Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues.

Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single-cell level.

SHAPE-enabled fragment-based ligand discovery for RNA.

The transcriptome represents an attractive but underused set of targets for small-molecule ligands. Here, we devise a technology that leverages fragment-based screening and SHAPE-MaP RNA structure probing to discover small-molecule fragments that bind an RNA structure of interest. We identified fragments and cooperatively binding fragment pairs that bind to the thiamine pyrophosphate (TPP) riboswitch with millimolar to micromolar affinities. We then used structure-activity relationship information to efficiently design a linked-fragment ligand, with no resemblance to the native ligand, with high ligand efficiency and druglikeness, that binds to the TPP thiM riboswitch with high nanomolar affinity and that modulates RNA conformation during cotranscriptional folding. Principles from this work are broadly applicable, leveraging cooperativity and multisite binding, for developing high-quality ligands for diverse RNA targets.

Utility of a pharmacist-managed Anticoagulation Program in patients with congenital heart disease.

BACKGROUND: Warfarin remains the preferred anticoagulant for many patients with CHD. The complexity of management led our centre to shift from a nurse-physician-managed model with many providers to a pharmacist-managed model with a centralized anticoagulation team. We aim to describe the patient cohort managed by our Anticoagulation Program and evaluate the impact of implementation of this consistent, pharmacist-managed model on time in therapeutic range, an evidence-based marker for clinical outcomes. METHODS: A single-centre retrospective cohort study was conducted to evaluate the impact of the transition to a pharmacist-managed model to improve anticoagulation management at a tertiary pediatric heart centre. The percent time in therapeutic range for a cohort managed by both models was compared using a paired t-test. Patient characteristics and time in therapeutic range of the program were also described. RESULTS: After implementing the pharmacist-managed model, the time in therapeutic range for a cohort of 58 patients increased from 65.7 to 80.2% (p < .001), and our Anticoagulation Program consistently maintained this improvement from 2013 to 2022. The cohort of patients managed by the Anticoagulation Program in 2022 included 119 patients with a median age of 24 years (range 19 months-69 years) with the most common indication for warfarin being mechanical valve replacement (n = 81, 68%). CONCLUSIONS: Through a practice change incorporating a collaborative, centralized, pharmacist-managed model, this cohort of CHD patients on warfarin had a fifteen percent increase in time in therapeutic range, which was sustained for nine years.

The indirect impact of infant negative emotionality on interparental conflict via perceptions of coparenting challenges: What prenatal resources mitigate this risk?

Research clearly demonstrates that conflictual interparental relationship dynamics can create a family context that contributes to child emotional insecurity and psychopathology. Significantly less research has examined familial factors that contribute to maladaptive conflict between parents. Scholars have alluded to the disruptive impacts of parenting a child with certain temperamental characteristics (e.g., negative emotionality). Yet, there is a lack of empirical research examining if and how child temperament contributes to later interparental conflict. Using an established multi-informant, multi-method sample of 150 families first assessed during pregnancy, and again when the child was 1, 2, and 3.5 years of age, the present study aimed to test an integrated conceptual model examining whether infants' negative emotionality assessed at age 1 predicts interparental conflict at age 3.5, as mediated through destructive coparenting dynamics in toddlerhood, and identifying prenatal protective factors mitigating this maladaptive pathway. Findings suggest that greater infant negative emotionality predicts worse interparental conflict management during preschool age by undermining the mother's (but not the father's) report of coparenting relationship quality during toddlerhood. However, these results were significant only to the extent that parents were lacking certain prenatal regulatory resources (i.e., low paternal self-compassion; less secure relationship between parents). Importantly, results point to the need for intervention and prevention efforts during pregnancy that might disrupt the deleterious impacts of parenting a child who is more reactive and prone to expressing negative emotions.

Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.

