The value of using ELISA to detect orexin-A in cerebrospinal fluid in the diagnosis of narcolepsy.

Orexin in cerebrospinal fluid (CSF) is a neuropeptide synthesized by a cluster of neurons in the lateral hypothalamus. It mainly functions to maintain arousal, regulate feeding, and participate in reward mechanisms. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) can detect CSF orexin. At present, RIA is widely used but is limited by various conditions, which is not conducive to its widespread development. We aimed to determine whether ELISA can replace RIA in detecting orexin in CSF. We investigated the results of 20 patients with central disorders of hypersomnolence, including 11 with narcolepsy type 1, 2 with narcolepsy type 2, 5 with idiopathic hypersomnia, and 2 with other causes of somnolence. RIA and ELISA were used to detect CSF orexin, and P values <.05 were considered to be significant. In the narcolepsy and non-narcolepsy type 1 groups, there was no correlation between the RIA and ELISA results (P > .05). In the narcolepsy type 1 group, the ELISA and RIA results were significantly different (P < .05), but this was not observed in the non-narcolepsy type 1 group (P > .05). The accuracy of ELISA to detect CSF orexin was lower than that of RIA (P < .05). ELISA cannot replace RIA in the measurement of CSF orexin, and RIA is recommended as the first choice when narcolepsy is suspected.

ATF5-Mediated Mitochondrial Unfolded Protein Response (UPRmt) Protects Neurons Against Oxygen-Glucose Deprivation and Cerebral Ischemia.

BACKGROUND: The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved mitochondrial response that is critical for maintaining mitochondrial and energetic homeostasis under cellular stress after tissue injury and disease. Here, we ask whether UPRmt may be a potential therapeutic target for ischemic stroke. METHODS: We performed the middle cerebral artery occlusion and oxygen-glucose deprivation models to mimic ischemic stroke in vivo and in vitro, respectively. Oligomycin and meclizine were used to trigger the UPRmt. We used 2,3,5-triphenyltetrazolium chloride staining, behavioral tests, and Nissl staining to evaluate cerebral injury in vivo. The Cell Counting Kit-8 assay and the Calcein AM Assay Kit were conducted to test cerebral injury in vitro. RESULTS: Inducing UPRmt with oligomycin protected neuronal cultures against oxygen-glucose deprivation. UPRmt could also be triggered with meclizine, and this Food and Drug Administration-approved drug also protected neurons against oxygen-glucose deprivation. Blocking UPRmt with siRNA against activating transcription factor 5 eliminated the neuroprotective effects of meclizine. In a mouse model of focal cerebral ischemia, pretreatment with meclizine was able to induce UPRmt in vivo, which reduced infarction and improved neurological outcomes. CONCLUSIONS: These findings suggest that the UPRmt is important in maintaining the survival of neurons facing ischemic/hypoxic stress. The UPRmt mechanism may provide a new therapeutic avenue for ischemic stroke.

Prediction of miRNAs and diseases association based on sparse autoencoder and MLP.

Introduction: MicroRNAs (miRNAs) are small and non-coding RNA molecules which have multiple important regulatory roles within cells. With the deepening research on miRNAs, more and more researches show that the abnormal expression of miRNAs is closely related to various diseases. The relationship between miRNAs and diseases is crucial for discovering the pathogenesis of diseases and exploring new treatment methods. Methods: Therefore, we propose a new sparse autoencoder and MLP method (SPALP) to predict the association between miRNAs and diseases. In this study, we adopt advanced deep learning technologies, including sparse autoencoder and multi-layer perceptron (MLP), to improve the accuracy of predicting miRNA-disease associations. Firstly, the SPALP model uses a sparse autoencoder to perform feature learning and extract the initial features of miRNAs and diseases separately, obtaining the latent features of miRNAs and diseases. Then, the latent features combine miRNAs functional similarity data with diseases semantic similarity data to construct comprehensive miRNAs-diseases datasets. Subsequently, the MLP model can predict the unknown association among miRNAs and diseases. Result: To verify the performance of our model, we set up several comparative experiments. The experimental results show that, compared with traditional methods and other deep learning prediction methods, our method has significantly improved the accuracy of predicting miRNAs-disease associations, with 94.61% accuracy and 0.9859 AUC value. Finally, we conducted case study of SPALP model. We predicted the top 30 miRNAs that might be related to Lupus Erythematosus, Ecute Myeloid Leukemia, Cardiovascular, Stroke, Diabetes Mellitus five elderly diseases and validated that 27, 29, 29, 30, and 30 of the top 30 are indeed associated. Discussion: The SPALP approach introduced in this study is adept at forecasting the links between miRNAs and diseases, addressing the complexities of analyzing extensive bioinformatics datasets and enriching the comprehension contribution to disease progression of miRNAs.

