Time-Optimal Trajectory Planning and Tracking for Autonomous Vehicles.

This article presents a hierarchical control framework for autonomous vehicle trajectory planning and tracking, addressing the challenge of accurately following high-speed, at-limit maneuvers. The proposed time-optimal trajectory planning and tracking (TOTPT) framework utilizes a hierarchical control structure, with an offline trajectory optimization (TRO) module and an online nonlinear model predictive control (NMPC) module. The TRO layer generates minimum-lap-time trajectories using a direct collocation method, which optimizes the vehicle's path, velocity, and control inputs to achieve the fastest possible lap time, while respecting the vehicle dynamics and track constraints. The NMPC layer is responsible for precisely tracking the reference trajectories generated by the TRO in real time. The NMPC also incorporates a preview algorithm that utilizes the predicted future travel distance to estimate the optimal reference speed and curvature for the next time step, thereby improving the overall tracking performance. Simulation results on the Catalunya circuit demonstrated the framework's capability to accurately follow the time-optimal raceline at an average speed of 116 km/h, with a maximum lateral error of 0.32 m. The NMPC module uses an acados solver with a real-time iteration (RTI) scheme, to achieve a millisecond-level computation time, making it possible to implement it in real time in autonomous vehicles.

Synergic effect of combined xenogeneic mesenchymal stem cells and ceftriaxone on acute septic arthritis.

BACKGROUND: This study tested the hypothesis that combined ceftriaxone (Cef) and human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) was better than either therapy for alleviating acute septic arthritis (ASA). METHODS AND RESULTS: Adult-male C57BL/6 mice were categorized into control group (Clt), group A (ASA only), group B [ASA + Cef (5 mg/kg, IM per day, at days 2 to 16 after ASA induction)], group C [ASA + HUCDMSCs (5 × 105 per mice at days 2, 3, 4 after ASA induction)], and group D (ASA + Cef + HUCDMSCs). Animals were euthanized by day 28. The result demonstrated that the body weight was significantly lower, whereas the ratio of kidney or spleen weight to WB, circulatory WBC count, bacterial colony-formation-unit from circulatory/kidney extraction were significantly higher in group A than in other groups (all P < .001). The proinflammatory cytokines (IL-6/TNF-α) of knee joint fluid were lowest in Clt and significantly and progressively reduced from groups A to D, whereas the circulatory levels of these 2 parameters at the time points of days 3/7/28 exhibited an identical pattern as knee joint fluid among the groups (all P-value < .0001). The scores of vertebral-bone destructions/inflamed synovium were lowest in Clt, highest in group A, significantly higher in group C than in groups B/D, and significantly higher in group C than in group D (all P < .0001). CONCLUSION: Combined antibiotics and Cef and HUCDMSCs was superior to just one therapy for suppressing circulatory and tissue levels of inflammation and knee joint destruction in ASA.

MicroRNAs in Umbilical Cord Blood and Development in Full-Term Newborns: A Prospective Study.

Background: Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays. Objectives: Hence, this research seeks to investigate if the expression of miRNA in the umbilical cord blood of infants can forecast their developmental outcomes as they grow older. Design and method: We enrolled 143 full-term newborns, delivered either via cesarean section (CS) or through natural spontaneous delivery (NSD). We then analyzed the profiles of specific miRNAs (miR-486-5p, miR-126-5p, miR-140-3p, miR-151a-3p, miR-142-5p, and miR-30e-5p) in the umbilical cord blood of these infants. Subsequently, we performed follow-up assessments using Bayley-III scores when the cohort reached 1 year of age. Furthermore, we conducted pathway-enrichment analyses on the target genes associated with these examined miRNAs. Results: When comparing newborns delivered via cesarean section (CS) to those born via natural spontaneous delivery (NSD), we observed notable differences. Specifically, newborns through NSD displayed significantly higher ΔCt values for miR-486-5p, alongside lower ΔCt values for miR-126-5p and miR-151a-3p in their cord blood. At 1 year of age, cognitive development was significantly linked to the ΔCt values of miR-140-3p and miR-142-5p, while language development showed a significant association with the ΔCt values of miR-140-3p. Moreover, our pathway enrichment analyses revealed that the target genes of these miRNAs were consistently involved in the pathways related to neurons, such as axon guidance and the neurotrophin signaling pathway. Conclusion: In summary, this study represents a pioneering effort in elucidating the potential connections between miRNA levels in cord blood and the health indicators and neurodevelopment of newborns at 1 year of age. Our findings underscore the significance of miRNA levels at birth in influencing mechanisms related to neurodevelopment.

