Phylogenomic discordance is driven by wide-spread introgression and incomplete lineage sorting during rapid species diversification within rattlesnakes (Viperidae: Crotalus and Sistrurus).

Phylogenomics allows us to uncover the historical signal of evolutionary processes through time and estimate phylogenetic networks accounting for these signals. Insight from genome-wide data further allows us to pinpoint the contributions to phylogenetic signal from hybridization, introgression, and ancestral polymorphism across the genome. Here we focus on how these processes have contributed to phylogenetic discordance among rattlesnakes (genera Crotalus and Sistrurus), a group for which there are numerous conflicting phylogenetic hypotheses based on a diverse array of molecular datasets and analytical methods. We address the instability of the rattlesnake phylogeny using genomic data generated from transcriptomes sampled from nearly all known species. These genomic data, analyzed with coalescent and network-based approaches, reveal numerous instances of rapid speciation where individual gene trees conflict with the species tree. Moreover, the evolutionary history of rattlesnakes is dominated by incomplete speciation and frequent hybridization, both of which have likely influenced past interpretations of phylogeny. We present a new framework in which the evolutionary relationships of this group can only be understood in light of genome-wide data and network-based analytical methods. Our data suggest that network radiations, like seen within the rattlesnakes, can only be understood in a phylogenomic context, necessitating similar approaches in our attempts to understand evolutionary history in other rapidly radiating species.

Exploring Venom Diversity in Mixcoatlus browni and Mixcoatlus barbouri: A Comparative Analysis of Two Rare Mexican Snake Species with Crotoxin-like Presence.

The genus Mixcoatlus is composed of three species: Mixcoatlus barbouri, M. browni, and M. melanurus, of which the venom composition of M. melanurus, the most common species of the three, has only recently been described. However, very little is known about the natural history of M. barbouri and M. browni, and the venom composition of these two species has remained thus far unexplored. In this study we characterize the proteomic profiles and the main biochemical and toxic activities of these two venoms. Proteomic data obtained by shotgun analysis of whole venom identified 12 protein families for M. barbouri, and 13 for M. browni. The latter venom was further characterized by using a quantitative 'venomics' protocol, which revealed that it is mainly composed of 51.1% phospholipases A2 (PLA2), 25.5% snake venom serine proteases (SVSP), 4.6% L-amino oxidases (LAO), and 3.6% snake venom metalloproteases (SVMP), with lower percentages other six protein families. Both venoms contained homologs of the basic and acidic subunits of crotoxin. However, due to limitations in M. barbouri venom availability, we could only characterize the crotoxin-like protein of M. browni venom, which we have named Mixcoatlutoxin. It exhibited a lethal potency in mice like that described for classical rattlesnake crotoxins. These findings expand knowledge on the distribution of crotoxin-like heterodimeric proteins in viper snake species. Further investigation of the bioactivities of the venom of M. barbouri, on the other hand, remains necessary.

Fangs and foliage: Unearthing the haemotoxic secrets of cannabis-dwelling rattlesnakes.

Despite a recent surge in high-throughput venom research that has enabled many species to be studied, some snake venoms remain understudied. The long-tailed rattlesnakes (Crotalus ericsmithi, C. lannomi, and C. stejnegeri) are one group where such research lags, largely owing to the rarity of these snakes and the hazardous areas, ripe with drug (marijuana and opium) production, they inhabit in Mexico. To fill this knowledge gap, we used multiple functional assays to examine the coagulotoxic (including across different plasma types), neurotoxic, and myotoxic activity of the venom of the long-tailed rattlesnakes. All crude venoms were shown to be potently anticoagulant on human plasma, which we discovered was not due to the destruction of fibrinogen, except for C. stejnegeri displaying minor fibrinogen destruction activity. All venoms exhibited anticoagulant activity on rat, avian, and amphibian plasmas, with C. ericsmithi being the most potent. We determined the mechanism of anticoagulant activity by C. ericsmithi and C. lannomi venoms to be phospholipid destruction and inhibition of multiple coagulation factors, leading to a net disruption of the clotting cascade. In the chick biventer assay, C. ericsmithi and C. lannomi did not exhibit neurotoxic activity but displayed potential weak myotoxic activity. BIRMEX® (Faboterápico Polivalente Antiviperino) antivenom was not effective in neutralising this venom effect. Overall, this study provides an in-depth investigation of venom function of understudied long-tailed rattlesnakes and provides a springboard for future venom and ecology research on the group.

