Severe Abnormalities Research Articles

Strain Elastography Evaluation of Patellar Tendons in Dogs after TPLO/TTA for Cranial Cruciate Ligament Rupture, Qualitative and Semiquantitative Evaluation Compared with Healthy Subjects.

Strain elastography (SE) evaluates tissue stiffness, providing qualitative and semiquantitative evaluation, with a strain ratio (SR) > 1 indicating that the target lesion is stiffer than the reference tissue. The patellar tendon has been described as soft in healthy dogs and hard in dogs with cranial cruciate ligament rupture, but SR usefulness has not been assessed. Dogs were divided into healthy (G1) and at least 1 month after surgery (G2) groups. Thickness was recorded, and a B-mode score of 0-3 was determined based on the abnormality's severity. SE was qualitatively performed with a score of 1-4, and EI was recorded on the whole ligament and in proximal, intermediate and distal areas; SR was collected with the fat pad and cutis/subcutis. G1 was significantly thinner, with a lower score than G2 and a more elastic pattern. EI for G1 was significantly lower than G2 for the whole tendon and the single portions, and EI for the distal portion was significantly lower than the proximal and intermediate one in G2. SR was <1 in G1 and >1 in G2 for both the fat pad and cutis/subcutis. These data suggest that after surgery, the tendon may become non-uniformly stiffer. The cutis/subcutis appears to be a more reliable reference tissue than the infrapatellar fat pad.

Bovine aortic arch: a potential indicator that may not serve in prenatal diagnosis - a study based on fetal anatomy, genetics, and postnatal clinical outcomes

ObjectiveTo investigate the structural abnormalities, genetic results, and postnatal clinical outcomes of fetuses with bovine aortic arch (Bovine Aortic Arch, BAA) to provide a basis for prenatal counseling and management.MethodsA retrospective analysis was conducted on 216 fetuses diagnosed with bovine aortic arch through prenatal ultrasound screening at the First Affiliated Hospital of Anhui Medical University and the No.901 Hospital of the Joint Service of the People’s Liberation Army from January 2019 to February 2023. Their family history of genetic diseases, prenatal screening results, and postnatal follow-up data were collected. The fetuses were divided into an isolated BAA group (n = 192) and a non-isolated BAA group (n = 24). Chromosomal karyotyping and copy number variation (CNV) testing were conducted, and statistical analysis was performed using SPSS 22.0 software.ResultsOf the 216 fetuses with BAA, 192 were isolated BAA (88.89%), and 24 were non-isolated BAA (11.11%). Among the isolated BAA fetuses, only 1 case (0.52%) had chromosomal karyotype and pathogenic CNV abnormalities. Among the non-isolated BAA fetuses, 4 cases (16.67%) had chromosomal or CNV abnormalities, but the overall risk was low. The postnatal outcomes of isolated BAA fetuses were good (99.48%), while 79.17% of non-isolated BAA fetuses had good postnatal outcomes.ConclusionMost BAA fetuses are isolated, with a very low incidence of chromosomal abnormalities and pathogenic CNVs, and have good postnatal outcomes. The clinical value of isolated BAA is limited, and invasive prenatal diagnosis is not recommended for low-risk populations. Prenatal screening should focus on the risk of concurrent severe structural anomalies and chromosomal abnormalities.

Deep learning-driven ultrasound-assisted diagnosis: optimizing GallScopeNet for precise identification of biliary atresia.

