Abnormal Shape Research Articles

False HbA1c value due to a rare variant of hemoglobin Petie Salpetriere coinherited with alpha thalassemia

Abstract Objectives To describe a variant hemoglobin that interferes with HbA1c analysis by cation exchange HPLC. Case presentation A 78 years-old Spanish male patient visited the Internal Medicine Clinic for a routine check-up, with HbA1c included to screen for diabetes. He had suffered hypertension and dyslipidemia, and the patient had no previous symptoms suggestive of diabetes such as hyperglycemia, weight loss, polydipsia, polyuria or tiredness. Diabetes screening by HbA1c measurement was assessed using cation exchange HPLC and an immunoassay point-of-care analyzer. Routine hemoglobinopathy screening was performed including CBC, HbF and HbA2 measurement by cation exchange HPLC and capillary electrophoresis (CE). Further variant characterization was undertaken by DNA sequencing. Discordant HbA1c results were obtained for our subject, with elevated HbA1c of 52 mmol/mol measured by cation exchange HPLC and a normal level of 34 mmol/mol by immunoassay. Abnormal HbA1c peak shape prompted hemoglobinopathy screening to investigate potential variant interference. A globin gene analysis was performed, and the results showed a variant hemoglobin named ‘Hb Petie Salpetriere’. This variant arises from a Val → Phe substitution due to a mutation of c.103G>T of the beta-globin gene [BETA34 (B16) Val>Phe; HBB:c.103G>T]. Conclusions This is the first reported case involving the Hb Petie Salpetriere variant in a Spanish patient. The present results show that the Hb Petie Salpetriere variant can affect the results of HbA1c analysis through ion-exchange HPLC, but not that obtained from the latex agglutination immunoassay. Only ion-exchange HPLC suggested the presence of the Hb variant in this case, suggesting that a careful review of the resulting chromatogram might reveal a potential variant.

Reexamining the Role of Pulmonary Lipids in the Pathogenesis of Pulmonary Fibrosis.

Pulmonary fibrosis (PF) can be idiopathic or driven by a specific insult, genetic susceptibility, or disease process. Inflammation plays a role in the pathophysiology, the extent of which remains a longstanding topic of debate. More recently, there has been increasing interest in a potential inciting role for aberrant lipid metabolism. Lipids are essential for the structure and function of all cell membranes, but specifically in the lung for surfactant composition, intra- and intercellular lipid mediators, and lipofibroblasts. Clinically, there is evidence of increased lipid deposition in the subpleural space and at a whole-lung tissue level in PF. There is evidence of increased parenchymal lipid deposition and abnormal mediastinal fat shape on chest computed tomography. A protective role for cholesterol-lowering drugs, including statins and ezetimibe, has been described in PF. At a cellular level, fatty acid, phospholipid, and glucose metabolism are disordered, as is the production of lipid mediators. Here we put forward the argument that there is substantive clinical and biological evidence to support a role for aberrant lipid metabolism and lipid mediators in the pathogenesis of PF.

A comprehensive numerical procedure for high-intensity focused ultrasound ablation of breast tumour on an anatomically realistic breast phantom.

High-Intensity Focused Ultrasound (HIFU) as a promising and impactful modality for breast tumor ablation, entails the precise focalization of high-intensity ultrasonic waves onto the tumor site, culminating in the generation of extreme heat, thus ablation of malignant tissues. In this paper, a comprehensive three-dimensional (3D) Finite Element Method (FEM)-based numerical procedure is introduced, which provides exceptional capacity for simulating the intricate multiphysics phenomena associated with HIFU. Furthermore, the application of numerical procedures to an anatomically realistic breast phantom (ARBP) has not been explored before. The integrity of the present numerical procedure has been established through rigorous validation, incorporating comparative assessments with previous two-dimensional (2D) simulations and empirical data. For ARBP ablation, the administration of a 0.1 MPa pressure input pulse at a frequency of 1.5 MHz, sustained at the focal point for 10 seconds, manifests an ensuing temperature elevation to 80°C. It is noteworthy that, in contrast, the prior 2D simulation using a 2D phantom geometry reached just 72°C temperature under the identical treatment regimen, underscoring the insufficiency of 2D models, ascribed to their inherent limitations in spatially representing acoustic energy, which compromises their overall effectiveness. To underscore the versatility of this numerical platform, a simulation of a more clinically relevant HIFU therapy procedure has been conducted. This scenario involves the repositioning of the ultrasound focal point to three separate lesions, each spaced at 3 mm intervals, with ultrasound exposure durations of 6 seconds each and a 5-second interval for movement between focal points. This approach resulted in a more uniform high-temperature distribution at different areas of the tumour, leading to the ablation of almost all parts of the tumour, including its verges. In the end, the effects of different abnormal tissue shapes are investigated briefly as well. For solid mass tumors, 67.67% was successfully ablated with one lesion, while rim-enhancing tumors showed only 34.48% ablation and non-mass enhancement tumors exhibited 20.32% ablation, underscoring the need for multiple lesions and tailored treatment plans for more complex cases.

