Oncolytic adenovirus coding for shedding-resistant MICA enhances immune responses against tumors.

Cancer immunotherapies strive to overcome tumor-induced immune suppression and activate antitumor immune responses. Although cytotoxic T lymphocytes (CTLs) play a pivotal role in this process, natural killer (NK) cells have also demonstrated remarkable tumor-killing abilities, given their ability to discriminate tumor cells from normal cells and mediate specific antitumoral cytotoxicity. NK cells activation depends on a balance between activation and inhibition signals from several ligands/receptors. Among them, MICA/NKG2D axis is a master regulator of NK activation. MHC class I chain-related polypeptide A (MICA) expression is upregulated by many tumor cell lines and primary tumors and serves as a ligand for the activating NK group 2D (NKG2D) receptor on NK cells and subpopulations of T cells. However, cancer cells can cleave MICA, making it soluble and de-targeting tumor cells from NK cells, leading to tumor immune escape.In this study, we present ICOVIR15KK-MICAMut, an oncolytic adenovirus (OAdv) armed with a transgene encoding a non-cleavable MICA to promote NK-mediated cell-killing capacity and activate the immune response against cancer cells. We first demonstrated the correct MICA overexpression from infected cells. Moreover, our MICA-expressing OAdv promotes higher NK activation and killing capacity than the non-armed virus in vitro. In addition, the armed virus also demonstrated significant antitumor activity in immunodeficient mice in the presence of human PBMCs, indicating the activation of human NK cells. Finally, OAdv-MICA overexpression in immunocompetent tumor-bearing mice elicits tumor-specific immune response resulting in a greater tumor growth control.In summary, this study highlights the significance of NK cells in cancer immunotherapy and presents an innovative approach using a modified oncolytic virus to enhance NK cell activation and antitumor immune response. These findings suggest promising potential for future research and clinical applications.

Effect of drought stress during seed development on charcoal rot and yield of soybean.

The primary controls for charcoal rot in soybean, caused by the fungal pathogen Macrophomina phaseolina, are to avoid drought stress and to plant a moderately resistant cultivar. The effects of irrigation and cultivar were determined in 2011 and 2013 at the Lon Mann Cotton Research Station, Marianna, AR. Four soybean cultivars (Hutcheson, Osage, Ozark, and R01581F), were planted in plots with or without added M. phaseolina inoculum and subjected to three furrow irrigation regimes: full season irrigation (Full), irrigation terminated at R5 (CutR5), and non-irrigated (NonIrr). Normalized difference vegetative index (NDVI) was measured at R3 and R6. At harvest, plants and yields were collected. Roots and stems were split and the extent of visible colonization by M. phaseolina microsclerotia was assessed in the roots with a 1-5 scale (RSS) and the percent plant height stem discoloration (PHSD) measured. Precipitation in September and October was 54 and 65% below the 30-year average in 2011 and 2013, respectively. The CutR5 irrigation treatment resulted in one less irrigation than Full each year, but CutR5 NDVI's at R6 and yields were significantly lower than those with Full and not significantly different than those of NonIrr. The CutR5 RSS ratings were greater than either Full or NonIrr. Plant colonization by M. phaseolina was negatively correlated to yield in 2011 but not in 2013. No premature plant death caused by charcoal rot was observed in either year. These results indicated that late season drought stress may be more important to charcoal rot development than drought stress throughout the season, but other factors are needed to trigger early plant death and subsequent yield losses observed in grower fields.

Multistate Sensitivity Monitoring of Fusarium virguliforme to the SDHI Fungicides Fluopyram and Pydiflumetofen in the United States.

