Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients. METHODS: A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center. RESULTS: A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P = .10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P < .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P < .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P < .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P = .04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P = .03). CONCLUSION: Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.

Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. METHODS: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. RESULTS: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1-89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373-1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0-1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. DISCUSSION/CONCLUSION: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients' electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

Comparing confirmatory biopsy outcomes between MRI-targeted biopsy and standard systematic biopsy among men being enrolled in prostate cancer active surveillance.

OBJECTIVES: To evaluate the ability of magnetic resonance imaging (MRI)-targeted biopsy combined with systematic biopsy (MRI-biopsy) to reduce negative biopsies and detect clinically significant prostate cancer compared to systematic biopsy (SB) alone in the confirmatory biopsy setting using matched cohorts. PATIENTS AND METHODS: Patients were identified from an active surveillance database who had a previously positive transrectal ultrasonography-guided SB followed by a confirmatory biopsy at a single institution between 2006 and 2019. Patients were divided into two cohorts based on confirmatory biopsy technique: SB alone or MRI-biopsy (which included MRI-targeted and systematic biopsies). Cohorts were then matched on age, prostate-specific antigen (PSA) level, number of positive cores on initial biopsy and initial biopsy Gleason grade group (GG). Logistic regression was performed to identify associations with confirmatory biopsy upgrading. RESULTS: After matching, 514 patients were identified (257 per cohort). PSA, prostate volume and PSA density prior to initial biopsy, in addition to total number of initial biopsy positive cores and GG, were similar between the matched cohorts. After confirmatory biopsy, 118/257 patients (45.9%) in the MRI-biopsy cohort were upgraded compared to 46/257 patients (17.9%) in the SB cohort (P < 0.001). The rate of negative confirmatory biopsy was 32/257 (12.5%) compared to 97/257 (37.7%) in the MRI-biopsy and SB cohorts, respectively (P < 0.001). Confirmatory MRI-biopsy was associated with greater odds of confirmatory biopsy upgrade from GG 1 to ≥GG 2 compared to SB alone (odds ratio 3.62, 95% confidence interval 1.97-6.63; P < 0.001). CONCLUSION: The addition of MRI-targeted biopsies to SB in the confirmatory biopsy setting among men with previously detected prostate cancer resulted in fewer negative confirmatory biopsies and detection of more clinically significant prostate cancer compared to SB alone.

Description of parallel and sequential configurations for concurrent therapeutic plasma exchange and continuous kidney replacement therapy in adults.

Therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) are extracorporeal therapeutic procedures often implemented in management of patients. Critically ill patients may be afflicted with disease processes that require both TPE and CKRT. Performing TPE discontinuous with CKRT is technically easier, however, it disrupts CKRT and may compromise with CKRT efficiency or hemofilter life. Concurrent TPE with CKRT offers several advantages including simultaneous control of disease process and correction of electrolyte, fluid, and acid-base disturbances that may accompany TPE. Additionally, TPE may be performed by either centrifugation method or membrane plasma separation method. The technical specifications of these methods may influence the methodology of concurrent connections. This report describes and reviews two different approaches to circuit arrangements when establishing concurrent TPE and CKRT.

Radical Cystectomy and Perioperative Sexual Function: A Cross-Sectional Analysis.