Klasifikasi Penyakit dan Kelainan Bentuk Kuku Manusia Menggunakan Convolutional Neural Network

Nails are one of the body parts that have an important role, because nails can provide signals of a disease starting from the color, shape, and size of the nails. This study aims to identify diseases and abnormalities of human nail shape using digital images. This study uses seven classes of diseases, namely beausline, clubbing, koilonychia, yellow nail, white nail, onychomycosis, and normal nail. To identify diseases and abnormalities of human nail shape, the method used is Convolutional Neural Network with VGG-16 architecture. The results obtained from this study are an accuracy of 92.9% from a total dataset that has been augmented as much as 3900 data, for an average precision measurement result of 86.1%, an average recall result of 85.8%, an average f-1 score result of 85.8%.

Unraveling the complex interplay between abnormal hemorheology and shape asymmetry in flow through stenotic arteries

Background and Objective:Stenosis or narrowing of arteries due to the buildup of plaque is a common occurrence in atherosclerosis and coronary artery disease (CAD), limiting blood flow to the heart and posing substantial cardiovascular risk. While the role of geometric irregularities in arterial stenosis is well-documented, the complex interplay between the abnormal hemorheology and asymmetric shape in flow characteristics remains unexplored. Methods:This study investigates the influence of varying hematocrit (Hct) levels, often caused by conditions such as diabetes and anemia, on flow patterns in an idealized eccentric stenotic artery using computational fluid dynamics simulations. We consider three physiological levels of Hct, 25%, 45%, and 65%, representing anemia, healthy, and diabetic conditions, respectively. The numerical simulations are performed for different combinations of shape eccentricity and blood rheological parameters, and hemodynamic indicators such as wall shear stress (WSS), oscillatory shear index (OSI), are relative residence time (RRT) are calculated to assess the arterial health. Results:Our results reveal the significant influence of Hct level on stenosis progression. CAD patients with anemia are exposed to lower WSS and higher OSI, which may increase the propensity for plaque progression and rupture. However, for CAD patients with high Hct level—as is often the case in diabetes—the WSS at the minimal lumen area increases rapidly, which may also lead to plaque rupture and cause adverse events such as heart attacks. These disturbances promote endothelial dysfunction, inflammation, and thrombus formation, thereby intensifying cardiovascular risk. Conclusions:Our findings underscore the significance of incorporating hemorheological parameters, such as Hct, into computational models for accurate assessment of flow dynamics. We envision that insights gained from this study will inform the development of tailored treatment strategies and interventions in CAD patients with common comorbidities such as diabetes and anemia, thus mitigating the adverse effects of abnormal hemorheology and reducing the ever-growing burden of cardiovascular diseases.

First report of potato virus H infecting tomato (Solanum lycopersicum) in China.