Biliary atresia (BA) is a severe congenital biliary developmental abnormality threatening neonatal health. Traditional diagnostic methods rely heavily on experienced radiologists, making the process time-consuming and prone to variability. The application of deep learning for the automated diagnosis of BA remains underexplored. This study introduces GallScopeNet, a deep learning model designed to improve diagnostic efficiency and accuracy through innovative architecture and advanced feature extraction techniques. The model utilizes data from a carefully constructed dataset of gallbladder ultrasound images. A dataset comprising thousands of ultrasound images was employed, with the majority used for training and validation and a subset reserved for external testing. The model's performance was evaluated using five-fold cross-validation and external assessment, employing metrics such as accuracy and the area under the receiver operating characteristic curve (AUC), compared against clinical diagnostic standards. GallScopeNet demonstrated exceptional performance in distinguishing BA from non-BA cases. In the external test dataset, GallScopeNet achieved an accuracy of 81.21% and an AUC of 0.85, indicating strong diagnostic capabilities. The results highlighted the model's ability to maintain high classification performance, reducing misdiagnosis and missed diagnosis. GallScopeNet effectively differentiates between BA and non-BA images, demonstrating significant potential and reliability for early diagnosis. The system's high efficiency and accuracy suggest it could serve as a valuable diagnostic tool in clinical settings, providing substantial technical support for improving diagnostic workflows.

Imaging Findings and MRI Patterns in a Cohort of 18q Chromosomal Abnormalities.

The abnormalities of the long arm of chromosome 18 (18q) constitute a complex spectrum. We aimed to systematically analyze their MR imaging features. We hypothesized that there would be variable but recognizable white matter and structural patterns in this cohort. In this retrospective cohort study, we included pediatric patients with a proved abnormality of 18q between 2000-2022. An age- and sex-matched control cohort was also constructed. Thirty-six cases, median MR imaging age 19.6 months (4.3-59.3), satisfied our inclusion criteria. Most were female (25, 69%, F:M ratio 2.2:1). Fifty MR imaging studies were analyzed, and 35 (70%) had delayed myelination. Two independent readers scored brain myelination with excellent interrater reliability. Three recognizable evolving MR imaging patterns with distinct age distributions and improving myelination scores were identified: Pelizaeus-Merzbacher disease-like (9.9 months, 37), intermediate (22 months, 48), and washed-out pattern (113.6 months, 53). Etiologically, MRIs were analyzed across 3 subgroups: 18q deletion (34, 69%), trisomy 18 (10, 21%), and ring chromosome 18 (5, 10%). Ring chromosome 18 had the highest myelination lag (27, P = .005) and multifocal white matter changes (P = .001). Trisomy 18 had smaller pons and cerebellar dimensions (anteposterior diameter pons, P = .002; corpus callosum vermis, P < .001; and transverse cerebellar diameter, P = .04). In this cohort of 18q chromosomal abnormalities, MR imaging revealed recognizable patterns correlating with improving brain myelination. Imaging findings appear to be on a continuum with more severe white matter abnormalities in ring chromosome 18 and greater prevalence of structural abnormalities of the pons and cerebellum in trisomy 18.

Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial

IntroductionDeep brain stimulation (DBS) and vagus nerve stimulation (VNS) can improve motor function in patients with poststroke hemiplegia. No comparison study exists.Methods and analysisThis is a randomised, double-blind, controlled clinical...

Repeated treatment with VEGF receptor inhibitors induces phenotypic changes in endothelial cells and pericytes in the rat retina