Cognitive and interpersonal moderators of two evidence-based depression prevention programs.

OBJECTIVE: To test potential cognitive and interpersonal moderators of two evidence-based youth depression prevention programs. METHOD: Two hundred four adolescents (Mage = 14.62 years, SD = 1.65; 56% female; 71% White, 11% Black, 11% multiracial, 5% Asian, 2% other races, 18% Hispanic/Latinx) were randomized to either a cognitive-behavioral (Coping With Stress [CWS]) or interpersonal (Interpersonal Psychotherapy-Adolescent Skills Training [IPT-AST]) prevention program. Potential moderators, selected based on theory and research, included rumination, negative cognitive style, dysfunctional attitudes, hopelessness, parent-adolescent conflict, negative interactions with parents and friends, and social support from parents and friends. Depression symptoms were assessed repeatedly through 18 months postintervention. RESULTS: After adjusting for multiple comparisons, rumination (B = -2.02, SE = .61, p = .001, d = .47), hopelessness (B = -2.03, SE = .72, p = .005, d = .41), and conflict with father (B = 1.68, SE = .74, p = .02, d = .32) moderated intervention effects on change in depression symptoms from postintervention through 18-month follow-up. For example, at high levels of conflict with father, youth in IPT-AST reported a significant decrease in symptoms during follow-up, whereas youth in CWS reported a nonsignificant change in symptoms. At low levels of conflict with father, youth in IPT-AST reported a significant increase in symptoms during follow-up, whereas youth in CWS reported a nonsignificant change in symptoms. CONCLUSIONS: These exploratory secondary analyses of Personalized Depression Prevention study data highlight specific cognitive and interpersonal risk factors that could be considered when determining which prevention program may be most effective for a given adolescent. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Developmental trajectories of adolescent internalizing symptoms and parental responses to distress.

Parents' responses to their children's negative emotions are a central aspect of emotion socialization that have well-established associations with the development of psychopathology. Yet research is lacking on potential bidirectional associations between parental responses and youth symptoms that may unfold over time. Further, additional research is needed on sociocultural factors that may be related to the trajectories of these constructs. In this study, we examined associations between trajectories of parental responses to negative emotions and adolescent internalizing symptoms and the potential role of youth sex and racial identity. Adolescents and caregivers (N = 256) completed six assessments that spanned adolescent ages 13-18 years. Multivariate growth models revealed that adolescents with higher internalizing symptoms at baseline experienced increasingly non-supportive parental responses over time (punitive and distress responses). By contrast, parental responses did not predict initial levels of or changes in internalizing symptoms. Parents of Black youth reported higher minimization and emotion-focused responses and lower distress responses compared to parents of White youth. We found minimal evidence for sex differences in parental responses. Internalizing symptoms in early adolescence had enduring effects on parental responses to distress, suggesting that adolescents may play an active role in shaping their emotion socialization developmental context.

Adolescent Depression Symptom Trajectories Detected Via Universal Screening in Pediatric Primary Care.