Sudden death syndrome (SDS), caused by Fusarium virguliforme, is an important yield-limiting disease of soybean (Glycine max). From 1996 to 2022, cumulative yield losses attributed to SDS in North America totaled over 25 million metric tons, which was valued at over US $7.8 billion. Seed treatments are widely used to manage SDS by reducing early season soybean root infection by F. virguliforme. Fluopyram (succinate dehydrogenase inhibitor [SDHI] - FRAC 7), a fungicide seed treatment for SDS management, has been registered for use on soybean in the United States since 2014. A baseline sensitivity study conducted in 2014 evaluated 130 F. virguliforme isolates collected from five states to fluopyram in a mycelial growth inhibition assay and reported a mean EC50 of 3.35 mg/liter. This baseline study provided the foundation for the objectives of this research: to detect any statistically significant change in fluopyram sensitivity over time and geographical regions within the United States and to investigate sensitivity to the fungicide pydiflumetofen. We repeated fluopyram sensitivity testing on a panel of 80 historical F. virguliforme isolates collected from 2006 to 2013 (76 of which were used in the baseline study) and conducted testing on 123 contemporary isolates collected from 2016 to 2022 from 11 states. This study estimated a mean absolute EC50 of 3.95 mg/liter in isolates collected from 2006 to 2013 and a mean absolute EC50 of 4.19 mg/liter in those collected in 2016 to 2022. There was no significant change in fluopyram sensitivity (P = 0.1) identified between the historical and contemporary isolates. A subset of 23 isolates, tested against pydiflumetofen under the same conditions, estimated an absolute mean EC50 of 0.11 mg/liter. Moderate correlation was detected between fluopyram and pydiflumetofen sensitivity estimates (R = 0.53; P < 0.001). These findings enable future fluopyram and pydiflumetofen resistance monitoring and inform current soybean SDS management strategies in a regional and national context.

Navigated augmented reality through a head-mounted display leads to low deviation between planned, intra- and post-operative parameters during glenoid component placement of reverse shoulder arthroplasty: a proof-of-concept case series.

BACKGROUND: Navigated augmented reality (AR) through a head-mounted display (HMD) has led to accurate glenoid component placement in reverse shoulder arthroplasty (RSA) in an in-vitro setting. The purpose of this study is to evaluate the deviation between planned, intra-, and postoperative inclination, retroversion, entry point and depth of the glenoid component placement during RSA, assisted by navigated AR through a HMD, in a surgical setting. METHODS: A prospective, multicenter study was conducted. All consecutive patients undergoing RSA in two institutions, between August 2021 and January 2023, were considered potentially eligible for inclusion in the study. Inclusion criteria were: age >18 years, surgery assisted by AR through a HMD, and postoperative computed tomography (CT) scans at six weeks. All participants agreed to participate in the study and an informed consent was provided in all cases. Preoperative CT scans were undertaken for all cases and used for three-dimensional (3D) planning. Intra-operatively, glenoid preparation and component placement were assisted by a navigated AR system through a HMD in all patients. Intraoperative parameters were recorded by the system. A postoperative CT scan was undertaken at 6 weeks, and 3D reconstruction was used for obtaining postoperative parameters. The deviation between planned, intra-, and postoperative inclination, retroversion, entry point, and depth of the glenoid component placement was calculated. Outliers were defined as >5° for inclination and retroversion and >5 mm for entry point. RESULTS: 17 patients (9 females, 12 right shoulders) with a mean age of 72.8±9.1 years old (range, 47.0 to 82.0) met inclusion criteria. The mean deviation between intra- and postoperative measurements was 1.5°±1.0° (range, 0.0° to 3.0°) for inclination, 2.8°±1.5° (range, 1.0° to 4.5°) for retroversion, 1.8±1.0 mm (range, 0.7mm to 3.0mm) for entry point, and 1.9±1.9 mm (range, 0.0mm to 4.5mm) for depth. The mean deviation between planned and postoperative values was 2.5°±3.2° (range, 0.0° to 11.0°) for inclination, 3.4°±4.6° (range, 0.0° to 18.0°) for retroversion, 2.0±2.5 mm (range, 0.0° to 9.7°) for entry point, and 1.3±1.6 mm (range, 1.3mm to 4.5mm) for depth. There were no outliers between intra- and postoperative values and there were three outliers between planned and postoperative values. The mean time (minutes:seconds) for the tracker unit placement and the scapula registration was 03:02 (range, 01:48 to 04:26) and 08:16 (range, 02:09 to 17:58), respectively. CONCLUSION: The use of a navigated AR system through a HMD in RSA led to low deviations between planned, intra-operative and postoperative parameters for glenoid component placement.

Lower Trapezius and Latissimus Dorsi Transfer relieve Teres Minor Activity into the Physiological Range in Collin D Irreparable Posterosuperior Massive Rotator Cuff Tears: A Biomechanical Analysis.