BACKGROUND: Procaspase-3 (PC-3) is overexpressed in multiple tumour types and procaspase-activating compound 1 (PAC-1) directly activates PC-3 and induces apoptosis in cancer cells. This report describes the first-in-human, phase I study of PAC-1 assessing maximum tolerated dose, safety, and pharmacokinetics. METHODS: Modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered orally at 7 dose levels (DL) on days 1-21 of a 28-day cycle. Dose-limiting toxicity (DLT) was assessed during the first two cycles of therapy, and pharmacokinetics analysis was conducted on days 1 and 21 of the first cycle. Neurologic and neurocognitive function (NNCF) tests were performed throughout the study. RESULTS: Forty-eight patients were enrolled with 33 completing ≥2 cycles of therapy and evaluable for DLT. DL 7 (750 mg/day) was established as the recommended phase 2 dose, with grade 1 and 2 neurological adverse events noted, while NNCF testing showed stable neurologic and cognitive evaluations. PAC-1's t1/2 was 28.5 h after multi-dosing, and systemic drug exposures achieved predicted therapeutic concentrations. PAC-1 clinical activity was observed in patients with neuroendocrine tumour (NET) with 2/5 patients achieving durable partial response. CONCLUSIONS: PAC-1 dose at 750 mg/day was recommended for phase 2 studies. Activity of PAC-1 in treatment-refractory NET warrants further investigation. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov: NCT02355535.

Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses.

Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have often been linked by statistical associations, but rarely mechanistically, to a wide range of disease states. One potential explanation for these associations is that IgG allotype alters host cell receptors' affinity for IgG, dampening or enhancing an immune response depending on the nature of the change and the receptors. In this work, a panel of allotypic antibody variants were evaluated using multiplexed, label-free biophysical methods and cell-based functional assays to determine what effect, if any, human IgG polymorphisms have on antibody function. While we observed several differences in FcγR affinity among allotypes, there was little evidence of dramatically altered FcγR-based effector function or antigen recognition activity associated with this aspect of genetic variability.

Sex Hormones, Neurosteroids, and Glutamatergic Neurotransmission: A Review of the Literature.

Glutamatergic dysfunction has been implicated in the pathophysiology of multiple conditions including epilepsy, chronic pain, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD), raising interest in potential ways of modifying glutamate in the nervous system. Emerging research has suggested an interactive effect between sex hormones and glutamatergic neurotransmission. The objective of this paper was to review existing literature on the mechanism of interaction between sex hormones and glutamatergic neurotransmission, as well as to explore what is known about these interactions in various neurological and psychiatric conditions. This paper summarizes knowledge regarding mechanisms for these effects, and glutamatergic response to direct modulation of sex hormones. Research articles were identified via scholarly databases including PubMed, Google Scholar, and ProQuest. Articles were included if they were original research from peer-reviewed academic journals that dealt with glutamate, estrogen, progesterone, testosterone, neurosteroids, glutamate and sex hormone interactions, or the potential impact of glutamate and sex hormone interactions in the following conditions: chronic pain, epilepsy, PTSD, and PMDD. Current evidence suggests that sex hormones can directly modulate glutamatergic neurotransmission, with specific protective effects against excitotoxicity noted for estrogens. An effect of monosodium glutamate consumption on sex hormone levels has also been demonstrated, suggesting a possible bidirectional effect. Overall, there is a good deal of evidence suggesting a role for sex hormones, and specifically for estrogens, in the modulation of glutamatergic neurotransmission.

Geographic Variation in Operative Management of Adhesive Small Bowel Obstruction.