Potato virus H (PVH), belonging to the genus Carlavirus in the family Betaflexiviridae, was initially discovered in potato plants in Inner Mongolia, China (Li et al., 2013). Subsequently, it was documented to infect pepino, a perennial shrub of the Solanaceae family like potatoes (Abouelnasr et al., 2014). Tomato (Solanum lycopersicum L.), a major global crop, faces threats from various plant viruses. In an open field survey in Yunnan, China during July 2023, tomatoes (cultivar: Liangsi) showed typical virus symptoms: leaf yellowing, curling, mottling, and fruit with abnormal shape and color. Eleven symptomatic tomato samples were collected for high-throughput sequencing to identify the potential pathogen. RNA sequencing libraries were prepared using the TruSeq RNA sample prep kit (Illumina, San Diego, CA, USA), followed by RNA-seq sequencing on an Illumina HiSeq4000 platform (LC Sciences, USA). Approximately 77,928,560 paired-end reads (150-bp each) were generated. After quality control, 75,808,296 reads were retained and subjected to de novo assembly using Trinity (version 2.8.5). The assembled contigs, ranging from 198 nt to 15865 nt, were used as queries to search against the NCBI non-redundant protein sequence database (NR) or nucleotide sequence database (NT) to detect the potential pathogens using BLASTx and BLASTn program with a cutoff e-value of 10-5. As a consequence, certain contigs were assigned to 3 plant viruses, including PVH (the highest RdRp blastx identity to UAD82396.1: 97.8%), Capsicum chlorosis virus (CaCV, the highest RdRp blastx identity to APQ31267.1: 98.4%), and southern tomato virus (STV, the highest CP-RdRp fusion protein blastx identity to QOW17541.1: 99.74%). The presence of the identified 3 viruses was subsequently screened in the 11 tomato samples originally collected from the corresponding field. Notably, the specific detection primers for the PVH genome was designed from the newly assembled PVH genome (Forward primer: 5'- ATAGTTGTGCACTGTGTGCCTG-3'; Reverse primer: 5'-GCTTAAGGTTCTTAGCGTATTC-3'), targeting ~1.1kb. Consequently, PVH was detected in 3 out of 11 samples: 2 leaf samples and 1 fruit sample, with one leaf sample showing a single infection. The complete genome sequence of PVH in tomatoes (PVH-tomato) was successfully obtained by assembling nine overlapping regions spanning the entire PVH-tomato genome, following the RT-PCR and the 5' RACE and 3' RACE approaches, and deposited in NCBI nucleotide database with accession number OR397130.1Phylogenetic analysis based on the full genome sequences of PVH-tomato and other publicly available PVH isolates revealed that PVH-tomato was closely related to a PVH isolate found in potatoes in Yunnan (blastn similarity: 97.76%) (Fig. S1A). To test PVH-tomato infectivity and pathogenicity, four healthy Nicotiana benthamiana and four healthy tomato plants were mechanically inoculated with PVH-infected leaf sap; controls used sap from healthy plants. Three weeks post-inoculation, all N. benthamiana (4/4) and three tomato plants (3/4) were PVH-positive by RT-PCR. Symptoms were milder in N. benthamiana, and only two tomato plants (2/4) showed leaf curling. No PVH was detected in control samples (Figure S1B, S1C). Sanger sequencing confirmed the amplicons' expected length of 1093 bp. Previously, PVH was documented only in potato and pepino. This is the first report of tomatoes as natural PVH hosts and PVH infecting N. benthamiana under lab conditions.

Abnormal Cellular Populations Shape Thymic Epithelial Tumor Heterogeneity and Anti-Tumor by Blocking Metabolic Interactions in Organoids.

A variety of abnormal epithelial cells and immature and mature immune cells in thymic epithelial tumors (TETs) affect histopathological features, the degree of malignancy, and the response to treatment. Here, gene expression, trajectory inference, and T cell antigen receptor (TCR)-based lineage tracking are profiled in TETs at single-cell resolution. An original subpopulation of KRT14+ progenitor cells with a spindle cell phenotype is shown. An abnormal infiltration of immature T cells with a TCR hyper-rearrangement state is revealed, due to the lack of CCL21+ medullary epithelial cells. For thymic carcinoma, the novel biomarkers of MSLN, CCL20, and SLC1A5 are identified and observed an elevated expression of LAG3 and HAVCR2 in malignant tumorn-infiltrating mature T cells. These common features based on the single-cell populations may inform pathological reclassification of TETs. Meanwhile, it is found that macrophages (MACs) attract thymic tumor cells through the LGALS9-SLC1A5 axis, providing them with glutamine to elicit metabolic reprogramming. This MAC-based metabolic pattern can promote malignancy progression. Additionally, an interactive immune environment in TETs is identified that correlates with the infiltration of abnormal FOXI1+ CFTR- ionocytes. Collectively, the data broaden the knowledge of TET cellular ecosystems, providing a basis for tackling histopathological diagnosis and related treatment.

Classification of Microtia With Unusable Remnant Ear and Techniques in the First Stage of Two-Stage Auricular Reconstruction.