BACKGROUND: Cancer-related changes in sexual function (SF) negatively impact quality of life and intimate partner relationships. There is a lack of data regarding SF among patients who underwent radical cystectomy (RC). AIM: To comparatively evaluate perioperative SF among patients who underwent RC. METHODS: A prospective cohort of 150 patients undergoing RC for bladder cancer and participating in an internal validation study at a single institution from 2016 to 2019 were eligible for analysis. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-Bladder Cancer Muscle Invasive (EORTC QLQ-BLM 30) and Functional Assessment of Cancer Therapy-Bladder were administered; those completing the SF subscale of the EORTC QLQ-BLM 30 were included in final analysis. Analysis was performed using descriptive statistics and generalized linear modeling. OUTCOMES: The primary outcome was interest or engagement in sexual activity within 4 weeks of survey completion, whereas the secondary outcome was a mean score on the EORTC QLQ-BLM 30 SF subscale. RESULTS: Overall, 132 of 150 (88%) of patients were eligible, of whom 82% were male, and the median age was 68.5 years. 53% reported at least a little interest in sexual activity, and 40% endorsed sexual activity within the last 4 weeks. The mean SF subscale score was 61.5 ± 25.2. Women had significantly worse mean scores of 72.9 ± 27.1 versus 59.1 ± 24.2 for men (P = .02). On multivariate analysis, both age and female gender were independently associated with higher SF domain scores. CLINICAL IMPLICATIONS: A substantial portion of patients who underwent RC endorse being sexually active or express interest in sexually activity in the perioperative period. Given the recent increase in attention given to SF outcomes and quality of life, this work supports further efforts to explore this area and develop novel interventions to improve outcomes. STRENGTHS AND LIMITATIONS: Strengths include rigorously collected, cross-sectional data using standardized methodology. Limitations include a relatively small sample size of female patients and unknown meaningful clinical difference. CONCLUSIONS: A substantial portion of patients report sexual interest and activity in the perioperative period; however, female gender is associated with worse SF domain scores. These findings support further inquiry into this topic. Westerman ME, Kokorovic A, Wang XS, et al. Radical Cystectomy and Perioperative Sexual Function: A Cross-Sectional Analysis. J Sex Med 2020;17:1995-2004.

Better together: multidisciplinary approach improves adherence to pelvic floor physical therapy.

INTRODUCTION AND HYPOTHESIS: To determine whether consultation with pelvic floor physical therapy (PFPT) at the time of initial urogynecologic evaluation increases adherence to PFPT and to identify factors associated with PFPT attendance and completion. METHODS: We performed a retrospective chart review of all patients evaluated for new urogynecology consultation at our institution in a 1-year period, abstracting data about demographics, diagnoses, and PFPT referral, attendance, and completion. Descriptive analyses compared patients who were referred to, attended, and completed PFPT, stratified by whether they saw PFPT the same day as their initial urogynecologic consultation. Logistic regression identified factors associated with PFPT attendance, completion, and referral. RESULTS: PFPT referral was made for 35% (335/958), of whom 67% attended and 42% completed PFPT. Patients who saw PFPT the same day as their first urogynecology visit were significantly more likely to attend PFPT than those who did not (91% vs. 61%, p < 0.001), but completion rates did not differ (49% vs. 41%, p = 0.15). PFPT attendance was higher among women who saw a PFPT the same day as their initial urogynecology appointment (p < 0.001) and among those aged ≥ 65 years (p = 0.015). Age ≥ 65 years and white, non-Hispanic race/ethnicity were associated with PFPT completion. Patients with a diagnosis of pelvic organ prolapse or urinary incontinence and those seen in multidisciplinary clinic were more likely to be referred to PFPT. CONCLUSIONS: PFPT consultation at the time of initial urogynecologic evaluation improves attendance of initial PFPT appointment, but does not improve completion rates.

Confidence is sexy and it can be trained: Examining male social confidence in initial, opposite-sex interactions.

OBJECTIVE: We investigated whether men's social confidence in an initial, opposite-sex chatting context can be improved through a video tutorial and the extent to which being perceived as socially confident results in being seen as more romantically desirable and worthy of future contact. METHOD: Women chatted with men who had received or not received a tutorial on how to handle speed-dating chats (Study 1: N = 129; Study 2: N = 60) or with male targets selected for having high versus moderate confidence in handling initial, opposite-sex encounters (Study 3: N = 46). RESULTS: Tutorial-trained men felt more confident going into the chats and they, as well as male targets selected for their confidence, were perceived by female chat partners to be higher in social confidence, status, and dominance. However, only perceptions of social confidence were further associated with being perceived as more romantically desirable (as a short-term mate) and worthy of future contact. CONCLUSIONS: Findings indicate that social confidence is trainable and that other-perceived social confidence can impact the outcomes of social interactions.

Lynch syndrome and urologic malignancies: a contemporary review.

