[Clinical and genetic characteristics analysis of two children with comorbidity of two rare genetic diseases].

Objective: To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously.

Methods: Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed.

The Combined Effect of the Systemic Immune-Inflammation Index and Aortic Valve Calcification on Major Adverse Cardiovascular Events in Patients with Coronary Heart Disease.

Background: The combined effect of systemic immune-inflammation index (SII) and aortic valve calcification (AVC) on the risk of major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD) remains unclear. This study aimed to investigate their combined association with MACE in CHD.

Methods: This retrospective cohort study included 846 CHD patients.

Novel homozygous missense variants in associated with neurodevelopmental disorder: Clinical and pathogenetic research.

Background: Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia (NEDSCAC), induced by gene, is an autosomal recessive rare disorder characterized by widespread developmental delay with varying degrees of intellectual impairment. Other symptoms include limb spasticity, cataracts, and cerebellar hypoplasia. So far there have been limited reports on NEDSCAC.

Causal relationship between iron deficiency anemia and asthma: a Mendelian randomization study.

Background: Observational studies have suggested an association between iron deficiency anemia (IDA) and asthma, which may affect the occurrence of asthma. However, whether IDA is a new management goal for asthma remains to be determined.

Objective: We conducted a two-sample Mendelian randomization(MR)analysis to assess the association between IDA and asthma.

Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.

Objective: This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD).

Methods: A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes.

Aggregate IND Safety Reporting for Smaller Companies and Programs.

The United States (US) Food and Drug Administration (FDA) Investigational New Drug (IND) Final Rule (US FDA, Final rule: Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans, 2010) applies to all human drugs and biological products being studied under an IND. The Final Rule specifies that a sponsor must file an IND safety report for any Suspected Unexpected Serious Adverse Reaction (SUSAR) of a medicinal product being investigated. To make a proper SUSAR classification, sponsors need to go beyond conventional Data Monitoring Committees (DMCs) with an interdisciplinary effort, using all relevant data (including data outside clinical trials), to make judgments on the possibility of serious adverse events being caused by the study drug-rather than the underlying condition of the patient or a concomitant therapy.

Integration of multiomics analysis to reveal the major pathways of vitamin A deficiency aggravates acute respiratory distress syndrome in neonatal rats.

Acute respiratory distress syndrome (ARDS) is a major disease that threatens the life and health of neonates. Vitamin A (VA) can participate in early fetal lung development and affect lung immune function. Researches revealed that the serum VA level in premature infants with ARDS was lower than that in premature infants without ARDS of the same gestational age, and premature infants with VA deficiency (VAD) were more likely to develop ARDS.

Crucial involvement of fast waves and Delta band in the brain network attributes of infantile epileptic spasms syndrome.

Objective: This study aims to describe the characteristics of the brain network attributes in children diagnosed with Infantile Epileptic Spasms Syndrome (IESS) and to determine the influence exerted by adrenocorticotrophic hormone (ACTH) or methylprednisolone (MP) on network attributes.

Methods: In this retrospective cohort study, we recruited 19 infants diagnosed with IESS and 10 healthy subjects as the control from the Pediatric Neurology Department at the Third Affiliated Hospital of Zhengzhou University between October 2019 and December 2020. The first thirty-minute processed electroencephalograms (EEGs) were clipped and filtered into EEG frequency bands (2 s each).

The Safety and Tolerability of Linezolid in Novel Short-Course Regimens Containing Bedaquiline, Pretomanid, and Linezolid to Treat Rifampicin-Resistant Tuberculosis: An Individual Patient Data Meta-analysis.

Background: Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials.

Clinical and genetic analysis of Christianson syndrome caused by variant of : case report and literature review.

Background: Intellectual disability, X-linked, syndromic, Christianson type (MRXSCH, OMIM: 300243)-known as Christianson syndrome (CS)-is characterized by microcephaly, epilepsy, ataxia, and absence of verbal language ability. CS is attributed to mutations in the solute carrier family 9 member A6 gene ().

Materials And Methods: This study reports the case of a boy 1 year and 3 months of age who was diagnosed with CS in our department.

Important Considerations for Signal Detection and Evaluation.

Safety clinicians have a wealth of resources describing how to perform signal detection. Nevertheless, there are some nuances concerning approaches taken by regulatory authorities and statistical considerations that should be appreciated. New approaches, such as the FDA Medical Queries, illustrate the value of considering medical concepts over individual adverse events.

Assessing adverse events in clinical trials during the era of the COVID-19 pandemic.

Interpretation of safety data for clinical trials that were ongoing at the onset of the COVID-19 pandemic or were started subsequent to the beginning of the pandemic may be affected in a variety of ways. Pandemic-related issues can influence the extent of study participation and introduce data collection gaps. A SARS-CoV-2 infection among study subjects as a post-randomization event may introduce a number of confounding factors that can alter the frequency of adverse events, in some cases appearing as an increase in the frequency of an adverse event associated with a study drug relative to a comparator.

Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.

Background: The bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear.

Methods: We enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.

Vascular Endothelial Growth Factor May Be Involved in the Behavioral Changes of Progeny Rats after Exposure to Ceftriaxone Sodium during Pregnancy.

