Dissecting the Genetic Diversity of USDA Cowpea Germplasm Collection Using Kompetitive Allele Specific PCR-Single Nucleotide Polymorphism Markers.

Cowpea (Vigna unguiculata L. Walp) is an important grain legume crop of the subtropics, particularly in West Africa, where it contributes to the livelihoods of small-scale farmers. Despite being a drought-resilient crop, cowpea production is hampered by insect pests, diseases, parasitic weeds, and various abiotic stresses. Genetic improvement can help overcome these limitations, and exploring diverse cowpea genetic resources is crucial for cowpea breeding. This study evaluated the genetic diversity of 361 cowpea accessions from the USDA core collection for the species using 102 Kompetitive Allele Specific PCR (KASP) single nucleotide polymorphism (SNP) markers. A total of 102 KASP-SNP was validated in the germplasm panel, and 72 showed polymorphism across the germplasm panel. The polymorphism information content (PIC) of all SNPs ranged from 0.1 to 0.37, with an average of 0.29, while the mean observed heterozygosity was 0.52. The population structure revealed three distinct populations that clustered into two major groups after phylogenetic analysis. Analysis of molecular variance (AMOVA) indicated greater genetic variation within populations than among populations. Although cowpea generally has a narrow genetic diversity, the accessions used in this study exhibited considerable variation across geographical regions, sub-species, and improvement status. These results indicated that the selected KASP genotyping assay can provide robust and accurate genotyping data for application in the selection and management of cowpea germplasm in breeding programs and genebanks.

Maternal infections during pregnancy and child cognitive outcomes.

BACKGROUND: Maternal prenatal infections have been linked to children's neurodevelopment and cognitive outcomes. It remains unclear, however, whether infections occurring during specific vulnerable gestational periods can affect children's cognitive outcomes. The study aimed to examine maternal infections in each trimester of pregnancy and associations with children's developmental and intelligence quotients. The ALSPAC birth cohort was used to investigate associations between maternal infections in pregnancy and child cognitive outcomes. METHODS: Infection data from mothers and cognition data from children were included with the final study sample size comprising 7,410 mother-child participants. Regression analysis was used to examine links between maternal infections occurring at each trimester of pregnancy and children's cognition at 18 months, 4 years, and 8 years. RESULTS: Infections in the third trimester were significantly associated with decreased verbal IQ at age 4 (p < .05, adjusted R2 = 0.004); decreased verbal IQ (p < .01, adjusted R2 = 0.001), performance IQ (p < .01, adjusted R2 = 0.0008), and total IQ at age 8 (p < .01, adjusted R2 = 0.001). CONCLUSION: Results suggest that maternal infections in the third trimester could have a latent effect on cognitive development, only emerging when cognitive load increases over time, though magnitude of effect appears to be small. Performance IQ may be more vulnerable to trimester-specific exposure to maternal infection as compared to verbal IQ. Future research could include examining potential mediating mechanisms on childhood cognition, such as possible moderating effects of early childhood environmental factors, and if effects persist in future cognitive outcomes.

Whole Genome Re-sequencing and Bulk Segregant Analysis Reveals Chromosomal Location for Papaya Ringspot Virus W Resistance in Squash.

Squash (Cucurbita moschata) is among the most important cucurbit crops grown worldwide. Plant pathogen, Papaya ringspot virus W (PRSV-W) causes significant yield loss in commercial squash production globally. The development of virus-resistant cultivars can complement integrated disease management and mitigate losses due to viral infections. However, the genetic loci and molecular markers linked to PRSV-W resistance that could facilitate marker-assisted selection (MAS) for accelerated cultivar development are unknown. In this study, quantitative trait loci (QTL), molecular markers, and candidate genes associated with PRSV-W resistance in squash were identified in an F2 population (n = 118) derived from a cross between Nigerian Local accession (resistant) and Butterbush cultivar (susceptible). Whole genome re-sequencing-based bulked segregant analysis (QTLseq method; n = 10 for each bulk) and non-parametric interval mapping were used to identify a major QTL associated with PRSV-W resistance on chromosome 9 (QtlPRSV-C09) (p < 0.05) of C. moschata. QtlPRSV-C09 extended from 785,532 to 5,093,314 bp and harbored 12,245 SNPs among which 94 were high-effect variants. To validate QtlPRSV-C09, 13 SNP markers were assayed as Kompetitive allele-specific PCR (KASP) markers in the F2 population and tested for the association with PRSV-W resistance. Among these, two KASP markers (Ch09_2080834 and Ch09_5023865-1) showed significant association with PRSV-W resistance (p < 0.05). The two SNPs were located within exons of putative disease-resistant genes encoding the clathrin assembly family and actin cytoskeleton-regulatory complex proteins, which are implicated in disease resistance across plant species. The findings of this study will facilitate MAS for PRSV-W resistance in squash and allow further understanding of the functional mechanisms underlying potyvirus resistance in Cucurbita species.

