Hypertension and Ventilatory Responses During Exercise in the Fitness Registry and the Importance of Exercise National Database (FRIEND).

BACKGROUND: A high minute ventilation/rate of carbon dioxide production (V̇E/V̇co2) slope during exercise is prognostic for cardiovascular death. Recent data indicate that adults with either controlled or untreated primary hypertension, but not those with uncontrolled hypertension, exhibit a higher V̇E/V̇co2 slope during exercise. However, the sample sizes were modest. Therefore, we used the Fitness Registry and the Importance of Exercise National Database to determine whether adults with hypertension, particularly those with controlled or untreated hypertension, exhibit higher V̇E/V̇co2 slopes compared with adults without hypertension. METHODS AND RESULTS: Using the Fitness Registry and the Importance of Exercise National Database, we isolated primary hypertension by excluding those with any disease other than hypertension or taking any medications other than antihypertension medications. We also excluded current smokers and those with obesity. The V̇E/V̇co2 slope was determined during a peak cycling exercise test. All data are presented as median [interquartile range]. We compared groups using linear regression adjusted for age, male/female, and body mass index. The characteristics of the entire sample (n=4109) were age, 42 [18] years; 48% women; body mass index, 26 [4] kg/m2. The V̇E/V̇co2 slope did not differ between adults with hypertension (n=1940; 24.7 [3.7]) compared with those without hypertension (n=2169; 24.9 [3.8]) (hypertension versus no hypertension, P=0.31; overall model: R2=0.07, F4,4104=73.0; P<0.001). Further, the V̇E/V̇co2 slope did not differ between adults with medication-controlled hypertension (n=107; 24.4 [3.0]), untreated hypertension (n=1626; 24.8 [3.9]), uncontrolled hypertension (n=207; 24.8 [3.0]), or those without hypertension (n=2169; 24.9 [3.8]) (hypertension subgroup versus no hypertension, P≥0.06; overall model: R2=0.07, F6,4102=49.6, P<0.001). CONCLUSIONS: Primary hypertension is not associated with V̇E/V̇co2 slope in the Fitness Registry and the Importance of Exercise National Database.

Efficacy and Safety of Long-term Ketogenic Diet Therapy in a Patient With Type 1 Diabetes.

Fewer than 1% of patients with type 1 diabetes achieve normal glycemic control (glycated hemoglobin [HbA1c] < 5.7%/ < 39 mmol/mol). Additionally, exogenous insulin administration often causes "iatrogenic hyperinsulinemia," leading to whole-body insulin resistance and increased risk of cardiovascular complications. We present data on the clinical efficacy and safety of a long-term (10-year) ketogenic diet (≤50 g carbohydrates/day) therapy in a patient with type 1 diabetes. The use of a ketogenic diet resulted in successful glycemic control, assessed by HbA1c (5.5%; 36.6 mmol/mol), continuous glucose monitoring median glucose (98 mg/dL; 5.4 mmol/L), and glucose time-in-range of 70 to 180 mg/dL (90%) without acute glycemic complications. In conjunction, there was a 43% decrease in daily insulin requirements. Low-density lipoprotein cholesterol increased, whereas small-dense low-density lipoprotein was in the normal range (<90 nmol/L). No adverse effects were observed on thyroid function, kidney function, or bone mineral density. This case report demonstrates that a long-term ketogenic diet in a person with type 1 diabetes has considerable therapeutic benefits.

Cryopreservation of stem cell-derived beta-like cells enriches for insulin-producing cells with improved function.

The generation of stem cell-derived beta-like cells (sBC) holds extreme promise as not only an abundant insulin-producing cell source for replacement therapy of Type 1 diabetes (T1D), but also as an invaluable model system for investigating human beta cell development, immunogenicity, and function. Several groups have developed methodology to direct differentiate human pluripotent stem cells into pancreatic cell populations that include glucose responsive sBC. Nevertheless, the process of generating sBC poses significant experimental challenges. It involves lengthy differentiation periods, experiences substantial variability in efficiency, and inconsistencies in obtaining functional sBC. Here, we described a simple and effective cryopreservation approach for sBC cultures that yields homogeneous sBC clusters that are enriched for insulin expressing cells while simultaneous depleting proliferative progenitors. Thawed sBC display enhanced glucose-stimulated insulin release compared to controls in vitro and can effectively engraft and function in vivo. Collectively, this approach alleviates current challenges with inefficient and variable sBC generation while improving their functional state. We anticipate that these findings can inform ongoing clinical application of sBC for the treatment of patients with T1D and serve as an important resource for the wider diabetes field that will allow for accelerated research discoveries.