BACKGROUND: Tendon transfers are established techniques to regain external rotation mobility in patients suffering from an irreparable, posterosuperior massive rotator cuff tear (MRCT). Posterosuperior MRCT with intact teres minor (Type D MRCT) can lead to excessive teres minor loading to maintain external rotation. We hypothesize that tendon transfers are effective in relieving teres minor loading in Type D MRCTs. Our aim was to biomechanically assess muscle synergism with latissimus dorsi (LD-Transfer) and lower trapezius (LT-Transfer) tendon transfer during external rotation at different abduction heights. METHODS: Using musculoskeletal modeling, we analyzed and compared the moment arm, muscle torque and muscle activity between a healthy and Type D MRCT pathological model with and without the LD- or LT-Transfer at infraspinatus and teres minor insertion sites. Output measures were analyzed during external rotation at different abduction angles and 10 to 50N resistance against external rotation. We assessed its impact on teres minor loading in a Type D MRCT. Morphological variations were parameterized using the critical shoulder angle and the acromiohumeral distance to address variations among patients. RESULTS: Both transfer types reduced teres minor torque and activity significantly, reaching physiological state at 40N external resistance (p<0.001), with insertion to infraspinatus site being more effective than teres minor site (p<0.001). External rotation moment arms of LD-Transfer were larger than LT-Transfer at 90° abduction (25.1±0.8mm vs. 21.2±0.6mm, p<0.001) and vice versa at 0° abduction (17.4±0.5mm vs. 24.0±0.2mm, p<0.001). While the healthy infraspinatus was the main external rotator in all abduction angles (50-70% torque), a Type D MRCT resulted in a 70-90% increase of teres minor torque and an up to sevenfold increase in its activity leading to excessive loadings beyond 10N resistance against external rotation. Varying the critical shoulder angle and the acromiohumeral distance led to minor variations in muscle moment arm and muscle activity. CONCLUSION: We identified biomechanical efficacy of both tendon transfers in Type D MRCT regarding teres minor load relieve and superior performance of the transfers at the infraspinatus insertion site.

Comparative productive performance of cows born through embryo transfer, artificial insemination and natural mating in dairy and dual-purpose herds raised in tropical conditions.

A populational, observational and longitudinal-retrospective study with records of 28 dairy-specialized and dual-purpose farms was carried out to compare the productive performance of cows born by embryo transfer (ET), artificial insemination (AI) and natural mating (NM), using the database of Centro Regional de Investigación para la Producción Animal Sostenible (CRIPAS) of cattle herds in Costa Rica. Herds (system × altitude), conception method (ET, AI and NM), genetic background (DSpB: specialized dairy breeds [Bos taurus] and crosses, GYR × HOL: Gyr × Holstein Crossbred and DSpB × BI: crosses between dairy breeds and Bos indicus), year of birth (or at calving), lactation number and days in milk were evaluated for the productive parameters age at first calving (AFC), calving to conception interval (CCI) and lactation milk yield (LMY) using a GLIMMIX procedure on SAS. The AFC, CCI and LMY were affected (p < .0001) by all factors considered in each parameter. ET has lower (p < .0001) AFC in months (33.1) than AI (35.2) and NM (36.44). NM had lower (p = .004) CCI (110 days) than AI or ET (121 days) values which were similar (p > .05). The higher LMY (p < .0001) was observed in ET (4140 kg), compared to AI (3706 kg) and NM (3595 kg). There was no difference between AI and NM. In conclusion, the method of conception in calves affected their future reproduction and production during puberty, postpartum and lactation. The effects on management decisions will require a rigorous economical study to discern whether ET would be a cost-effective alternative to AI or NM.

Glenoid component placement in reverse shoulder arthroplasty assisted with augmented reality through a head-mounted display leads to low deviation between planned and postoperative parameters.

