Pleiotropy in FOXC1-attributable phenotypes involves altered ciliation and cilia-dependent signaling.

Alterations to cilia are responsible for a wide range of severe disease; however, understanding of the transcriptional control of ciliogenesis remains incomplete. In this study we investigated whether altered cilia-mediated signaling contributes to the pleiotropic phenotypes caused by the Forkhead transcription factor FOXC1. Here, we show that patients with FOXC1-attributable Axenfeld-Rieger Syndrome (ARS) have a prevalence of ciliopathy-associated phenotypes comparable to syndromic ciliopathies. We demonstrate that altering the level of Foxc1 protein, via shRNA mediated inhibition, CRISPR/Cas9 mutagenesis and overexpression, modifies cilia length in vitro. These structural changes were associated with substantially perturbed cilia-dependent signaling [Hedgehog (Hh) and PDGFRα], and altered ciliary compartmentalization of the Hh pathway transcription factor, Gli2. Consistent with these data, in primary cultures of murine embryonic meninges, cilia length was significantly reduced in heterozygous and homozygous Foxc1 mutants compared to controls. Meningeal expression of the core Hh signaling components Gli1, Gli3 and Sufu was dysregulated, with comparable dysregulation of Pdgfrα signaling evident from significantly altered Pdgfrα and phosphorylated Pdgfrα expression. On the basis of these clinical and experimental findings, we propose a model that altered cilia-mediated signaling contributes to some FOXC1-induced phenotypes.

Transcriptome analysis of Drosophila suzukii reveals molecular mechanisms conferring pyrethroid and spinosad resistance.

Drosophila suzukii lay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach for D. suzukii management, resulting in development of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveraged D. melanogaster mutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistant D. suzukii to demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance in D. suzukii and provides insights into how current management practices can be optimized.

Identification of a novel recombinant polerovirus and other emergent viruses and tombusvirus-like associated RNA species associated with carrot motley dwarf disease in the United States.

Carrot motley dwarf (CMD) is a viral disease complex caused by co-infection of the polerovirus carrot red leaf virus with the umbraviruses carrot mottle virus or carrot mottle mimic virus, and/or a tombusvirus like associated RNA (tlaRNA), which depend on co-infection with a helper polerovirus to gain aphid transmissibility. In 2020 and 2021 carrot samples from Washington, United States (U.S.), and parsley and cilantro samples from California, U.S., exhibiting typical symptoms of CMD were submitted for diagnosis. Initial RT-PCR diagnostic assays identified the typical CMD viruses in the carrot samples, however only the umbraviruses and tlaRNAs were detected in the parsley and cilantro samples; as such, these samples were retested with another RT-PCR assay for generic polerovirus detection. Unexpectedly, the poleroviruses Torilis crimson leaf virus (TorCLV) and fennel motley virus were identified. Subsequent RNA sequencing analysis was conducted to confirm these results and look for other emergent viruses. In addition to confirming the diagnostic results, the recently described polerovirus Foeniculum vulgare polerovirus, the umbraviruses Pastinaca umbravirus 1 and wild carrot mottle virus, and the tlaRNA Arracacha latent virus E associated RNA were identified, making this the first report of these viruses and tlaRNA in the U.S. Using phylogenetic and pairwise identity comparisons and RDP4 recombination analyses, we also identified a putative novel polerovirus, for which we propose the name parsley polerovirus, that appears to be a recombinant between carrot polerovirus 1, sharing 92% amino acid (aa) identity with the RNA dependent RNA polymerase in the 5' gene block, and TorCLV, sharing >98% aa identity with the capsid protein in the 3 gene block. This work adds to the growing list of polerovirus species exhibiting recombination between the 5' and 3' gene blocks, and highlights the unique, variable, and dynamic associations that can occur in polerovirus, umbravirus, and tlaRNA disease complexes.

Soliton synchronization in microresonators with a modulated pump.