Interplay of Race and Neighborhood Deprivation on Resting and Ambulatory Blood Pressure in Young Adults.

BACKGROUND: Nighttime BP and BP dipping (daytime-nighttime BP) are prognostic for cardiovascular disease. Compared with other racial/ethnic groups, Black Americans exhibit elevated nighttime BP and attenuated BP dipping. Neighborhood deprivation may contribute to disparities in cardiovascular health, but its effects on resting and ambulatory BP patterns in young adults is unclear. Therefore, we examined associations between neighborhood deprivation with resting and nighttime BP and BP dipping in young Black and White adults. METHODS: We recruited 19 Black and 28 White participants (23 M/24 F, 21±1 years, body mass index: 26±4 kg/m2) for 24-hour ambulatory BP monitoring. We assessed resting BP, nighttime BP, and BP dipping (absolute dip and nighttime:daytime BP ratio). We used the area deprivation index (ADI) to assess average neighborhood deprivation during early- and mid-childhood, and adolescence. RESULTS: Compared with White participants, Black participants exhibited higher resting systolic and diastolic BP (ps≤0.029), nighttime systolic BP (114±9 vs. 108±9 mmHg, p=0.049), diastolic BP (63±8 vs. 57±7 mmHg, p=0.010), and attenuated absolute systolic BP dipping (12±5 vs. 9±7 mmHg, p=0.050). Black participants experienced greater average ADI scores compared with White participants (110(10) vs. 97(22), p=0.002), and select ADI scores correlated with resting BP and some ambulatory BP measures. Within each race, select ADI scores correlated with some BP measures for Black participants, but there were no ADI and BP correlations for White participants. CONCLUSIONS: Our findings suggest neighborhood deprivation may contribute to higher resting BP and impaired ambulatory BP patterns in young adults warranting further investigation in larger cohorts.

Percutaneous removal of hardware after orthopedic surgery: Is it safe? and What are patients saying?

OBJECTIVES: To analyze our patient's complication profile and rate after removal of hardware (ROH) surgery, and survey our patients to ask their overall status and improvement in symptomatology post-operatively. DESIGN: Retrospective chart review and survey. SETTING: Academic, tertiary referral center. PATIENTS/PARTICIPANTS: 173 patients with 314 pieces of hardware. Seventy-six patients (43.9%) responded to our survey. INTERVENTION: ROH surgery. MAIN OUTCOME MEASUREMENTS: Patient demographics and complications were recorded. All patients were sent a brief 3-question survey which asked: (1) Why did you get your hardware removed? (2) How did your overall status change after ROH? (3) How did the ROH affect your stiffness, pain, swelling, and mobility? RESULTS: There were 10 complications (5.5%): 5 infections, 2 with unresolved pain, 1 hematoma, 1 chronic regional pain syndrome exacerbation, and 1 recurrent deformity. All infections were treated with oral antibiotics and improved. All other complications resolved with treatment except for the patient who developed recurrent deformity. Patients underwent ROH surgery because their doctor suggested it (76.3%) and to improve mobility (39.5%). 86.9% reported their overall status improved after ROH. They improved regarding stiffness (73.7%), pain (73.6%), swelling (61.8%), and mobility (76.3%). Similar results were seen among different implants removed. CONCLUSIONS: The majority of patients who underwent percutaneous ROH were satisfied. They reported improvement in stiffness, pain, swelling and mobility (greatest improvement). The complication rate was low (5.5%). ROH can be a meaningful operation to patients allowing them to improve their quality of life with a low complication rate. LEVEL OF EVIDENCE: Level IV.

Deep mutational scanning reveals sequence to function constraints for SWEET family transporters.