Genomic Position and Markers Associated with the Hull-Less Seed Trait in Pumpkin.

Pumpkin (Cucurbita pepo) seeds are nutritious and valued as a source of vegetable oil, protein, healthy fatty acids, and minerals. Pumpkin seeds that are naturally devoid of the seedcoat (hull-less) are preferred by the industry as they eliminate the need for de-hulling prior to use. A single recessive gene, designated as n or h, controls the hull-less seed trait in pumpkin. Visual selection for the trait is easy, however, it is resource intensive when applied to large breeding populations. High throughput genotyping assays can aid in the identification of suitable individuals in segregating populations through marker-assisted selection. In the current study, the QTL-seq approach was used to identify genetic loci, SNP markers and candidate genes associated with the hull-less trait in a segregating F2 population (n = 143) derived from a cross between Kakai (hull-less) × Table Gold Acorn (hulled). The segregation of the hull-less trait in the F2 population fit a 3:1 ratio (p < 0.05). QTL-seq analysis detected a single QTL on chromosome 12 (Qtlhull-less-C12) which was significantly associated with the hull-less trait in C. pepo. Twenty-eight SNPs were genotyped in the population, two among which (Ch12_3412046 and Ch12_3417142) were significantly associated (p < 0.05) with the hull-less trait in cultivars and accessions of diverse genetic background. Several candidate genes fall within the Qtlhull-less-C12 interval, among them is the No Apical meristem (NAC) domain-containing protein and a Fiber Protein fb11 gene involved in lignin accumulation and cell wall deposition across plant species, respectively. The findings of this study will facilitate the marker-assisted selection for the hull-less seed trait in pumpkin and further our understanding of the functional mechanisms underlying the trait across cucurbit crops.

Advances in immunotherapy for cervical cancer: recent developments and future directions.

There is an unmet need for novel therapies to improve clinical outcomes for patients with locally advanced, recurrent, or metastatic cervical cancer. Most cases of cervical cancer are driven by infection with human papillomavirus (HPV), which uses multiple mechanisms to avoid immune surveillance. Several classes of agents have been developed that seek to activate the immune system in order to overcome this resistance and improve treatment outcomes. These include immune checkpoint inhibitors, therapeutic vaccines, engineered T cells, and antibody-drug conjugates. Here, we review the immune landscape of cervical cancer and the growing clinical data regarding the use of immunotherapy. Checkpoint inhibitors are the best studied treatments, with encouraging phase II studies available in the definitive setting and recently published phase III data defining a new standard of care for patients with recurrent or metastatic disease. Vaccines and engineered T cells are generally in earlier phases of development but use unique mechanisms of immune activation. It is possible that combination of immunotherapy, with either conventional systemic therapy or multiple immunomodulatory agents, may provide further benefit. We also discuss possible synergies between immunotherapy and radiation therapy, which is frequently used in the management of cervical cancer. Ultimately, immunotherapy represents an emerging treatment option for patients with cervical cancer. It is an appropriate component of first-line treatment in the recurrent or metastatic setting and may soon be incorporated into definitive management of locally advanced disease.

Polygenic risks for joint developmental trajectories of internalizing and externalizing problems: findings from the ALSPAC cohort.