The remnant ear is a very important material in auricular reconstruction surgery; its dimension, position, and shape determine how it is used. However, the local conditions of microtia patients are complex and variable. Situations may be encountered where a series of abnormal remnant ears cannot be utilized in clinical practice. Currently, there are no literature that elaborates on this type of microtia and provides systematic treatment methods. The purpose of this article is to systematically classify them and optimize the two-stage method auricular reconstruction, to provide an effective surgical method for these patients. Based on the size, shape, and relative position of the residual ears, the unusable remnant ears were classified into three types: tiny size, abnormal shape, and relative position anomaly (over 1-cm higher than the contralateral earlobe). Fifty-three microtia patients with unusable remnant ear (54 ears) who underwent two-stage auricular reconstruction from August 2020 to August 2023 were reviewed. All patients had experienced earlobe reconstruction by using autologous rib cartilage during the first stage of surgery. Aesthetic assessments were evaluated from the naturalness of the earlobe reconstructed with autologous rib cartilage and the connection with the overall framework. The data on any complications that occurred during the follow-up period and patient satisfaction were collected. Among all patients, 31 had tiny size, 14 had abnormal shape, and 8 had excessively high positions. Patients were followed up for an average period of 9.2 months (6 to 12 months). No complex complications such as infection, skin necrosis, or cartilage exposure occurred. Fifty patients (94.3%) achieved excellent or good aesthetic outcomes. Fifty-one patients (96.2%) were satisfied with the reconstruction outcomes. An accurate assessment of the residual ear preoperatively is essential. Reconstructing and splicing the earlobe with autologous rib cartilage in cases where the residual ear cannot be utilized compensate for the defect that the soft tissue cannot provide the earlobe flap. This is an effective surgical method for the ear reconstruction in such patients.

Effect of seminal plasma cholesterol and triacylglycerides concentrations and sperm morphology on semen freezability in domestic cats (Felis silvestris catus)

There is scarce information about the effect of sperm morphology and seminal plasma composition on cat semen freezability. Thus, this study aims to assess the effect of cat sperm morphology and seminal plasma cholesterol (CHOL) and triacylglyceride (TAG) concentrations on sperm post-thaw survival. Ejaculates (n = 49) were evaluated, and seminal plasma was separated and frozen until CHOL and TAG concentrations were measured. The sperm pellet was diluted in a tris-based egg yolk extender, frozen (n = 38), or processed for sperm ultrastructure study (n = 11). Abnormalities recorded were abnormal head shape and size, detached heads, knobbed or ruffled acrosomes, eccentric mid-piece insertion, proximal and distal cytoplasmic droplets, folded and coiled tails, and Dag defect. Ultramicroscopic evaluation detected several sperm abnormalities in fresh semen and some sperm damage in frozen semen. Seminal plasma lipids components were positively correlated with post-thaw motility and acrosome integrity. Higher freezability indices for motility and acrosome integrity were observed in frozen-thawed semen with high seminal plasma CHOL and TAG concentrations. No freezability differences were observed between teratozoospermic and normozoospermic ejaculates. Our results showed that even when seminal plasma was removed before cryopreservation, sperm survival after thawing was significantly higher in samples with high seminal plasma CHOL and TAG concentrations, indicating a rapid adherence to these compounds to the sperm plasma membrane, protecting sperm cells from temperature changes. Nevertheless, there were no differences in sperm freezability by sperm morphology.

ENPP1 enzyme replacement therapy improves ectopic calcification but does not rescue skeletal phenotype in a mouse model for craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANKF377del mutation (AnkKI/KI ) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in AnkKI/KI mice. PPi is a potent inhibitor of mineralization. To examine the extent to which restoration of circulating PPi levels may prevent the development of a CMD-like phenotype, we treated AnkKI/KI mice with the recombinant human ENPP1-Fc protein IMA2a. ENPP1 hydrolyzes ATP into AMP and PPi. Male and female Ank+/+ and AnkKI/KI mice (n ≥ 6/group) were subcutaneously injected with IMA2a or vehicle weekly for 12wk, starting at the age of 1wk. Plasma ENPP1 activity significantly increased in AnkKI/KI mice injected with IMA2a (Vehicle/IMA2a: 28.15 ± 1.65/482.7 ± 331.2 mOD/min; p <.01), which resulted in the successful restoration of plasma PPi levels (Ank+/+ /AnkKI/KI vehicle treatment/AnkKI/KI IMA2a: 0.94 ± 0.5/0.43 ± 0.2/1.29 ± 0.8μM; p <.01). We examined the skeletal phenotype by X-Ray imaging and μCT. IMA2a treatment of AnkKI/KI mice did not significantly correct CMD features such as the abnormal shape of femurs, increased bone mass of mandibles, hyperostotic craniofacial bones, or the narrowed foramen magnum. However, μCT imaging showed ectopic calcification near basioccipital bones at the level of the foramen magnum and on joints of AnkKI/KI mice. Interestingly, IMA2a treatment significantly reduced the volume of calcified nodules at both sites. Our data demonstrate that IMA2a is sufficient to restore plasma PPi levels and reduce ectopic calcification but fails to rescue skeletal abnormalities in AnkKI/KI mice under our treatment conditions.

