Assessing the Relationship of Psychological Sport Readiness, Single-leg Vertical Jump, and Non-Sagittal Single-Leg Hops to Quadriceps Strength After Anterior Cruciate Ligament Reconstruction.

Background: Limitations exist with current ACLR functional testing assessments that may be mitigated by including single-leg multi-directional testing. Hypothesis/Purpose: To compare Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI) scores, limb symmetry index (LSI) of the single-leg vertical jump (SLVJ), single-leg medial rotation hop (SLMRH), single-leg lateral hop (SLLH), and isokinetic quadriceps strength between participants with an ACLR and healthy controls and assess predictors of quadriceps strength asymmetry. It was hypothesized that ACL-RSI scores and LSIs for all tests would differ between ACLR and healthy control groups and within the ACLR group a strong correlation would exist between all outcome measures and quadriceps strength. Study Design: Cross-Sectional Study. Methods: Twenty-six participants with an ACLR (median 13 months after surgery) and twenty-six matched healthy controls were recruited to participate in this study. Performance was assessed via SLVJ, SLMRH, SLLH, and isokinetic quadriceps strength. Between-group comparisons were made with independent t-tests and Mann-Whitney U test. Within the ACLR group, bivariate correlation and multivariate regression analysis were performed to assess the relationship between the outcome measures and quadriceps strength asymmetry. Results: Significant between-limb differences were only identified in the ACLR group (p< 0.05): SLVJ LSI: 88.5%, SLMRH LSI: 93.6%, SLLH LSI: 92.7%, quadriceps strength LSI 80.9% - 83.9%, which were significantly lower (p <0.05) than the healthy control group. Within the ACLR group, a moderate-strong significant (p < 0.05) correlations existed with quadriceps strength and SLVJ (r=0.44-0.65), SLMRH (r =0.43-0.83), and SLLH (r=0.54-0.63); while ACL-RSI had a weak non-significant (p > 0.05) correlation with quadriceps strength (r= 0.12-0.30). Conclusion: Single-leg multidirectional test LSIs were less in ACLR participants than matched healthy controls and all were directly related to quadriceps strength. Psychological readiness to return to sport was not related to quadriceps strength.

Use of VESsel GENeration with Optical Coherence Tomography Angiography and Fluorescein Angiography for Detection and Quantification of Vascular Changes in Mild and Moderate Diabetic Retinopathy.

(1) Background: Previously, VESsel GENeration (VESGEN) software was used to map and quantify vascular changes observed on fluorescein angiography (FA) in subjects (n = 15 eyes) with retinal pathology ranging from mild non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). In the current study, we used VESGEN for the assessment of individuals with early-stage NPDR imaged by FA (Cohort 1) and by optical coherence tomography angiography (OCTA; Cohort 2). (2) Methods: Cohort 1 included type 2 diabetics (T2D), represented 21 eyes (ranging from no DR to moderate DR), and also included nondiabetic controls (NDC; n = 15 eyes). Cohort 2 consisted of 23 eyes from T2D subjects (including no DR subjects and moderate DR subjects) and NDC (n = 18 eyes). (3) Results: In the FA-VESGEN study, total tortuosity (Tv) of microvessels (G ≥ 6) increased in T2D with mild DR compared to the controls. In contrast, the VESGEN analysis of OCTA images showed that vessel length (characterized as density) was lower in T2D subjects before the diagnosis of DR and following the diagnosis of DR when compared to the controls. Additionally, T2D showed a significant decrease in vessel area (density). (4) Conclusions: FA elucidated the vessel morphology of small-generation microvessels to a greater degree than OCTA; however, OCTA identified changes in vessel density better than FA. VESGEN analysis can be used with both standard FA and OCTA to facilitate our understanding of early events in DR, including before the clinical diagnosis of DR.

15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSE: Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS AND METHODS: This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS: 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION: In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

Stress-induced Rab11a-exosomes induce amphiregulin-mediated cetuximab resistance in colorectal cancer.