BACKGROUND: Joint developmental trajectories of internalizing and externalizing problems show considerable heterogeneity; however, this can be parsed into a small number of meaningful subgroups. Doing so offered insights into risk factors that lead to different patterns of internalizing/externalizing trajectories. However, despite both domains of problems showing strong heritability, no study has yet considered genetic risks as predictors of joint internalizing/externalizing problem trajectories. METHODS: Using parallel process latent class growth analysis, we estimated joint developmental trajectories of internalizing and externalizing difficulties assessed across ages 4 to 16 using the Strengths and Difficulties Questionnaire. Multinomial logistic regression was used to evaluate a range of demographic, perinatal, maternal mental health, and child and maternal polygenic predictors of group membership. Participants included 11,049 children taking part in the Avon Longitudinal Study of Parents and Children. Polygenic data were available for 7,127 children and 6,836 mothers. RESULTS: A 5-class model was judged optimal: Unaffected, Moderate Externalizing Symptoms, High Externalizing Symptoms, Moderate Internalizing and Externalizing Symptoms and High Internalizing and Externalizing Symptoms. Male sex, lower maternal age, maternal mental health problems, maternal smoking during pregnancy, higher child polygenic risk scores for ADHD and lower polygenic scores for IQ distinguished affected classes from the unaffected class. CONCLUSIONS: While affected classes could be relatively well separated from the unaffected class, phenotypic and polygenic predictors were limited in their ability to distinguish between different affected classes. Results thus add to existing evidence that internalizing and externalizing problems have mostly shared risk factors.

Examining the relationship between psychosis and immigration in Spain: The effect of cannabis use and language barrier in a large psychosis sample.

The main aim of this study is to examine the association between psychosis and immigration, independent of the language barrier, drug consumption, and the social support index. The second aim is to explore the clinical and demographic characteristics of the immigrants in the catchment area, compared with the native Spanish population suffering from psychosis. All consecutive patients admitted to a hospital in Spain during 2018 and 2019 (n = 1484) were identified through the hospital's clinical records. The general representative sample (n=1484) was divided into two groups: immigrants (n=131) and non-immigrants (n=1353). Demographic, clinical, and social variables were then obtained and included in a logistic regression model. A subsample with all consecutive cases with psychosis (93 immigrants and 543 no immigrants) was also analysed to describe the diagnosis and evolution after admission. Our results show that there is higher significant prevalence of admissions due to psychosis in the immigrant population than in the non-immigrant population. This association is prominent in the population of Sub-Saharans, and is independent of cannabis use, a low social support index, or a language barrier. Understanding the specificities not only in the social context of this population but also the clinical needs is determinant for being able to shape the therapeutic intervention.

A Novel QTL for Resistance to Phytophthora Crown Rot in Squash.

Phytophthora capsici Leonian causes significant yield losses in commercial squash (Cucurbita pepo) production worldwide. The deployment of resistant cultivars can complement integrated management practices for P. capsici, but resistant cultivars are currently unavailable for growers. Moderate resistance to Phytophthora crown rot in a selection of accession PI 181761 (C. pepo) (designated line #181761-36P) is controlled by three dominant genes (R4, R5 and R6). Introgression of these loci into elite germplasm through marker-assisted selection (MAS) can accelerate the release of new C. pepo cultivars resistant to crown rot, but these tools are currently unavailable. Here we describe the identification of a quantitative trait locus (QTL), molecular markers and candidate genes associated with crown rot resistance in #181761-36P. Five hundred and twenty-three SNP markers were genotyped in an F2 (n = 83) population derived from a cross between #181761-36P (R) and Table Queen (S) using targeted genotyping by sequencing. A linkage map (2068.96 cM) consisting of twenty-one linkage groups and an average density of 8.1 markers/cM was developed for the F2 population. The F2:3 families were phenotyped in the greenhouse with a virulent strain of P. capsica, using the spore-spray method. A single QTL (QtlPC-C13) was consistently detected on LG 13 (chromosome 13) across three experiments and explained 17.92-21.47% of phenotypic variation observed in the population. Nine candidate disease resistance gene homologs were found within the confidence interval of QtlPC-C13. Single nucleotide polymorphism (SNP) markers within these genes were converted into Kompetitive Allele Specific PCR (KASP) assays and tested for association with resistance in the F2 population. One SNP marker (C002686) was significantly associated with resistance to crown rot in the F2 population (p < 0.05). This marker is a potential target for MAS for crown rot resistance in C. pepo.

Genetic Loci Associated with Resistance to Zucchini Yellow Mosaic Virus in Squash.