Myopia and Other Refractive Error and Their Relationships to Glaucoma Screening.

A large disk, a large parapapillary delta zone and a long axial length may be used as screening criteria to detect glaucomatous optic neuropathy in highly myopic eyes. To describe aspects for screening of glaucomatous optic neuropathy in dependence of refractive error, under special consideration of high myopia. Studies on the anatomy of the myopic optic nerve head and results of investigations on the relationship between glaucomatous optic neuropathy and axial myopia were included. In the range from hyperopia to moderate myopia, refractive error is not a strong glaucoma risk factor and may not be included in glaucoma screening strategies. Care should be taken, that in moderate myopia, a shift of Bruch´s membrane opening usually into the temporal direction leads to parapapillary gamma zone and a corresponding shortening of the horizontal disk diameter. In these moderately myopic eyes, a secondarily small optic disk with a correspondingly small optic cup should not lead to an overlooking of intrapapillary glaucomatous changes. Prevalence of glaucomatous or glaucoma-like optic nerve atrophy (GOA) steeply increases with longer axial length in highly myopic eyes (cutoff approximately -8 diopters/axial length 26.5mm), with prevalences higher than 50% in extremely high myopia. Besides longer axial length, morphological parameters associated with GOA in highly myopic eyes are a secondarily enlarged disk and large parapapillary delta zone. Both parameters, together with long axial length, may be used as screening criteria in high myopia for GOA. The latter is characterized by an abnormal neuroretinal rim shape, that is, vessel kinking close to the intrapapillary disk border. Factors associated with nonglaucomatous optic neuropathy are larger gamma zone and longer axial length, potentially due to an axial elongation-related retinal nerve fiber stretching.

Umbilical Vein Flows and Cardiac Size, Shape, and Ventricular Contractility in Fetuses With Estimated Weight Less-Than 10th Centile.

In a cohort of patients with estimated fetal weights (EFWs) <10th centile, we aimed 1) to compare the prevalence of abnormalities of fetal 4-chamber view (4CV) cardiac size, shape, and ventricular contractility in fetal growth restricted (FGR) and small-for-gestational-age (SGA) fetuses and 2) to compare umbilical vein flow (UVF) measurements to standard Doppler surveillance in predicting abnormalities of cardiac function. Prospective observational cohort study of fetuses with EFW <10th percentile. Measurements of size and shape used were 4CV transverse width, 4CV cardiac area, 4CV global sphericity index, and right-to-left ventricular mid-chamber width ratio. Variables of contractility used were fractional shortening change at the mid-ventricle chamber, global longitudinal strain, fractional area change, and left ventricular cardiac output. The UVF and standard Doppler surveillance including umbilical artery (UA), middle cerebral artery, and cerebroplacental ratio (CPR) were collected. Control data were from previously published studies. A total of 95 fetuses with EFWs <10th centile were included in the study. The rates of abnormalities of cardiac size and shape and ventricular contractility were all significantly elevated compared with normally grown control fetuses but similar between FGR and SGA fetuses. In a subset of 76 patients with UVF data, evaluation UVF identified more patients with any abnormality of contractility compared with UA (37.9 vs 17.2%, P = .02). The addition of UVF doubled the detection rate of ventricular contractility abnormalities. The addition of UVF should be considered in the surveillance of FGR and SGA fetuses to further stratify the severity of hypoxemia and to identify those at greater risk for future cardiovascular dysfunction.

Emphasis on Early Prenatal Diagnosis and Perinatal Outcomes Analysis of Apert Syndrome.