Unique trajectories of adolescent depression symptoms have been identified, yet less is known about whether such patterns translate to real-world clinical settings. Because annual adolescent depression screening is becoming more prevalent in primary care, we examined whether longitudinal patterns of depression symptoms documented in the developmental psychopathology literature can also be detected via routine screening in primary care and explored how membership in the identified trajectories varied based on concurrent suicide risk and sociodemographic factors. A total of 1,359 adolescents aged 12-16 years old at the first timepoint were included in the current analyses. These adolescents completed three depression screeners during their well-visits in a large pediatric primary care network between November 15, 2017 and February 1, 2020. Retrospective electronic health record data were extracted, including sociodemographic variables and depression screening results. Dynamic functional time series clustering results indicated the optimal number of clusters was five. The five depression symptom trajectories were: (1) A-Shaped (i.e., relatively low depression symptoms at Time 1, a substantial increase in symptoms at Time 2, and a return to low symptoms at Time 3), (2) Increasing, (3) Low-Stable, (4) High-Decreasing, and (5) Low-Decreasing. Cluster differences in suicide risk largely mapped onto depression symptom levels at each assessment. We found cluster differences based on practice location, insurance type, and adolescent race. The symptom trajectories observed in this study resemble those found in the developmental psychopathology literature, though some key differences were noted. Findings can inform future research and symptom monitoring in primary care.

Emerging Risk of Adolescent Depression and Suicide Detected Through Pediatric Primary Care Screening.

OBJECTIVE: The goal of the current study was to document patterns of stability and change in adolescent depression and suicide risk detected via universal depression screening in pediatric primary care and to determine who may go on to experience emerging risk. METHODS: Retrospective electronic health record information (sociodemographic data and depression screening results for 2 timepoints) was extracted for adolescents aged 12-17 who attended well-visits between November 15, 2017, and February 1, 2020, in a large pediatric primary care network. A total of 27,335 adolescents with 2 completed depression screeners were included in the current study. RESULTS: While most adolescents remained at low risk for depression and suicide across the 2 timepoints, others experienced emerging risk (i.e., low risk at time 1 but elevated risk at time 2), decreasing risk (i.e., high risk at time 1 but low risk at time 2) or stable high risk for depression or suicide. Odds of experiencing emerging depression and suicide risk were higher among adolescents who were female (compared to males), Black (compared to White), and had Medicaid insurance (compared to private insurance). Odds of experiencing emerging depression risk were also higher among older adolescents (compared to younger adolescents) as well as adolescents who identified as Hispanic/Latino (compared to non-Hispanic/Latino). CONCLUSIONS: Findings can inform symptom monitoring and opportunities for prevention in primary care.

American public opinion on artificial intelligence in healthcare.

Billions of dollars are being invested into developing medical artificial intelligence (AI) systems and yet public opinion of AI in the medical field seems to be mixed. Although high expectations for the future of medical AI do exist in the American public, anxiety and uncertainty about what it can do and how it works is widespread. Continuing evaluation of public opinion on AI in healthcare is necessary to ensure alignment between patient attitudes and the technologies adopted. We conducted a representative-sample survey (total N = 203) to measure the trust of the American public towards medical AI. Primarily, we contrasted preferences for AI and human professionals to be medical decision-makers. Additionally, we measured expectations for the impact and use of medical AI in the future. We present four noteworthy results: (1) The general public strongly prefers human medical professionals make medical decisions, while at the same time believing they are more likely to make culturally biased decisions than AI. (2) The general public is more comfortable with a human reading their medical records than an AI, both now and "100 years from now." (3) The general public is nearly evenly split between those who would trust their own doctor to use AI and those who would not. (4) Respondents expect AI will improve medical treatment but more so in the distant future than immediately.

Use of Stroke Alert Sticker in the Field Decreases Time to Acute Interventions for Ischemic Stroke Patients.