Protein science is entering a transformative phase enabled by deep mutational scans that provide an unbiased view of the residue level interactions that mediate function. However, it has yet to be extensively used to characterize the mutational and evolutionary landscapes of plant proteins. Here, we apply the method to explore sequence-function relationships within the sugar transporter AtSWEET13. DMS results describe how mutational interrogation throughout different regions of the protein affects AtSWEET13 abundance and transport function. Our results identify novel transport-enhancing mutations that are validated using the FRET sensor assays. Extending DMS results to phylogenetic analyses reveal the role of transmembrane helix 4 (TM4) which makes the SWEET family transporters distinct from prokaryotic SemiSWEETs. We show that transmembrane helix 4 is intolerant to motif swapping with other clade-specific SWEET TM4 compositions, despite accommodating single point-mutations towards aromatic and charged polar amino acids. We further show that the transfer learning approaches based on physics and ML based In silico variant prediction tools have limited utility for engineering plant proteins as they were unable to reproduce our experimental results. We conclude that DMS can produce datasets which, when combined with the right predictive computational frameworks, can direct plant engineering efforts through derivative phenotype selection and evolutionary insights.

Increased BMI associated with decreased breastfeeding initiation in Million Veteran Program participants.

Background: Breastfeeding has been associated with maternal and infant health benefits but has been inversely associated with body mass index (BMI) prepartum. Breastfeeding and BMI are both linked to socioeconomic factors. Methods: Data from parous female participants with available breastfeeding information from the Million Veteran Program cohort was included. BMI at enrollment and earliest BMI available were extracted, and polygenic scores (PGS) for BMI were calculated. We modeled breastfeeding for one month or more as a function of BMI at enrollment; earliest BMI where available pre-pregnancy; and PGS for BMI. We conducted Mendelian randomization for breastfeeding initiation using PGS as an instrumental variable. Results: A higher BMI predicted a lower likelihood of breastfeeding for one month or more in all analyses. A +5 kg/m 2 BMI pre-pregnancy was associated with a 24% reduced odds of breastfeeding, and a +5 kg/m 2 genetically predicted BMI was associated with a 17% reduced odds of breastfeeding. Conclusions: BMI predicts a lower likelihood of breastfeeding for one month or longer. Given the high success of breastfeeding initiation regardless of BMI in supportive environments as well as potential health benefits, patients with elevated BMI may benefit from additional postpartum breastfeeding support.

Extra-articular Osteotomy for the Management of Intra-articular Tibial Plateau Valgus Malunion.

OBJECTIVES: To report a case series of extra-articular osteotomies for the management of intra-articular tibial plateau malunions and to assess the ability to correct deformity and improve knee range of motion (ROM). METHODS: . DESIGN: Retrospective case series. SETTING: Academic, tertiary, referral center. PATIENT SELECTION CRITERIA: Adult patients with tibial plateau fracture malunion treated with extra-articular osteotomy of the femur and/or tibia between 2014 and 2023. OUTCOME MEASURES AND COMPARISON: Mechanical axis deviation (MAD), medial proximal tibia angle (MPTA), lateral distal femoral angle (LDFA), and posterior proximal tibia angle (PPTA) correction; knee ROM; and time to weight bearing. RESULTS: There were 7 patients included, 6 (85.7%) were female and 1 (14.3%) were male. The median age was 43.5 years (IQR 38.5-51, range 32-62). Four (57.1%) patients were treated with a high tibial osteotomy (HTO), and 3 (42.9%) patients were treated with an HTO and distal femoral osteotomy. One patient had concomitant supramalleolar osteotomy with HTO to address distal tibia procurvatum and valgus. Four were treated with hexapod frames, and 3 were treated with plates and screws. Median follow-up was 22.5 months (IQR 10.5-107 months, range 7-148 months). Surgical intervention corrected median radiographic measures of valgus malalignment preoperatively relative to postoperative values. This included MAD (42.5 mm-0 mm), valgus angle (12.5 degrees-1.5 degrees), MPTA (95 degrees-88.0°), and LDFA (86.0°-87.3 degrees). Surgical intervention increased maximal knee range of motion preoperatively to postoperatively. Median time to full weight bearing was 81.5 days (IQR 46-57 days, range 41-184 days). Two patients were converted to total knee arthroplasty after 5 and 10 years following HTO with hexapod frame. CONCLUSIONS: Extra-articular osteotomy is an effective treatment for addressing intra-articular malunion after tibia plateau fractures. It is effective in correcting the MAD, valgus deformity, MPTA, LDFA, PPTA, and improving knee ROM (measured through knee extension and flexion). LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cretaceous and Paleocene fossils reveal an extinct higher clade within Cornales, the dogwood order.