Zucchini Yellow Mosaic Virus (ZYMV) is an aphid-transmitted potyvirus that causes severe yield losses in squash (Cucurbita moschata) production worldwide. Development of resistant cultivars using traditional breeding approaches relies on rigorous and resource-intensive phenotypic assays. QTL-seq, a whole genome re-sequencing based bulked segregant analysis, is a powerful tool for mapping quantitative trait loci (QTL) in crop plants. In the current study, the QTL-seq approach was used to identify genetic loci associated with ZYMV resistance in an F2 population (n = 174) derived from a cross between Nigerian Local (resistant) and Butterbush (susceptible). Whole genome re-sequencing of the parents and bulks of resistant and susceptible F2 progeny revealed a mapping rate between 94.04% and 98.76%, and a final effective mapping depth ranging from 81.77 to 101.73 across samples. QTL-seq analysis identified four QTLs significantly (p < 0.05) associated with ZYMV resistance on chromosome 2 (QtlZYMV-C02), 4 (QtlZYMV-C04), 8 (QtlZYMV-C08) and 20 (QtlZYMV-C20). Seven markers within the QTL intervals were tested for association with ZYMV resistance in the entire F2 population. For QtlZYMV-C08, one single nucleotide polymorphism (SNP) marker (KASP-6) was found to be significantly (p < 0.05) associated with ZYMV resistance, while two SNPs (KASP-1 and KASP-3) and an indel (Indel-2) marker were linked to resistance within QtlZYMV-C20. KASP-3 and KASP-6 are non-synonymous SNPs leading to amino acid substitutions in candidate disease resistant gene homologs on chromosomes 20 (CmoCh20G003040.1) and 8 (CmoCh08G007140.1), respectively. Identification of QTL and SNP markers associated with ZYMV resistance will facilitate marker-assisted selection for ZYMV resistance in squash.

Estimating the Severity of Visual Field Damage From Retinal Nerve Fiber Layer Thickness Measurements With Artificial Intelligence.

Purpose: The purpose of this study was to assess the accuracy of artificial neural networks (ANN) in estimating the severity of mean deviation (MD) from peripapillary retinal nerve fiber layer (RNFL) thickness measurements derived from optical coherence tomography (OCT). Methods: Models were trained using 1796 pairs of visual field and OCT measurements from 1796 eyes to estimate visual field MD from RNFL data. Multivariable linear regression, random forest regressor, support vector regressor, and 1D convolutional neural network (CNN) models with sectoral RNFL thickness measurements were examined. Three independent subsets consisting of 698, 256, and 691 pairs of visual field and OCT measurements were used to validate the models. Estimation errors were visualized to assess model performance subjectively. Mean absolute error (MAE), root mean square error (RMSE), median absolute error, Pearson correlation, and R-squared metrics were used to assess model performance objectively. Results: The MAE and RMSE of the ANN model based on the testing dataset were 4.0 dB (95% confidence interval = 3.8-4.2) and 5.2 dB (95% confidence interval = 5.1-5.4), respectively. The ranges of MAE and RMSE of the ANN model on independent datasets were 3.3-5.9 dB and 4.4-8.4 dB, respectively. Conclusions: The proposed ANN model estimated MD from RNFL measurements better than multivariable linear regression model, random forest, support vector regressor, and 1-D CNN models. The model was generalizable to independent data from different centers and varying races. Translational Relevance: Successful development of ANN models may assist clinicians in assessing visual function in glaucoma based on objective OCT measures with less dependence on subjective visual field tests.

Genetic diversity among wild pomegranate (Punica granatum) in Azad Jammu and Kashmir region of Pakistan