Ureter mixed neuroendocrine-non-neuroendocrine neoplasm: a case report and literature review.

Cases of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the urinary system are rare, and reports of primary MiNENs in the ureter are lacking. Herein, we present the case of a 71-year-old man who presented with painless gross hematuria and weight loss. Contrast-enhanced abdominal computed tomography (CT) revealed a tumor, comprising small cell neuroendocrine carcinoma (SCNEC) and adenocarcinomatous components, attached to the ureter. The SCNEC components were strongly positive for synaptophysin, CD56 and INSM1 and adenocarcinomatous components were strongly positive for CDX2 and cytokeratin 20, respectively. Four weeks post-surgery, the patient received four cycles of cisplatin-based chemotherapy; the 7-month follow-up CT confirmed that he was healthy without disease recurrence. The occurrence of MiNEN in the ureter with SCNEC and adenocarcinomatous components is extremely rare, wherein histopathological and immunohistochemical features aid in the diagnosis MiNEN. With its aggressive nature, MiNEN can only be effectively treated by early diagnosis and radical surgery.

Daily Online Adaptive Radiation Therapy of Postoperative Endometrial and Cervical Cancer With PTV Margin Reduction to 5 mm: Dosimetric Outcomes, Acute Toxicity, and First Clinical Experience.

Purpose: This study evaluated the first clinical implementation of daily iterative cone beam computed tomography (iCBCT)-guided online adaptive radiation therapy (oART) in the postoperative treatment of endometrial and cervical cancer. Methods and Materials: Seventeen consecutive patients treated with daily iCBCT-guided oART were enrolled in this prospective study, with a reduced uniform 3-dimensional PTV margin of 5 mm. Treatment plans were designed to deliver 45 or 50.4 Gy in 1.8 Gy daily fractions to PTV. Pre- and posttreatment ultrasound and iCBCT scans were performed to record intrafractional bladder and rectal volume changes. The accuracy of contouring, oART procedure time, dosimetric outcomes, and acute toxicity were evaluated. Results: The average time from first iCBCT acquisition to completion of treatment was 22 minutes and 26 seconds. During this period, bladder volume increased by 44 cm3 using iCBCT contouring, whereas rectal volume remained stable (62.9 cm3 pretreatment vs 61.9 cm3 posttreatment). A total of 91.6% of influencers and 88.1% of CTVs required no or minor edits. The adapted plan was selected in all (434) fractions and significantly improved the dosimetry coverage for CTV and PTV, especially the vaginal PTV coverage by nearly 7% (P < .05). The adapted bladder Dmean was 104.61 cGy, and the rectum Dmean was 123.67 cGy, significantly lower than the scheduled plan of 108.24 and 128.19 cGy, respectively. The bone marrow and femur head left and right dosimetry were also improved with adaptation. Grade 2 acute gastrointestinal and genitourinary toxicities were 24% and 0, respectively. There was a grade 3 acute toxicity of decreased white blood cell count in 1 patient. Conclusions: Daily oART was associated with favorable dosimetry improvement and low acute toxicity, supporting its safety and efficacy for postoperative treatment of endometrial and cervical cancer. These results need to be validated in a larger prospective randomized controlled cohort.