Apert syndrome is an inherited condition with autosomal dominant transmission. It is also known as acrocephalosyndactyly type I, being characterized by a syndrome of craniosynostosis with abnormal head shape, facial anomalies (median hypoplasia), and limb deformities (syndactyly, rhizomelic shortening). The association can suspect the prenatal diagnosis of these types of anomalies. The methodology consisted of revising the literature, by searching the PubMed/Medline database in which 27 articles were selected and analyzed, comprising 32 cases regarding the prenatal diagnosis of Apert syndrome. A series of ultrasound parameters, the anatomopathological abnormalities found, the obstetric results, and the genetic tests were followed. The distribution of imaging results (US, MRI) identified in the analyzed cases was as follows: skull-shaped abnormalities were evident in 96.8% of cases, facial abnormalities (hypertelorism 43.7%, midface hypoplasia 25%, proptosis 21.8%), syndactyly in 87.5%, and cardiovascular abnormalities in 9.3%. The anomalies detected by the ultrasound examination of the fetus were confirmed postnatally by clinical or gross evaluation or imaging. The management of these cases requires an early diagnosis, an evaluation of the severity of the cases, and appropriate parental counseling.

Posterior Eye Shape in Myopia

PurposeTo explore prevalence and associated factors of abnormalities of the posterior eye shape in dependence of axial length. DesignPopulation-based study. ParticipantsOut of the participants (n=3468) of the Beijing Eye Study, we included all eyes with an axial length of ≥25 mm, and a randomized sample of eyes with an axial length of <25 mm. MethodsUsing 30°-wide, serial horizontal, and fovea-centered radial, optical coherence tomographic (OCT) images, we examined location and depth of the most posterior point of the retinal pigment epithelium/Bruch´s membrane line (PP-RPE/BML). Main Outcome ParametersPrevalence and depth of an extrafoveal PP-RPE/BML. ResultsThe study included 366 eyes (314 individuals;age:63.7±9.7 years). On the radial OCT scans, the PP-RPE/BML was located in the foveola in 190 (51.9%;95%CI:46.9,56.9) eyes, in 121 (33.1%;95%CI:28.1,38.1) eyes in the 6 o´clock part of the vertical meridian at a mean distance of 1.73±0.70mm from the foveola, and in 54 (14.8%;95%CI:11.1,18.4) eyes in the 12 o´clock part of the vertical meridian at a distance of 2.01±0.66mm from the foveola. Deeper PP-RPE/BML depth increased with longer axial length (beta:0.28;B:12.3;95%CI:7.5,17.1;P<0.001), female sex (beta:0.17;B:30.2;95%CI:10.7,49.6;P=0.002), and higher corneal astigmatism (beta:0.12;B:13.9;95%CI:1.50,26.3;P=0.03). On the horizontal OCT scans, the PP-RPE/BML was located in the foveola in 304 (83.1%;95%CI:79.2,86.9) eyes, between the foveola and the optic disc in 36 (9.8%;95%CI:6.8,12.9) eyes (mean depth: 119±142μm; mean distance:1.59±0.76mm from the foveola), and temporal to the foveola in 26 (7.1%;95%CI:4.5,9.8) eyes (depth:71±46μm; distance:1.20±0.60mm). Higher prevalence of an extrafoveal PP-RPE/BML correlated with longer axial length (OR:1.55;95%CI:1.28,1.89;P<0.001), higher corneal astigmatism (OR:1.78;95%CI:1.14,2.79;P=0.01) and female sex (OR:2.74;95%CI:1.30,5.77;P=0.008). The curvature of the RPE/BM line at the posterior pole was similar to the RPE/BM line curvature outside of the posterior pole in 309 (84.4%;95%CI:80.7,88.2) eyes, and it was steeper (i.e., smaller curvature radius) in 57 (15.6%;95%CI:12.1,19.1) eyes. In these eyes, axial length was longer (24.41±1.78mm versus 27.74±1.88mm;P<0.001). ConclusionsWith longer axial length, the foveola is more often located outside of the geometrical posterior pole. It may be of importance for biometric axial length measurements. An extrafoveal location of the PP-RPE/BML may be due to an axial elongation-associated, meridionally asymmetric enlargement of Bruch´s membrane in the fundus midperiphery.

Decreased susceptibility to viscosin in Streptococcus pneumoniae.