BACKGROUND: Pomegranate (Punica granatum L.), one of the most important tropical fruits in Azad Jammu and Kashmir regions of Pakistan, is highly valued for its nutrition and medicinal purposes. Although pomegranate is native to this region, the genetic diversity among wild pomegranate accessions is currently unknown. Such information would be vital for germplasm conservation and breeding efforts. In the current study, genetic diversity among forty-eight wild pomegranate accessions collected from different agro-ecological zones of Azad Jammu and Kashmir was assessed using 41 simple sequence repeat (SSR) markers. RESULTS: The markers revealed 303 alleles averaging 7.39 alleles per marker. Polymorphic information content ranged from 0.12 (PGCT093B) to 0.88 (Pom006), with a mean of 0.54. The average genetic distance (GD) across all genotypes was 0.52, and was lowest between Chattar Class and Thorar genotypes (GD = 0.27), but highest between Khun Bandway and Akhor Ban (GD = 0.74). A neighbor-joining dendrogram separated the genotypes into three major clusters, with further sub-clustering within each cluster. CONCLUSIONS: Overall, the results presented here show significant genetic diversity among wild pomegranate accessions in Azad Jammu and Kashmir region of Pakistan. These accessions present a valuable genetic resource to breeding and cultivar improvement programs within the region.

QTL-seq for identification of loci associated with resistance to Phytophthora crown rot in squash.

Phytophthora capsici Leonian, the causal agent of foliar blight, root rot, fruit rot and crown rot syndromes in squash (Cucurbita moschata), is a devastating pathogen worldwide. Resistance to Phytophthora crown rot in University of Florida breeding line #394-1-27-12 (C. moschata) is conferred by three independent dominant genes (R1R2R3). Availability of DNA markers linked to R1R2R3 genes would allow efficient breeding for Phytophthora crown rot resistance through marker-assisted selection (MAS). The goal of the current study was to identify quantitative trait loci (QTLs) associated with resistance to Phytophthora crown rot in an F2 population (n = 168) derived from a cross between #394-1-27-12 (R) and Butter Bush (S) using QTL-seq bulk segregant analysis. Whole-genome resequencing of the resistant (n = 20) and susceptible (n = 20) bulk segregants revealed ~900,000 single nucleotide polymorphisms distributed across C. moschata genome. Three QTLs significantly (P < 0.05) associated with resistance to Phytophthora crown rot were detected on chromosome 4 (QtlPC-C04), 11 (QtlPC-C11) and 14 (QtlPC-C14). Several markers linked to these QTLs are potential targets for MAS against Phytophthora crown rot in C. moschata. The present study reports the first QTLs associated with Phytophthora crown rot resistance in C. moschata.

Enteric infection induces Lark-mediated intron retention at the 5' end of Drosophila genes.

BACKGROUND: RNA splicing is a key post-transcriptional mechanism that generates protein diversity and contributes to the fine-tuning of gene expression, which may facilitate adaptation to environmental challenges. Here, we employ a systems approach to study alternative splicing changes upon enteric infection in females from classical Drosophila melanogaster strains as well as 38 inbred lines. RESULTS: We find that infection leads to extensive differences in isoform ratios, which results in a more diverse transcriptome with longer 5' untranslated regions (5'UTRs). We establish a role for genetic variation in mediating inter-individual splicing differences, with local splicing quantitative trait loci (local-sQTLs) being preferentially located at the 5' end of transcripts and directly upstream of splice donor sites. Moreover, local-sQTLs are more numerous in the infected state, indicating that acute stress unmasks a substantial number of silent genetic variants. We observe a general increase in intron retention concentrated at the 5' end of transcripts across multiple strains, whose prevalence scales with the degree of pathogen virulence. The length, GC content, and RNA polymerase II occupancy of these introns with increased retention suggest that they have exon-like characteristics. We further uncover that retained intron sequences are enriched for the Lark/RBM4 RNA binding motif. Interestingly, we find that lark is induced by infection in wild-type flies, its overexpression and knockdown alter survival, and tissue-specific overexpression mimics infection-induced intron retention. CONCLUSION: Our collective findings point to pervasive and consistent RNA splicing changes, partly mediated by Lark/RBM4, as being an important aspect of the gut response to infection.

Hydrogen peroxide (H2O2): a review of its use in surgery.

Hydrogen peroxide has been used in medicine for more than 100 years. It is known in surgery as a highly useful irrigation solution by virtue of both its hemostatic and its antimicrobial effects. Due to its possible negative effect on wound healing and its cytotoxic effect in higher concentrations, there are concerns about the safety of its use. The objective of this paper is to review the safety and beneficial effects of hydrogen peroxide.