INTRODUCTION: Variation in surgical management exists nationally. We hypothesize that geographic variation exists in adhesive small bowel obstruction (aSBO) management. MATERIALS AND METHODS: A retrospective analysis of a national commercial insurance claims database (MarketScan) sample (2017-2019) was performed in adults with hospital admission due to aSBO. Geographic variation in rates of surgical intervention for aSBO was evaluated by state and compared to a risk-adjusted national baseline using a Bayesian spatial rates Poisson regression model. For individual-level analysis, patients were identified in 2018, with 365-d look back and follow-up periods. Logistic regression was performed for individual-level predictors of operative intervention for aSBO. RESULTS: Two thousand one hundred forty-five patients were included. State-level analysis revealed rates of operative intervention for aSBO were significantly higher in Missouri and lower in Florida. On individual-level analysis, age (P < 0.01) and male sex (P < 0.03) but not comorbidity profile or prior aSBO, were negatively associated with undergoing operative management for aSBO. Patients presenting in 2018 with a history of admission for aSBO the year prior experienced a five-fold increase in odds of representation (odds ratio: 5.4, 95% confidence interval: 3.1-9.6) in 2019. Patients who received an operation for aSBO in 2018 reduced the odds of readmission in the next year by 77% (odds ratio: 0.23, 95% confidence interval: 0.1-0.5). The volume of operations performed within a state did not influence readmission. CONCLUSIONS: Surgical management of aSBO varies across the continental USA. Operative intervention is associated with decreased rates of representation in the following year. These data highlight a critical need for standardized guidelines for emergency general surgery patients.

Surgical Providers' Perceptions of the Patient Portal: Before and After the 21st Century Cures Act.

INTRODUCTION: In April 2021, the Information Blocking Rule (IBR) of the 21st Century Cures Act went into effect giving patients immediate access to notes, radiology reports, lab results, and surgical pathology. We aimed to examine changes in surgical providers' perceptions of patient portal usage before and after its implementation. METHODS: We administered a 37-question survey prior to the implementation of the IBR and a 39-question follow-up survey 3 mo later. The survey was sent to all surgeons, advanced practice providers, and clinic nurses in our surgical department. RESULTS: The response rate to pre surveys and post surveys was 33.7% and 30.7%, respectively. Providers' preference for communication via the patient portal (compared to phone or in person) regarding lab, radiology, or pathology results remained similar. While there was an increase in messages received from patients, there was no difference in the self-reported time spent on the electronic health record (EHR). Prior to the implementation of the blocking rule, 75.8% of providers believed that the portal increased workload which decreased to 57.4% on our follow-up survey. About one-third of providers screened positive for burnout before (32%) which decreased slightly (27.4%). CONCLUSIONS: Although 43.9% of providers reported the Cures Act had changed their practice, there was no difference in self-reported EHR usage, preferred method of interaction with patients, overall workload, or burnout. Initial concerns regarding the IBR's effect on job satisfaction, patient anxiety, and quality of care had lessened. Further exploration into how patients having immediate access to their EHRs has changed surgical practice is needed.

Extreme Elevation of Baseline Intraoperative Parathyroid Hormone Measurements: Should Usual Protocols Apply?

INTRODUCTION: Intraoperative parathyroid hormone (IOPTH) monitoring is routinely used to facilitate minimally invasive parathyroidectomy. Many IOPTH protocols exist for predicting biochemical cure. Some patients are found to have extremely high baseline IOPTH levels (defined in this study as >500 pg/mL), which may affect the likelihood of satisfying certain final IOPTH criteria. We aimed to discover whether clinically significant differences exist in patients with extremely high baseline IOPTH and which IOPTH protocols are most appropriately applied to these patients. MATERIALS AND METHODS: This is a retrospective review of 237 patients who underwent parathyroidectomy with IOPTH monitoring for primary hyperparathyroidism (pHPT) from 2016 to 2020. Baseline IOPTH levels, drawn prior to manipulation of parathyroid glands, were grouped into categories labeled "elevated" (>65-500 pg/mL) and "extremely elevated" (>500 pg/mL). Final IOPTH levels were analyzed to determine whether there was a >50% decrease from baseline and whether a normal IOPTH value was achieved. 6-wk postoperative calcium levels were also examined. RESULTS: Of the patients in this cohort, 76% were in the elevated group and 24% in the extremely elevated group. Male sex and higher preoperative PTH levels were correlated with higher baseline IOPTH levels. Patients with extremely elevated baseline IOPTH were less likely to have IOPTH fall into normal range at the conclusion of the case (P = 0.019), and final IOPTH levels were higher (P < 0.001), but the IOPTH was equally likely to decrease >50% from baseline. There was no difference in the mean postoperative calcium levels between the two groups at 6-wk or at longer term follow-up (mean 525 d). CONCLUSIONS: Detection of baseline IOPTH levels >500 pg/mL during parathyroidectomy performed for pHPT is not uncommon. IOPTH in patients with extremely elevated baseline levels were less likely to fall into normal range, but follow-up calcium levels were equal, suggesting that applying more stringent IOPTH criteria for predicting biochemical cure may not be appropriate for this population.