BACKGROUND: Navigated augmented reality (AR) through a head-mounted display (HMD) may lead to accurate glenoid component placement in reverse shoulder arthroplasty (RSA). The purpose of this study is to evaluate the deviation between planned, intra- and postoperative inclination, retroversion, entry point, depth, and rotation of the glenoid component placement assisted by a navigated AR through HMD during RSA. METHODS: Both shoulders of 6 fresh frozen human cadavers, free from fractures or other bony pathologies, were used. Preoperative computed tomography (CT) scans were used for the 3-dimensional (3D) planning. The glenoid component placement was assisted using a navigated AR system through an HMD in all specimens. Intraoperative inclination, retroversion, depth, and rotation were measured by the system. A postoperative CT scan was performed. The pre- and postoperative 3D CT scan reconstructions were superimposed to calculate the deviation between planned and postoperative inclination, retroversion, entry point, depth, and rotation of the glenoid component placement. Additionally, a comparison between intra- and postoperative values was calculated. Outliers were defined as >10° inclination, >10° retroversion, >3 mm entry point. RESULTS: The registration algorithm of the scapulae prior to the procedure was correctly completed for all cases. The deviations between planned and postoperative values were 1.0° ± 0.7° for inclination, 1.8° ± 1.3° for retroversion, 1.1 ± 0.4 mm for entry point, 0.7 ± 0.6 mm for depth, and 1.7° ± 1.6° for rotation. The deviation between intra- and postoperative values were 0.9° ± 0.8° for inclination, 1.2° ± 1.1° for retroversion, 0.6 ± 0.5 mm for depth, and 0.3° ± 0.2° for rotation. There were no outliers between planned and postoperative parameters. CONCLUSION: In this study, the use of a navigated AR system through an HMD for RSA led to low deviation between planned and postoperative values and between intra- and postoperative parameters.

Massive rotator cuff tears with short tendon length can be successfully repaired using synthetic patch augmentation.

BACKGROUND: Choosing the optimal treatment for massive rotator cuff tears (MRCTs) still poses a surgical problem. In MRCTs with good muscle quality, but short tendon length, nonaugmented repairs lead to high failure rates of up to 90%. The aim of the study was to evaluate midterm clinical and radiologic outcomes of massive rotator cuff tears with good muscle quality, but short tendon length, which were repaired with synthetic patch augmentation. METHODS: A retrospective study of patients who underwent arthroscopic or open rotator cuff repairs with patch augmentation between 2016 and 2019 was performed. We included patients older than 18 years, who presented with an MRCT confirmed by an magnetic resonance imaging (MRI) arthrogram showing good muscle quality (Goutallier ≤ II) and short tendon length (length <15 mm). Constant-Murley score (CS), Subjective Shoulder Value (SSV), and range of motion (ROM) were compared pre- and postoperatively. We excluded patients older than 75 years or with presence of rotator cuff arthropathy Hamada stage ≥2a. Patients were followed up for 2 years minimum. Clinical failures were defined by reoperation, forward flexion <120° or a relative CS < 70. Structural integrity of the repair was assessed using an MRI scan. Comparison between different variables and outcomes was performed using Wilcoxon-Mann-Whitney and χ2 tests. RESULTS: Fifteen patients (mean age 57 years, 13 [86.7%] male, 9 [60%] right shoulders) were reevaluated with a mean follow-up of 43.8 months (27-55 months). There was a significant improvement in the absolute CS (from 33 to 81 points, P = .03), the relative CS (from 41% to 88%, P = .04), the SSV (from 31% to 93%, P = .007), and forward flexion (from 111° to 163°, P = .004) but not in external rotation (from 37° to 38°, P = .5). There were 3 clinical failures (1 atraumatic, 2 traumatic) with reoperations (2 reverse total shoulder arthroplasties and 1 refixation). Structurally, there were 3 Sugaya grade 4 and 5 Sugaya grade 5 reruptures resulting in a retear rate of 53%. The presence of a complete or partial rerupture was not associated with inferior outcomes compared with intact cuff repairs. There were no correlations between the grade of retraction, muscle quality, or rotator cuff tear configuration and rerupture or functional outcomes. CONCLUSION: Patch augmented cuff repair leads to a significant improvement of functional and structural outcomes. Partial reruptures were not associated with inferior functional outcomes. Prospective randomized trials are needed to confirm the results found in our study.

Regulation of CO2 by the sea in areas around Latin America in a context of climate change.