Microresonator frequency comb generation from Kerr solitons has become a cutting edge technology, but challenges remain in creating, maintaining, and controlling the solitons. Pump modulation and dual pumping are promising techniques for meeting these challenges. Here we derive the equation of motion of solitons interacting with a modulated pump in the framework of synchronization theory. It implies that the soliton repetition rate locks to the modulation frequency whenever the latter is within a locking range of frequencies around an integer multiple of the free spectral range of the microresonator. We calculate explicitly, numerically, and in perturbation theory the width of the locking range as a function of the amplitude and frequency of the pump and the modulation phase. We show that a highly red-detuned, strong pump that is amplitude-modulated provides the best conditions for entrainment, and that the width of the locking range is proportional to the square of the modulation frequency, limiting the effectiveness of RF modulation as an entrainment method.

Study of an MoS 2 phototransistor using a compact numerical method enabling detailed analysis of 2D material phototransistors.

Research on two-dimensional material-based phototransistors has recently become a topic of great interest. However, the high number of design features, which impact the performance of these devices, and the multi-physical nature of the device operation make the accurate analysis of these devices a challenge. Here, we present a simple yet effective numerical framework to overcome this challenge. The one-dimensional framework is constructed on the drift-diffusion equations, Poisson's equation, and wave propagation in multi-layered medium formalism. We apply this framework to study phototransistors made from monolayer molybdenum disulfide ( MoS 2 ) placed on top of a back-gated silicon-oxide-coated silicon substrate. Numerical results, which show good agreement with the experimental results found in the literature, emphasize the necessity of including the inhomogeneous background for accurately calculating device metrics such as quantum efficiency and bandwidth. For the first time in literature, we calculate the phase noise of these phototransistors, which is a crucial performance metric for many applications where precise timing and synchronization are critical. We determine that applying a low drain-to-source voltage is the key requirement for low phase noise.

Validation of Selected MicroRNA Transcriptome Data in the Bovine Corpus Luteum during Early Pregnancy by RT-qPCR.

In cattle, the corpus luteum (CL) is pivotal in maintaining early pregnancy by secreting progesterone. To establish pregnancy, the conceptus produces interferon-τ, preventing luteolysis and initiating the transformation of the CL spurium into a CL verum. Although this transformation is tightly regulated, limited data are available on the expression of microRNAs (miRNAs) during and after this process. To address this gap, we re-analyzed previously published RNA-Seq data of CL from pregnant cows and regressed CL from non-pregnant cows. This analysis identified 44 differentially expressed miRNAs. From this pool, three miRNAs-bta-miR-222-3p, bta-miR-29c, and bta-miR-2411-3p-were randomly selected for relative quantification. Using bovine ovaries (n = 14) obtained from an abattoir, total RNA (including miRNAs) was extracted and converted to cDNA for RT-qPCR. The results revealed that bta-miR-222-3p was downregulated (p = 0.016) in pregnant females compared to non-pregnant cows with regressed CL. However, no differences in miRNA expression were observed between CL of pregnant and non-pregnant cows for bta-miR-29c (p > 0.32) or bta-miR-2411-3p (p > 0.60). In silico prediction approaches indicated that these miRNAs are involved in pathways regulating pregnancy maintenance, such as the VEGF- and FoxO-signaling pathways. Additionally, their biogenesis is regulated by GABPA and E2F4 transcription factors. The validation of selected miRNA expression in the CL during pregnancy by RT-qPCR provides novel insights that could potentially lead to the identification of biomarkers related to CL physiology and pregnancy outcome.

Assessment of urinary 6-oxo-pipecolic acid as a biomarker for ALDH7A1 deficiency.