Antibiotic exposure during pregnancy have an adversely effects on offspring behavior and development. However, its mechanism is still poorly understood. To uncover this, we added ceftriaxone sodium to the drinking water of rats during pregnancy and conducted three-chamber sociability test, open-field test, and Morris water maze test in 3- and 6-week-old offspring.

MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway.

Background: Osteosarcoma is the most prevalent primary malignant bone tumor containing mesenchymal cells with poor prognosis. Being a hot spot of anti-tumor therapy researches, AKT/mammalian target of rapamycin (mTOR) signaling pathway could affect various cellular processes including transcription, protein synthesis, apoptosis, autophagy and growth.

Materials And Methods: The levels of RNA and protein were detected by quantitative real-time polymerase chain reaction (q-PCR) and western blot analyses respectively.

Lateralized Contributions of Medial Prefrontal Cortex Network to Episodic Memory Deficits in Subjects With Amnestic Mild Cognitive Impairment.

Both episodic memory and executive function are impaired in amnestic mild cognitive impairment (aMCI) subjects, but it is unclear if these impairments are independent or interactive. The present study aimed to explore the relationship between episodic memory deficits and executive function deficits, and the underlying functional mechanisms in aMCI subjects. Thirty-one aMCI subjects and 27 healthy subjects underwent neuropsychological tests and multimodal magnetic resonance imaging (MRI) scans.

A New Paradigm for Safety Data Signal Detection and Evaluation Using Open-Source Software Created by an Interdisciplinary Working Group.

Techniques to evaluate large amounts of safety data continue to evolve based on a greater understanding of how the brain processes visual information and the advancement of programing tools. The Interactive Safety Graphics Task Force of the American Statistical Association Biopharmaceutical Safety Working Group has assembled a multidisciplinary team of experts in a variety of domains to develop the next generation of open-source visual analytical tools for safety data based on these advances. The multidisciplinary approach resulted in the rapid development of the first tool, a novel interactive version of the familiar Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) graphic along with a unique clinical workflow to guide the reviewer through the data analysis.

Effects of S24-7 on the weight of progeny rats after exposure to ceftriaxone sodium during pregnancy.

Antibiotic exposure during pregnancy will adversely affect the growth of offspring; however, this remains controversial and the mechanism is poorly understood. To study this phenomenon, we added ceftriaxone sodium to the drinking water of pregnant rats and continuously monitored the body weight of their offspring. The results showed that compared with the control group, the offspring exposed to antibiotics during pregnancy had a higher body weight up to 3 weeks old but had a lower body weight at 6 weeks old.

Early Segmental White Matter Fascicle Microstructural Damage Predicts the Corresponding Cognitive Domain Impairment in Cerebral Small Vessel Disease Patients by Automated Fiber Quantification.

To characterize earlier damage pattern of white matter (WM) microstructure in cerebral small vessel disease (CSVD) and its relationship with cognitive domain dysfunction. A total of 144 CSVD patients and 100 healthy controls who underwent neuropsychological measurements and diffusion tensor imaging (DTI) examination were recruited. Cognitive function, emotion, and gait were assessed in each participant.

Phase 1 Study of the Effects of the Tuberculosis Treatment Pretomanid, Alone and in Combination With Moxifloxacin, on the QTc Interval in Healthy Volunteers.

Tuberculosis (TB) continues to be a serious threat to public health throughout the world. Newer treatments are needed that could offer simplified regimens with activity against both drug-sensitive and drug-resistant bacilli, while optimizing safety. Pretomanid (PA-824), a nitroimidazooxazine compound, is a new drug for the treatment of pulmonary TB that was recently approved in the United States and Europe in the context of a regimen combined with bedaquiline and linezolid.

Long Longitudinal Tract Lesion Contributes to the Progression of Alzheimer's Disease.

The degenerative pattern of white matter (WM) microstructures during Alzheimer's disease (AD) and its relationship with cognitive function have not yet been clarified. The present research aimed to explore the alterations of the WM microstructure and its impact on amnestic mild cognitive (aMCI) and AD patients. Mechanical learning methods were used to explore the validity of WM microstructure lesions on the classification in AD spectrum disease.

An Exposure-Response Perspective on the Clinical Dose of Pretomanid.

Pretomanid was approved by the U.S. FDA, via the limited population pathway for antibacterial and antifungal drugs, as part of a three-drug regimen with bedaquiline and linezolid for the treatment of extensively drug-resistant and treatment-intolerant or nonresponsive multidrug-resistant tuberculosis.

Aberrant White Matter Microstructure as a Potential Diagnostic Marker in Alzheimer's Disease by Automated Fiber Quantification.

Neuroimaging evidence has suggested white matter microstructure are heavily affected in Alzheimer's disease (AD). However, whether white matter dysfunction is localized at the specific regions of fiber tracts and whether they would be a potential biomarker for AD remain unclear. By automated fiber quantification (AFQ), we applied diffusion tensor images from 25 healthy controls (HC), 24 amnestic mild cognitive impairment (aMCI) patients and 18 AD patients to create tract profiles along 16 major white matter fibers.