Anthropogenic activities are increasing the atmospheric carbon dioxide (CO2); around a third of the CO2 emitted by these activities has been taken up by the ocean. Nevertheless, this marine ecosystem service of regulation remains largely invisible to society, and not enough is known about regional differences and trends in sea-air CO2 fluxes (FCO2), especially in the Southern Hemisphere. The objectives of this work were as follows: first to put values of FCO2 integrated over the exclusive economic zones (EEZ) of five Latin-American countries (Argentina, Brazil, Mexico, Peru, and Venezuela) into perspective regarding total country-level greenhouse gases (GHG) emissions. Second, to assess the variability of two main biological factors affecting FCO2 at marine ecological time series (METS) in these areas. FCO2 over the EEZs were estimated using the NEMO model, and GHG emissions were taken from reports to the UN Framework Convention on Climate Change. For each METS, the variability in phytoplankton biomass (indexed by chlorophyll-a concentration, Chla) and abundance of different cell sizes (phy-size) were analyzed at two time periods (2000-2015 and 2007-2015). Estimates of FCO2 at the analyzed EEZs showed high variability among each other and non-negligible values in the context of greenhouse gas emissions. The trends observed at the METS indicated, in some cases, an increase in Chla (e.g., EPEA-Argentina) and a decrease in others (e.g., IMARPE-Peru). Evidence of increasing populations of small size-phytoplankton was observed (e.g., EPEA-Argentina, Ensenada-Mexico), which would affect the carbon export to the deep ocean. These results highlight the relevance of ocean health and its ecosystem service of regulation when discussing carbon net emissions and budgets.

Ecology and diversity of culturable fungal species associated with soybean seedling diseases in the Midwestern United States.

AIMS: To isolate and characterize fungi associated with diseased soybean seedlings in Midwestern soybean production fields and to determine the influence of environmental and edaphic factors on their incidence. METHODS AND RESULTS: Seedlings were collected from fields with seedling disease history in 2012 and 2013 for fungal isolation. Environmental and edaphic data associated with each field was collected. 3036 fungal isolates were obtained and assigned to 76 species. The most abundant genera recovered were Fusarium (73%) and Trichoderma (11.2%). Other genera included Mortierella, Clonostachys, Rhizoctonia, Alternaria, Mucor, Phoma, Macrophomina and Phomopsis. Most recovered species are known soybean pathogens. However, non-pathogenic organisms were also isolated. Crop history, soil density, water source, precipitation and temperature were the main factors influencing the abundance of fungal species. CONCLUSION: Key fungal species associated with soybean seedling diseases occurring in several US production regions were characterized. This work also identified major environment and edaphic factors affecting the abundance and occurrence of these species. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification and characterization of the main pathogens associated with seedling diseases across major soybean-producing areas could help manage those pathogens, and devise more effective and sustainable practices to reduce the damage they cause.

Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study.

BACKGROUND AND AIMS: Coronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD. METHODS AND RESULTS: This was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131-3.136]), C-reactive protein (1.046 [1.020-1.073]), blood pressure >140/90 mmHg (2.686 [1.506-4.791]), fibrates (2.032 [1.160-3.562]), calcium channel blockers (2.082 [1.158-3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240-4.721]), heart failure (2.139 [1.032-4.433]), LDL-C >70 mg/dL (4.594 [1.401-15.069]), and diuretics (3.328 [1.677-6.605]) were associated with cardiovascular mortality. CONCLUSIONS: The composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.

Association of bilateral oophorectomy and menopause hormone therapy with mild cognitive impairment: the REDLINC X study.

BACKGROUND: Dementia is a major public health problem. Estrogen is a regulator of the central nervous system and its deficit could be involved in cognitive decline in older women. OBJECTIVE: This study aimed to evaluate the association of bilateral oophorectomy, menopause hormone therapy (MHT) and other factors on mild cognitive impairment (MCI). METHOD: The case-control study included 941 otherwise healthy postmenopausal women aged 60 years and over from six Latin American countries. Personal and family data were recorded and MCI was assessed using the Montreal Cognitive Assessment test (MoCA). RESULTS: Average age, years of education and body mass index were 66.1 ± 5.8 years, 12.4 ± 5.0 years and 26.0 ± 4.3 kg/m2, respectively. A total of 30.2% had undergone bilateral oophorectomy and 40.3% had used MHT. A total of 232 women (24.7%) had MCI. The prevalence of MCI was higher in women with intact ovaries and non-MHT users as compared to MHT users (29.3% vs. 11.7% [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.20-0.51]). Among oophorectomized women, MCI prevalence was higher among non-MHT users as compared to MHT users (45.2% vs. 12.8% [OR 0.18; 95% CI 0.10-0.32]). Logistic regression analysis determined that the variables associated with MCI were age >65 years (OR 1.69; 95% CI 1.20-2.38), parity (having >2 children; OR 1.69; 95% CI 1.21-2.37), bilateral oophorectomy (OR 1.56; 95% CI 1.09-2.24), hypertension (OR 1.41; 95% CI 1.01-1.96), being sexually active (OR 0.56; 95% CI 0.40-0.79), education >12 years (OR 0.46; 95% CI 0.32-0.65) and MHT use (OR 0.31; 95% CI 0.21-0.46). CONCLUSION: Age, parity, bilateral oophorectomy and hypertension are independent factors associated with MCI; contrary to this, higher educational level, maintaining sexual activity and using MHT are protective factors.