[A longitudinal study of subjective olfactory function post-operatively in chronic rhinosinusitis patients with asthma and analysis of influencing factors].

Objective:To evaluate the subjective olfactory function in chronic sinusitis（CRS）patients with asthma after nasal endoscopic surgery and associated factors that may affect olfactory function. Methods：The study included 90 CRS patients with asthma from January 2008 to December 2020，and all of them underwent endoscopic sinus surgery（ESS）. VAS score of olfactory function before and after surgery were collected，and the data at baseline，3 months，6 months，1 year，3 years，5 years，8 years and 10 years after surgery were compared. Factors affecting olfactory function were analyzed in a generalized mixed linear model，which including age，surgical procedure，allergic rhinitis and so on.Results： The olfactory VAS scores were significantly lower at 3 months，6 months，1 year，3 years，and 5 years postoperatively compared with baseline，and the difference was statistically significant（P<0.05）.Olfactory VAS scores at 8 and 10 years postoperatively were not statistically different from baseline（P>0.05）.Age（≥60 years），aspirin intolerance syndrome，Lund-Kennedy score，modified sinus CT olfactory cleft score，and follow-up time were risk factors, and radical sinus surgery is a protective factor.Conclusion：Subjective olfactory scores in CRS patients with asthma after ESS remain relatively stable for 5 years postoperatively.Prior history of surgery did not affect postoperative subjective olfactory scores. Age，aspirin intolerance syndrome, Lund-Kennedy score，modified sinus CT olfactory cleft score, follow-up time，and surgical approach were strongly associated with subjective olfactory scores in CRS patients with asthma，and radical surgery had a protective effect on olfaction.

Gallium-based metal-organic frameworks with antibacterial and anti-inflammatory properties for oral health protection.

The fascial space of the oral and maxillofacial region contains loose connective tissues, which possess weak anti-infection ability and are often prone to infection, leading to acute suppurative inflammation and sepsis through blood. Although antibiotic use can reduce the probability of bacterial infections, owing to the emergence of antibiotic-resistant bacteria, the search for new antimicrobial drugs is imminent. Herein, we report a metal-organic framework (MOF) antibacterial material designed and synthesized with gallium (Ga) as the central atom, which possesses significant antibacterial, anti-inflammatory, and antioxidant effects. Our data suggested that GA-based MOFs (Ga-MOFs; 1 µg/mL) could sufficiently kill Porphyromonas gingivalis, Streptococcus pyogenes, and Staphylococcus aureus. Ga-MOFs exhibited a bactericidal effect against these three pathogens by disrupting biofilm formation, exopolysaccharide production, and bacterial membrane integrity. In addition, we found that 1 µg/mL of Ga-MOFs was not cytotoxic to human oral epithelial cell (HOEC) lines and it significantly reduced the adhesion of the three pathogens to HOEC. Ga-MOFs protect macrophages from excessive oxidative stress by scavenging excess intracellular reactive oxygen species and upregulating antioxidant gene levels, thereby enhancing cellular antioxidant defense. In addition, Ga-MOFs can promote the transformation of macrophages from the proinflammatory phenotype to the anti-inflammatory phenotype, thereby protecting oral health. Herein, novel Ga-MOF materials were chemically synthesized for therapeutic applications in oral infections, which provides new ideas for the development of novel nonantibiotic drugs to accelerate patient recovery.

Gold nanourchin on multiple-point dielectrode for glucose biosensing by current-potential measurement.