Performance of single-gene noninvasive prenatal testing for autosomal recessive conditions in a general population setting.

OBJECTIVE: Carrier screening with reflex to single-gene noninvasive prenatal testing (sgNIPT) is an alternative approach for identifying pregnancies at risk for inherited autosomal recessive conditions without the need for a sample from the reproductive partner. This study is the largest clinical validation of this approach in a general population setting. METHODS: The clinical performance of carrier screening with reflex to sgNIPT for cystic fibrosis, spinal muscular atrophy, alpha thalassemias, and beta hemoglobinopathies was assessed by collecting pregnancy outcome data on patients who underwent this testing and comparing the neonatal outcome to the assay-predicted fetal risk. RESULTS: Of 42,067 pregnant individuals who underwent screening, 7538 carriers (17.9%) had reflex sgNIPT, and neonatal or fetal outcomes were obtained for 528 cases, including 25 affected pregnancies. Outcomes demonstrated high concordance with sgNIPT, for example, all pregnancies with 9 in 10 personalized fetal risk results were affected (positive predictive value (PPV) of 100% for the sub-group) and the sgNIPT assay showed a sensitivity of 96.0% (95% CI: 79.65%-99.90%), specificity of 95.2% (95% CI: 92.98%-96.92%), average PPV of 50.0% (95% CI: 35.23%-64.77%), and negative predictive value (NPV) of 99.8% (95% CI: 98.84%-99.99%). The end-to-end performance of carrier screening with reflex to sgNIPT was calculated to have a sensitivity of 92.4% and specificity of 99.9%, which are unaffected by partner carrier screening or misattributed paternity unlike a traditional carrier screening workflow, which has a 35% sensitivity and a maximum of 25% PPV (1 in 4) in a real-life setting. CONCLUSION: This study builds upon earlier findings to confirm that carrier testing with reflex to sgNIPT is highly accurate for general population screening. Given this high accuracy and an NPV of 99.8%, this workflow should be considered as an option for most of the general pregnant population. When the biological partner sample is unavailable, this workflow should be recommended as the first-line approach.

Effect of Playing Position on Heart Rate and Blood Pressure in Brass and Wind Musicians.

OBJECTIVE: The purpose of this study was to compare the impact of playing brass and wind instruments in seated versus standing positions on cardiovascular parameters in musicians. We hypothesized that heart rate (HR) and blood pressure (BP) would be higher while playing compared to resting, and would be higher in standing compared to seated positions. METHODS: Ten musicians completed two study visits. In both, resting, supine HR and BP were recorded, followed by 30 minutes of playing. In one visit, participants played seated, and in the other, played while standing. The order of these positions was randomized. BP and HR were recorded every 5 minutes during playing. RESULTS: Systolic BP was not affected by playing (p = 0.09, eta2 = 0.046) or position (p = 0.35, eta2 = 0.024). Diastolic BP increased while playing (p < 0.0001, eta2 = 0.32), but did not differ between positions (p = 0.21, eta2 = 0.03). Mean arterial pressure (MAP) increased while playing (p < 0.0001, eta2 = 0.25), but did not differ between positions (p = 0.68, eta2 = 0.03). There was a significant time X position interaction for HR (p = 0.0001, eta2 = 0.037). Simple main effects analysis revealed that HR was higher while playing in the standing compared to the seated position at all but one time point. CONCLUSION: Playing brass and wind instruments increases diastolic BP and MAP, regardless of playing position, while playing in the standing position induces a higher HR compared to the seated position.

Professionalism of Admitting and Consulting Services and Trauma Patient Outcomes.