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair.

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

The Feasibility and Efficacy of Remote App-Guided Home Exercises for Frozen Shoulder: A Pilot Study.

Home exercise programs are beneficial in managing frozen shoulder (FS), yet adherence remains challenging. This pilot study introduces the remote app, Defrozen, designed for home exercises and assesses its feasibility and clinical outcomes in FS patients undergoing intra-articular and sub-acromial corticosteroid treatment. Over a four-week period, patients used the Defrozen-app, engaging in guided exercises. The feasibility of the intervention was assessed through several measurement scales, including adherence, the Technology Acceptance Model 2 (TAM2), the System Usability Scale (SUS), and User Satisfaction and Engagement (USE). Clinical outcomes included pain scale, Oxford Shoulder Score (OSS), Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) Score, and passive range of motion. The TAM2 results indicated high perceived usefulness (4.5/5), ease of use (4.8/5), and intention to use (4.4/5); the SUS score was high at 81.7/100, complemented by USE scores reflecting ease of learning (4.9/5) and satisfaction (4.3/5). Clinical outcomes showed significant pain reduction, improved shoulder function, reduced shoulder-related disability, and increased shoulder range of motion. These findings suggest the Defrozen-app as a promising solution for FS, significantly improving adherence and showing potential to enhance clinical outcomes. However, these clinical outcome results are preliminary and necessitate further validation through a large-scale randomized controlled trial to definitively confirm efficacy and assess long-term benefits.

Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of Lactiplantibacillus plantarum intervention.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic Lactiplantibacillus plantarum PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 in vivo. Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp. and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.

Anomalies of the Corpus Callosum in Prenatal Ultrasound: A Narrative Review for Diagnosis and Further Counseling.

The corpus callosum is the major interhemispheric tract that plays an important role in neurological function. Understanding the etiology and embryology development helps the ultrasound diagnosis for disorders of the corpus callosum and further counseling. The nonvisualization of cavum septum pellucidum or dysmorphic cavum septum pellucidum in axial view are indirect signs for beginners to diagnose complete agenesis of corpus callosum (cACC) and partial agenesis of the corpus callosum (pACC). Further coronal view, sagittal view, and fetal magnetic resonance imaging are also important for evaluation. Genetic testing plays an essential tool in anomalies of corpus callosum by revealing the underlying genetic pathophysiology, such as chromosomal anomalies and numerous monogenetic disorders in 30%-45% of ACC. Diagnosis and prediction of prognosis for hypoplasia or hyperplasia of the corpus callosum are more difficult compared to cACC and pACC because of the limited reports in the literature. However, the complex types often had poorer prognostic outcomes compared to the isolated types. Hence, it is important to evaluate and follow fetal conditions thoroughly to rule out intracranial or extracranial anomalies in other systems.

Invasive cribriform carcinoma of the breast presenting as an erythematous papule on the nipple: A case report.

Invasive cribriform carcinoma (ICC) is a rare form of invasive breast carcinoma with good prognosis. To date, case reports considering skin manifestations of ICC are scarce. We herein report a case of pure ICC presenting as an erythematous papule on the nipple with mammary Paget's disease in the epidermis. We aim to bring awareness to skin manifestation of ICC.

The combined effect of cardiorespiratory and muscular fitness on the incidence of metabolic syndrome before midlife.