Gestational diabetes (GD) is a condition characterized by elevated blood sugar levels during pregnancy. GD poses various health risks, such as serious birth injuries, the need for cesarean delivery, and the necessity of newborn care. Monitoring glucose levels is essential for ensuring safe delivery and reducing the risks to both the mother and fetus. Various sensors are readily available for monitoring glucose levels, and researchers are continually working to develop highly sensitive glucose sensors. This research aimed to develop a gold nanourchin (AuNU)-hybrid biosensor for quantifying glucose on a multi-point electrode sensor. Glucose oxidase (GOx) was attached to the AuNU and seeded on the sensing surface using an amine linker. The current-potential (1-2 V at 0.1 V sweep) was recorded for the GOx-glucose interaction, with a limit of detection of 560 µM and a regression coefficient (R2) of 0.9743 [y = 0.9106x - 0.9953] on the linear curve. The sensitivity was estimated to be 3.5 mAcm-2M-1. Furthermore, control experiments with galactose, sucrose, and fructose did not yield an increase in current-potential, confirming specific glucose detection. This experiment helps in monitoring glucose levels to manage conditions associated with GD.

The efficacy and safety of JAK inhibitors in patients with adult-onset still's disease: A meta-analysis and systematic review.

OBJECTIVE: To evaluate the efficacy and safety of Janus kinases inhibitors (JAKi) for adult-onset Still's disease (AOSD) patients. METHODS: We searched the Embase, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and the China National Knowledge Infrastructure (CNKI) from inception up to 22 October 2023. The results were supplemented by a backward search of relevant publications. Two authors independently selected trials. The available studies were comprehensively reviewed and analysed. RESULTS: A total of 9 studies with a total of 35 patients were included in the review. Of these patients, 17 (48.6%) patients were treated with tofacitinib, 14 (40%) with baricitinib, 4 (11.4%) with ruxolitinib and 1 (2.9%) with upadacitinib. After treatment with JAKi, 17 (48.6%) patients showed complete remission, 12 (34.3%) patients showed partial remission, and 7 (20%) patients showed loss of efficacy or relapse. The use of ruxolitinib showed a remission rate of 100% in AOSD patients with macrophage activation syndrome (MAS). The incidence of adverse events (AEs) reported were mild and rare overall. Most AEs were abnormal lipid parameters (9.7%), bacterial pneumonia (3.2%), organised pneumonia (3.2%), diarrhoea (3.2%), increased heart rate (3.2%), menometrorrhagia (3.2%) and leukopenia (3.2%). One patient died from bacterial pneumonia. CONCLUSION: JAKi therapy may be an option for patients with AOSD, especially for refractory AOSD. For patients with AOSD complicated by MAS, ruxolitinib seems to be a better choice than other JAKi agents. Although our study shows that JAKi are well tolerated in AOSD patients, we still need to be on the lookout for fatal infections.

Exploring the relationship between creatine supplementation and renal function: insights from Mendelian randomization analysis.

BACKGROUND: Creatine supplementation is ubiquitously consumed by fitness enthusiasts due to its perceived advantages in enhancing athletic performance. Although there is an increasing concern within this demographic regarding its possible impact on renal function, there is still a lack of rigorous scientific investigations into this alleged association. METHODS: Data were collected through an online survey on the participants' demographics, creatine usage and concerns related to renal function. The reliability and validity of the survey were assessed using SPSS software. A total of 1129 participants responded to the survey, and chi-square tests were utilized for data analysis. To explore the potential association between creatine levels (as the exposure) and renal function (as the outcome), we utilized open-access genetic databases, and Mendelian randomization (MR) techniques were used to confirm this correlation. RESULTS: Chi-square analysis revealed no significant association between creatine usage and renal function among the participants. Our MR analysis further supported this finding, demonstrating no significant association between creatine levels and six indicators assessing renal function (IVW, all with p values exceeding 0.05). Similar p values were consistently observed across other MR methods, confirming the absence of a statistical correlation. CONCLUSIONS: This MR study offers compelling evidence indicating that creatine levels are not statistically associated with renal function, suggesting the potential to alleviate concerns within the fitness community and emphasizing the significance of evidence-based decision-making when considering nutritional supplementation.

The impact of macroeconomic policy uncertainty on micro-enterprise investment efficiency-Empirical evidence from China.