Growing numbers of infections caused by antibiotic-resistant Streptococcus pneumoniae strains are a major concern for healthcare systems that will require new antibiotics for treatment as well as preventative measures that reduce the number of infections. Lipopeptides are antimicrobial molecules, of which some are used as antibiotics, including the last resort antibiotics daptomycin and polymyxins. Here we have studied the antimicrobial effect of the cyclic lipopeptide viscosin on S. pneumoniae growth and morphology. Most lipopeptides function as surfactants that create pores in membrane layers, which is regarded as their main antimicrobial activity. We show that viscosin can inhibit growth of S. pneumoniae without disintegration of the cytoplasmic membrane. Instead, the cells developed abnormal shapes and misplaced new division sites. The cell wall of these bacteria appeared less dense in electron microscopy images, suggesting that viscosin interfered with normal cell wall synthesis. Corroborating this observation, a luciferase reporter assay was used to show that the two-component systems LiaFSR and CiaRH, which are known to be activated upon cell wall stress, were strongly induced by viscosin. Furthermore, a mutant displaying 1.8-fold decreased susceptibility to viscosin was generated by sequential exposure to increasing concentrations of the lipopeptide. The mutant suffered from significant fitness loss and had mutations in genes involved in fatty acid synthesis, teichoic acid synthesis, and cell wall synthesis as well as transcription and translation. How these mutations might be linked to decreased viscosin susceptibility is discussed.IMPORTANCEStreptococcus pneumoniae is a leading cause of bacterial pneumonia, sepsis, and meningitis in children, and the incidence of infections caused by antibiotic-resistant strains is increasing. Development of new antibiotics is therefore necessary to treat these types of infections in the future. Here, we have studied the activity of the antimicrobial lipopeptide viscosin on S. pneumoniae and show that in addition to having the typical membrane destabilizing activity of lipopeptides, viscosin inhibits pneumococcal growth by obstructing normal cell wall synthesis. This suggests a more specific mode of action than just the surfactant activity. Furthermore, we show that S. pneumoniae does not easily acquire resistance to viscosin, which makes it a promising molecule to explore further, for example, by synthesizing less toxic derivates that can be tested for therapeutic potential.

YEATS domain-containing protein GAS41 regulates nuclear shape by working in concert with BRD2 and the mediator complex in colorectal cancer

The maintenance of nuclear shape is essential for cellular homeostasis and disruptions in this process have been linked to various pathological conditions, including cancer, laminopathies, and aging. Despite the significance of nuclear shape, the precise molecular mechanisms controlling it are not fully understood. In this study, we have identified the YEATS domain-containing protein 4 (GAS41) as a previously unidentified factor involved in regulating nuclear morphology. Genetic ablation of GAS41 in colorectal cancer cells resulted in significant abnormalities in nuclear shape and inhibited cancer cell proliferation both in vitro and in vivo. Restoration experiments revealed that wild-type GAS41, but not a YEATS domain mutant devoid of histone H3 lysine 27 acetylation or crotonylation (H3K27ac/cr) binding, rescued the aberrant nuclear phenotypes in GAS41-deficient cells, highlighting the importance of GAS41’s binding to H3K27ac/cr in nuclear shape regulation. Further experiments showed that GAS41 interacts with H3K27ac/cr to regulate the expression of key nuclear shape regulators, including LMNB1, LMNB2, SYNE4, and LEMD2. Mechanistically, GAS41 recruited BRD2 and the Mediator complex to gene loci of these regulators, promoting their transcriptional activation. Disruption of GAS41-H3K27ac/cr binding caused BRD2, MED14 and MED23 to dissociate from gene loci, leading to nuclear shape abnormalities. Overall, our findings demonstrate that GAS41 collaborates with BRD2 and the Mediator complex to control the expression of crucial nuclear shape regulators.

The Association Between Dental Caries and Salivary Buffering Capacity in Syrian Patients Diagnosed with Sickle Cell Disease.