PREMISE: Characterization and phylogenetic integration of fossil angiosperms with uncertain affinities is relatively limited, which may obscure the diversity of extinct higher taxa in the flowering plant tree of life. The order Cornales contains a diversity of extinct taxa with uncertain familial affinities that make it an ideal group for studying turnover in angiosperms. Here, we describe a new extinct genus of Cornales unassignable to an extant family and conduct a series of phylogenetic analyses to reconstruct relationships of fossils across the order. METHODS: Two permineralized endocarps were collected from the Cedar District Formation (Campanian, 82-80 Ma) of Sucia Island, State of Washington, United States. Fossils were sectioned with the cellulose acetate peel technique and incorporated into a morphological dataset. To assess the utility of this dataset to accurately place taxa in their respective clades, we used a series of phylogenetic pseudofossilization analyses. We then conducted a total-evidence analysis and a scaffold-based approach to determine relationships of fossils. RESULTS: Based on their unique combination of characters, the fossils represent a new genus, Fenestracarpa washingtonensis gen. nov. et sp. nov. Pseudofossilization analyses indicate that our morphological dataset can be used to accurately recover taxa at the major clade to family level, generally with moderate to high support. The total-evidence and scaffold-based analyses recovered Fenestracarpa and other fossil genera in an entirely extinct clade within Cornales. CONCLUSIONS: Our findings increase the reported diversity of extinct Cornales and indicate that the order's initial radiation likely included the divergence of an extinct higher clade that endured the end-Cretaceous Mass extinction but perished during the Cenozoic.

Bifunctional Ligands: Evaluating the Role of Acidic Protons in the Secondary Coordination Sphere.

To evaluate bifunctional ligand reactivity involving NH acidic sites in the secondary coordination sphere of metal complexes, complexes where the proton has been substituted with a methyl group (NMe) are often investigated. An alternative strategy would involve substitution of the NH group for an O. This contribution considers and compares the merits of these approaches; the synthesis and characterization of cationic square planar Rh carbonyl complexes bearing diprotic bispyrazole pyridine ligand L1, and the bis-methylated pyrazole pyridine ligand L1Me are described. The syntheses and characterization of the novel monoprotic pyrazole isoxazole pyridine ligand L2 and aprotic bisisoxazole pyridine ligand L3, and their corresponding Rh carbonyl complexes are also described. The different CO stretching frequencies of all four Rh-complexes suggest that substitutions of NH with NMe, as well as O, lead to significant electronic differences, and these differences are further demonstrated to lead to different ligand addition/substitution reactivities of the four isoelectronic Rh-complexes. Overall, the results suggest that the electronic differences arising due to NH substitutions can be significant and must be accounted for prior to invoking the participation of the proton.

Ambient air pollution and the risk of violence in primary and secondary school settings: a cross-sectional study.

BACKGROUND: Individual and social characteristics are attributed to violent behavior in schools, yet environmental hazards may play an understudied role. Ambient air pollution has been linked to neurological dysfunction that inhibits decision-making and may result in violent behavior in adult populations. However, little is known on how air pollution may be associated with violent behaviors in children. METHODS: A cross-sectional ecologic study was designed to estimate the associations between air pollution (fine particulate matter, carbon monoxide, and nitrogen dioxide) with the occurrence of violent incidents and incidents involving a weapon among a cohort of children in Minnesota schools (2008-2012). Differences by urban and rural status of schools were also explored. Negative binomial regression models were developed to estimate incidence rate ratios (IRR) and incidence rate differences (IRD) to describe associations between air pollution and violent incidents in school settings. RESULTS: Our results indicate that the highest levels of carbon monoxide, nitrogen dioxide and fine particulate matter concentrations were associated with increased violent disciplinary incidents. Among the total student population, the 4th quartile of carbon monoxide exposure was associated with an IRD of 775.62 (95% CI 543.2, 1008.05) violent incidents per 100,000 students per school year compared to schools in the lowest quartile of exposure. Comparing the 4th to the 1st quartiles of exposure, nitrogen dioxide and fine particulate matter had an IRD of 629.16 (95% CI 384.87, 873.46), and 510.49 (95% CI 274.92, 746.05) violent incidents per 100,000 students per school year respectively. Schools in urban settings shared a larger burden of violent incidents associated with air pollution compared to rural schools. CONCLUSIONS: Modifying environmental pollutants surrounding school environments, particularly for high exposure communities, may be a novel tool for reducing violence and subsequent injuries in schools.