Exosomes are secreted vesicles made intracellularly in the endosomal system. We have previously shown that exosomes are not only made in late endosomes, but also in recycling endosomes marked by the monomeric G-protein Rab11a. These vesicles, termed Rab11a-exosomes, are preferentially secreted under nutrient stress from several cancer cell types, including HCT116 colorectal cancer (CRC) cells. HCT116 Rab11a-exosomes have particularly potent signalling activities, some mediated by the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG). Mutant activating forms of KRAS, a downstream target of EGFR, are often found in advanced CRC. When absent, monoclonal antibodies, such as cetuximab, which target the EGFR and block the effects of EGFR ligands, such as AREG, can be administered. Patients, however, inevitably develop resistance to cetuximab, either by acquiring KRAS mutations or via non-genetic microenvironmental changes. Here we show that nutrient stress in several CRC cell lines causes the release of AREG-carrying Rab11a-exosomes. We demonstrate that while soluble AREG has no effect, much lower levels of AREG bound to Rab11a-exosomes from cetuximab-resistant KRAS-mutant HCT116 cells, can suppress the effects of cetuximab on KRAS-wild type Caco-2 CRC cells. Using neutralising anti-AREG antibodies and an intracellular EGFR kinase inhibitor, we show that this effect is mediated via AREG activation of EGFR, and not transfer of activated KRAS. Therefore, presentation of AREG on Rab11a-exosomes affects its ability to compete with cetuximab. We propose that this Rab11a-exosome-mediated mechanism contributes to the establishment of resistance in cetuximab-sensitive cells and may explain why in cetuximab-resistant tumours only some cells carry mutant KRAS.

Long-Term Outcomes of Vitrectomy for Idiopathic Epiretinal Membrane With Internal Limiting Membrane Removal in Patients With Good Preoperative Visual Acuity.

Purpose: To evaluate the long-term visual results of vitrectomy with epiretinal membrane (ERM) and internal limiting membrane (ILM) removal for idiopathic ERM in eyes with a preoperative visual acuity (VA) of 20/50 or better. Methods: This retrospective review of a consecutive case series comprised 337 patients. Of these, 36 eyes of 36 patients had ERM and ILM removal from 2017 to 2018. Inclusion criteria included a subjective decrease in VA, a preoperative VA of 20/50 or better, vitrectomy with ERM and ILM removal for ERM, and a minimum 6-month follow-up. Paired t tests were used to determine the statistical significance (P < .05) of VA changes postoperatively. Results: The mean (±SD) best-corrected logMAR VA improved to a maximum of 0.125 ± 0.09 (Snellen equivalent 20/26.4) at a mean of 11.1 months postoperatively (P < .001). The VA continued to significantly improve over the long term (mean, 41.6 months; range, 6-63; P < .001). Overall long-term data trended heavily toward VA improvement (25/36 patients [69.4%]) and stability (10/36 patients [27.7%)] after ERM and ILM removal, with only 1 patient (2.8%) having worse VA. There were no intraoperative or postoperative complications related to ERM and ILM removal. Conclusions: Surgery to remove idiopathic ERM and ILM for patients with significant symptoms and good preoperative VA may result in excellent long-term visual results.

Psychological Factors Are Related to Neuromuscular Asymmetries After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: After an anterior cruciate ligament reconstruction (ACLR), only 47% of military members return to full duty, possibly due to persistent neuromuscular asymmetries. Psychological factors may also contribute to reduced return to duty in military members. HYPOTHESIS: Psychological factors and time since surgery would be associated negatively with neuromuscular asymmetries, asymmetries would be greater in cadets postsurgery when compared with healthy controls, and asymmetries would be greater at earlier timepoints after ACLR. STUDY DESIGN: Case control. LEVEL OF EVIDENCE: Level 4. METHODS: This study examined the relationship between psychological factors and time since surgery with neuromuscular asymmetry, compared neuromuscular asymmetries between cadets with and without a history of ACLR, and explored differences in neuromuscular asymmetries at different timepoints in cadets with a history of ACLR. A total of 37 cadets post-ACLR (18.3 ± 9 months) and 28 controls participated. Psychological factors were assessed using the Tampa Scale of Kinesiophobia and Anterior Cruciate Ligament-Return to Sport after Injury scale (ACL-RSI). Participants performed a drop-jump landing, joint positioning sense (JPS), and isometric quadriceps strength testing. Peak vertical ground-reaction forces (vGRF), absolute angle of replication, peak quadriceps torque, rate of torque development (RTD), and RTD time torque interval 200 ms (TTI200) were analyzed. RESULTS: The ACL-RSI score was significantly related to limb symmetry index (LSI) peak quadriceps torque (r = 0.617, P < 0.01), LSI RTD (r = 0.367, P = 0.05), and LSI TTI200 (r = 0.0489, P < 0.01), but not time since surgery, JPS, or LSI peak vGRF. Cadets with a history of ACLR had significantly lesser ACL-RSI scores and greater asymmetries compared with controls. CONCLUSION: Reduced psychological readiness was associated with increased neuromuscular asymmetries after ACLR. CLINICAL RELEVANCE: Clinicians should assess psychological readiness during rehabilitation after ACLR.

Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL(ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA-sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription (JUNB), and epigenetic regulators (TET1, KMT2B, KMT2A, KMT2C, KMT2E). Gene expression and methylation profiling consistently subclassified ALK+ ALCLs into two groups characterized by diferential ALK expression levels. The ALK-low group showed enrichment of pathways associated with immune response, cytokine signaling, and a hypermethylated predominant pattern compared to the ALK- high group, which had more frequent copy number changes, and was enriched with pathways associated with cell growth, proliferation, metabolic pathways, and. Taken together, these findings suggest that there is molecular heterogeneity within pediatric ALK+ALCL, predicting distinct biological mechanisms that may provide novel insights into disease pathogenesis and represent prognostic markers.

Modified fructan accumulation through overexpression of wheat fructan biosynthesis pathway fusion genes Ta1SST:Ta6SFT.

BACKGROUND: Fructans are water-soluble carbohydrates that accumulate in wheat and are thought to contribute to a pool of stored carbon reserves used in grain filling and tolerance to abiotic stress. RESULTS: In this study, transgenic wheat plants were engineered to overexpress a fusion of two fructan biosynthesis pathway genes, wheat sucrose: sucrose 1-fructosyltransferase (Ta1SST) and wheat sucrose: fructan 6-fructosyltransferase (Ta6SFT), regulated by a wheat ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit (TaRbcS) gene promoter. We have shown that T4 generation transgene-homozygous single-copy events accumulated more fructan polymers in leaf, stem and grain when compared in the same tissues from transgene null lines. Under water-deficit (WD) conditions, transgenic wheat plants showed an increased accumulation of fructan polymers with a high degree of polymerisation (DP) when compared to non-transgenic plants. In wheat grain of a transgenic event, increased deposition of particular fructan polymers such as, DP4 was observed. CONCLUSIONS: This study demonstrated that the tissue-regulated expression of a gene fusion between Ta1SST and Ta6SFT resulted in modified fructan accumulation in transgenic wheat plants and was influenced by water-deficit stress conditions.

Electrographic screening for infantile epileptic spasms syndrome in a single sleep-wake cycle.

OBJECTIVE: Infantile epileptic spasms syndrome (IESS) is a common and urgent diagnosis with seizure and nonseizure mimics. Evaluation with prolonged video-electroencephalography (EEG) can be time-consuming and costly. This study investigated the use of EEG review of a single sleep-wake cycle to exclude IESS. METHODS: We retrospectively reviewed video-EEG studies to rule out IESS in children between the ages of 2 months and 2 years in the period from January 2019 through June 2020. EEG studies were reviewed from the start of the recording through the first sleep-wake cycle and scored as "normal," "consistent with IESS," or "abnormal but not diagnostic of IESS." Scores were compared to the clinical report created by analysis of the entire video-EEG. RESULTS: Inclusion criteria were met in 238 EEG studies. The mean patient age was 7.6 months. The median duration of the full study was 908 min, compared to 107.5 min for the first sleep-wake cycle only. The median difference in recording time was 801 min, p-value < .01. Scored outcomes were similar. Sixty-eight percent of EEG studies were scored as "normal" on first sleep-wake cycle review as compared to 63% on full study review, 13% scored as "consistent with IESS" compared to 16% and 19% scored as "abnormal but not diagnostic of IESS" compared to 21%. Sensitivity and specificity of the first sleep-wake cycle review for studies "consistent with IESS" was 84% and 100%, respectively. No cases of IESS were scored as normal on first sleep-wake cycle review. SIGNIFICANCE: A single sleep-wake cycle captured on EEG can triage studies when IESS is suspected. A normal first sleep-wake cycle did not miss cases of IESS and could result in reduced EEG recording time. Because most of these cases presented to an emergency department, a normal first sleep-wake cycle may help providers determine the acuity, or necessity, of further testing.