ALDH7A1 deficiency is an epileptic encephalopathy whose seizures respond to treatment with supraphysiological doses of pyridoxine. It arises as a result of damaging variants in ALDH7A1, a gene in the lysine catabolism pathway. α-Aminoadipic semialdehyde (α-AASA) and Δ1-piperideine-6-carboxylate (P6C), which accumulate because of the block in the lysine pathway, are diagnostic biomarkers for this disorder. Recently, it has been reported that 6-oxo-pipecolic acid (6-oxo-PIP) also accumulates in the urine, CSF and plasma of ALDH7A1-deficient individuals and that, given its improved stability, it may be a more suitable biomarker for this disorder. This study measured 6-oxo-PIP in urine from a cohort of 30 patients where α-AASA was elevated and showed that it was above the normal range in all those above 6 months of age. However, 6-oxo-PIP levels were within the normal range in 33% of the patients below 6 months of age. Levels increased with age and correlated with a decrease in α-AASA levels. Longitudinal analysis of urine samples from ALDH7A1-deficient patients who were on a lysine restricted diet whilst receiving supraphysiological doses of pyridoxine showed that levels of 6-oxo-PIP remained elevated whilst α-AASA decreased. Similar to α-AASA, we found that elevated urinary excretion of 6-oxo-PIP can also occur in individuals with molybdenum cofactor deficiency. This study demonstrates that urinary 6-oxo-PIP may not be a suitable biomarker for ALDH7A1 deficiency in neonates. However, further studies are needed to understand the biochemistry leading to its accumulation and its potential long-term side effects.

Dietary management for pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency, a follow-on from the international consortium guidelines.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a neurometabolic disorder in the lysine metabolism pathway. In 2014 and 2021, the International PDE consortium published consensus guidelines about diagnosis and management. In this follow-on, a literature review was performed and nutrition management was evaluated through an international dietary questionnaire with 40 respondents. This manuscript discusses consensus dietary statements and the practical provision of lysine reduction therapies. Results from the questionnaire, statements from the PDE consensus guidelines, new data from the literature, as well as clinical practice experience of the metabolic dietitian group form the basis of these updated practical diet recommendations. These dietary management recommendations can support dietitians, nutritionists, and physicians in initiation and monitoring of lysine reduction therapies for PDE-ALDH7A1 patients and families.

mARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes.

BACKGROUND: Mutations in the gene MTARC1 (mitochondrial amidoxime-reducing component 1) protect carriers from metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MTARC1 encodes the mARC1 enzyme, which is localized to the mitochondria and has no known MASH-relevant molecular function. Our studies aimed to expand on the published human genetic mARC1 data and to observe the molecular effects of mARC1 modulation in preclinical MASH models. METHODS AND RESULTS: We identified a novel human structural variant deletion in MTARC1, which is associated with various biomarkers of liver health, including alanine aminotransferase levels. Phenome-wide Mendelian Randomization analyses additionally identified novel putatively causal associations between MTARC1 expression, and esophageal varices and cardiorespiratory traits. We observed that protective MTARC1 variants decreased protein accumulation in in vitro overexpression systems and used genetic tools to study mARC1 depletion in relevant human and mouse systems. Hepatocyte mARC1 knockdown in murine MASH models reduced body weight, liver steatosis, oxidative stress, cell death, and fibrogenesis markers. mARC1 siRNA treatment and overexpression modulated lipid accumulation and cell death consistently in primary human hepatocytes, hepatocyte cell lines, and primary human adipocytes. mARC1 depletion affected the accumulation of distinct lipid species and the expression of inflammatory and mitochondrial pathway genes/proteins in both in vitro and in vivo models. CONCLUSIONS: Depleting hepatocyte mARC1 improved metabolic dysfunction-associated steatotic liver disease-related outcomes. Given the functional role of mARC1 in human adipocyte lipid accumulation, systemic targeting of mARC1 should be considered when designing mARC1 therapies. Our data point to plasma lipid biomarkers predictive of mARC1 abundance, such as Ceramide 22:1. We propose future areas of study to describe the precise molecular function of mARC1, including lipid trafficking and subcellular location within or around the mitochondria and endoplasmic reticulum.

Th2 Cells Are Associated with Tumor Recurrence Following Radiation.