ABSTRACT: BACKGROUND: Stroke is a medical emergency requiring timely intervention to optimize patient outcomes. The only treatments currently Food and Drug Administration approved for acute stroke are intravenous (IV) thrombolytics, which require obtaining specific medical history to be administered safely. This medical history may be overlooked in the prehospital setting or lost during patient handoff between emergency medical services (EMS) personnel and hospital staff, delaying treatment. We evaluated whether utilization of a "stroke alert sticker" by EMS to capture key information in the field would decrease door-to-needle (DTN) time. METHODS: Bright-orange "stroke alert stickers" were disseminated to our local EMS agency to be placed on all suspected stroke patients in the field prompting documentation of key elements needed for timely treatment decisions. The "stroke alert sticker" included time last known well, contact information, presenting symptoms, and relevant medications. We evaluated the impact of the "stroke alert sticker" on acute stroke metrics, including DTN time. RESULTS: The project included 220 consecutive stroke alert patients brought to our comprehensive stroke center by a single EMS agency from May 2021 through February 2022. Twenty-one patients were treated with an IV thrombolytic. Overall "stroke alert sticker" use compliance was 40%; for the subgroup of patients who were given an IV thrombolytic, the "stroke alert sticker" was used 60% of the time. In patients who received an IV thrombolytic, prehospital EMS notification was 100% with "stroke alert sticker" use, compared with 75% without (P = .13). In addition, with "stroke alert sticker" utilization, DTN time was reduced by 20 minutes (31 [11] minutes with sticker vs 51 [21] minutes without, P = .04). CONCLUSION: Utilization of the "stroke alert sticker" significantly improved DTN times compared with patients without the sticker. This evidence supports continued use of the "stroke alert sticker" to improve DTN times and patient outcomes.

Spindle Cell-Predominant Trichodiscoma With Palisading Arrangement: A Rare Variant.

ABSTRACT: Spindle cell-predominant trichodiscoma (SCPT) is a benign adnexal neoplasm, best categorized within the trichodiscoma-fibrofolliculoma continuum. SCPTs clinically present as dome-shaped papules usually on the face, particularly on the nose or the nasolabial fold. The SCPT variant has been described as a particularly cellular trichodiscoma composed of small interweaving fascicles and sheets of spindle cells. Identical lesions were previously referred to as neurofollicular hamartomas because of their predominantly fascicular stromal cellularity and focal S100 positivity. In this article, we report a rare variant of SCPT with a palisaded arrangement. The patient is a middle-aged man with no significant dermatologic history who presented with a skin-colored papule on the left nasal ala. It had been present for approximately 10 years with only minimal growth over that time. A biopsy was obtained. Histopathological analysis revealed a dermal papule composed of bland spindle cells arranged in a striking palisading pattern within a fibromyxoid stroma with associated peripheral hyperplasia of sebaceous glands. The palisaded pattern shared features reminiscent of Verocay bodies of a schwannoma. Immunohistochemical studies revealed stromal spindled cells with a strong and diffuse pattern of CD34 expression and absent S100 and SOX10 expressions. To our knowledge, only 2 cases of SCPT with a palisaded pattern have been presented. SCPT with a palisaded pattern is a rare histopathologic variant that may resemble a schwannoma but can be recognized by its strong epithelial components and immunohistochemical staining pattern.

Accelerating radiochemistry development: Automated robotic platform for performing up to 64 droplet radiochemical reactions in a morning.

The growing discovery and development of novel radiopharmaceuticals and radiolabeling methods requires an increasing capacity for radiochemistry experiments. However, such studies typically rely on radiosynthesizers designed for clinical batch production rather than research, greatly limiting throughput. Two general solutions are being pursued to address this: developing new synthesis optimization algorithms to minimize how many experiments are needed, and developing apparatus with enhanced experiment throughput. We describe here a novel high-throughput system based on performing arrays of droplet-based reactions at 10 µL volume scale in parallel. The automatic robotic platform can perform a set of 64 experiments in ~3 h (from isotope loading to crude product, plus sampling onto TLC plates), plus ~1 h for off-line radio-TLC analysis and radioactivity measurements, rather than the weeks or months that would be needed using a conventional system. We show the high repeatability and low crosstalk of the platform and demonstrate optimization studies for two 18F-labeled tracers. This novel automated platform greatly increases the practicality of performing arrays of droplet reactions by eliminating human error, vastly reducing tedium and fatigue, minimizing radiation exposure, and freeing up radiochemist time for other intellectually valuable pursuits.

Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study.

BACKGROUND: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC. PATIENTS AND METHODS: Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.75 mg for moderate renal impairment) followed by surgery. The primary endpoint was pathologic complete response (pCR) by independent central review (ICR). Secondary endpoints included residual cancer burden (RCB) by ICR. Safety and tolerability of talazoparib and patient-reported outcomes were assessed. RESULTS: Of 61 patients, 48 received ≥80% talazoparib doses, underwent surgery, and were assessed for pCR or progressed before pCR assessment and considered nonresponders. pCR rate was 45.8% (95% confidence interval [CI], 32.0%-60.6%) and 49.2% (95% CI, 36.7%-61.6%) in the evaluable and intent-to-treat (ITT) population, respectively. RCB 0/I rate was 45.8% (95% CI, 29.4%-63.2%) and 50.8% (95% CI, 35.5%-66.0%) in the evaluable and ITT population, respectively. Treatment-related adverse events (TRAE) were reported in 58 (95.1%) patients. Most common grade 3 and 4 TRAEs were anemia (39.3%) and neutropenia (9.8%). There was no clinically meaningful detriment in quality of life. No deaths occurred during the reporting period; 2 deaths due to progressive disease occurred during long-term follow-up (>400 days after first dose). CONCLUSIONS: Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated. CLINICALTRIALS.GOV IDENTIFIER: NCT03499353.

Parent-youth convergence (and divergence) in reports about pediatric quality of life.

PURPOSE: Researchers and service providers typically assess pediatric Health-Related Quality of Life (HRQOL) by collecting independent reports from parents and youth. An emerging body of work indicates that patterns of parent-youth reports yield information germane to understanding youth outcomes. We identified patterns of HRQOL among youth and their parents seeking mental health treatment and examined links between agreement patterns and mental and physical health functioning. METHODS: Participants included 227 youth (mean age = 14.40 years, SD = 2.42; 63% female) and parent dyads presenting at a mood disorders clinic between 2013 and 2020. We assessed HRQOL using parallel youth and parent forms of the Pediatric Quality of Life Inventory Generic Core Scales. We also assessed youth clinical correlates of depression, suicidal ideation, and impairment, as well as health information via electronic health record (e.g., psychotropic medication usage, BMI). RESULTS: Latent class analysis showed three parent-youth reporting patterns: Low-Low (LL), High-High (HH), and Parent Low-Youth High (PL-YH). Relative to youth in the HH group, youth in the LL and PL-YH groups reported significantly greater depressive symptoms and had higher rates of suicidal ideation and psychotropic medication use. In addition, youth in the LL group reported significantly greater levels of impairment. CONCLUSIONS: Parent-youth patterns of HRQOL reporting can reveal clinically meaningful information and indicate poorer functioning for certain groups (LL, PL-YH) of youth. These findings have implications for improving accuracy of risk assessments that leverage HRQOL data.

Personalized Depression Prevention Reduces Dependent Stressors Among Adolescents: Results from a Randomized Controlled Trial.