The impact of macroeconomic policy uncertainty (EPU) on micro-level entities has garnered increasing attention in economic circles. This study examines the influence of EPU on the efficiency of investments made by China's A-share listed companies between 2016 and 2021. Using a panel fixed effect model for analysis, the research reveals that EPU has a notable adverse effect on the investment efficiency of enterprises. Furthermore, it suggests that advancements in digital finance, strong ESG performance, and enhanced entrepreneurial confidence can mitigate this negative impact effectively. The study also highlights that enterprises with lower valuation, shareholder control, limited audit reputation, and no bank connections are more vulnerable to the impact of EPU on investment efficiency compared to those with higher valuation, manager control, strong audit reputation, and bank connections. Consequently, future efforts should be directed towards enhancing the stability and relevance of economic policies, promoting digital finance, and enhancing corporate governance structures.

Platelet membrane biomimetic nanoparticle-targeted delivery of TGF-ß1 siRNA attenuates renal inflammation and fibrosis.

The progression of renal fibrosis to end-stage renal disease (ESRD) is significantly influenced by transforming growth factor-beta (TGF-beta) signal pathway. This study aimed to develop nanoparticles (PMVs@PLGA complexes) with platelet membrane camouflage, which can transport interfering RNA to target and regulate the TGF-ß1 pathway in damaged renal tissues. The aim is to reduce the severity of acute kidney injury and to reduce fibrosis in chronic kidney disease. Hence, we formulated PMVs@TGF-ß1-siRNA NP complexes and employed them for both in vitro and in vivo therapy. From the experimental findings we know that the PMVs@siRNA NPs could effectively target the kidneys in unilateral ureteral obstruction (UUO) mice and ischemia/reperfusion injury (I/R) mice. In animal models of treatment, PMVs@siRNA NP complexes effectively decreased the expression of TGF-ß1 and mitigated inflammation and fibrosis in the kidneys by blocking the TGF-ß1/Smad3 pathway. Therefore, these PMVs@siRNA NP complexes can serve as a promising biological delivery system for treating kidney diseases.

Mitral Geometry on the Mechanism of Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy.

OBJECTIVE: The mechanism of left ventricular outflow tract obstruction (LVOTO) is complex in hypertrophic cardiomyopathy (HCM). We aimed to evaluate the impact of mitral valve geometry on LVOTO by echocardiography. MATERIALS AND METHODS: The study population comprised 177 consecutive patients with HCM. Morphological findings of left ventricular hypertrophy and LVOTO-related abnormalities were assessed by comprehensive transthoracic echocardiography. Aortomitral angle, mitral leaflet length, and coaptation height were measured and analyzed at rest. Multivariable stepwise forward logistic regression analysis was performed to identify geometric predictors of LVOTO. RESULTS: One hundred thirty-seven patients had an LVOT gradient ≥30 mm Hg. Multivariable logistic regression showed that aortomitral angle (odds ratio [OR], 0.89; 95% CI, 0.83-0.95, P < .001), coaptation height (OR, 1.96; 95% CI, 1.41-2.72, P < .001), and accessory mitral valve chordae tendineae (OR, 13.1; 95% CI, 4.32-39.95; P < .001) were independently associated with LVOTO. Receiver operating characteristic analysis showed that the area under the curve of mitral coaptation height was higher (area under the curve = 0.815) than the other 2 indicators (P < .05). CONCLUSION: Mitral coaptation height, aortomitral angle, and accessory mitral valve chordae tendineae were important predictors of SAM and LVOTO in HCM independent of septal hypertrophy.

Ultrastrong and ductile medium-entropy alloys via hierarchical ordering.