OBJECTIVE: To determine whether trauma patients managed by an admitting or consulting service with a high proportion of physicians exhibiting patterns of unprofessional behaviors are at greater risk of complications or death. SUMMARY BACKGROUND DATA: Trauma care requires high-functioning interdisciplinary teams where professionalism, particularly modeling respect and communicating effectively, is essential. METHODS: This retrospective cohort study used data from 9 level I trauma centers that participated in a national trauma registry linked with data from a national database of unsolicited patient complaints. The cohort included trauma patients admitted January 1, 2012 through December 31, 2017. The exposure of interest was care by 1 or more high-risk services, defined as teams with a greater proportion of physicians with high numbers of patient complaints. The study outcome was death or complications within 30 days. RESULTS: Among the 71,046 patients in the cohort, 9553 (13.4%) experienced the primary outcome of complications or death, including 1875 of 16,107 patients (11.6%) with 0 high-risk services, 3788 of 28,085 patients (13.5%) with 1 high-risk service, and 3890 of 26,854 patients (14.5%) with 2+ highrisk services (P < 0.001). In logistic regression models adjusting for relevant patient, injury, and site characteristics, patients who received care from 1 or more high-risk services were at 24.1% (95% confidence interval 17.2% to 31.3%; P < 0.001) greater risk of experiencing the primary study outcome. CONCLUSIONS: Trauma patients who received care from at least 1 service with a high proportion of physicians modeling unprofessional behavior were at an increased risk of death or complications.

Joint-Predominant Rheumatic Complications of Immune Checkpoint Inhibitor Therapy in Patients with Thymic Epithelial Tumors.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. However, activation of the immune system can occasionally cause life-threatening toxicity involving critical organs. Induction of immune-mediated toxicity is a significant concern for patients with thymic epithelial tumors (TETs) due to defects in immune tolerance. An increased risk of skeletal and cardiac muscle inflammation following treatment with ICIs is well recognized in patients with advanced TETs. However, uncommon musculoskeletal and rheumatic complications can also occur. The cases presented in this report highlight the spectrum of presentation of immune-mediated, joint-predominant musculoskeletal adverse events in patients with advanced TETs treated with ICIs, including polymyalgia rheumatica-like illness and inflammatory arthritis.

The RNA Export Factor ALY1 Enables Genome-Wide RNA-Directed DNA Methylation.

RNA-directed DNA methylation (RdDM) is a set of mechanisms by which transcriptionally repressive DNA and histone methylation are targeted to viruses, transposable elements, and some transgenes. We identified an Arabidopsis (Arabidopsis thaliana) mutant in which all forms of RdDM are deficient, leading to transcriptional activation of some transposable elements and the inability to initiate transgene silencing. The corresponding gene, ALY1, encodes an RNA binding nuclear export protein. Arabidopsis ALY proteins function together to export many messenger RNAs (mRNAs), but we found that ALY1 is unique among this family for its ability to enable RdDM. Through the identification of ALY1 direct targets via RNA immunoprecipitation sequencing, coupled with mRNA sequencing of nuclear and cytoplasmic fractions, we identified mRNAs of known RdDM factors that fail to efficiently export from the nucleus in aly1 mutants. We found that loss of RdDM in aly1 is a result of deficient nuclear export of the ARGONAUTE6 mRNA and subsequent decreases in ARGONAUTE6 protein, a key effector of RdDM. One aly1 allele was more severe due to an additional loss of RNA Polymerase V function, which is also necessary for RdDM. Together, our data reconcile the broad role of ALY1 in mRNA export with the specific loss of RdDM through the activities of ARGONAUTE6 and RNA Polymerase V.

The utility of erythrocyte sedimentation rate, C-reactive protein, and procalcitonin in detecting infections in patients with systemic lupus erythematosus: A systematic review.