The curative treatment of multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC), utilizes radiation. The outcomes for HPV/p16-negative HNSCC are significantly worse than HPV/p16-positive tumors, with increased radiation resistance leading to worse locoregional recurrence (LRR) and ultimately death. This study analyzed the relationship between immune function and outcomes following radiation in HPV/p16-negative tumors to identify mechanisms of radiation resistance and prognostic immune biomarkers. A discovery cohort of 94 patients with HNSCC treated uniformly with surgery and adjuvant radiation and a validation cohort of 97 similarly treated patients were utilized. Tumor immune infiltrates were derived from RNAseq gene expression. The immune cell types significantly associated with outcomes in the discovery cohort were examined in the independent validation cohort. A positive association between high Th2 infiltration and LRR was identified in the discovery cohort and validated in the validation cohort. Tumor mutations in CREBBP/EP300 and CASP8 were significantly associated with Th2 infiltration. A pathway analysis of genes correlated with Th2 cells revealed the potential repression of the antitumor immune response and the activation of BRCA1-associated DNA damage repair in multiple cohorts. The Th2 infiltrates were enriched in the HPV/p16-negative HNSCC tumors and associated with LRR and mutations in CASP8, CREBBP/EP300, and pathways previously shown to impact the response to radiation.

Potential role of the light-adjustable lens in flanged intrascleral haptic fixation.

PURPOSE: To compare maximum tensile strength between commonly used 3-piece intraocular lens (IOL) for flanged intrascleral haptic fixation (FISHF). SETTING: Willis-Knight Eye Institute, Shreveport, Louisiana. DESIGN: Laboratory investigation. METHODS: Haptic tensile strength was compared with MA60AC, CT Lucia 602, AR40E, and the light-adjustable lens (LAL). Haptic strength with a 24-diopter (D) IOL was compared across all lenses, as well as across a range of 10 to 30 D with the MA60AC. A custom device was created to hold the IOL in correct haptic orientation. The maximum tension (mean ± SD) was recorded in Newtons (N) when the haptic lost tension or broke. RESULTS: CT Lucia was the strongest at 1.53 ± 0.11 N vs 1.00 ± 0.15 (MA60AC), 0.87 ± 0.19 (AR40E), and 0.83 ± 0.14 N (LAL) ( P < .001). The LAL and AR40E were similar to a 9-0 polypropylene suture while being significantly stronger than 10-0 polypropylene suture ( P < .001). No difference in haptic tension for the MA60AC from 10 to 30 D ( P > .05). High magnification revealed the highest haptic fractures for MA60AC at 40% compared with LAL, AR40E, and CT Lucia at 0%. CT Lucia and AR40E had 100% of haptics disinserted from the IOL without any damage compared with 60% LAL and 60% MA60AC. CT Lucia, AR40E, and LAL have a flatter haptic angulation at 5 degrees. CONCLUSIONS: Haptic strength, durability, and angulation of the LAL may support the possibility of FISHF in the hands of experienced surgeons. However, further testing is strongly recommended to verify whether physiologic conditions or light treatments may compromise long-term haptic stability.

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden.

Purpose: Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies. Methods: We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. Results: Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Conclusions: Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.

Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer.

BACKGROUND: Extranodal extension (ENE) of lymph node metastasis is one of the most reliable prognostic indicators for patients with locally advanced oral cancer. Although multiple reports have found a close relationship between immune infiltration of tumors and patient clinical outcomes, its association with ENE is unknown. METHODS: We identified 234 human papillomavirus-negative (HPV-) oral cavity squamous cell carcinoma (OSCC) patients in The Cancer Genome Atlas and investigated the immune infiltration profiles of primary tumors and their association with survival. RESULTS: Hierarchical clustering analysis clearly classified the overall immune infiltration status in OSCC into high immune or low immune groups. The combination of ENE positivity and low immune infiltration was strongly associated with poor overall survival (OS) compared to the combination of ENE positivity and high immune infiltration [hazard ratio 2.04 (95 %CI, 1.08-3.83); p = 0.024]. The immune infiltration status was not associated with OS rates in patients with ENE-negative or node negative tumors. CONCLUSION: Overall Immune infiltration at the primary site was significantly associated with clinical outcome of OSCC patients with ENE.