Association between perceived family functionality and teenage pregnancies

Background@#Teenage pregnancy is a public health concern because of its increasing incidence and its dire consequences. Numerous studies document the role of family in initiating sexual activity and teenage pregnancy, but there is a lack of studies that assess the effects of families and peers on teenage sexual behavior in the Philippines.@*Objective@#To determine the association between perceived family functionality as measured by the Family APGAR and teenage pregnancy in selected barangays in District 2, Quezon City, Philippines@*Methodology@#The study enrolled 233 women who are residents of Barangays Commonwealth and Payatas in Quezon City. Cases consisted of 133 women aged 18 to 24 years at the time of the interview who have become pregnant in 2011-2016, while they were 13 to 19 years old, while controls (N=100) were similar but had never been pregnant before age 20. Consecutive respondents who consented to participate in the study were enrolled and interviewed using the Filipino version of the Family APGAR. Respondents were then classified as having functional or dysfunctional families. Odds ratio was computed to determine the relationship between family functionality and teenage pregnancy.@*Results@#Family dysfunction based on the Family APGAR score was significantly associated with increased risk of teenage pregnancy with an OR 16.69, 1.93-144 (p=0.010) along with having both parents as caregivers with an OR of 29.69, 2.46-345, and teenage pregnancy in the mother with an OR of 15.87, 2.006-125.@*Conclusion@#Perception of dysfunction in the family based on the Family APGAR score, having both parents as caregivers and teenage pregnancy in the mother are associated with teenage pregnancy. Future researches should investigate the interactions of these factors but targeting family functionality may be key to curbing teenage pregnancies.

Effect of Surface Modification on Nano-Structured LiNi(0.5)Mn(1.5)O4 Spinel Materials.

Fine-tuning of particle size and morphology has been shown to result in differential material performance in the area of secondary lithium-ion batteries. For instance, reduction of particle size to the nanoregime typically leads to better transport of electrochemically active species by increasing the amount of reaction sites as a result of higher electrode surface area. The spinel-phase oxide LiNi0.5Mn1.5O4 (LNMO), was prepared using a sol-gel based template synthesis to yield nanowire morphology without any additional binders or electronic conducting agents. Therefore, proper experimentation of the nanosize effect can be achieved in this study. The spinel phase LMNO is a high energy electrode material currently being explored for use in lithium-ion batteries, with a specific capacity of 146 mAh/g and high-voltage plateau at ∼4.7 V (vs Li/Li(+)). However, research has shown that extensive electrolyte decomposition and the formation of a surface passivation layer results when LMNO is implemented as a cathode in electrochemical cells. As a result of the high surface area associated with nanosized particles, manganese ion dissolution results in capacity fading over prolonged cycling. In order to prevent these detrimental effects without compromising electrochemical performance, various coating methods have been explored. In this work, TiO2 and Al2O3 thin films were deposited using atomic layer deposition (ALD) on the surface of LNMO particles. This resulted in effective surface protection by prevention of electrolyte side reactions and a sharp reduction in resistance at the electrode/electrolyte interface region.

Compilation of an informative microsatellite set for genetic characterisation of East African finger millet (Eleusine coracana)

Background Genetic diversity of finger millet (Eleusine coracana), a nutritious neglected staple cereal in Africa and South Asia is largely uncharacterized. This study analysed 82 published SSR markers for finger millet across 10 diverse accessions to compile an informative set for genetic characterisation. Extensive optimization compared single samples with bulked leaf or bulked DNA samples for capturing within accession genetic diversity. The markers were evaluated to determine (1) how efficiently they amplified target loci during high-throughput genotyping with a generic PCR protocol, (2) ease of scoring PCR products and (3) polymorphism and ability to discern genetic diversity within the tested finger millet germplasm. Results Across 88 samples, the 52 markers that worked well amplified 274 alleles, ranging from 2 to 14 per locus with a mean of 4.89. Major allele frequency ranged from 0.18 to 0.93 with a mean of 0.57. Polymorphic Information Content (PIC) ranged from 0.13 to 0.88 with a mean of 0.5 and availability varied between 64 and 100% with a mean of 92.8%. Heterozygosity ranged from 0 to 1.0, with a mean of 0.26. Discussion Five individual samples from an accession captured the largest number of alleles per locus compared to the four different bulked sampling strategies but this difference was not significant. The identified set comprised 20 markers: UGEP24, UGEP53, UGEP84, UGEP27, UGEP98, UGEP95, UGEP64, UGEP33, UGEP67, UGEP106, UGEP110, UGEP57, UGEP96, UGEP66, UGEP46, UGEP79, UGEP20, UGEP12, UGEP73 and UGEP5 and was since used to assess East African finger millet genetic diversity in two separate studies.

