UNASSIGNED: Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the molecular mechanism of macrophages in pre-eclampsia is not well understood.
UNASSIGNED: In this study, the key biomarkers during the development of pre-eclampsia were identified using bioinformatics analysis. The GSE75010 and GSE74341 datasets from the GEO database were obtained and merged for differential analysis. A weighted gene co-expression network analysis (WGCNA) was constructed based on macrophage content, and machine learning methods were employed to identify key genes. Immunoinfiltration analysis completed by the CIBERSORT method, R package \"ClusterProfiler\" to explore functional enrichment of these intersection genes, and potential drug predictions were conducted using the CMap database. Lastly, independent analysis of protein levels, localization, and quantitative analysis was performed on placental tissues collected from both preeclampsia patients and healthy control groups.
UNASSIGNED: We identified 70 differentially expressed NETs genes and found 367 macrophage-related genes through WGCNA analysis. Machine learning identified three key genes: FNBP1L, NMUR1, and PP14571. These three key genes were significantly associated with immune cell content and enriched in multiple signaling pathways. Specifically, these genes were upregulated in PE patients. These findings establish the expression patterns of three key genes associated with M2 macrophage infiltration, providing potential targets for understanding the pathogenesis and treatment of PE. Additionally, CMap results suggested four potential drugs, including Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin, which may have the potential to reverse pre-eclampsia.
UNASSIGNED: Studying the expression levels of three key genes in pre-eclampsia provides valuable insights into the prevention and treatment of this condition. We propose that these genes play a crucial role in regulating the maternal-fetal immune microenvironment in PE patients, and the pathways associated with these genes offer potential avenues for exploring the molecular mechanisms underlying preeclampsia and identifying therapeutic targets. Additionally, by utilizing the Connectivity Map database, we identified drug targets like Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin as potential clinical treatments for preeclampsia.

OBJECTIVE: Sacral neuromodulation (SNM) therapy standard of care relies on visual-motor responses and patient-reported sensory responses in deciding optimized lead placement and programming. Automatic detection of stimulation responses could offer a simple, consistent indicator for optimizing SNM. The purpose of this study was to measure and characterize sacral evoked responses (SERs) resulting from sacral nerve stimulation using a commercial, tined SNM lead.
METHODS: A custom external research system with stimulation and sensing hardware was connected to the percutaneous extension of an implanted lead during a staged (tined lead) evaluation for SNM. The system collected SER recordings across a range of prespecified stimulation settings (electrode configuration combinations for bipolar stimulation and bipolar sensing) during intraoperative and postoperative sessions in 21 subjects with overactive bladder (OAB) and nonobstructive urinary retention (NOUR). Motor and sensory thresholds were collected during the same sessions.
RESULTS: SERs were detected in all 21 subjects. SER morphology (number of peaks, magnitude, and timing) varied across electrode configurations within and across subjects. Among subjects and electrode configurations tested, recordings contained SERs at motor threshold and/or sensory threshold in 75% to 80% of subjects.
CONCLUSIONS: This study confirmed that implanted SNM leads can be used to directly record SERs elicited by stimulation in subjects with OAB and NOUR. SERs were readily detectable at typical SNM stimulation settings and procedural time points. Using these SERs as possible objective measures of SNM response has the capability to automate patient-specific SNM therapy, potentially providing consistent lead placement, programming, and/or closed-loop therapy.