Temporal changes in ewe vaginal microbiota throughout gestation.

Introduction: Numerous factors are known to influence reproductive efficiency in ewes, but few studies have investigated the potential role of vaginal microbiota in sheep reproductive success. The objective of this study was to thoroughly characterize the ewe vaginal microbiota throughout the course of pregnancy. Methods: Vaginal samples were collected from 31 pregnant Hampshire and Hampshire X Suffolk crossbred ewes on a weekly basis from pre-breeding to pregnancy testing and then biweekly until just after lambing. To characterize the vaginal microbial communities, DNA was extracted and 16S rRNA gene Illumina MiSeq amplicon sequencing was performed. Results and Discussion: Alpha diversity metrics indicated an increase in species richness, evenness, and overall diversity throughout gestation. Distinct shifts in the bacterial communities were observed during gestation and were segregated into three periods: early gestation, a transitional period and mid/late gestation. During early gestation, Actinobacillus, Histophilus, and unclassified Leptotrichiaceae were found in greater relative abundance. During the transitional period, a population shift occurred characterized by increasing relative abundance of Streptococcus and Staphylococcus. During mid/late gestation, Staphylococcus, Streptococcus, and Ureaplasma had the greatest relative abundance. These shifts in the microbial population throughout the ewe's gestation are likely related to hormonal changes triggered by the growing conceptus, specifically increasing blood concentration of progesterone. The transitional period shift in vaginal microbial communities potentially aligns with the placental take-over of progesterone production from the corpus luteum at approximately day 50 after conception (gestational week 7). Understanding the observed variability of the vaginal microbiota throughout pregnancy will allow for future comparison of ewes that did not become pregnant or had abnormal pregnancies, which could lead to the discovery of potential bacterial biomarkers for pregnancy outcome; this understanding could also lead to development of probiotics to improve sheep reproductive success.

Emergent Coronary Thrombectomy for Acute Myocardial Infarction Immediately Following Craniotomy with Tumor Resection.

The management of perioperative acute myocardial infarction (AMI) following oncologic neurosurgery requires balancing competing risks of myocardial ischemia and postoperative bleeding. There are limited human data to establish the safest timing of antiplatelet or anticoagulation therapy following neurosurgical procedures. For patients with malignancy experiencing AMI in the acute postoperative period, staged percutaneous coronary intervention (PCI) with upfront coronary aspiration thrombectomy followed by delayed completion PCI may offer an opportunity for myocardial salvage while minimizing postoperative bleeding risks. CYP2C19 genotyping and platelet aggregation studies can help confirm adequate platelet inhibition once antiplatelet therapy is resumed.

Collagen Networks under Indentation and Compression Behave Like Cellular Solids.

Simple synthetic and natural hydrogels can be formulated to have elastic moduli that match biological tissues, leading to their widespread application as model systems for tissue engineering, medical device development, and drug delivery vehicles. However, two different hydrogels having the same elastic modulus but differing in microstructure or nanostructure can exhibit drastically different mechanical responses, including their poroelasticity, lubricity, and load bearing capabilities. Here, we investigate the mechanical response of collagen-1 networks to local and bulk compressive loads. We compare these results to the behavior of polyacrylamide, a fundamentally different class of hydrogel network consisting of flexible polymer chains. We find that the high bending rigidity of collagen fibers, which suppresses entropic bending fluctuations and osmotic pressure, facilitates the bulk compression of collagen networks under infinitesimal applied stress. These results are fundamentally different from the behavior of flexible polymer networks in which the entropic thermal fluctuations of the polymer chains result in an osmotic pressure that must first be overcome before bulk compression can occur. Furthermore, we observe minimal transverse strain during the axial loading of collagen networks, a behavior reminiscent of open-celled cellular solids. Inspired by these results, we applied mechanical models of cellular solids to predict the elastic moduli of the collagen networks and found agreement with the moduli values measured through contact indentation. Collectively, these results suggest that unlike flexible polymer networks that are often considered incompressible, collagen hydrogels behave like rigid porous solids that volumetrically compress and expel water rather than spreading laterally under applied normal loads.