Effects of acute simulated altitude on the maximal lactate steady state in humans.

We sought to determine the effects of acute simulated altitude on the maximal lactate steady state (MLSS) and physiological responses to cycling at and 10 W above the MLSS-associated power output (PO) (MLSSp and MLSSp+10, respectively). Eleven (4 female) participants (mean [SD]; 28 [4] years; V̇O2max: 54.3 [6.9] mL×kg-1×min-1) acclimatized to ~1100 m performed 30-min constant PO trials in simulated altitudes of 0 m (SL), 1111 m (MILD), and 2222 m (MOD). MLSSp, defined as the highest PO with stable (<1mM change) blood lactate concentration ([BLa]) between 10 and 30 min, was significantly lower in MOD (209 [54] W) compared to SL (230 [56] W; p<0.001) and MILD (225 [58] W; p=0.001), but MILD and SL were not different (p=0.12). V̇O2 and V̇CO2 decreased at higher simulated altitudes due to lower POs (p<0.05), but other end-exercise physiological responses (e.g., [BLa], ventilation (V̇E), heart rate (HR)) were not different between conditions at MLSSp or MLSSp+10 (p>0.05). At the same absolute intensity (MLSSp for MILD), [BLa], HR, and V̇E and all perceptual variables were exacerbated in MOD compared to SL and MILD (p<0.05). Maximum voluntary contraction, voluntary activation, and potentiated twitch forces were exacerbated at MLSSp+10 relative to MLSSp within conditions (p<0.05); however, condition did not affect performance fatiguability at the same relative or absolute intensity (p>0.05). As MLSSp decreased in hypoxia, adjustments in PO are needed to ensure the same relative intensity across altitudes, but common indices of exercise intensity may facilitate exercise prescription and monitoring in hypoxia.

Congenital cranial dysinnervation disorder with homozygous KIF26A variant.

Congenital fibrosis of the extraocular muscles (CFEOM) type 1 is associated with heterozygous missense variants in KIF21A, which encodes a kinesin-like motor protein. Individuals with CFEOM1 have severe paralysis of upgaze and ptosis, resulting in a pronounced chin-up head posture. There can also be limitations of horizontal eye movements. Loss of function of KIF26A, an unconventional kinesin motor protein that lacks ATP-dependent motor activity, has been recently reported to cause a spectrum of congenital brain malformations associated with defects in migration, localization, and growth of excitatory neurons. It has also been associated with megacolon resembling Hirschsprung's disease. We report the case of a boy with homozygous loss of function of KIF26A with restricted eye movements, specifically restricted upgaze and downgaze with variable nystagmus and dissociated vertical eye movements. This case represents a congenital cranial dysinnervation disorder, most similar to CFEOM, and is the first report of a congenital cranial dysinnervation disorder caused by a kinesin other than KIF21A.

Interplay between phosphorylation and oligomerization tunes the conformational ensemble of SWEET transporters.

SWEET sugar transporters are desirable biotechnological targets for improving plant growth. One engineering strategy includes modulating how SWEET transporters are regulated. Phosphorylation and oligomerization have been shown to positively regulate SWEET function, leading to increased sugar transport activity. However, constitutive phosphorylation may not be beneficial to plant health under basal conditions. Structural and mechanistic understanding of the interplay between phosphorylation and oligomerization in functional regulation of SWEETs remains limited. Using extensive molecular dynamics simulations coupled with Markov state models, we demonstrate the thermodynamic and kinetic effects of SWEET phosphorylation and oligomerization using OsSWEET2b as a model. We report that the beneficial effects of these SWEET regulatory mechanisms bias outward-facing states and improved extracellular gating, which complement published experimental findings. Our results offer molecular insights to SWEET regulation and may guide engineering strategies throughout the SWEET transport family.

Advanced Cardiovascular Physiology in an Individual with Type 1 Diabetes After 10-Year Ketogenic Diet.