BACKGROUND: Cardiorespiratory fitness (CRF) could reduce the risk of metabolic syndrome (MetS) while the association between muscular endurance capacity (MEC) and incident MetS has rarely been investigated in young adults. METHODS: A total of 2890 military men and women, aged 18-39 years, free of baseline MetS in Taiwan, were followed for incident MetS from baseline (2014) until the end of 2020. All subjects received annual health examinations for assessment of MetS. Physical fitness was assessed by CRF (estimated maximal oxygen uptake, VO2 max [mL/kg/min], in a 3000-m run) and MEC (numbers of 2-min push-ups). MetS was defined according to the International Diabetes Federation (IDF) criteria. Multiple Cox regression analysis was conducted with adjustments for baseline age, sex, substance use status and physical activity to determine the associations of CRF and MEC with incidences of new-onset MetS and related features, for example, central obesity, hypertension, dyslipidaemia and prediabetes or diabetes. To examine the combined effects of CRF and MEC status on incidence of MetS, high and low levels of CRF and MEC were separately defined by over and under the sex-specific median in each exercise test. RESULTS: During a median follow-up of 5.8 years, there were 673 (23.3%) new-onset MetS. Higher CRF was associated with a lower incidence of MetS (hazard ratio [HR] and 95% confidence interval: 0.905 [0.877-0.933]), and its components separately, except hypertension. No association was observed between MEC and incident MetS, and its components separately, except hypertension. When evaluating the combined effects of MEC and CRF status on the incidence of MetS, it was observed that compared with the low CRF/low MEC, the high CRF/high MEC (HR: 0.553 [0.439-0.697]) and the high CRF/low MEC (HR: 0.730 [0.580-0.918]) had a lower incidence of new-onset MetS (P value for the intergroup difference = 0.04). There was no significant result for the low CRF/high MEC. CONCLUSIONS: This study highlights that although the protective effects of MEC to reduce the incidence of MetS and most of its related features were mainly driven by CRF in young adults, there was an addictive effect of greater MEC on CRF to prevent the development of new-onset MetS before midlife.

Comparisons of three different modes of digital mirror therapy for post-stroke rehabilitation: Preliminary results of randomized controlled trial.

Objective: Technologically adapted mirror therapy shows promising results in improving motor function for stroke survivors. The treatment effects of a newly developed multi-mode stroke rehabilitation system offering multiple training modes in digital mirror therapy remain unknown. This study aimed to examine the effects of unilateral mirror visual feedback (MVF) with unimanual training (UM-UT), unilateral MVF with bimanual training (UM-BT), and bilateral MVF with bimanual training (BM-BT) on clinical outcomes in stroke survivors, compared to classical mirror therapy (CMT). Methods: Thirty-five participants were randomly assigned to one of four groups receiving fifteen 60-minute training sessions for 3-4 weeks. The Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Chedoke Arm and Hand Activity Inventory (CAHAI), Revised Nottingham Sensory Assessment (rNSA), Motor Activity Log (MAL), and EQ-5D-5L were administered at pre- and post-intervention and at 1-month follow-up. Results: After intervention and follow-up, significant within-group treatment efficacies were found on most primary outcomes of the FMA-UE and CAHAI scores in all four groups. Significant within-group improvements in the secondary outcomes were found on the MAL and EQ-5D-5L index in the UM-BT group, and the rNSA tactile sensation and MAL quality of movement subscales in the BM-BT group. No significant between-group treatment efficacies were found. Conclusions: UM-UT, UM-BT, BM-BT, and CMT led to similar clinical effects on the FMA-UE and can be considered effective alternative interventions for post-stroke upper-limb motor rehabilitation. UM-BT and BM-BT showed within-group improvements in functional performance in the patients' affected upper limbs in real-life activities.

Faecalibacterium taiwanense sp. nov., isolated from human faeces.