Abnormal ocular angiogenesis is a major cause of visual impairment and vision loss in neovascularization-related diseases. Currently, anti-vascular endothelial growth factor (VEGF) drugs are used to treat ocular neovascularization, but repeated injections are needed to maintain their therapeutic effects. However, repeated injection of anti-VEGF drugs may affect the retinal blood vessel phenotype and diminish therapeutic effects. In this study, we aimed to investigate the phenotypic changes in endothelial cells and pericytes caused by the repeated interruption of the VEGF receptor signaling pathway in neonatal rats. KRN633 (10 mg/kg), a VEGF receptor tyrosine kinase inhibitor, was subcutaneously administered on postnatal day (P)-7 and P8 (first round), P14 and P15 (second round), and P21 and P22 (third round). The rat eyes were collected on P7, P9, P14, P16, P21, P23, P28, and P35. Using retinal flat-mount specimens stained with specific markers for vascular endothelial cells, basement membranes, and pericytes, the arteriolar tortuosity, capillary area density, and distribution of pericytes were evaluated. Significant loss of capillaries was observed the day after the first round of KRN633 treatment, after which aggressive angiogenesis occurred, leading to the formation of tortuous arterioles. Rats that completed second and third rounds of KRN633 treatment showed more severe abnormalities in the retinal vasculature than those that only completed first round treatment. Repeated treatment with KRN633 decreased the anti-angiogenic effects but increased the immunoreactivity of α-smooth muscle actin in the pericytes on veins and capillaries. α-Smooth muscle actin expression was inversely correlated to anti-angiogenic effects. Overall, these results revealed that repeated interruption of VEGF receptor signaling pathway altered the phenotypes of endothelial cells and pericytes and induced anti-VEGF drug resistance. Therefore, careful follow-up is necessary when using anti-VEGF drugs to treat abnormal angiogenesis-associated ocular diseases.

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.

Assessing the Impact of Clove (Syzygium Aromaticum) Extract on Intestinal and Hepatic Histological Alterations in Broiler Chickens Infected with Salmonella typhimurium

This study investigated effects of aqueous and ethanolic clove extracts in small intestine and liver of chickens exposed to Salmonella typhimurium. Two hundred fifty-day-old chicks were divided into five groups. Group 1 served as the control and received a basic diet.Group 2 was orally infected with Salmonella typhimurium. Group 3 received same infection but was treated with Ciprofloxacin. Groups 4 and 5 were infected but received treatments of aqueous and ethanolic clove extracts, respectively. The findings revealed that Group 1 exhibited normal small intestine, while Group 2 displayed severe abnormalities, including flattened mucosa, damaged villi, and inflammation. Group 3 showed improvements, increased cell growth and goblet cells in the small intestine. Group 4 displayed nearly normal intestinal features. Group 5 had fully restored intestinal health. In the liver, Group 1 showed typical hepatic structure, whereas Group 2 exhibited signs of inflammation and hepatocyte necrosis. Group 3 displayed severe hepatocyte damage, while Group 4 demonstrated restored liver structure with slight sinusoidal dilation. Group 5 had a well-preserved hepatic architecture with minor inflammation. Administration of 2 mg/kg of aqueous and ethanolic clove extracts demonstrated alleviate histological alterations in small intestine and liver caused by Salmonella typhimurium infection. Notably, the aqueous extract is more effective than ethanolic extract in reducing liver and intestine damage.

Palmitoylation regulates myelination by modulating the ZDHHC3-Cadm4 axis in the central nervous system

The downregulation of Cadm4 (Cell adhesion molecular 4) is a prominent feature in demyelination diseases, yet, the underlying molecular mechanism remains elusive. Here, we reveal that Cadm4 undergoes specific palmitoylation at cysteine-347 (C347), which is crucial for its stable localization on the plasma membrane (PM). Mutation of C347 to alanine (C347A), blocking palmitoylation, causes Cadm4 internalization from the PM and subsequent degradation. In vivo experiments introducing the C347A mutation (Cadm4-KI) lead to severe myelin abnormalities in the central nervous system (CNS), characterized by loss, demyelination, and hypermyelination. We further identify ZDHHC3 (Zinc finger DHHC-type palmitoyltransferase 3) as the enzyme responsible for catalyzing Cadm4 palmitoylation. Depletion of ZDHHC3 reduces Cadm4 palmitoylation and diminishes its PM localization. Remarkably, genetic deletion of ZDHHC3 results in decreased Cadm4 palmitoylation and defects in CNS myelination, phenocopying the Cadm4-KI mouse model. Consequently, altered Cadm4 palmitoylation impairs neuronal transmission and cognitive behaviors in both Cadm4-KI and ZDHHC3 knockout mice. Importantly, attenuated ZDHHC3-Cadm4 signaling significantly influences neuroinflammation in diverse demyelination diseases. Mechanistically, we demonstrate the predominant expression of Cadm4 in the oligodendrocyte lineage and its potential role in modulating cell differentiation via the WNT-β-Catenin pathway. Together, our findings propose that dysregulated ZDHHC3-Cadm4 signaling contributes to myelin abnormalities, suggesting a common pathological mechanism underlying demyelination diseases associated with neuroinflammation.

