Short-term changes in serum miRNA levels and patient-reported clinical outcomes in myasthenia gravis.

INTRODUCTION/AIMS: The circulating microRNAs (miRNAs) miR-150-5p, miR-30e-5p, and miR-21-5p have been suggested as potential biomarkers for myasthenia gravis (MG); however, the relationships between short-term natural changes of the miRNAs and patient-reported MG outcome scores have not been well-studied. We assessed the short-term fluctuations in miRNA levels and patient-reported outcome measures in MG. METHODS: This prospective cohort study included 39 MG patients with regular follow-ups and unchanged medications at the Neurology outpatient clinic at Uppsala University Hospital. Patients had weekly follow-up visits for 1 month, at which blood samples were drawn, and scores from MG activities of daily living (MG-ADL), MG quality-of-life-15 (MG-QoL15), and Fatigue Severity Scale (FSS) were assessed. Serum levels of miRNA miR-150-5p, miR-30e-5p, and miR-21-5p were analyzed using quantitative real-time PCR. RESULTS: Intra-individual levels of miR-30e-5p and miR-150-5p were stable, whereas a significant reduction in miR-21-5p was observed from week 1 to week 2 (p = .0024) and from week 2 to week 3 (p < .0001). There were intra-individual differences over a short time in MG-ADL, with higher scores in female patients (p = .0281) and a significant reduction from the first to the second weeks (p = .0281), whereas MG-QoL15 and FSS scores were stable. DISCUSSION: The suggested MG biomarkers miR-30e-5p and miR-150-5p were more stable than miR-21-5p over a short time, indicating their short-term stability as biomarkers. Prospective multi-center studies with longer periods of follow-up and matched controls are needed to validate these miRNAs as biomarkers in MG.

Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis.

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.

Probabilistic risk assessment of dietary exposure to benzophenone derivatives in cereals in Taiwan.

Benzophenone (BP) and BP derivatives (BPDs) are widely used as ultraviolet (UV) stabilizers in food packaging materials and as photoinitiators in UV-curable inks for printing on food-contact materials. However, our knowledge regarding the sources and risks of dietary exposure to BP and BPDs in cereals remains limited, which prompted us to conduct this study. We measured the levels of BP and nine BPDs-BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone, 4-hydroxybenzophenone, 4-methylbenzophenone (4-MBP), methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl-in three types of cereals (rice flour, oatmeal, and cornflakes; 180 samples in total). A Bayesian Markov-chain Monte Carlo (MC) simulation approach was used for deriving the posterior distributions of BP and BPD residues. This approach helped in addressing the uncertainty in probabilistic distribution for the sampled data under the detection limit. Through an MC simulation, we calculated the daily exposure levels of dietary BP and BPDs and corresponding health risks. The results revealed the ubiquitous presence of BP, BP-3, and 4-MBP in cereals. Older adults (aged >65 years) had the highest (97.5 percentile) lifetime carcinogenic risk for BP exposure through cereals (9.41 × 10-7), whereas children aged 0-3 years had the highest (97.5 percentile) hazard indices for BPD exposure through cereals (2.5 × 10-2). Nevertheless, across age groups, the lifetime carcinogenic risks of BP exposure through cereals were acceptable, and the hazard indices for BPD exposure through cereals were <1. Therefore, BPD exposure through cereals may not be a health concern for individuals in Taiwan.

Safety evaluation of single-sperm cryopreservation technique applied in intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

Clinical features and prognosis of cardiac metastatic tumors.

BACKGROUND: This study aimed to explore the clinical features and prognosis of cardiac metastatic tumors. In addition, whether continuing antitumor therapy after the development of cardiac metastases can benefit patients and the response of cardiac metastases were investigated. METHODS: A retrospective analysis was conducted on patients with malignancies who were admitted to Fujian Cancer Hospital and Fujian Provincial Hospital from January 2007 to September 2022, and the follow-up period ended in March 2023. Clinical data were gathered, treatment efficacy was evaluated, and survival analysis was performed. RESULTS: After the patients developed cardiac metastasis, the overall 30-day, 3-month, 6-month, and 12-month survival rates were 85.00%, 59.00%, 51.00% and 38.00%, respectively. With continued treatment, the average survival time was 27.33 months (95% confidence interval [CI]: 16.88-37.79), which exceeded the 6.6 months (95% confidence interval [CI]: 0.03-13.69) observed for patients who withdrew from treatment (P < 0.001). The responses of cardiac metastases corresponded to the responses of the primary tumors. Patients with a cardiac response had a median survival time of 55.60 months, which exceeded the 13.40 months observed for those without a cardiac response. However, there was no significant difference (P = 0.375). CONCLUSIONS: In conclusion, continuing antitumor therapy after the development of cardiac metastases can significantly prolong patient survival. Cardiac metastases and primary tumors respond consistently to antitumor treatment. The risk of death due to heart failure in cancer patients with cardiac metastases needs to be further investigated.