Effects of ATLAS 2030 gait exoskeleton on strength and range of motion in children with spinal muscular atrophy II: a case series.

BACKGROUND: Children with spinal muscular atrophy (SMA) present muscle weakness and atrophy that results in a number of complications affecting their mobility, hindering their independence and the development of activities of daily living. Walking has well-recognized physiological and functional benefits. The ATLAS 2030 exoskeleton is a paediatric device that allows gait rehabilitation in children with either neurological or neuromuscular pathologies with gait disorders. The purpose is to assess the effects in range of motion (ROM) and maximal isometric strength in hips, knees and ankles of children with SMA type II after the use of ATLAS 2030 exoskeleton. METHODS: Three children (mean age 5.7 ± 0.6) received nine sessions bi-weekly of 60 min with ATLAS 2030. ROM was assessed by goniometry and strength by hand-held dynamometer. All modes of use of the exoskeleton were tested: stand up and sit down, forward and backward walking, and gait in automatic and active-assisted modes. In addition, different activities were performed during the gait session. A descriptive analysis of all variables was carried out. RESULTS: The average time of use was 53.5 ± 12.0 min in all sessions, and all participants were able to carry out all the proposed activities as well as to complete the study. Regarding isometric strength, all the measurements increased compared to the initial state, obtaining the greatest improvements for the hip flexors (60.2%) and extensors muscles (48.0%). The ROM increased 12.6% in hip and 34.1% in the ankle after the study, while knee ROM remained stable after the study. CONCLUSION: Improvements were showed in ROM and maximal isometric strength in hips, knees and ankles after using ATLAS 2030 paediatric gait exoskeleton in all three children. This research could serve as a preliminary support for future clinical integration of ATLAS 2030 as a part of a long-term rehabilitation of children with SMA. TRIAL REGISTRATION: The approval was obtained (reference 47/370329.9/19) by Comunidad de Madrid Regional Research Ethics Committee with Medical Products and the clinical trial has been registered on Clinical Trials.gov: NCT04837157.

Patient-specific instrumentation reduces deviations between planned and postosteotomy humeral retrotorsion and height in shoulder arthroplasty.

BACKGROUND: Patient-specific instrumentation (PSI) may potentially improve humeral osteotomy in shoulder arthroplasty. The purpose of this study was to compare the deviation between planned and postosteotomy humeral inclination, retrotorsion, and height in shoulder arthroplasty, using PSI vs. standard cutting guides (SCG). METHODS: Twenty fresh-frozen cadaveric specimens were allocated to undergo humeral osteotomy using either PSI or SCG, such that the 2 groups have similar age, gender, and side. Preosteotomy computed tomography (CT) scan was performed and used for the 3-dimensional (3D) planning. The osteotomy procedure was performed using a PSI designed for each specimen or an SCG depending on the group. A postosteotomy CT scan was performed. The preosteotomy and postosteotomy 3D CT scan reconstructions were superimposed to calculate the deviation between planned and postosteotomy inclination, retrotorsion, and height. Outliers were defined as cases with 1 or more of the following deviations: >5° inclination, >10° retrotorsion, and >3 mm height. The deviation and outliers in inclination, retrotorsion, and height were compared between the 2 groups. RESULTS: The deviations between planned and postosteotomy parameters were similar among the PSI and SCG groups for inclination (P = .260), whereas they were significantly greater in the SCG group for retrotorsion (P < .001) and height (P = .003). There were 8 outliers in the SCG group, compared with only 1 outlier in the PSI group (P = .005). Most outliers in the SCG group were due to deviation >10° in retrotorsion. CONCLUSION: After 3D planning, PSI had less deviation between planned and postosteotomy humeral retrotorsion and height, relative to SCG.

Cycloaddition between nitrogen-doped graphene (6π-component) and benzene (4π-component): a theoretical approach using density functional theory with vdW-DF correction.