PURPOSE OF REVIEW: An overview of urologic malignancies in Lynch syndrome and the current state of research. RECENT FINDINGS: Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Establishment and utilization of a sensitive and practical screening method for Lynch syndrome in patients presenting with UTUC is overdue. Next-generation sequencing to evaluate for microsatellite instability (MSI) and detect mutations of mismatch repair (MMR) genes may be the future of Lynch syndrome screening. Epidemiologic data and molecular characterization suggest bladder urothelial carcinoma (BUC) and prostate cancer (PCA) as unrecognized components of Lynch syndrome. Small studies suggest that Lynch syndrome may predispose individuals to adrenocortical carcinoma. Testicular cancer literature focuses on characterizing MSI and MMR gene expression as it relates to chemotherapy sensitivity; outcomes suggest a potential avenue to investigate its relationship to Lynch syndrome. SUMMARY: Patients with Lynch syndrome have an increased risk of urologic malignancies, including UTUC and likely BUC and PCA. BUC and PCA have a lower penetrance than UTUC for unknown reasons. Established Lynch syndrome-associated genitourinary tumors will necessitate the development of methods to diagnose Lynch syndrome in patients presenting with these malignancies, in addition to establishing screening guidelines for patients with Lynch syndrome-associated genitourinary tumors.

Clinical use of patient decision-making aids for stone patients.

INTRODUCTION: Patient decision-making aids (PDMAs) help patients make informed healthcare decisions and improve patient satisfaction. The utility of PDMAs for patients considering treatments for urolithiasis has not yet been published. We report our experience using PDMAs developed at our institution in the outpatient clinical setting in patients considering a variety of treatment options for stones. MATERIALS AND METHODS: Patients with radiographically confirmed urolithiasis were given PDMAs regarding treatment options for their stone(s) based on their clinical profile. We assessed patients' satisfaction, involvedness, and feeling of making a more informed decision with utilization of the PDMAs using a Likert Scale Questionnaire. Information was also collected regarding previous stone passage, history and type of surgical intervention for urolithiasis, and level of education. RESULTS: Patients (n = 43; 18 males, 23 females and two unknown) 53 +/- 14years old were included. Patients reported that they understood the advantages and disadvantages outlined in the PDMAs (97%), that the PDMAs helped them make a more informed decision (83%) and felt more involved in the decision making process (88%). Patients reported that the aids were presented in a balanced manner and used up-to-date scientific information (100%, 84% respectively). Finally, a majority of the patients prefer an expert's opinion when making a treatment decision (98%) with 73% of patients preferring to form their own opinion based on available information. Previous stone surgery was associated with patients feeling more involved with the decision making process (p = 0.0465). CONCLUSIONS: PDMAs have a promising role in shared decision-making in the setting of treatment options for nephrolithiasis.

Utility of routine urinalysis and urine culture testing in an ambulatory urology clinic: a quality improvement initiative in a Veterans healthcare facility.

INTRODUCTION: Urinalysis (UA) and urine culture (UCx) are commonly performed tests in the urology clinic. Many of these urine studies are performed prior to the patient visit may not always be indicated, thus contributing to unintended consequences such as antibiotic use and costs without enhancing patient care. Our objective was to perform a quality improvement initiative aimed to assess the utility of routine UA/UCx. MATERIALS AND METHODS: The practice pattern at our site's Veteran Affairs (VA) urology clinic prior to 2014 was to obtain routine UA/UCx on most clinic visits prior to patient evaluation. Starting in 2014, we designed an intervention whereby our nurse practitioner triaged all new patient referrals and selectively ordered UA/UCx. We performed multivariable logistic regression to assess for predictors of obtaining UA or UCx. RESULTS: A total of 1308 patients were seen in January-March 2013 and 1456 in June-August 2014 and were included in this analysis. Fewer patients in 2014 received UA (59.8% versus 70.0%, p < 0.001) and UCx (49.6% versus 64.2%, p < 0.001). There was a decreased odds of obtaining UA in 2014 (OR 0.52, p < 0.001) as well as a decreased odds of obtaining UCx in 2014 (OR0.38, p < 0.001) on multivariable logistic regression. The results of UA/UCx only rarely resulted in change of management in either cohort (3%). Selective ordering resulted in an estimated cost savings of $4915.08/month in UCx costs alone. CONCLUSIONS: Our quality improvement initiatives reduced rates of UA/UCx testing when providers assess patients prior to ordering these tests. The implication of this initiative is significant cost savings for the healthcare system.

Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent.

Binding of hepatocyte growth factor (HGF) to the receptor tyrosine kinase MET is implicated in the malignant process of multiple cancers, making disruption of this interaction a promising therapeutic strategy. However, targeting MET with bivalent antibodies can mimic HGF agonism via receptor dimerization. To address this limitation, we have developed onartuzumab, an Escherichia coli-derived, humanized, and affinity-matured monovalent monoclonal antibody against MET, generated using the knob-into-hole technology that enables the antibody to engage the receptor in a one-to-one fashion. Onartuzumab potently inhibits HGF binding and receptor phosphorylation and signaling and has antibody-like pharmacokinetics and antitumor activity. Biochemical data and a crystal structure of a ternary complex of onartuzumab antigen-binding fragment bound to a MET extracellular domain fragment, consisting of the MET Sema domain fused to the adjacent Plexins, Semaphorins, Integrins domain (MET Sema-PSI), and the HGF ß-chain demonstrate that onartuzumab acts specifically by blocking HGF α-chain (but not ß-chain) binding to MET. These data suggest a likely binding site of the HGF α-chain on MET, which when dimerized leads to MET signaling. Onartuzumab, therefore, represents the founding member of a class of therapeutic monovalent antibodies that overcomes limitations of antibody bivalency for targets impacted by antibody crosslinking.

Mirror movement-like defects in startle behavior of zebrafish dcc mutants are caused by aberrant midline guidance of identified descending hindbrain neurons.

Mirror movements are involuntary movements on one side of the body that occur simultaneously with intentional movements on the contralateral side. Humans with heterozygous mutations in the axon guidance receptor DCC display such mirror movements, where unilateral stimulation results in inappropriate bilateral motor output. Currently, it is unclear whether mirror movements are caused by incomplete midline crossing and reduced commissural connectivity of DCC-dependent descending pathways or by aberrant ectopic ipsilateral axonal projections of normally commissural neurons. Here, we show that in response to unilateral tactile stimuli, zebrafish dcc mutant larvae perform involuntary turns on the inappropriate body side. We show that these mirror movement-like deficits are associated with axonal guidance defects of two identified groups of commissural reticulospinal hindbrain neurons. Moreover, we demonstrate that in dcc mutants, axons of these identified neurons frequently fail to cross the midline and instead project ipsilaterally. Whereas laser ablation of these neurons in wild-type animals does not affect turning movements, their ablation in dcc mutants restores turning movements. Thus, our results demonstrate that in dcc mutants, turns on the inappropriate side of the body are caused by aberrant ipsilateral axonal projections, and suggest that aberrant ipsilateral connectivity of a very small number of descending axons is sufficient to induce incorrect movement patterns.

Motoneurons are essential for vascular pathfinding.

The neural and vascular systems share common guidance cues that have direct and independent signaling effects on nerves and endothelial cells. Here, we show that zebrafish Netrin 1a directs Dcc-mediated axon guidance of motoneurons and that this neural guidance function is essential for lymphangiogenesis. Specifically, Netrin 1a secreted by the muscle pioneers at the horizontal myoseptum (HMS) is required for the sprouting of dcc-expressing rostral primary motoneuron (RoP) axons and neighboring axons along the HMS, adjacent to the future trajectory of the parachordal chain (PAC). These axons are required for the formation of the PAC and, subsequently, the thoracic duct. The failure to form the PAC in netrin 1a or dcc morphants is phenocopied by laser ablation of motoneurons and is rescued both by cellular transplants and overexpression of dcc mRNA. These results provide a definitive example of the requirement of axons in endothelial guidance leading to the parallel patterning of nerves and vessels in vivo.

Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens.