Exposure to bisphenols, parabens and phthalates during pregnancy and postpartum anxiety and depression symptoms: Evidence from women with twin pregnancies.

BACKGROUND: Women are vulnerable to suffer from the common mental disorders like anxiety and depression during the postpartum period. Exposure to bisphenols, parabens, and phthalates has been linked to anxiety and depression symptoms in the general population. However, little is known about their impacts on postpartum women. OBJECTIVE: To evaluate the effects of individual and joint exposure to 11 nonpersistent chemicals during pregnancy on postpartum anxiety and depression. METHODS: Among 278 mothers from the Wuhan Twin Birth Cohort (WTBC), bisphenols, parabens, and phthalate metabolites were measured in maternal urine samples from each trimester. Self-rating Anxiety Scale (SAS) and Edinburgh Postnatal Depression Scale (EPDS) were administrated at early pregnancy and 1 month and 6 months postpartum to determine anxiety and depression symptoms, respectively. Associations between urinary chemical biomarkers (individual or mixtures) and anxiety and depression symptoms were estimated using multiple informant model and quantile-based g-computation. RESULTS: With adjustment for confounders, one quartile increase in the overall chemical mixture (bisphenols, parabens and phthalate metabolites) during the second trimester was associated with 1.03-point (95% CI: 0.07, 1.99, P = 0.036) higher EPDS score at 1 month postpartum, in which bisphenol A (BPA) and bisphenol F (BPF) contributed the most to the positive association. Consistent effects were also observed in the multiple informant models. We found that second-trimester BPA and BPF exposure individually showed the strongest and significant associations with anxiety and depression symptoms, and some of associations differed across trimesters (Ptrimester-int < 0.05). CONCLUSIONS: Second-trimester nonpersistent chemical exposure was associated with increased postpartum anxiety and depression symptoms.

Lack of Association Between PDCD-1 Polymorphisms and Colorectal Cancer Risk: A Case-Control Study.

Functional variants of immune-related genes may be implicated in the occurrence of colorectal cancer (CRC). In this study, Programmed cell death (PDCD)-1.6 (rs10204525 T/C), PDCD-1.7 (rs7421861 A/G), and PDCD-1.9 (rs2227982 A/G) loci were selected to explore gene expression and the potential susceptibility to the development of CRC. Here, 1,003 CRC patients and 1,303 controls were included and three PDCD-1 tagging loci were selected and analyzed by using SNPscan genotyping assays. SHESIS software was harnessed to obtain the haplotypes of the PDCD-1 gene. We found that the genotype and allele distribution of PDCD-1 tagging loci did not significantly affect the risk of CRC. Adjustment for body mass index, age, smoking, alcohol using and sex also found that PDCD-1 tagging loci did not influence the occurrence of CRC. In conclusion, this study suggests that the PDCD-1 tagging loci (rs10204525, rs7421861, and rs2227982) are not correlated with CRC susceptibility.

Effect of Muller's muscle-conjunctival resection on the upper eyelid crease position in Asian eyelids: a retrospective cohort study.