Self-harm is an important predictor of a suicide death. Culturally appropriate strategies for the prevention of self-harm and suicide are needed but the evidence is very limited from low- and middle-income countries (LMICs). This study aims to investigate the effectiveness of a culturally adapted manual-assisted problem-solving intervention (CMAP) for patients presenting after self-harm.
This was a rater-blind, multicenter randomised controlled trial. The study sites were all participating emergency departments, medical wards of general hospitals and primary care centres in Karachi, Lahore, Rawalpindi, Peshawar, and Quetta, Pakistan. Patients presenting after a self-harm episode (n = 901) to participating recruitment sites were assessed and randomised (1:1) to one of the two arms; CMAP with enhanced treatment as usual (E-TAU) or E-TAU. The intervention (CMAP) is a manual-assisted, cognitive behaviour therapy (CBT)-informed problem-focused therapy, comprising six one-to-one sessions delivered over three months. Repetition of self-harm at 12-month post-randomisation was the primary outcome and secondary outcomes included suicidal ideation, hopelessness, depression, health-related quality of life (QoL), coping resources, and level of satisfaction with service received, assessed at baseline, 3-, 6-, 9-, and 12-month post-randomisation. The trial is registered on ClinicalTrials.gov. NCT02742922 (April 2016).
We screened 3786 patients for eligibility and 901 eligible, consented patients were randomly assigned to the CMAP plus E-TAU arm (n = 440) and E-TAU arm (N = 461). The number of self-harm repetitions for CMAP plus E-TAU was lower (n = 17) compared to the E-TAU arm (n = 23) at 12-month post-randomisation, but the difference was not statistically significant (p = 0.407). There was a statistically and clinically significant reduction in other outcomes including suicidal ideation (- 3.6 (- 4.9, - 2.4)), depression (- 7.1 (- 8.7, - 5.4)), hopelessness (- 2.6 (- 3.4, - 1.8), and improvement in health-related QoL and coping resources after completion of the intervention in the CMAP plus E-TAU arm compared to the E-TAU arm. The effect was sustained at 12-month follow-up for all the outcomes except for suicidal ideation and hopelessness. On suicidal ideation and hopelessness, participants in the intervention arm scored lower compared to the E-TAU arm but the difference was not statistically significant, though the participants in both arms were in low-risk category at 12-month follow-up. The improvement in both arms is explained by the established role of enhanced care in suicide prevention.
Suicidal ideation is considered an important target for the prevention of suicide, therefore, CMAP intervention should be considered for inclusion in the self-harm and suicide prevention guidelines. Given the improvement in the E-TAU arm, the potential use of brief interventions such as regular contact requires further exploration.

BACKGROUND: chronic idiopathic demyelinating polyneuropathy (CIDP) is an acquired, immune-mediated neuropathy characterized by weakness, sensory symptoms and significant reduction or loss of deep tendon reflexes evolving over 2 months at least, associated with electrophysiological evidence of peripheral nerve demyelination. Recently, subcutaneous immunoglobulins (SCIg) have been introduced in clinical practice as a maintenance therapy for CIDP; nevertheless, electrophysiological and efficacy data are limited.
METHODS: to evaluate SCIg treatment efficacy, we retrospectively reviewed data from 15 CIDP patients referring to our clinic, receiving SCIg treatment and who performed electrophysiological studies (NCS) and clinical scores (MRC sumscore, INCAT disability score and ISS) before starting the treatment and at least one year after.
RESULTS: NCS showed no significant changes before and during treatment for all the nerves explored. Clinical scores did not significantly change between evaluations. Correlation analysis evidenced a positive correlation of cMAPs distal amplitude with MRC sumscore and a trend of negative correlation with the INCAT disability score.
CONCLUSIONS: SCIg maintenance therapy preserves nerve function in CIDP with a good efficacy and safety. Treatment effectiveness can be assessed with ENG, which represents a useful instrument in the follow-up and prognostic assessment of CIDP.

BACKGROUND: Endometrial cancer (EC) is one kind of women cancers. Bioinformatic technology could screen out relative genes which made targeted therapy becoming conventionalized.
METHODS: GSE17025 were downloaded from GEO. The genomic data and clinical data were obtained from TCGA. R software and bioconductor packages were used to identify the DEGs. Clusterprofiler was used for functional analysis. STRING was used to assess PPI information and plug-in MCODE to screen hub modules in Cytoscape. The selected genes were coped with functional analysis. CMap could find EC-related drugs that might have potential effect. Univariate and multivariate Cox proportional hazards regression analyses were performed to predict the risk of each patient. Kaplan-Meier curve analysis could compare the survival time. ROC curve analysis was performed to predict value of the genes. Mutation and survival analysis in TCGA database and UALCAN validation were completed. Immunohistochemistry staining from Human Protein Atlas database. GSEA, ROC curve analysis, Oncomine and qRT-PCR were also performed.
RESULTS: Functional analysis showed that the upregulated DEGs were strikingly enriched in chemokine activity, and the down-regulated DEGs in glycosaminoglycan binding. PPI network suggested that NCAPG was the most relevant protein. CMap identified 10 small molecules as possible drugs to treat EC. Cox analysis showed that BCHE, MAL and ASPM were correlated with EC prognosis. TCGA dataset analysis showed significantly mutated BHCE positively related to EC prognosis. MAL and ASPM were further validated in UALCAN. All the results demonstrated that the two genes might promote EC progression. The profile of ASPM was confirmed by the results from immunohistochemistry. ROC curve demonstrated that the mRNA levels of two genes exhibited difference between normal and tumor tissues, indicating their diagnostic efficiency. qRT-PCR results supported the above results. Oncomine results showed that DNA copy number variation of MAL was significantly higher in different EC subtypes than in healthy tissues. GSEA suggested that the two genes played crucial roles in cell cycle.
CONCLUSIONS: BCHE, MAL and ASPM are tumor-related genes and can be used as potential biomarkers in EC treatment.