The interaction between nitrogen-doped graphene defects (N3V1 and N4V2 pyridinic, and N3V1 and N3V3 pyrrolic) and benzene have been investigated by applying density functional theory (DFT), together with the vdW-DF correction. We discovered that only the N3V3 pyrrolic defect is a reactive site (6π-component), forming a cycloadduct with benzene (4π-component) that has energy barriers below 154.38 kJ mol-1 (1.60 eV). The conduction and valence bands (HOMO and LUMO) for N3V3 form a degenerate pair of orbitals at the gamma point, with the same ionization potential (IP) and electron affinity (EA). Likewise, inspection of the orbital symmetries for both systems confirms that these must undergo concerted reactions based on the Woodward and Hoffmann principles of orbital symmetry, with the appropriate orbital occupancies. This is the first time that substitutionally doped graphene has been demonstrated to participate as a 6π-component for cycloaddition reactions with benzene.

First report of halo blight of hop (Humulus lupulus) caused by Diaporthe humulicola in Quebec, Canada.

Halo blight of hop caused by Diaporthe humulicola has recently been reported in Michigan and Connecticut (Higgins et al. 2021, Allan-Perkins et al 2020). In August 2020 growers in Quebec, Canada reported necrotic foliar lesions and desiccation of the hop strobile (cone) on Chinook and Nugget cultivars. The foliar lesions were dry concentric circles with a chlorotic halo surrounding the lesions; no pycnidia were observed on leaves or cones. Up to 100% of the infected bract tissue was dry and easily shattered, the grower estimated that more than 90% of the plants in the hopyard exhibited symptoms. Twenty-six isolates were obtained from surface-sterilized leaf and cone tissue by plating the leading edge of lesions on potato dextrose agar. Fungal isolates were hyphal tipped and were incubated at 22°C with a 12 h photoperiod. After 21-days, all cultures were white to beige with pycnidia. DNA was extracted from cultures using the MagMAX Plant DNA Isolation Kit (Applied Biosystems, Foster City, CA). DNA amplification of a representative isolate (CD6C) was performed with primers ITS1/ITS4 (White et al. 1990) for the internal transcribed spacer (ITS), CYLH3F/H3-1b (Glass and Donaldson 1995) for histone 3 (HIS), and Ef1728f/EF1-986R (Carbone and Kohn 1999) for translation elongation factor 1-α (TEF). Amplification primers were used for bidirectional Sanger sequencing, reads were assembled using Geneious Prime (Biomatters, New Zealand), and identified using NCBI BLAST. BLAST results showed that the sequences for TEF, ITS, and HIS all had 100% pairwise identity to Diaporthe sp. 1-MI (MT909101, MT909099, MT909093, OK001342, MZ934713, OK001341). Futhermore, BLAST results showed that ITS and HIS have 100% pairwise identity D. humulicola (MN152929, MN180214). The TEF sequence also had 99.7% pairwise identity to D. humulicola (MN180209). Koch's postulates were conducted by inoculating six 3-mo-old 'Chinook' plants with conidia harvested from 28-day-old cultures and spraying 50 ml of inoculum (6 x 105 conidia/ml) or water to each plant. Plants were then stored in a greenhouse at 100% relative humidity at 22°C with a 14-h photo period. Lesions appeared on the adaxial side of the leaf after 21 days. D. humulicola was re-isolated from all infected leaf tissue, but not from any water inoculated plants and identified by conidial morphology using descriptions from Higgins et al. (2021). So far, Diaporthe sp. 1-MI appears to be synonymous with Diaporthe humulicola, but currently two names are being utilized (i.e. Diaporthe leaf spot and halo blight). In Higgins et al., (2021) it was proposed that the name halo blight might be more appropriate because disease symptoms are not confined to the leaves and cause significant blighting of cones. Halo blight caused by D. humulicola appears widespread in Michigan and Canada and may become an issue in other eastern North American growing regions with humid conditions.

Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration-a randomized in vivo study in rabbits.

OBJECTIVES: Micro-computed tomography (µ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. MATERIALS AND METHODS: Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through µ-CT and histology. RESULTS: The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and µ-CT (r =-0.101, 95% CI [-0.445; 0.268]) or histology (r = 0.305, 95% CI [-0.133; 0.644]) findings on bone regeneration were observed. CONCLUSIONS: These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

Prediction of molecular mimicry between antigens from Leishmania sp. and human: Implications for autoimmune response in systemic lupus erythematosus.

