecular dynamics simulation studies.

The critical role of chitin synthases in oomycete hyphal tip growth has been established. A microtubule interacting and trafficking (MIT) domain was discovered in the chitin synthases of the oomycete model organism, Saprolegnia monoica. MIT domains have been identified in diverse proteins and may play a role in intracellular trafficking. The structure of the Saprolegnia monoica chitin synthase 1 (SmChs1) MIT domain has been recently determined by our group. However, although our in vitro assay identified increased strength in interactions between the MIT domain and phosphatidic acid (PA) relative to other phospholipids including phosphatidylcholine (PC), the mechanism used by the MIT domain remains unknown. In this work, the adsorption behavior of the SmChs1 MIT domain on POPA and POPC membranes was systematically investigated by molecular dynamics simulations. Our results indicate that the MIT domain can adsorb onto the tested membranes in varying orientations. Interestingly, due to the specific interactions between MIT residues and lipid molecules, the binding affinity to the POPA membrane is much higher than that to the POPC membrane. A binding hotspot, which is critical for the adsorption of the MIT domain onto the POPA membrane, was also identified. The lower binding affinity to the POPC membrane can be attributed to the self-saturated membrane surface, which is unfavorable for hydrogen-bond and electrostatic interactions. The present study provides insight into the adsorption profile of SmChs1 and additionally has the potential to improve our understanding of other proteins containing MIT domains.

From Desegregation and Integration to Diversity and Inclusion: The Environment Was Just Ice.

The process of desegregation at Southern schools of pharmacy was long and arduous. Despite persistent protests, struggles, and lawsuits, many schools of pharmacy did not graduate their first Black students until the 1970s. The School of Pharmacy at the University of North Carolina at Chapel Hill unintentionally desegregated in 1962 when its first Black student, William Wicker, was inadvertently admitted. His personal story and those of his fellow pioneers in desegregation, Mona (Boston) Reddick and James Barnes, provide valuable context to Diversity, Equity, and Inclusion efforts. The historical proximity of desegregation affords the pharmacy profession only one or two generations of Black pharmacists trained during an era when Southern pharmacy education was broadly available. These stories personify the legacy of segregation, confront the ongoing impact of structural racism, and meaningfully inform conversations about Diversity, Equity, and Inclusion in pharmacy education.

Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport.

Significance: Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. Aim: To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. Approach: We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT's impact on brain tissue temperature. Results: The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = 200 J/cm2 at balloon wall) and assuming an initial photosensitizer concentration of 5 µM. Increases in treatment time and light power (light fluence = 400 J/cm2 at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to 10 µM and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer. Conclusions: With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.

Fundamentally mode-locked, femtosecond waveguide oscillators with multi-gigahertz repetition frequencies up to 15 GHz.

We demonstrate passively mode-locked Yb(3+)-doped glass waveguide lasers in a quasi-monolithic configuration with a maximum pulse repetition frequency up to 15.2 GHz. A semiconductor saturable absorber mirror (SESAM) is used to achieve stable mode-locking around 1050 nm with pulse durations as short as 811 fs and an average power up to 27 mW. Different waveguide samples are also employed to deliver pulses with repetition rates of 4.9 GHz, 10.4 GHz and 12 GHz with an average power of 32 mW, 60 mW and 45 mW, respectively. The group velocity dispersion control in the cavity is provided by changing the gap between the SESAM and the waveguide end-face to facilitate a soliton mode-locking regime.

Characterizing lift, drag, and pressure differences across wandering salamanders (Aneides vagrans) with computational fluid dynamics to investigate aerodynamics.

Wandering salamanders (Aneides vagrans), known to occupy the crowns of old growth coast redwood trees, have recently been found to decelerate and engage in controlled, nonvertical descent while falling. Closely related, nonarboreal species with seemingly minor morphological differences exhibit far less behavioral control while falling; however, the influence of salamander morphology on aerodynamics remains to be tested. Here, we examine differences in morphology and aerodynamics of two salamander species, A. vagrans and the nonarboreal ensatina salamander (Ensatina eschscholtzii), using a combination of traditional and contemporary techniques. Specifically, we compare morphometrics statistically, then use computational fluid dynamics (CFD) to characterize predicted airflow and pressure over digitally reconstructed models of the salamanders. While similar in body and tail lengths, A. vagrans are more dorsoventrally flattened with longer limbs and greater surface area of the foot relative to body size than the nonarboreal E. eschscholtzii. CFD results show dorsoventral pressure gradients differ between the two digitally reconstructed salamanders resulting in lift coefficients of approximately 0.02 and 0.00, and lift:drag ratios of approximately 0.40 and 0.00 for A. vagrans and E. eschscholtzii, respectively. We conclude that the morphology of A. vagrans is better suited for controlled descent than that of the closely related E. eschscholtzii and highlight the importance of subtle morphological features, such as dorsoventral flatness, foot size, and limb length, for aerial control. That our simulation reports align with real-world performance data underscores the benefits of CFD for studying the link between morphology and aerodynamics in other taxa.