The interactions between drugs and their target proteins induce altered expression of genes involved in complex intracellular networks. The properties of these functional network modules are critical for the identification of drug targets, for drug repurposing, and for understanding the underlying mode of action of the drug. The topological modules generated by a computational approach are defined as functional clusters. However, the functions inferred for these topological modules extracted from a large-scale molecular interaction network, such as a protein-protein interaction (PPI) network, could differ depending on different cluster detection algorithms. Moreover, the dynamic gene expression profiles among tissues or cell types causes differential functional interaction patterns between the molecular components. Thus, the connections in the PPI network should be modified by the transcriptomic landscape of specific cell lines before producing topological clusters. Here, we systematically investigated the clusters of a cell-based PPI network by using four cluster detection algorithms. We subsequently compared the performance of these algorithms for target gene prediction, which integrates gene perturbation data with the cell-based PPI network using two drug target prioritization methods, shortest path and diffusion correlation. In addition, we validated the proportion of perturbed genes in clusters by finding candidate anti-breast cancer drugs and confirming our predictions using literature evidence and cases in the ClinicalTrials.gov. Our results indicate that the Walktrap (CW) clustering algorithm achieved the best performance overall in our comparative study.

OBJECTIVE: Nerve disorders are commonly encountered in clinical practice. Ultrasonography (USG) is a useful modality in the evaluation of most of the peripheral and superficial pathologies amenable to penetration by ultrasound. The primary objective is to study the USG findings of various peripheral nerve pathologies and to correlate them with electrophysiological (EMG-NCV) findings.
METHODS: 42 patients referred with suspicion of peripheral nervous system affection were evaluated with USG along with EMG-NCV. After reviewing detailed anatomy of the region, the affected nerve was visualized along the major neurovascular bundle or at a known anatomical landmark with a high-frequency (9-20 MHz) linear/hockey stick transducer.
RESULTS: The USG parameters, namely loss of fibrillary pattern, hypoechogenicity and nerve thickening, showed significant p value (p < 0.05) on the tests of significance, suggesting these parameters are significant predictors of nerve affection/pathology on USG. Each ultrasound parameter was correlated individually with SNAP and CMAP. The results revealed positive correlation of echogenicity (r = 0.210, p = 0.05), fibrillary pattern (r = 0.209, p = 0.05) and thickening (r = 0.387, p < 0.05) with sensory nerve action potential (SNAP) and compound muscle action potential (CMAP).
CONCLUSIONS: USG can be used as corroborative investigation to strengthen the findings of EMG-NCV. This combination represents a powerful tool in enabling appropriate planning for treatment, preventing unnecessary intervention and thus improving overall outcomes in patients with peripheral neuropathy.
UNASSIGNED: le malattie neurologiche periferiche sono comuni nella pratica clinica. L’ ecografia (US) è una modalità utile nella valutazione della maggior parte delle patologie periferiche e superficiali. L’ obiettivo primario del lavoro è studiare i reperti delle varie patologie del nervo periferico e correlarli con quelli elettrofisiologici (EMG–NCV).
UNASSIGNED: 42 Pazienti con sospette patologie del sistema nervoso periferico sono stati valutati con US ed EMG–NCV. Dopo un dettagliato studio anatomico della regione, il nervo affetto è stato visualizzato lungo tutto il fascio neurovascolare o in prossimità di un repere anatomico noto, con una sonda lineare/hockey stick ad alta frequenza (9-20 MHz).
UNASSIGNED: alcuni parametri ecografici quali la perdita del pattern fibrillare, l’ ipoecogenicità e l’ ispessimento del nervo hanno mostrato un p value significativo (p < 0.05), suggerendo che essi sono indicatrori ecografici affidabili della patologia dei nervi. Ogni parametro ecografico è stato correlato singolarmente con il SNAP ed il CMAP. I risultati hanno rivelato una correlazione positiva tra ecogenicità (r = 0.210; p = 0.05), pattern fibrillare (r = 0.209; p = 0.05), ispessimento (r = 0.387; p < 0.05) ed il potenziale d’ azione del nervo sensitivo (SNAP) ed il potenziale d’ azione della componente muscolare.
UNASSIGNED: L’ ecografia può essere utilizzata come strumento diagnostico aggiuntivo per aumentare l’accuratezza dei reperti EMG–NCV. Questa combinazione rappresenta un valido strumento al fine di programmare il trattamento, prevenire interventi non necessari e conseguentemente migliorare l’ outcome dei Pazienti con neuropatia periferica.