Functional reconstruction of a combined tendocutaneous defect of the achilles using a segmental rectus femoris myofascial construct: a viable alternative.

The composite anterolateral thigh flap with vascularized fascia lata has emerged as a workhorse at our institution for complex Achilles defects requiring both tendon and soft tissue reconstruction. Safe elevation of this flap, however, is occasionally challenged by absent or inadequate perforators supplying the anterolateral thigh. When discovered intraoperatively, alternative options derived from the same vascular network can be pursued. We present the case of a 74-year-old male who underwent composite Achilles defect reconstruction using a segmental rectus femoris myofascial free flap. Following graduated rehabilitation, postoperatively, the patient resumed full activity and was able to ambulate on his tip-toes. At 1-year follow-up, active total range of motion of the reconstructed ankle exceeded 85% of the unaffected side, and donor site morbidity was negligible. American Orthopaedic Foot and Ankle Society and Short Form-36 scores improved by 78.8% and 28.8%, respectively, compared to preoperative baseline assessments. Based on our findings, we advocate for use of the combined rectus femoris myofascial free flap as a rescue option for reconstructing composite Achilles tendon/posterior leg defects in the setting of inadequate anterolateral thigh perforators. To our knowledge, this is the first report to describe use of this flap for such an indication.

Functional Reconstruction of a Combined Tendocutaneous Defect of the Achilles Using a Segmental Rectus Femoris Myofascial Construct: A Viable Alternative

The composite anterolateral thigh flap with vascularized fascia lata has emerged as a workhorse at our institution for complex Achilles defects requiring both tendon and soft tissue reconstruction. Safe elevation of this flap, however, is occasionally challenged by absent or inadequate perforators supplying the anterolateral thigh. When discovered intraoperatively, alternative options derived from the same vascular network can be pursued. We present the case of a 74-year-old male who underwent composite Achilles defect reconstruction using a segmental rectus femoris myofascial free flap. Following graduated rehabilitation, postoperatively, the patient resumed full activity and was able to ambulate on his tip-toes. At 1-year follow-up, active total range of motion of the reconstructed ankle exceeded 85% of the unaffected side, and donor site morbidity was negligible. American Orthopaedic Foot and Ankle Society and Short Form-36 scores improved by 78.8% and 28.8%, respectively, compared to preoperative baseline assessments. Based on our findings, we advocate for use of the combined rectus femoris myofascial free flap as a rescue option for reconstructing composite Achilles tendon/posterior leg defects in the setting of inadequate anterolateral thigh perforators. To our knowledge, this is the first report to describe use of this flap for such an indication.

Prognostic implications of mutation-specific QTc standard deviation in congenital long QT syndrome.

BACKGROUND: Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. OBJECTIVES: To hypothesize that the assessment of QTc variance in patients with congenital LQTS who carry the same mutation provides incremental prognostic information on the patient-specific QTc. METHODS: The study population comprised 1206 patients with LQTS with 95 different mutations and ≥ 5 individuals who carry the same mutation. Multivariate Cox proportional hazards regression analysis was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years in the total population and by genotype. RESULTS: Assessment of mutation-specific QTcSD showed large differences among carriers of the same mutations (median QTcSD 45 ms). Multivariate analysis showed that each 20 ms increment in QTcSD was associated with a significant 33% (P = .002) increase in the risk of cardiac events after adjustment for the patient-specific QTc duration and the family effect on QTc. The risk associated with QTcSD was pronounced among patients with long QT syndrome type 1 (hazard ratio 1.55 per 20 ms increment; P<.001), whereas among patients with long QT syndrome type 2, the risk associated with QTcSD was not statistically significant (hazard ratio 0.99; P = .95; P value for QTcSD-by-genotype interaction = .002). CONCLUSIONS: Our findings suggest that mutations with a wider variation in QTc duration are associated with increased risk of cardiac events. These findings appear to be genotype-specific, with a pronounced effect among patients with the long QT syndrome type 1 genotype.