Artemisinin Ameliorates the Neurotoxic Effect of 3-Nitropropionic Acid: A Possible Involvement of the ERK/BDNF/Nrf2/HO-1 Signaling Pathway.

Neurodegenerative disorders like Huntington's disease (HD) are a major threat to human health, with severe gait abnormalities and pathological changes (oxidative stress, neuroinflammation, and apoptosis) playing important roles in their development. The effects of artemisinin (ART) alone and in combination with the ERK antagonist PD98059 against 3-nitropropionic acid (3-NPA)-induced cell death and oxidative stress in SH-SY5Y cells were determined using the MTT and DCFH-DA assays, as well as RT-qPCR assays. In vivo, possible neuroprotective effects of ART (10, 20, and 40mg/kg i.p.) against the neurotoxicity generated by 21-day 3-NPA (10mg/kg i.p.) treatment was evaluated in rats by assessing behavioral parameters on days 1, 14, and 21. Further, various biochemical, inflammatory, apoptotic markers, histopathological changes, and protein expression were assessed using brain striatal samples. ART significantly mitigated the neurotoxic effect of 3-NPA in SH-SY5Y cells by regulating the mRNA expression of ERK, Bax, Bcl2, and cytochrome C. However, ART's neuroprotective activity was reduced in the presence of PD98059. Also, ART treatment for 21days substantially alleviated the behavioral impairments associated with 3-NPA toxicity. It reduced the oxidative stress induced by 3-NPA, as evidenced by the lower levels of MDA, nitrite, and improved catalase, SOD activity, and GSH levels. ART treatment restored 3-NPA-induced histopathological alterations in the striatal area. ART effectively suppressed neuroinflammatory (IL-6) and apoptotic markers (caspase 3 and 9), increasing BDNF levels and restoring the p-ERK1/2, Nrf2, and HO-1 expression. ART could exert its neuroprotective effect via antioxidant, anti-inflammatory, and antiapoptotic properties with a possible involvement of the ERK/BDNF/Nrf2/HO-1 pathway.

Deciphering Developmental Epileptic Encephalopathies (DEE): Unravelling the Key Signs

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Epilepsy, a chronic neurological disorder affecting over 50 million people worldwide, is marked by recurrent seizures and loss of consciousness. It is categorized based on EEG features, etiologies, and comorbidities. Developmental Encephalopathy (DE) involves developmental delays and early-onset seizures without causing developmental regression. In contrast, Epileptic Encephalopathy (EE) features severe epilepsy syndromes where frequent seizures result in developmental delays or regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This review explores the clinical definitions, epidemiology, and diagnostic criteria for DE, EE, and DEEs. It covers their etiologies, clinical features, diagnostic methods, and treatment strategies, including genetic, structural, metabolic, and immune-related factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; DE features developmental impairment with epilepsy, while EE involves severe epilepsy causing cognitive and behavioral dysfunction. DEEs are marked by early-onset severe epilepsy and EEG abnormalities that worsen developmental impairments. Essential diagnostic tools include EEG, neuroimaging, and genetic testing. Effective management requires personalized interventions to control seizures and address cognitive deficits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; DEEs are a complex epilepsy subset with major developmental and cognitive challenges. Early diagnosis and targeted treatments are crucial for improving outcomes. Ongoing research into DEEs' genetic and pathophysiological mechanisms is key to enhancing understanding and management.&lt;/p&gt;