Two Gram-stain-negative, straight rods, non-motile, asporogenous, catalase-negative and obligately anaerobic butyrate-producing strains, HLW78T and CYL33, were isolated from faecal samples of two healthy Taiwanese adults. Phylogenetic analyses of 16S rRNA and DNA mismatch repair protein MutL (mutL) gene sequences revealed that these two novel strains belonged to the genus Faecalibacterium. On the basis of 16S rRNA and mutL gene sequence similarities, the type strains Faecalibacterium butyricigenerans AF52-21T(98.3-98.1 % and 79.0-79.5 % similarity), Faecalibacterium duncaniae A2-165T(97.8-97.9 % and 70.9-80.1 %), Faecalibacterium hattorii APC922/41-1T(97.1-97.3 % and 80.3-80.5 %), Faecalibacterium longum CM04-06T(97.8-98.0% and 78.3 %) and Faecalibacterium prausnitzii ATCC 27768T(97.3-97.4 % and 82.7-82.9 %) were the closest neighbours to the novel strains HLW78T and CYL33. Strains HLW78T and CYL33 had 99.4 % both the 16S rRNA and mutL gene sequence similarities, 97.9 % average nucleotide identity (ANI), 96.3 % average amino acid identity (AAI), and 80.5 % digital DNA-DNA hybridization (dDDH) values, indicating that these two strains are members of the same species. Phylogenomic tree analysis indicated that strains HLW78T and CYL33 formed an independent robust cluster together with F. prausnitzii ATCC 27768T. The ANI, AAI and dDDH values between strain HLW78T and its closest neighbours were below the species delineation thresholds of 77.6-85.1 %, 71.4-85.2 % and 28.3-30.9 %, respectively. The two novel strains could be differentiated from the type strains of their closest Faecalibacterium species based on their cellular fatty acid compositions, which contained C18 : 1 ω7c and lacked C15 : 0 and C17 : 1 ω6c, respectively. Phenotypic, chemotaxonomic and genotypic test results demonstrated that the two novel strains HLW78T and CYL33 represented a single, novel species within the genus Faecalibacterium, for which the name Faecalibacterium taiwanense sp. nov. is proposed. The type strain is HLW78T (=BCRC 81397T=NBRC 116372T).

Elevated tissue status of omega-3 fatty acids protects against age-related telomere attrition in fat-1 transgenic mice.

BACKGROUND & AIMS: Leukocyte telomere length (LTL) is a biomarker of aging that may be influenced by dietary factors. Omega-3 fatty acids (n-3 FA) have been suggested to affect LTL. However, research on this effect has been inconclusive. The aim of the study was to test the hypothesis about the positive effect of n-3 FA on LTL. METHODS: Fat-1 transgenic mice, which can convert omega-6 fatty acids (n-6 FA) to n-3 FA and have elevated levels of endogenous n-3 FA in their tissues, were used to study the effects of n-3 FA on LTL at different ages. Blood samples from 10-month-old wild-type (WT) mice (n = 10) and fat-1 mice (n = 10) and 3-month-old WT mice (n = 5) and fat-1 mice (n = 5) were used to measure relative and absolute LTL. The levels of proteins critical for telomere maintenance were examined by Western blot analysis. RESULTS: Fat-1 transgenic mice had longer leukocyte telomeres than their WT siblings, suggesting a slower rate of age-related telomere shortening in fat-1 mice. In animals aged 10 months, the LTL was significantly longer in fat-1 than in WT mice (mean ± SEM; relative LTL: WT = 1.00 ± 0.09 vs. fat-1: 1.25 ± 0.05, P = 0.031; absolute LTL: WT = 64.41 ± 6.50 vs. fat-1: 78.53 ± 3.86, P = 0.048). The difference in LTL observed in three-month-old mice was insignificant, however the mean LTL was still longer in fat-1 mice than in the WT mice. Fat-1 mice also had abundant levels of two shelterin proteins: TRF1 (27%, P = 0.028) and TRF2 (47%, P = 0.040) (telomeric repeat binding factor 1 and 2) compared to WT animals. CONCLUSION: This study, for the first time in a unique animal model free of dietary confounders, has demonstrated that increased levels of n-3 FA in tissues can reduce telomere attrition. The data presented indicate the possibility of using omega-3 fatty acids to reduce accelerated telomere attrition and, consequently, counteract premature aging and reduce the risk of age-related diseases.