OBJECTIVE: Depression and stressors both increase during adolescence. The stress generation model posits that depression symptoms and associated impairment contribute to the generation of dependent stressors. Adolescent depression prevention programs have been shown to reduce the risk of depression. Recently, risk-informed personalization approaches have been adopted to enhance the efficacy of depression prevention, and preliminary evidence supports the beneficial effects of personalized prevention on depression symptoms. Given the close association between depression and stress, we examined the hypothesis that personalized depression prevention programs would reduce adolescents' experience of dependent stressors (interpersonal and non-interpersonal) over longitudinal follow-up. METHOD: The present study included 204 adolescents (56% girls, 29% racial minority) who were randomized to receive either a cognitive-behavioral or an interpersonal prevention program. Youth were categorized as high or low on cognitive and interpersonal risk using a previously established risk classification system. Half of the adolescents received a prevention program that matched their risk profile (e.g., high cognitive risk randomized to cognitive-behavioral prevention); half received a mismatched program (e.g., high interpersonal risk randomized to cognitive-behavioral prevention). Exposure to dependent and independent stressors was assessed repeatedly over an 18-month follow-up period. RESULTS: Matched adolescents reported fewer dependent stressors during the post-intervention follow-up period (d = .46, p = .002) and from baseline through 18-months post-intervention (d = .35, p = .02) compared to mismatched youth. As expected, there were no differences between matched and mismatched youth on the experience of independent stressors. CONCLUSIONS: These findings further highlight the potential of personalized approaches to depression prevention and demonstrate benefits that go beyond depression symptom reduction.

Risk and Resilience Measures Related to Psychopathology in Youth.

Childhood adversity places youth at risk for multiple negative outcomes. The current study aimed to understand how a constellation of risk and resilience factors influenced mental health outcomes as a function of adversities: socioeconomic status (SES) and traumatic stressful events (TSEs). Specifically, we examined outcomes related to psychosis and mood disorders, as well as global clinical functioning. The current study is a longitudinal follow up of 140 participants from the Philadelphia Neurodevelopmental Cohort (PNC) assessed for adversities at Time 1 (Mean age: 14.11 years) and risk, resilience, and clinical outcomes at Time 2 (mean age: 21.54 years). In the context of TSE, a limited set of predictors emerged as important; a more diverse set of moderators emerged in the context of SES. Across adversities, social support was a unique predictor of psychosis spectrum diagnoses and global functioning; emotion dysregulation was an important predictor for mood diagnoses. The current findings underscore the importance of understanding effects of childhood adversity on maladaptive outcomes within a resilience framework.

Depression Prevention in Pediatric Primary Care: Implementation and Outcomes of Interpersonal Psychotherapy-Adolescent Skills Training.

This study evaluated the fidelity, feasibility, acceptability, and preliminary outcomes of a depression prevention program, interpersonal psychotherapy-adolescent skills training (IPT-AST), in urban pediatric primary care (PC) with a sample of primarily Black youth. Twenty-two adolescents with elevated depressive symptoms participated in this open clinical trial. Adolescents were identified through a screening questionnaire completed at well visits. Ratings of IPT-AST fidelity and session attendance were recorded. Youth and caregivers reported on their attitudes toward the intervention and completed measures of adolescents' symptoms and functioning pre- and post-intervention. Results demonstrated high levels of fidelity, attendance, and acceptability, despite some difficulties with recruitment. Adolescents and caregivers reported significant improvements in functioning. There were marginally significant reductions in self-reported depression, anxiety, and total mental health symptoms. Caregivers reported a significant decrease in total mental health symptoms. Findings provide preliminary information regarding the implementation and effects of IPT-AST when delivered in PC.

The Depression Prevention Initiative: Trauma as a Moderator of Prevention Outcomes.

Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) is an evidence-based indicated depression prevention program that has been shown to reduce depression symptoms. Research is needed to identify moderators of IPT-AST's effects. Although trauma history has emerged as a moderator of depression treatment outcomes, the impact of trauma on short- and long-term outcomes in the context of preventive interventions for adolescent depression is unknown. This study examines the impact of trauma on prevention outcomes in a school-based randomized controlled trial (RCT) in which 186 adolescents (mean age = 14.01 years, SD = 1.22; 67% female) were randomly assigned to IPT-AST delivered by research staff or group counseling (GC) provided by school counselors. Trauma history significantly moderated intervention outcomes during the active phase of the intervention, but not during long-term follow-up. During the active phase, youth in IPT-AST with low or no trauma exposure experienced significantly greater reductions in depression symptoms than youth in GC with low or no trauma exposure, but there were no significant differences in rates of change between the two interventions for youth with high or any trauma exposure. These findings highlight the importance of assessing trauma and investigating whether these interventions can be tailored or supplemented to enhance the effects for youth with trauma exposure.