Pathogens and humans share an intrinsic relation related to molecular mimicry in their antigens. Interactions between immune system and pathogenic antigens result in a production of antibodies that could protect against infection, but develop autoreactive responses mediated by autoantibodies that react to pathogenic and human antigens because they share epitopes. In this study, a pipeline of bioinformatic tools was used to explore the repertory of autoantigens implicated in the develop of Systemic Lupus Erythematosus and their homologous in Leishmania sp. With this, we screened and selected 33 molecular mimicry candidates. In 17 autoantigens from lupus was possible to perform epitope prediction and was found that, at least one potential cross epitope. Some of autoantigens with molecular mimicry were Aquaporin 4, nuclear autoantigens such as: Ubiquitin-related modifier 1 and Small nuclear ribonucleoprotein Sm. Also, mitochondrial, and ribosomal autoantigens were found to share molecular mimicry with antigens from Leishmania sp. In conclusion, this is the first study that provide evidence of molecular mimicry between antigens from Leishmania sp. and human. Implications for the develop of SLE and clinical manifestation deserve more study.

Expectation and variance of the estimator of the maximized selection response of linear selection indices with normal distribution.

KEY MESSAGE: The expectation and variance of the estimator of the maximized index selection response allow the breeders to construct confidence intervals and to complete the analysis of a selection process. The maximized selection response and the correlation of the linear selection index (LSI) with the net genetic merit are the main criterion to compare the efficiency of any LSI. The estimator of the maximized selection response is the square root of the variance of the estimated LSI values multiplied by the selection intensity. The expectation and variance of this estimator allow the breeder to construct confidence intervals and determine the appropriate sample size to complete the analysis of a selection process. Assuming that the estimated LSI values have normal distribution, we obtained those two parameters as follows. First, with the Fourier transform, we found the distribution of the variance of the estimated LSI values, which was a Gamma distribution; therefore, the expectation and variance of this distribution were the expectation and variance of the variance of the estimated LSI values. Second, with these results, we obtained the expectation and the variance of the estimator of the selection response using the Delta method. We validated the theoretical results in the phenotypic selection context using real and simulated dataset. With the simulated dataset, we compared the LSI efficiency when the genotypic covariance matrix is known versus when this matrix is estimated; the differences were not significant. We concluded that our results are valid for any LSI with normal distribution and that the method described in this work is useful for finding the expectation and variance of the estimator of any LSI response in the phenotypic or genomic selection context.

A minimal coarse-grained model for the low-frequency normal mode analysis of icosahedral viral capsids.

The main goal of this work is the design of a coarse-grained theoretical model of minimal resolution for the study of the physical properties of icosahedral virus capsids within the linear-response regime. In this model the capsid is represented as an interacting many-body system whose composing elements are capsid subunits (capsomers), which are treated as three-dimensional rigid bodies. The total interaction potential energy is written as a sum of pairwise capsomer-capsomer interactions. Based on previous work [Gomez Llorente et al., Soft Matter, 2014, 10, 3560], a minimal and complete anisotropic binary interaction that includes a full Hessian matrix of independent force constants is proposed. In this interaction model, capsomers have rotational symmetry around an axis of order n > 2. The full coarse-grained model is applied to analyse the low-frequency normal-mode spectrum of icosahedral T = 1 capsids. The model performance is evaluated by fitting its predicted spectrum to the full-atom results for the Satellite Tobacco Necrosis Virus (STNV) capsid [Dykeman and Sankey, Phys. Rev. Lett., 2008, 100, 028101]. Two capsomer choices that are compatible with the capsid icosahedral symmetry are checked, namely pentamers (n = 5) and trimers (n = 3). Both subunit types provide fair fits, from which the magnitude of the coarse-grained force constants for a real virus is obtained. The model is able to uncover latent instabilities whose analysis is fully consistent with the current knowledge about the STNV capsid, which does not self-assemble in the absence of RNA and is thermally unstable. The straightforward generalisability of the model beyond the linear regime and its completeness make it a promising tool to theoretically interpret many experimental data such as those provided by the atomic force microscopy or even to better understand processes far from equilibrium such as the capsid self-assembly.