Aspectos epidemiológicos y entomólogicos de la enfermedad de lengua azul en ganado bovino / Epidemiologic and entomologic aspects of bluetongue in cattle in the Isthmus of Tehuantepec, Oaxaca, Mexico

Se realizó un estudio prospectivo de la enfermedad de lengua azul en 2 hatos de ganado bovino en la región del Istmo de Tehuantepec. El estudio incluyó la detección menstrual de anticuerpos grupo-específicos contra el virus de lengua azul (VLA) y la captura de moscas culicoides. En enero de 1988, el total de ganado bovino en los 2 hatos (600) fue clasificado seropositivo al VLA, utilizando un método ELISA. Con base en este resultado, 40 bovinos adultos y 35 becerros nacidos entre octubre de 1987 y enero de 1988 fueron evaluados mensualmente (enero a diciembre de 1988) para detectar la producción de anticuerpos grupo-específicos VLA. Se detectó un patrón positivo de seroconversión contra el VLA en becerros, durante la temporada de lluvia en los meses del verano (junio-septiembre). Sin embargo, en algunos becerros se determinó serológicamente actividad de VLA en la temporada seca, durante marzo y abril. Debido a la ausencia de anticuerpos maternos, la mayoría de los becerros fueron susceptibles de infección con el VLA a los 6 meses de edad. La evidencia serológica de la actividad del VLA en becerros se relacionó con la abundancia de moscas Culicoides insignis capturadas durante el estudio

Consideraciones nutricionales para la planificación de proyectos: un estudio de caso para métodos de evaluación / Nutritional considerations in project planning: a case study for assessment of evaluation methods

En este documento se analizan algunos procedimientos para una evaluación ex-ante de los probables efectos nutricionales de los proyectos de desarrollo. Los aspectos que se tratan, se refieren: a la selección de los grupos más necesitados como meta de los componentes de un proyecto; a la necesidad de evitar situaciones en las que el aumento en los ingresos en realidad empeora la nutrición; y a la identificación de componentes adicionales para un proyecto. Se describe la evaluación de un proyecto de desarrollo a gran escala en las Filipinas. Esa evaluación condujo a establecer prioridades para las áreas distantes para los pequeños agricultortes, y para los pescadores de subsistencia, concluyendo que los componentes orientados hacia la producción mejoran la nutrición de los participantes, y que era probable que una intervención frente a los problemas de abastecimiento de agua, resultaría efectiva. Se considera importante la futura aplicación de tales procedimientos, si es que pueden ser integrados de manera completa en la planificación de todo el proyecto. El trabajo de campo que se describe aquí recibió el apoyo de la División de Política de Alimentación y Nutrición de la Organización de la Naciones Unidas para la Agricultura y la Alimentación (FAO) Roma, y del Consejo Nacional de Nutrición (NNC), del Gobierno de la Filipinas. Los análisis se efectuaron en el NNC en las Filipinas y en el Cornell, El Programa de Vigilancia Nutricional de Cornell es financiado mediante el Convenio Cooperativo AID, DSAN, CA, -0240, entre la Oficina de Nutrición, División de Ciencia y Tecnología, USAID, y la Universidad de Cornell. Agradecemos al Consejo Nacional de Nutrición de las Filipinas y a la División de Política de Alimentación y Nutrición de la FAO, por su autorización para usar los resultados. También agradecemos los consejos y comentarios de muchos colegas en Cornell, las Filipinas y Roma