Exploring the internal medicine comorbidities associated with eating disorders: correlation between disease severity and cardiac abnormalities in adolescent patients with anorexia nervosa

ABSTRACT Anorexia Nervosa (AN) is a psychiatric disorder characterized by caloric restriction, weight loss, and fear of gaining weight. Cardiac complications are among the most severe medical consequences. Despite the importance of regular cardiac assessments, there is a lack of standardized protocols for timing and patient selection. This retrospective cohort study has aimed to assess the correlation between AN severity, Body Mass Index, weight loss percentage, and cardiac abnormalities in pediatric patients. A total of 123 patients admitted to a child and adolescent psychiatry unit between January 2019 and March 2022 were included. Data on demographics, clinical characteristics, cardiac evaluations were collected from electronic health records. The study revealed a prevalence of cardiac abnormalities in 57.7% of patients, with bradycardia being the most common (49.5%), followed by QTc prolongation (4%) and pericardial effusion (4%). However, no significant correlation was found between AN severity and cardiac alterations, suggesting that disease severity alone is not a reliable predictor of cardiac risk. The study highlights the need for individualized risk assessment and targeted cardiac evaluations based on specific risk factors rather than disease severity alone. Early diagnosis and comprehensive care contribute to better outcomes, emphasizing the importance of multidisciplinary approaches in managing AN.

Using cerebral regional oxygen saturation and amplitude-integrated electroencephalography in neonates on extracorporeal membrane oxygenation: preliminary experience from a single center

ObjectiveThis study aims to evaluate the application value in neurological outcome of cerebral regional oxygen saturation (CrSO2) and amplitude-integrated electroencephalography (aEEG) monitoring during neonatal extracorporeal membrane oxygenation (ECMO) courses.Methods We retrospectively analyzed 18 neonates receiving veno-arterial ECMO (V-A ECMO) support at our hospital from July 2021 to December 2022. Continuous monitoring of CrSO2 and brain electrical activity was conducted using near-infrared spectroscopy (NIRS) and aEEG throughout the ECMO treatment. We collected and analyzed related clinical data.ResultsAmong the 11 survivors, 5 were categorized as the normal group (N group) and 6 as the abnormal group (AN group) based on post-ECMO brain MRI outcomes. The N group exhibited shorter time percentage of significant CrSO2 reduction (> 25% from baseline or absolute value < 40%), better fractional tissue oxygen extraction (FTOE) rates, and more stable mean percentage changes in CrSO2 compared to the AN group. Neonates in the N group predominantly showed mildly abnormal aEEG readings, with one patient displaying disrupted sleep-wake cycles. This particular patient also had more significant CrSO2 reduction and poorer FTOE compared to others in the N group. Additionally, the Test of Infant Motor Performance (TIMP) scores indicated hypoevolutism in this patient before discharge, while others in the N group had normal TIMP scores. In the AN group, 4 exhibited moderate and 2 severe aEEG abnormalities; 5 had hypoevolutism TIMP scores, and 1 with moderate aEEG abnormalities maintained a normal TIMP score, exhibiting lesser CrSO2 reduction and improved FTOE.ConclusionCrSO2 and aEEG monitoring show potential as routine assessments for neurological outcomes during neonatal ECMO. In our cohort, a tendency was observed where neonates with greater reductions in CrSO2 and more severe aEEG abnormalities experienced poorer neurological outcomes.

Associations between Fetal Symptoms during Pregnancy and Neonatal Clinical Complications with Toxoplasmosis.