Nucleocapsid protein-specific monoclonal antibodies protect mice against Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO priority pathogen. Antibody-based medical countermeasures offer an important strategy to mitigate severe disease caused by CCHFV. Most efforts have focused on targeting the viral glycoproteins. However, glycoproteins are poorly conserved among viral strains. The CCHFV nucleocapsid protein (NP) is highly conserved between CCHFV strains. Here, we investigate the protective efficacy of a CCHFV monoclonal antibody targeting the NP. We find that an anti-NP monoclonal antibody (mAb-9D5) protected female mice against lethal CCHFV infection or resulted in a significant delay in mean time-to-death in mice that succumbed to disease compared to isotype control animals. Antibody protection is independent of Fc-receptor functionality and complement activity. The antibody bound NP from several CCHFV strains and exhibited robust cross-protection against the heterologous CCHFV strain Afg09-2990. Our work demonstrates that the NP is a viable target for antibody-based therapeutics, providing another direction for developing immunotherapeutics against CCHFV.

Phylogenetic and Recombination Analysis of Clinical Vitreous Humor-Derived Adenovirus Isolates Reveals Discordance Between Serotype and Phylogeny.

Purpose: To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye Institute. Methods: The PacBio Sequel II was used to sequence the genomes of the three clinical adenovirus isolates. To identify the isolates, a full genome-based multiple sequence alignment (MSA) of 722 mastadenoviruses was generated using multiple alignment using fast Fourier transform (MAFFT). MAFFT was also used to generate genome-based human adenovirus B (HAdV-B) MSAs, as well as HAdV-B fiber, hexon, and penton protein-based MSAs. To examine recombination within HAdV-B, RF-Net 2 and Bootscan software programs were used. Results: In the course of classifying three new atypical ocular adenovirus samples, taken from the vitreous humor, we found that all three isolates were HAdV-B species. The three Bascom Palmer HAdV-B genomes were then combined with over 300 HAdV-B genome sequences, including nine ocular HAdV-B genome sequences. Attempts to categorize the penton, hexon, and fiber serotypes using phylogeny of the three Bascom Palmer samples were inconclusive due to incongruence between serotype and phylogeny in the dataset. Recombination analysis using a subset of HAdV-B strains to generate a hybridization network detected recombination between nonhuman primate and human-derived strains, recombination between one HAdV-B strain and the HAdV-E outgroup, and limited recombination between the B1 and B2 clades. Conclusions: The discordance between serotype and phylogeny detected in this study suggests that the current classification system does not accurately describe the natural history and phylogenetic relationships among adenoviruses.

Preventing the Argentinian flag sign and managing anterior capsular tears: A review.

The Argentinian flag sign (AFS) is a feared complication during cataract extraction. Intralenticular pressures, especially excessive posterior pressure, have been identified as potential mechanisms for capsular stress and tearing associated with AFS. Capsular tension is created by positive intralenticular pressures, which cause the irido-lens diaphragm to move anteriorly once the manual capsulorhexis has been initiated. This tension can cause inadvertent tears that self-propagate to the lens equator, causing an AFS, among other intraoperative complications. Thus, this review highlights the importance of identifying intumescent cataracts as well as a combination of techniques to relieve intracapsular pressures needed to prevent AFS. However, some instances of anterior capsular tears are unavoidable. Therefore, focus will also be placed on techniques during cataract extraction used to manage anterior capsular tears, mitigating extension to the posterior capsule.