Long-range ordered phases in most high-entropy and medium-entropy alloys (HEAs/MEAs) exhibit poor ductility, stemming from their brittle nature of complex crystal structure with specific bonding state. Here, we propose a design strategy to severalfold strengthen a single-phase face-centered cubic (fcc) Ni2CoFeV MEA by introducing trigonal κ and cubic L12 intermetallic phases via hierarchical ordering. The tri-phase MEA has an ultrahigh tensile strength exceeding 1.6 GPa and an outstanding ductility of 30% at room temperature, which surpasses the strength-ductility synergy of most reported HEAs/MEAs. The simultaneous activation of unusual dislocation multiple slip and stacking faults (SFs) in the κ phase, along with nano-SF networks, Lomer-Cottrell locks, and high-density dislocations in the coupled L12 and fcc phases, contributes to enhanced strain hardening and excellent ductility. This work offers a promising prototype to design super-strong and ductile structural materials by harnessing the hierarchical ordered phases.

Levels of antibodies against the monkeypox virus compared by HIV status and historical smallpox vaccinations: a serological study.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

FNDC5 inhibits malignant growth of human cervical cancer cells via restraining PI3K/AKT pathway.

Cervical cancer (CxCa) is the fourth most frequent cancer in women. This study aimed to determine the role and underlying mechanism of fibronectin type III domain-containing protein 5 (FNDC5) in inhibiting CxCa growth. Experiments were performed in human CxCa tissues, human CxCa cell lines (HeLa and SiHa), and xenograft mouse model established by subcutaneous injection of SiHa cells in nude mice. Bioinformatics analysis showed that CxCa patients with high FNDC5 levels have a longer overall survival period. FNDC5 expression was increased in human CxCa tissues, HeLa and SiHa cells. FNDC5 overexpression or FNDC5 protein not only inhibited proliferation, but also restrained invasion and migration of HeLa and SiHa cells. The effects of FNDC5 were prevented by inhibiting integrin with cilengitide, activating PI3K with recilisib or activating Akt with SC79. FNDC5 inhibited the phosphorylation of PI3K and Akt, which was attenuated by recilisib. PI3K inhibitor LY294002 showed similar effects to FNDC5 in HeLa and SiHa cells. Intravenous injection of FNDC5 (20 µg/day) for 14 days inhibited the tumor growth, and reduced the proliferation marker Ki67 expression and the Akt phosphorylation in the CxCa xenograft mouse model. These results indicate that FNDC5 inhibits the malignant phenotype of CxCa cells through restraining PI3K/Akt signaling. Upregulation of FNDC5 may play a beneficial role in retarding the tumor growth of CxCa.

Switchable Regioselective C-H Activation/Annulation of Acrylamides with Alkynes for the Synthesis of 2-Pyridones.

A catalyst-based switchable regioselective C-H activation/annulation of acrylamides with propargyl carbonates has been developed, delivering C5 or C6 alkenyl substituted 2-pyridones. This robust protocol proceeds with a broad substrate scope and good functional group tolerance under redox-neutral reaction conditions. More significantly, this reaction is highly effective with previously challenging unsymmetrical alkynes, including unbiased alkyl-alkyl substituted alkynes, with perfect and switchable regioselectivity. Additionally, mechanistic studies and DFT calculations were performed to shed light on the switchable regioselectivity.

Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women.

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA. Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects. To validate the accuracy of our findings, we also utilized the Multiplex Ligation-dependent Probe Amplification (MLPA) to confirm the reliability of screening results obtained by quantitative real-time PCR. Result: Among the 39,647 participants who were screened, 726 participants were the carriers of SMN1. The overall carrier rate was calculated to be 1.83% (95% confidence interval: 0.86-2.8%). After undergoing screening, a total of 592 pregnancy carriers were provided with genetic counseling and only 503 of their spouses (84.97, 95% confidence interval: 82.09-87.85%) voluntarily underwent SMA screening. Conclusion: This study provides crucial insights into the prevalence and distribution of SMA carriers among the female population. The identification of 726 asymptomatic carriers highlights the necessity of comprehensive screening programs to identify at-risk individuals and ensure appropriate interventions are in place to minimize the impact of SMA-related conditions.