Toxoplasmosis is a parasitism transmitted by Toxoplasma gondii, part of the TORCH complex, the most prevalent parasitism worldwide. It is asymptomatic in immunocompetent individuals but causes severe infections and developmental abnormalities in pregnant women, mainly affecting the central nervous system and the gastrointestinal system. In our prospective study, we analyzed cases of recent maternal Toxoplasma infections confirmed by serological testing between 1996 and 2020 at the Department of Obstetrics and Gynecology, Semmelweis University. Amniocentesis, followed by PCR, was performed in cases of recent infection confirmed by serological testing during pregnancy. After birth, a neonatological, microbiological, pediatric neurological and ophthalmological examination and a follow-up was carried out. During the study period, a total of 238 cases of amniotic fluid Toxoplasma PCR testing due to Toxoplasma recent infection were performed. In terms of pregnancies, there were 219 deliveries and seven abortions. Twelve cases had no data available on the outcome of the pregnancy. In total, 133 cases of ultrasound abnormalities were detected during pregnancy, while in 105 cases, no abnormalities were detected on ultrasound examination. During amniocentesis, eight cases of Toxoplasma infection were revealed in amniotic fluid samples by PCR, and in 230 cases, the result was negative. Neonatal follow-up was performed in 139 cases, with no abnormalities during follow-up in 117 cases, and in 22 cases, there was a detectable complication that was likely to be related to Toxoplasma infection. In all 22 cases, amniotic fluid PCR Toxoplasma testing was negative. The most common ultrasound abnormalities involve the nervous system and the gastrointestinal system. In cases of suspicion, it is recommended to perform amniocentesis Toxoplasma PCR testing besides the indirect methods to help the pregnant woman decide whether to carry the pregnancy to term. During follow-up, a multidisciplinary team experienced in pregnancies complicated by toxoplasmosis must carry out the follow-up, care and subsequent development.

Biallelic TYR and TKFC variants in Egyptian patients with OCA1 and new expanded TKFC features

BackgroundOculocutaneous albinism type1 (OCA1) is caused by the TYR gene's homozygous and compound heterozygous variants. TKFC gene variants cause triokinase & FMN cyclase deficiency syndrome with variable multisystemic disorders.ObjectivesTo determine the potential disease-causing variants in two deceased patients presenting atypical OCA1 features by demonstrating three generations for a single family. The two deceased neonates had severe skeletal abnormalities and fatal hypertrophic cardiomyopathy. We also explored the potential mechanisms for the causative relationship between TKFC and multisystem disorders.Patients and methodsDue to the new emerging symptoms that weren’t reported before with the TYR gene, the following methods were performed: Sanger sequencing for the TYR gene, followed by whole exome sequencing, co-segregation, and computational analyses.ResultsExtensive parental consanguinity was found, and consequently an autosomal recessive mode of inheritance was prioritized. Upon performing sequencing and segregation data, the following has been confirmed: positive co-segregation of nonsense homozygous NM_000372.5:c.346C > T p.(Arg116*) variant in TYR gene and multisystem disease-missense homozygous NM_015533.4:c.598G > A p.(Val200Ile) variant in TKFC gene in the two affected index patients who deceased due to hypertrophic cardiomyopathy. Using computational analysis, we found that c.598G > A p.(Val200Ile) pathogenicity has led to the failure of L2-K1 active site closure due to the potential differential fluctuation between valine and isoleucine residues. Subsequently, disruption of endogenous DHA phosphorylation was found. Two potential mechanisms exploring the causative relationship between TKFC gene and multisystem disorders have been suggested.ConclusionsThis study presented a first family with the co-existence of biallelic variants in TYR and TKFC genes associating severe skeletal abnormalities and lethal hypertrophic cardiomyopathy. Neither of these genes would have been pursued in the standard genetic counseling. Such discovery is paving the way for more efficient genetic counseling. Comparing TKFC results with literature data showed that our relevant expanded TKFC variant is the 3rd worldwide.

Decreased spinal cord motor neuron numbers in mice depleted of central nervous system copper.