BACKGROUND: Extensive use of antibiotics has fostered the emergence of superbugs that are resistant to multidrugs, which becomes a great healthcare and public concern. Previous studies showed that quorum sensing signal DSF (diffusible signal factor) not only modulates bacterial antibiotic resistance through intraspecies signaling, but also affects bacterial antibiotic tolerance through interspecies communication. These findings motivate us to exploit the possibility of using DSF and its structurally related molecules as adjuvants to influence antibiotic susceptibility of bacterial pathogens. RESULTS: In this study, we have demonstrated that DSF signal and its structurally related molecules could be used to induce bacterial antibiotic susceptibility. Exogenous addition of DSF signal (cis-11-methyl-2-dodecenoic acid) and its structural analogues could significantly increase the antibiotic susceptibility of Bacillus cereus, possibly through reducing drug-resistant activity, biofilm formation and bacterial fitness. The synergistic effect of DSF and its structurally related molecules with antibiotics on B. cereus is dosage-dependent. Combination of DSF with gentamicin showed an obviously synergistic effect on B. cereus pathogenicity in an in vitro model. We also found that DSF could increase the antibiotic susceptibility of other bacterial species, including Bacillus thuringiensis, Staphylococcus aureus, Mycobacterium smegmatis, Neisseria subflava and Pseudomonas aeruginosa. CONCLUSION: The results indicate a promising potential of using DSF and its structurally related molecules as novel adjuvants to conventional antibiotics for treatment of infectious diseases caused by bacterial pathogens.

Gender and Professional Identities in Businesswomen's Negotiation.

Gender roles and expectations for women have been shown to account for why women tend to negotiate ineffectively in business settings. Drawing from the psychological literature on multiple identities, this paper examines how individual differences in perceived compatibility between gender and professional identities-captured by the construct Gender-Professional Identity Integration (G-PII)-shape businesswomen's negotiation behaviors. Two studies examined how G-PII interacts with identity cues and cue valence to influence negotiation outcomes. We found that those who perceived their gender and professional identities as compatible (high G-PII) exhibited an "assimilation" effect-they negotiate more effectively when their professional identity was primed by professional identity cues and when prototypical female traits were positively linked to negotiation success, and negotiated less effectively when their gender identity was primed by gender identity cues and when prototypical female traits were negatively linked to negotiation success. However, businesswomen who perceived their gender and professional identities as incompatible (low G-PII) exhibited the opposite "contrast" effect. These findings suggest that the way women negotiate is influenced in part by individual differences in perceptions of compatibility between multiple identities.

Advancing optometry education through global frameworks and international collaborations.

Global curriculum initiatives aim to enhance the education of optometrists across the world. This is done by establishing competencies and frameworks necessary for consistency in education and training. Through collaboration and knowledge exchange between educators and institutions, future optometrists can be equipped with the latest evidence-based knowledge and skills to deliver quality eye care, regardless of geographical location. This paper explores the concept of a global curriculum by investigating the global similarities and differences in definitions of optometry, regulation of the profession, assessment of competency, accreditation standards for education providers, curriculum frameworks, and scope of practice. Despite the challenges of advancing optometric education, there appear to be many opportunities to explore collaboration on an international scale. Three case studies are presented which demonstrate international collaborations among education providers to train local optometrists. Future technological advancements and the use of artificial intelligence may assist the development and delivery of a global curriculum.

Using optical coherence tomography and optical coherence tomography angiography to delineate neurovascular homeostasis in migraine: a review.

Migraine is one of the world's most debilitating disorders, and it has recently been shown that changes in the retina can be a potential biomarker for the disease. These changes can be detected by optical coherence tomography (OCT), which measures retinal thickness, and optical coherence tomography angiography (OCTA), which measures vessel density. We searched the databases Google Scholar, ProQuest, Scopus, and Web of Science for studies in English using OCT and OCTA in migraineurs, using the search terms "optical coherence tomography," "OCT," "optical coherence tomography angiography," "OCTA" and "migraine." We found 73 primary studies, 11 reviews, and 8 meta-analyses pertaining to OCT and OCTA findings in migraineurs. They showed that migraineurs had reduced retinal thickness (via OCT), retinal vessel density, and greater foveal avascular zone area (via OCTA) than controls. OCTA changes reflect a perfusion compromise occurring in migraineurs as opposed to in healthy controls. OCT and OCTA deficits were worse in migraine-with-aura and chronic migraine than in migraine-without-aura and episodic migraine. Certain areas of the eye, such as the fovea, may be more vulnerable to these perfusion changes than other parts. Direct comparison between study findings is difficult because of the heterogeneity between the studies in terms of both methodology and analysis. Moreover, as almost all case-control studies were cross-sectional, more longitudinal cohort studies are needed to determine cause and effect between migraine pathophysiology and OCT/OCTA findings. Current evidence suggests both OCT and OCTA may serve as retinal markers for migraineurs, and further research in this field will hopefully enable us to better understand the vascular changes associated with migraine, perhaps also providing a new diagnostic and therapeutic biomarker.