PURPOSE: Investigating the effect of Muller's muscle-conjunctival resection (MMCR) on the eyelid crease position. METHODS: This retrospective study included patients with unilateral acquired blepharoptosis who underwent MMCR during October 2018-December 2021. The following factors were recorded: preoperative, after phenylephrine, postoperative marginal reflex distance1 (MRD1) and tarsal platform show (TPS) of bilateral eyelids. The primary outcome was to measure the change in TPS and evaluate the factors associated with post-operative TPS. The secondary outcomes included exploring the rate of MRD1 and TPS symmetry after the operation. RESULTS: Forty patients were included in the final analysis. The mean MRD1 of the ptotic eye was 1.28 ± 0.78 mm, 2.79 ± 0.66 mm and 3.20 ± 0.67 mm before, after phenylephrine and after the operation, respectively. The mean TPS of the ptotic eye was 5.90 ± 1.86 mm, 3.96 ± 1.49 mm and 2.79 ± 1.63 mm before, after phenylephrine and after the operation, respectively. Changes in mean TPS after the phenylephrine test and post-operation were statistically significant (p < 0.001). The linear regression model revealed that the absolute change in TPS after phenylephrine drop and absolute change in MRD1 post-operation were significantly correlated with the absolute change in TPS post-operation. Besides, the ratio of symmetry in MRD1 and TPS was greatly improved post-operation (82.5% and 70.0% respectively). CONCLUSION: MMCR is an effective surgical method for ptosis correction as it can not only correct the eyelid crease position but also narrow the wide TPS. This method is particularly beneficial to patients with both mild to moderate ptosis and an asymmetric crease height.

Design of a Multi-Sensor System for Exploring the Relation between Finger Spasticity and Voluntary Movement in Patients with Stroke.

A novel wearable multi-sensor data glove system is developed to explore the relation between finger spasticity and voluntary movement in patients with stroke. Many stroke patients suffer from finger spasticity, which is detrimental to their manual dexterity. Diagnosing and assessing the degrees of spasticity require neurological testing performed by trained professionals to estimate finger spasticity scores via the modified Ashworth scale (MAS). The proposed system offers an objective, quantitative solution to assess the finger spasticity of patients with stroke and complements the manual neurological test. In this work, the hardware and software components of this system are described. By requiring patients to perform five designated tasks, biomechanical measurements including linear and angular speed, acceleration, and pressure at every finger joint and upper limb are recorded, making up more than 1000 features for each task. We conducted a preliminary clinical test with 14 subjects using this system. Statistical analysis is performed on the acquired measurements to identify a small subset of features that are most likely to discriminate a healthy patient from patients suffering from finger spasticity. This encouraging result validates the feasibility of this proposed system to quantitatively and objectively assess finger spasticity.

Coupled relationships among anammox, denitrification, and dissimilatory nitrate reduction to ammonium along salinity gradients in a Chinese estuarine wetland.

Salinization in estuarine wetlands significantly alters the balance between their nitrogen (N) removal and retention abilities but these processes have not yet been characterized effectively. In the present study, the potential rates of sediment denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) were mapped using N isotope tracing methods along salinity gradients across the Yellow River Delta wetland (YRDW) in China. The contribution of anammox to total dissimilatory N transformations in YRDW was merely 6.8%, whereas denitrification and DNRA contributed 52.3% and 40.9%, respectively. The potential rate of denitrification (5.82 µmol/kg/h) decreased significantly along salinity gradients and markedly exceeded DNRA potential rate (2.7 µmol/kg/h) in fresh wetlands, but was lower than that of DNRA in oligohaline wetlands (3.06 and 3.18 µmol/kg/h, respectively). Moreover, a significantly positive relationship between salinity and DNRA/denitrification was obeserved, indicating that increased salinity may favor DNRA over denitrification. Furthermore, total sulfur (TS) content and ratio of total organic carbon to total nitrogen (C/N) increased with the salinity gradient and showed evident positive relationships with the DNRA/denitrification ratio. In this study, we proved that increased salinization resulted in the dominance of DNRA over denitrification, possible through the addition of S and alteration of the C/N in estuarine wetlands, leading to increased N retention in estuarine wetlands during salinization, which would enhance the eutrophication potential within wetlands and in downstream ecosystems.

Fat-Water Swaps in Iterative Decomposition of Water and Fat With Echo Asymmetry and Least-Squares Estimation Magnetic Resonance Imaging for Postinstrumentation Spine.