Background Sickle cell disease (SCD) is a genetic disorder caused by mutations in the HBB gene, resulting in the abnormal shape of red blood cells. This condition is accompanied by various oral manifestations including salivary gland dysfunction leading to a heightened susceptibility to dental caries. This disorder is primarily treated with hydroxyurea. This study aims to assess dental caries utilizing the decay, missing, filling teeth (DMFT) index and evaluate salivary buffering capacity in patients diagnosed with SCD (HbSS type). The study also aims to assess the relationship between DMFT and salivary buffering capacity. Additionally, the study aimed to find a correlation between treatment with hydroxyurea and changes in both dental caries and salivary buffering capacity. Methods This case-control study enrolled a total of 100 participants aged between 20 and 50 years. The participants were divided into two groups: the study group, which comprised 70 individuals diagnosed with SCD (HbSS type), who were asked to report their current use of hydroxyurea, and the control group, which included 30 healthy individuals. Dental caries were assessed using the DMFT index, while salivary buffering capacity was measured using a pH meter model 420A device. Results The study group exhibited a mean DMFT index value of 6.39 compared to 5.20 in the control group. This difference was statistically significant (P-value=0.037), indicating higher DMFT values among patients with SCD. Salivary buffering capacity was significantly lower in the study group compared to the control group, with average values of 6.47 and 6.88, (P-value=.022). Interestingly, the administration of hydroxyurea impacted salivary buffering capacity, resulting in lower values for individuals using the drug (P-value=0.039). Conversely, hydroxyurea did not have a significant effect on DMFT values (P-value=0.317). Conclusion SCD increases susceptibility to dental caries and is associated with significant changes in salivary composition. At the same time, the potential negative impact of hydroxyurea is acknowledged.

Shape of the first mitotic spindles impacts multinucleation in human embryos

During human embryonic development, early cleavage-stage embryos are more susceptible to errors. Studies have shown that many problems occur during the first mitosis, such as direct cleavage, chromosome segregation errors, and multinucleation. However, the mechanisms whereby these errors occur during the first mitosis in human embryos remain unknown. To clarify this aspect, in the present study, we image discarded living human two-pronuclear stage zygotes using fluorescent labeling and confocal microscopy without microinjection of DNA or mRNA and investigate the association between spindle shape and nuclear abnormality during the first mitosis. We observe that the first mitotic spindles vary, and low-aspect-ratio-shaped spindles tend to lead to the formation of multiple nuclei at the 2-cell stage. Moreover, we observe defocusing poles in many of the first mitotic spindles, which are strongly associated with multinucleation. Additionally, we show that differences in the positions of the centrosomes cause spindle abnormality in the first mitosis. Furthermore, many multinuclei are modified to form mononuclei after the second mitosis because the occurrence of pole defocusing is firmly reduced. Our study will contribute markedly to research on the occurrence of mitotic errors during the early cleavage of human embryos.

Apert Syndrome with Combination of Synostosis: A Case Report

Apert syndrome is a rare condition affecting the skull, face, hands and feet due to premature closure of cranial sutures. This case report describes a 6-month-old boy with Apert syndrome presenting with an abnormal head shape. A CT scan revealed craniosynostosis (fused sutures) of both the coronal and lambdoid sutures. Surgery involved removing a 1-2 cm section of the fused sutures along the coronal suture and across the lambdoid suture. After 4 months, the boy showed improvement in both clinical appearance and imaging scans. While Apert syndrome is typically classified based on the suture involved, the specific timing of surgery depends on various factors. This case demonstrates that minimally invasive surgery can be effective with minimal complications. Even though unilateral coronal and lambdoid suture fusion in Apert syndrome is uncommon, it can still be successfully treated with surgery.

Multifactorial case of ascites and anemia in a Golden Retriever involving Babesia sp. and Toxocara canis infections

A seven-year-old male Golden Retriever presented with lethargy, anorexia, abdominal enlargement, and weakness. Hematology tests revealed lymphocytosis, microcytic hypochromic anemia with anisocytosis, hypoalbuminemia, hyperglobulinemia, and elevated levels of alkaline phosphatase (ALP), blood urea nitrogen (BUN), and creatinine. Radiographic examination showed pneumonia, an abnormal heart shape resembling an inverted "D," and fluid accumulation in the abdominal cavity. Blood smears indicated a Babesia sp. infection. Additionally, the dog expelled a worm identified as Toxocara canis. The complex interaction between T. canis infection, multiple organ dysfunction, Babesia sp. infection, and malnutrition contributed to the development of ascites and anemia in this case. Treatment included abdominocentesis and fluid therapy. The dog was also prescribed furosemide, methylprednisolone, digoxin, Hematodin®, VipAlbumin®, and Drontal® for the worm infection. Unfortunately, the dog died on the 5th day of treatment due to dehydration and worsening anemia.