HLA-DR/DQ eplet mismatch predicts de novo donor-specific antibody development in multi-ethnic Southeast Asian kidney transplant recipients on different immunosuppression regimens.

Eplet mismatch has been recognized as a more precise strategy for determining HLA compatibility by analyzing donor-recipient HLA differences at the molecular level. However, predicting post-transplant alloimmunity using single-molecule eplet mismatch categories has not been validated in Asian cohorts. We examined a cohort of Southeast Asian kidney transplant recipients (n = 234) to evaluate HLA-DR/DQ eplet mismatch as a predictor of de novo donor-specific antibody (dnDSA) development. HLA-DR/DQ single-molecule eplet mismatch was quantified using HLA Matchmaker, and we utilized previously published HLA-DR/DQ eplet mismatch thresholds to categorize recipients into alloimmune risk groups and evaluate their association with dnDSA development. Recognizing that the predominance of cyclosporine use (71%) may alter published eplet mismatch thresholds derived from a largely tacrolimus-based (87%) cohort, we evaluated cohort-specific thresholds for HLA-DR/DQ single-molecule eplet mismatch categories. Recipient ethnicities included Chinese (65%), Malays (17%), Indians (14%), and others (4%). HLA-DR/DQ dnDSA developed in 29/234 (12%) recipients after a median follow-up of 5.4 years, including against isolated HLA-DR (n = 7), isolated HLA-DQ (n = 11), or both (n = 11). HLA-DR/DQ single-molecule eplet mismatch risk categories correlated with dnDSA-free survival (p = 0.001) with low-risk recipients having a dnDSA prevalence of 1% over 5 years. The cohort-specific alloimmune risk categories improved correlation with HLA-DR/DQ dnDSA-free survival and remained significant after adjusting for calcineurin inhibitor and anti-metabolite immunosuppression (p < 0.001). We validated the performance of single-molecule eplet mismatch categories as a prognostic biomarker for HLA-DR/DQ dnDSA development in a cohort of predominantly Asian kidney transplant recipients after adjusting for different immunosuppression regimens.

Cis-2-dodecenoic acid signal modulates virulence of Pseudomonas aeruginosa through interference with quorum sensing systems and T3SS.

BACKGROUND: Cis-2-dodecenoic acid (BDSF) is well known for its important functions in intraspecies signaling in Burkholderia cenocepacia. Previous work has also established an important role of BDSF in interspecies and inter-kingdom communications. It was identified that BDSF modulates virulence of Pseudomonas aeruginosa. However, how BDSF interferes with virulence of P. aeruginosa is still not clear. RESULTS: We report here that BDSF mediates the cross-talk between B. cenocepacia and P. aeruginosa through interference with quorum sensing (QS) systems and type III secretion system (T3SS) of P. aeruginosa. Bioassay results revealed that exogenous addition of BDSF not only reduced the transcriptional expression of the regulator encoding gene of QS systems, i.e., lasR, pqsR, and rhlR, but also simultaneously decreased the production of QS signals including 3-oxo-C12-HSL, Pseudomonas quinolone signal (PQS) and C4-HSL, consequently resulting in the down-regulation of biofilm formation and virulence factor production of P. aeruginosa. Furthermore, BDSF and some of its derivatives are also capable of inhibiting T3SS of P. aeruginosa at a micromolar level. Treatment with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and zebrafish infection models. CONCLUSIONS: These results depict that BDSF modulates virulence of P. aeruginosa through interference with QS systems and T3SS.