Adults with type 1 diabetes (T1D) have an elevated risk for cardiovascular disease (CVD) compared with the general population. HbA1c is the primary modifiable risk factor for CVD in T1D. Fewer than 1% of patients achieve euglycemia (<5.7%HbA1c). Ketogenic diets (KD; ≤50g carbohydrate/day) may improve glycemia and downstream vascular dysfunction in T1D by reducing HbA1c and insulin load. However, there are concerns regarding the long-term CVD risk from a KD. Therefore, we compared data collected in a 60-day window in an adult with T1D on exogenous insulin who consumed a KD for 10 years versus normative values in those with T1D (T1D norms). The participant achieved euglycemia with an HbA1c of 5.5%, mean glucose of 98[5]mg/dL(median[IQR]), and 90[11]%time-in-range 70-180mg/dL (T1D norms: 1st percentile for all); and low insulin requirements of 0.38±0.03IU/kg/day (T1D norms: 8th percentile). Seated systolic blood pressure (SBP) was 113mmHg (T1D norms: 18th percentile) while ambulatory awake SBP was 132±15mmHg (T1D target: <130mmHg), blood triglycerides were 69mg/dL (T1D norms: 34th percentile), low-density lipoprotein was 129mg/dL (T1D norms: 60th percentile), heart rate was 56bpm (T1D norms: >1SD below the mean), carotid-femoral pulse wave velocity was 7.17m/s (T1D norms: lowest quartile of risk), flow-mediated dilation was 12.8% (T1D norms: >1SD above mean), and cardiac vagal baroreflex gain was 23.5ms/mmHg (T1D norms: >1SD above mean). Finally, there was no indication of left ventricular diastolic dysfunction from echocardiography. Overall, these data demonstrate below-average CVD risk relative to T1D norms despite concerns regarding the long-term impact of a KD on CVD risk.

The Arabidopsis AtSWEET13 transporter discriminates sugars by selective facial and positional substrate recognition.

Transporters are targeted by endogenous metabolites and exogenous molecules to reach cellular destinations, but it is generally not understood how different substrate classes exploit the same transporter's mechanism. Any disclosure of plasticity in transporter mechanism when treated with different substrates becomes critical for developing general selectivity principles in membrane transport catalysis. Using extensive molecular dynamics simulations with an enhanced sampling approach, we select the Arabidopsis sugar transporter AtSWEET13 as a model system to identify the basis for glucose versus sucrose molecular recognition and transport. Here we find that AtSWEET13 chemical selectivity originates from a conserved substrate facial selectivity demonstrated when committing alternate access, despite mono-/di-saccharides experiencing differing degrees of conformational and positional freedom throughout other stages of transport. However, substrate interactions with structural hallmarks associated with known functional annotations can help reinforce selective preferences in molecular transport.

Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3.

BACKGROUND: Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV). Neuronal/glial-vascular interactions influence the release of angiogenic and neurotrophic factors. We hypothesized that botulinum neurotoxin serotype A (BoNT/A) modulates pathological endothelial cell proliferation through glial cell activation and growth factor release. METHODS: A laser-induced choroidal NV (CNV) was employed to investigate the anti-angiogenic effects of BoNT/A. Fundus fluorescence angiography, immunohistochemistry, and real-time PCR were used to assess BoNT/A efficacy in inhibiting CNV and the molecular mechanisms underlying this inhibition. Neuronal and glial suppressor of cytokine signaling 3 (SOCS3) deficient mice were used to investigate the molecular mechanisms of BoNT/A in inhibiting CNV via SOCS3. FINDINGS: In laser-induced CNV mice with intravitreal BoNT/A treatment, CNV lesions decreased > 30%; vascular leakage and retinal glial activation were suppressed; and Socs3 mRNA expression was induced while vascular endothelial growth factor A (Vegfa) mRNA expression was suppressed. The protective effects of BoNT/A on CNV development were diminished in mice lacking neuronal/glial SOCS3. CONCLUSION: BoNT/A suppressed laser-induced CNV and glial cell activation, in part through SOCS3 induction in neuronal/glial cells. BoNT/A treatment led to a decrease of pro-angiogenic factors, including VEGFA, highlighting the potential of BoNT/A as a therapeutic intervention for pathological angiogenesis in retinopathies.