S309-CAR-NK cells bind the Omicron variants in vitro and reduce SARS-CoV-2 viral loads in humanized ACE2-NSG mice.

Recent progress on chimeric antigen receptor (CAR)-NK cells has shown promising results in treating CD19-positive lymphoid tumors with minimal toxicities [including graft versus host disease (GvHD) and cytokine release syndrome (CRS) in clinical trials. Nevertheless, the use of CAR-NK cells in combating viral infections has not yet been fully explored. Previous studies have shown that CAR-NK cells expressing S309 single-chain fragment variable (scFv), hereinafter S309-CAR-NK cells, can bind to SARS-CoV-2 wildtype pseudotyped virus (PV) and effectively kill cells expressing wild-type spike protein in vitro. In this study, we further demonstrate that the S309-CAR-NK cells can bind to different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants in vitro. We also show that S309-CAR-NK cells reduce virus loads in the NOD/SCID gamma (NSG) mice expressing the human angiotensin-converting enzyme 2 (hACE2) receptor challenged with SARS-CoV-2 wild-type (strain USA/WA1/2020). Our study demonstrates the potential use of S309-CAR-NK cells for inhibiting infection by SARS-CoV-2 and for the potential treatment of COVID-19 patients unresponsive to otherwise currently available therapeutics. IMPORTANCE: Chimeric antigen receptor (CAR)-NK cells can be "off-the-shelf" products that treat various diseases, including cancer, infections, and autoimmune diseases. In this study, we engineered natural killer (NK) cells to express S309 single-chain fragment variable (scFv), to target the Spike protein of SARS-CoV-2, hereinafter S309-CAR-NK cells. Our study shows that S309-CAR-NK cells are effective against different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants. The S309-CAR-NK cells can (i) directly bind to SARS-CoV-2 pseudotyped virus (PV), (ii) competitively bind to SARS-CoV-2 PV with 293T cells expressing the human angiotensin-converting enzyme 2 (hACE2) receptor (293T-hACE2 cells), (iii) specifically target and lyse A549 cells expressing the spike protein, and (iv) significantly reduce the viral loads of SARS-CoV-2 wild-type (strain USA/WA1/2020) in the lungs of NOD/SCID gamma (NSG) mice expressing hACE2 (hACE2-NSG mice). Altogether, the current study demonstrates the potential use of S309-CAR-NK immunotherapy as an alternative treatment for COVID-19 patients.

Complement decay-accelerating factor inhibits inflammation-induced myopia development.

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.

Genetic counseling of non-invasive prenatal testing (NIPT) trisomy 7-positive pregnancies.

Trisomy 7 is the most common observed type of rare autosomal trisomies (RATs) detected at expanded genome-wide non-invasive prenatal testing (NIPT). Genetic counseling of NIPT trisomy 7-positive pregnancies remains to be not easy because the parents may worry about the likelihood of adverse pregnancy outcomes, fetal abnormality and the necessity of invasive procedures for confirmation of fetal mosaic trisomy 7 and uniparental disomy (UPD) 7. This review provides a comprehensive information on the update issues concerning genetic counseling of NIPT trisomy 7-positive pregnancies.

An efficient deep neural network for automatic classification of acute intracranial hemorrhages in brain CT scans.

BACKGROUND: Recent advancements in deep learning models have demonstrated their potential in the field of medical imaging, achieving remarkable performance surpassing human capabilities in tasks such as classification and segmentation. However, these modern state-of-the-art network architectures often demand substantial computational resources, which limits their practical application in resource-constrained settings. This study aims to propose an efficient diagnostic deep learning model specifically designed for the classification of intracranial hemorrhage in brain CT scans. METHOD: Our proposed model utilizes a combination of depthwise separable convolutions and a multi-receptive field mechanism to achieve a trade-off between performance and computational efficiency. The model was trained on RSNA datasets and validated on CQ500 dataset and PhysioNet dataset. RESULT: Through a comprehensive comparison with state-of-the-art models, our model achieves an average AUROC score of 0.952 on RSNA datasets and exhibits robust generalization capabilities, comparable to SE-ResNeXt, across other open datasets. Furthermore, the parameter count of our model is just 3 % of that of MobileNet V3. CONCLUSION: This study presents a diagnostic deep-learning model that is optimized for classifying intracranial hemorrhages in brain CT scans. The efficient characteristics make our proposed model highly promising for broader applications in medical settings.

Perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II.

OBJECTIVE: We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II (TD2). CASE REPORT: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. However, craniofacial anomaly was found on prenatal ultrasound at 21 weeks of gestation, which showed a cloverleaf skull with severe craniosynostosis and relatively short straight long bones. Fetal magnetic resonance imaging (MRI) analysis at 22 weeks of gestation showed a cloverleaf skull, proptosis and relatively shallowing of the sylvian fissures. Prenatal ultrasound at 24 weeks of gestation showed a fetus with a cloverleaf skull with a biparietal diameter (BPD) of 6.16 cm (equivalent to 24 weeks), an abdominal circumference (AC) of 18.89 cm (equivalent to 24 weeks) and a femur length (FL) of 3.65 cm (equivalent to 21 weeks). A tentative diagnosis of TD2 was made. The pregnancy was subsequently terminated, and a 928-g malformed fetus was delivered with severe craniosynostosis, proptosis, midface retrusion, a cloverleaf skull, broad thumbs and broad big toes. The broad thumbs were medially deviated. Whole body X-ray showed a cloverleaf skull and straight long bones. However, molecular analysis of FGFR3 on the fetus revealed no mutation in the target regions. Subsequent whole exome sequencing (WES) on the DNA extracted from umbilical cord revealed a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in the FGFR2 gene. CONCLUSION: Fetuses with a Y340C mutation in FGFR2 may present a cloverleaf skull on prenatal ultrasound, and WES is useful for a rapid differential diagnosis of Pfeiffer syndrome from TD2 under such a circumstance.

Cardiomyocyte-specific overexpression of GPR22 ameliorates cardiac injury in mice with acute myocardial infarction.

BACKGROUND: The activation of G protein-coupled receptors (GPCR) signaling by external stimuli has been implicated in inducing cardiac stress and stress responses. GPR22 is an orphan GPCR expressed in brains and hearts, while its expression level is associated with cardiovascular damage in diabetes. Previous studies have suggested a protective role of GPR22 in mechanical cardiac stress, as loss of its expression increases susceptibility to heart failure post-ventricular pressure overload. However, the involvement and underlying signaling of GPR22 in cardiac stress response to ischemic stress remains unexplored. METHODS: In this study, we used cultured cells and a transgenic mouse model with cardiomyocyte-specific GPR22 overexpression to investigate the impact of ischemic stress on GPR22 expression and to elucidate its role in myocardial ischemic injury. Acute myocardial infarction (AMI) was induced by left coronary artery ligation in eight-week-old male GPR22 transgenic mice, followed by histopathological and biochemical examination four weeks post-AMI induction. RESULTS: GPR22 expression in H9C2 and RL-14 cells, two cardiomyocyte cell lines, was decreased by cobalt chloride (CoCl2) treatment. Similarly, reduced expression of myocardial GPR22 was observed in mice with AMI. Histopathological examinations revealed a protective effect of GPR22 overexpression in attenuating myocardial infarction in mice with AMI. Furthermore, myocardial levels of Bcl-2 and activation of PI3K-Akt signaling were downregulated by ischemic stress and upregulated by GPR22 overexpression. Conversely, the expression levels of caspase-3 and phosphorylated ERK1/2 in the infarcted myocardium were downregulated with GPR22 overexpression. CONCLUSION: Myocardial ischemic stress downregulates cardiac expression of GPR22, whereas overexpression of GPR22 in cardiomyocytes upregulates Akt signaling, downregulates ERK activation, and mitigates ischemia-induced myocardial injury.