Reproducibility of the Magnitude of Lens Rotation Following Implantation of a Toric Intraocular Lens with Modified Haptics.

Purpose: To evaluate the reproducibility of magnitude of postoperative IOL rotation following implantation of a toric intraocular lens (IOL) with modified haptics, in comparison with a Proof-of-Concept (POC) study of prototype IOLs featuring the same haptic design. Patients and Methods: A post-market, prospective, multicenter, single-arm, open-label clinical study was conducted. TECNIS Toric II IOL (Johnson & Johnson Vision, Irvine, CA, USA, Models ZCU150 to 600) were implanted in 125 subjects and evaluated at 1-day and 1-week postoperatively. An objective photographic method was used to determine postoperative IOL rotation. Uncorrected distance visual acuity (UCDVA), postoperative astigmatism, and surgeon satisfaction were also assessed. Rotation data were compared to the POC study in which two prototype non-toric monofocal IOLs, one with the same haptic design as Model ZCU, were studied. Results: Mean absolute rotation was 0.82° ± 1.0° and 0.84° ± 0.92°at 1-day and 1-week visits, respectively. The percentage of eyes with ≤5° of absolute rotation was 98.9% and 99.5% at the 1-day and 1-week visits, respectively. The magnitude of rotation was similar to the POC study prototype IOLs. At 1-week, mean monocular UCDVA was 0.026 ± 0.135 (~20/21) logMAR and mean residual manifest refractive cylinder was 0.30 D ± 0.35 D. The mean signed axis difference (postoperative minus operative) of the TECNIS Toric II IOL was 0.23° ± 1.27° at 1-day and -0.07° ± 1.25° at 1-week, indicating a clockwise drift. At 1-week, surgeons were very satisfied or satisfied with overall clinical outcomes and rotational stability in 98% of implanted eyes. Conclusion: The TECNIS Toric II IOL, with frosted, squared haptics, demonstrated low magnitude of postoperative IOL rotation, excellent uncorrected distance vision, and minimal residual astigmatism. The POC study design was supported, demonstrating that prototype non-toric monofocal IOLs can predict clinical performance of toric IOLs with the same haptic design.

Proteomic and toxicological characterization of the venoms of the most enigmatic group of rattlesnakes: The long-tailed rattlesnakes.

The most enigmatic group of rattlesnakes is the long-tailed rattlesnake group, consisting of three species: Crotalus ericsmithi, Crotalus lannomi and Crotalus stejnegeri. These species have been the least studied rattlesnakes in all aspects, and no study on the characterization of their venoms has been carried out to date. Our main objective was to investigate the proteomic composition, as well as some of the biochemical and toxic activities of these venoms, and their neutralization by commercial antivenom. The venom proteome of C. ericsmithi mainly contains metalloproteinases (SVMP; 49.3%), phospholipases A2 (PLA2; 26.2%), disintegrins (Dis; 12.6%), and snake venom serine proteases (SVSP; 6.8%), while C. lannomi venom mainly consists of SVMP (47.1%), PLA2 (19.3%), Dis (18.9%), SVSP (6%) and l-amino acid oxidase (LAAO; 2.6%). For these venoms high lethality was recorded in mice, the most potent being that of C. lannomi (LD50 of 0.99 µg/g body weight), followed by C. ericsmithi (1.30 µg/g) and finally C. stejnegeri (1.79 µg/g). The antivenoms Antivipmyn® from SILANES and Fabotherapic polyvalent antiviperin® from BIRMEX neutralized the lethal activity of the three venoms. Although this group of snakes is phylogenetically related to the C. viridis group, no neurotoxic components (crotoxin or crotoxin-like proteins) common in rattlesnakes were found in their venoms. This study expands current knowledge on the venoms of understudied snake species of the Mexican herpetofauna.