Disrupted copper availability in the central nervous system (CNS) is implicated as a significant feature of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Solute carrier family 31 member 1 (Slc31a1; Ctr1) governs copper uptake in mammalian cells and mutations affecting Slc31a1 are associated with severe neurological abnormalities. Here, we examined the impact of decreased CNS copper caused by ubiquitous heterozygosity for functional Slc31a1 on spinal cord motor neurons in Slc31a1+/- mice. Congruent with the CNS being relatively susceptible to disrupted copper availability, brain and spinal cord tissue from Slc31a1+/- mice contained significantly less copper than wild-type littermates, even though copper levels in other tissues were unaffected. Slc31a1+/- mice had less spinal cord α-motor neurons compared to wild-type littermates, but they did not develop any overt physical signs of motor impairment. By contrast, ALS model SOD1G37R mice had fewer α-motor neurons than control mice and exhibited clear signs of motor function impairment. With the expression of Slc31a1 notwithstanding, spinal cord expression of genes related to copper handling revealed only minor differences between Slc31a1+/- and wild-type mice. This contrasted with SOD1G37R mice where changes in the expression of copper handling genes were pronounced. Similarly, the expression of genes related to toxic glial activation was unchanged in spinal cords from Slc31a1+/- mice but highly upregulated in SOD1G37R mice. Together, results from the Slc31a1+/- mice and SOD1G37R mice indicate that although depleted CNS copper has a significant impact on spinal cord motor neuron numbers, the manifestation of overt ALS-like motor impairment requires additional factors.

KNEE DEFORMITIES AND KNEE REPLACEMENTS IN SAUDI POPULATION: OUR EXPERIENCE AND LITERATURE REVIEW

It takes precise alignment, adequate balance, and deformity correction to accomplish a successful total knee arthroplasty (TKA). In main TKA, this can be successfully achieved with a posterior stabilized (PS) design, either with or without sub-periosteal release. However, severe abnormalities with a major bone defect, stiffness, and instability are often associated with these disorders in some circumstances, such as knee osteoarthritis. Additional restrictive prostheses are required since it is extremely difficult to balance these anomalies with soft tissue release alone, even after main TKA. In this situation, the constrained condylar knee (CCK) design is the optimum choice. This studys primary objectives were to characterize the clinical outcomes, function recovery, and complications of patients who underwent primary CCK-TKA for severe knee osteoarthritis related knee deformity. The secondary aim was to find out the mid-term prostheses survival. Methods: Between March 2021 and March 2022, 36 consecutive patients with knee osteoarthritis had cemented primary CCK-TKA. Twenty-Eight women and eight men, totaling 36 patients, had at least a 6 month follow-up for this retrospective analysis. We used the Knee Society Score (KSS), the Hospital for Special Surgery (HSS) score, and the roentgenographic evaluation form to assess the patients. The survival of prosthesis was assessed using Kaplan-Meiers survival analysis. The patients follow-up periods averaged 12 month. The KSS knee score rose from 44 points (23–68) to 91 points (76–100) following surgery [P &lt; 0.001]. Following the procedure, the mean KSS functional score rose from 20–75 points to 91 points (65–100) [P &lt; 0.001]. The average HSS score rose from 51 points (27–83) to 91 points (75–100) following surgery [P &lt; 0.001]. The average range of motion (ROM) also increased after surgery, going from 68.09° ± 35.99° (0°–120°) to 113.68° ± 8.90° (100°–130°) [P &lt; 0.001]. The average hip-knee-ankle (HKA) angle was 180.24° ± 1.77° (175°–184°) following surgery, compared to 176.88° ± 14.48° (135°–199°) before to surgery. Radiolucencies were seen in thirteen knees, mostly on the tibial side. After an average follow-up of 12 month, 94.7% of prosthesis were still in use. Despite severe deformity, instability, and stiffness at a relatively young age, the mid-term follow-up of primary CCK-TKA in knee osteoarthritis gives satisfactory clinical and functional outcomes with 94.7% prosthesis survival. However, there are a few issues.

Ischemic stroke associated with amyloid-related imaging abnormalities in a patient treated with lecanemab.