Due to the shortage of exercise-related research in Myasthenia Gravis (MG), there are no consensus guidelines on physical exercise for MG patients.
In this prospective pilot study, 10 MG patients with mild disease performed supervised aerobic and resistance training twice weekly for 12 weeks. The Myasthenia Gravis Composite (MGC) score, compound motor action potential (CMAP), repetitive nerve stimulation, muscle force, physical performance-based measures, serum levels of interleukin-6, muscle enzymes, and immuno-microRNAs miR-150-5p and miR-21-5p were assessed before and after the training period.
Physical exercise was well tolerated, and the MGC score was unchanged. Muscle resistance weights and CMAP amplitudes increased for biceps brachii and rectus femoris muscles, and physical performance-based measures improved. Muscle enzymes remained normal, whereas disease-specific microRNAs miR-150-5p and miR-21-5p were reduced after the training period.
We propose that general recommendations regarding physical exercise can be applied safely to well-regulated MG patients. Muscle Nerve 56: 207-214, 2017.

Botulinum neurotoxin type A1 (BoNTs/A1) and type B (BoNT/B) have been used for treating hyperactive muscle contractions. In the present study, we compared the effect of botulinum neurotoxin subtype A2 (6.5 mouse LD50 units A2 neurotoxin, A2NTX) and onabotulinumtoxinA (10 mouse LD50 units BoNT/A1 product) by measuring the compound muscle action potentials (CMAPs) before and after administration. In total, 8 healthy subjects were examined in the present study. A2NTX was injected into the extensor digitorum brevis (EDB) muscle, followed by onabotulinumtoxinA injection into the contralateral EDB muscle after 16 weeks. The CMAP amplitudes from the EDB, abductor hallucis (AH), and abductor digiti minimi pedis (ADM) muscles were measured after each BoNT injection on days 1, 3, 7, 14, 28, 56, 84, and 112 to assess the effect of the toxin. On day 14, both A2NTX and onabotulinumtoxinA produced an approximately 70% decline in EDB CMAP amplitude compared to the baseline values; significant reduction of the CMAP continued through day 112. The CMAP amplitudes from neighboring muscles (AH and ADM) remained intact throughout the study period, except for a slight but significant drop at day 28 after onabotulinumtoxinA injection compared to A2NTX. The current findings indicate that small doses (6.5 units and 10 units) of A2NTX and onabotulinumtoxinA have at least comparable onset and duration of action, although similar clinical effects were obtained with lower dose using A2NTX.

Thirty patients with diabetic polyneuropathy were recruited from the diabetic clinic in Hospital Universiti Sains Malaysia from 1996 to 1998. They were randomly assigned either sulbutiamine (Arcalion(®)) (15 patients) or no treatment (control group; 15 patients). Glycaemic control was assessed by blood glucose and HbA1. Severity of neuropathy was assessed by symptom and sign score, and electrophysiological parameters (nerve conduction velocity and compound muscle action potential) at entry to the study and after 6 weeks. There were improvements in the electrophysiological parameters in the treatment group when compared to the controls with significant improvement in the median nerve conduction velocity (p<0.001), median compound muscle action potential (p<0.001), peroneal nerve conduction velocity (p<0.001), and peroneal compound muscle action potential (p<0.001). No significant improvement in symptom and sign scores were noted between the groups but a significant improvement compared to base line was noted for the sulbutiamine treated group. (p< 0.05). The glycaemic control in both groups was not significantly different at base line and was stable throughout the study. Sulbutiamine objectively improved peripheral nerve function in diabetic polyneuropathy although the symptom score did not improve, possibly due to the short duration of the study.