OBJECTIVES: We conducted a systematic review with metanalysis to investigate the utility of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) in diagnosing infections in hospitalized patients with SLE. METHODS: We searched Medline, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) with a search strategy developed by a medical librarian. We included retrospective, cross-sectional, case-control, and prospective studies in our analysis. We used the Quality Assessment of Diagnostic Studies (QUADAS-2) to assess for bias and applicability. We obtained mean differences, sensitivities, and specificities in our analysis. RESULTS: We included 26 studies in our analysis. Most studies had an unclear or high risk of bias and our results were widely heterogenous. For the diagnosis of infections, the CRP had a pooled sensitivity of 0.75 (95%CI 0.57-0.94) and specificity of 0.72 (0.59-0.85), PCT had a pooled sensitivity of 0.68 (95% CI 0.0.59-0.77) and specificity of 0.75 (0.59-0.90), and for ESR pooled estimates were not calculated but sensitivity ranged from 50 to 69.8 and specificity from 38.5 to 55.6. Modifying cut-offs improved sensitivities and specificities. The ESR, CRP, and PCT mean differences were all greater in infection groups versus non-infection (10.1, 95% CI 3.2-17.0; 46.8, 95% CI 36.5-57.0; 0.53, 95% CI 0.26-0.80; respectively). DISCUSSION: Poor sensitivities and specificities were observed for the evaluated biomarkers with substantial heterogeneity in the cut-offs used to determine infection. Although mean biomarker values were increased in the infection group compared with the non-infection, our findings do not support the widespread use of ESR, CRP, or PCT in diagnosing infection in hospitalized patients with SLE due to increased heterogeneity and risk of bias. Further investigation is needed.

Alcohol availability and prevalent Chlamydia trachomatis in young Australians: a multi-level analysis.

Background Prevalence of sexually transmissible infections (STIs) has been associated with availability of alcohol. This paper investigates potential associations between prevalent cases of chlamydia in young people in Australia and the availability of alcohol within their local area, defined as postcode of residence. Methods Alcohol availability was determined at the postcode level using liquor licensing data, classified as total number of licences, number of 'take-away' licences and number of licenses by population. Participant data were drawn from a survey targeting Australians aged 16-29years in rural and regional Australia, capturing demographic details including postcode of residence, indicators of sexual behaviour including condom use and chlamydia test results. Mixed-effects logistic regression was used to examine potential associations between first, alcohol availability and chlamydia, and second, between condom use and chlamydia. Results We found little evidence of associations between alcohol availability and chlamydia in either unadjusted or adjusted models. After adjusting for alcohol availability, we observed significant associations between inconsistent condom use and chlamydia prevalence, whether alcohol availability was measured as total number (adjusted odds ratio (AOR) 2.20; 95% confidence interval (CI) 1.20, 3.70), number of take-away licenses (AOR 2.19; 95% CI1.30, 3.69) or licenses per 1000 population (AOR 2.19; 95% CI 1.30, 3.68). Conclusion Little evidence of association between alcohol availability and chlamydia at the postcode level was found. Further research is required to determine appropriate measures of 'local area' and how characteristics thereof may impact on sexual health.

The Molecular Basis and Pathophysiology of Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.

COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients.

The COVID-19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased susceptibility and worsened outcomes of COVID-19 in immunosuppressed recipients. The consequences of COVID-19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID-19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID-19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID-19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID-19.

Structure-Property Relationship in Capillary Foams.

The recently discovered capillary foams are aqueous foams stabilized by the synergistic action of colloidal particles and a small amount of oil. Characteristically, their gas bubbles are coated by a particle-stabilized layer of oil and embedded in a gel network of oil-bridged particles. This unique foam architecture offers opportunities for engineering new foam-related materials and processes, but the necessary understanding of its structure-property relations is still in its infancy. Here, we study the effects of particle wettability, particle volume fraction, and oil-to-particle ratio on the structure and selected properties of capillary foams and use our findings to relate measured foamability, foam stability, and rheological key parameters to the observed foam microstructure. We see that particle wettability not only determines the type of gel network formed but also influences the prevalence of oil droplets included within the foam. Our results further show that the stability and rheology of capillary foams are mainly a function of the particle volume fraction whereas the foamability and observed microstructure are sensitive also to the oil-to-particle ratio. These insights expand our fundamental understanding of capillary foams and will greatly facilitate future work on new foam formulations.