Anti-amyloid antibody therapies such as lecanemab are increasingly being used to treat Alzheimer's disease (AD). These therapies are associated with a high rate of amyloid-related imaging abnormalities (ARIA). We review the case history of a patient who developed ARIA associated with lecanemab treatment. In addition to microhemorrhages and cerebral edema that are recognized features of ARIA, the patient developed several ischemic strokes. The patient also experienced frequent electrographic seizures without overt clinical seizures. The patient demonstrated clinical and radiographic improvement after steroid treatment. Our case suggests that ischemic strokes may be a feature of ARIA and highlights the importance of having a high clinical suspicion for seizures in ARIA. As anti-amyloid therapies are likely going to be increasingly used to treat AD, it is important to appreciate the spectrum of clinical and radiographic findings that can result as side effects from this class of therapies. We report a patient who developed severe amyloid-related imaging abnormalities (ARIA) after treatment with lecanemab. Our report suggests that ischemic strokes may be a novel imaging feature of ARIA. Our report highlights the need for high clinical suspicion for seizures in ARIA.

Correlation between meibomian gland dysfunction and sebaceous adenitis in dogs.

Sebaceous adenitis (SA) is an immune-mediated disease targeting the sebaceous glands. Meibomian gland dysfunction is a disease affecting meibomian glands with inflammatory features. Sebaceous and meibomian glands share anatomical, physiological and embryological similarities. The involvement of meibomian glands in dogs with SA is currently unknown. To evaluate meibomian glands in dogs affected by SA and compare them with healthy dogs. Eighteen dogs were enrolled. Nine dogs with SA were retrospectively identified from clinical records and represented the case group. Nine healthy, breed- and age-matched dogs were prospectively enrolled in the control group. Both groups underwent dermatological examination, Schirmer tear test-1 (STT-1), tear meniscus height (TMH), slit-lamp biomicroscopy, interferometry (INT) and noncontact infrared meibography (NIM). One third of SA dogs presented subepithelial crystalline opacities. No significant difference between groups was observed in TMH (p = 0.944) and STT-1 values (p = 0.066). INT (p = 0.016) and NIM grades (p = 0.010) were significantly higher and lower in the SA group compared to the control group, respectively. INT values decreased with age (η = 0.930), while NIM scores (η = 0.935) increased. Clinical Relevance: Subepithelial crystalline opacities in SA dogs might reflect a reduced tear film quality. In the absence of standardised methods, INT and NIM proved to be noninvasive and useful methods to examine meibomian glands. Dogs with SA showed a thinner lacrimal lipid layer and more severe meibomian gland abnormalities than control dogs, which seemed to progress with age.

Ultrasound Assessment of Sarcopenia in Alcoholic Liver Disease.

Malnutrition frequently affects patients with alcoholic liver disease (ALD), with important impacts on disease prognosis. Sarcopenia, the clinical phenotype of malnutrition characterized by skeletal muscle loss, is the major component responsible for adverse events in this population. The aim of this study is to assess the use of ultrasound (US) skeletal muscle performance in stratifying ALD disease severity. We recruited 43 patients with ALD and divided them into two groups: alcoholic hepatitis (AH) and alcoholic cirrhosis (AC). We evaluated disease-specific clinical and biological parameters and their relation to US Rectus Femoris muscle (RFM) measurements, including RFM thickness, stiffness (RFMS) and echogenicity (RFE). A thirty-seconds chairs stand test (30sCST) was used as the sarcopenia surrogate test. RMF thickness correlated with platelet count and serum albumin (p < 0.001). Both RFM and RFMS correlated with disease severity (p < 0.001) and 30sCST (p < 0.001, p = 0.002). Patients with AH had more severe US muscle abnormalities compared to AC (RFMS 1.78 m/s vs. 1.35 m/s, p = 0.001) and the highest prevalence of RFE (χ2 = 8.652, p = 0.003). Rectus Femoris US assessment could represent a reliable tool in the diagnosis and severity stratification of ALD-induced sarcopenia.