OBJECTIVE: To determine the frequencies of fat-water swaps in iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) water-only images of the postinstrumentation spine and discuss the efficiency of in-phase imaging in improving visibility of the thecal sac. MATERIALS AND METHODS: A total of 276 patients (167 women; mean age, 62.3 years; range, 23-89 years) with metallic devices on the lumbar spine who received complete routine 1.5 T MR imaging, including axial and sagittal images of T1-weighted, T2-weighted, and T2-weighted IDEAL sequences, were included. The exclusion criteria were significant motion artifacts and severe metallic artifacts in any one of the sequences. The images were reviewed by two radiologists to identify fat-water swaps that were divided into 3 groups: extraspinal swaps, intraspinal swaps in sagittal images, and intraspinal swaps in axial images. The qualitative evaluations for the spinal canal in axial images were performed by rating on a five-point scale. Side-by-side comparisons of T2-weighted images and IDEAL in-phase images were also performed. RESULTS: In patient-based data of 276 patients, extraspinal fat-water swaps were noted in 10 patients (3.6%) and intraspinal swaps were noted in 160 patients (58.0%). The intraspinal swaps had a higher incidence in the patients with more levels of metallic devices with screws and the trend was not noted in the extraspinal swaps. A total of 928 axial levels were evaluated in the level-based data of axial images. T1-weighted, T2-weighted, and IDEAL in-phase images had significantly better imaging quality than the IDEAL water-only images (3.9 ± 0.4, 3.9 ± 0.3, 3.8 ± 0.4 vs 3.0 ± 1.3, all P < 0.001). Compared with T2-weighted images, most of the IDEAL in-phase images (reader 1, 90.9%; reader 2, 86.7%) present similar quality. CONCLUSION: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation sequence can provide good fat suppression in most spine MRI with metallic devices but the loss of cerebrospinal fluid signal intensities due to fat-water swaps are noted in more than half of postinstrumentation spine. Routine reconstruction of in-phase images is recommended to improve evaluation of the thecal sac by avoiding pitfall caused by fat-water swaps.

Herbal complex 'Buyang Huanwu Tang' improves motor endplate function of denervated-dependent skeletal muscle atrophy in rat.

Denervated-dependent skeletal muscle atrophy is a disease induced by skeletal muscle associated peripheral neuro-disconnection. Its specific molecular mechanisms remain unknown. The treating for denervated-dependent skeletal muscle atrophy is applied with an herbal complex Buyang Huanwu Tang used in traditional Chinese medicine and subjected to the established denervated-dependent skeletal muscle atrophy in rat models, and the therapeutic effects and associated mechanisms were evaluated in the pathogenesis of denervated-dependent skeletal muscle atrophy. Denervated-dependent skeletal muscle atrophy in rats was established and randomly divided into eight groups, including Normal control, Model, Positive control, Model + Buyang Huanwu Tang, Model + astragalus extracts, Model + Buyang Huanwu Tang-astragalus, Buyang Huanwu Tang + LY294002, and astragalus extract + LY294002 group. Hematoxylin-eosin staining and quantitative RT-PCR (qRT-PCR) assay were used to examine the inflammatory response of muscle tissues. Quantitative RT-PCR and Western blotting assay were utilized to analyze mRNA and protein expression. Immunohistochemistry assay was used to detect molecule expression in anterior cervical muscle tissues. Motor endplate activity was examined using the wholemount acetylcholinesterase staining method. The wet mass ratio of anterior cervical muscle was measured. The results indicated that Buyang Huanwu Tang treatment significantly alleviated inflammatory response, enhanced acetylcholinesterase activity, and motor endplate functions, and promoted wet mass of anterior cervical muscle compared to denervated-dependent skeletal muscle atrophy rat models (P < 0.05). Buyang Huanwu Tang regulated molecules of PI3K/PKB/GSK3ß/FOXO1 signaling pathway. Buyang Huanwu Tang significantly reduced muscle atrophy F-box protein, MuFR-1, Bax and caspase 9 expression, significantly enhanced Bcl-2 expression, and remarkably increased element-binding protein and vascular endothelial growth factor levels, compared to Model group (P < 0.05). Buyang Huanwu Tang suppressed caspase 9 and caspase 3 activity and associated apoptosis. Moreover, PI3K specific blocker, LY294002, significantly inhibited the effects of Buyang Huanwu Tang on the above molecule expression (P < 0.05). In conclusion, Buyang Huanwu Tang improved motor endplate functions of denervated-dependent skeletal muscle atrophy rat model through suppressing mitochondria-mediated apoptosis and activating PI3K/PKB/FOXO1 signaling pathway.

Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy.

BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.

Red/green/blue LD mixed white-light communication at 6500K with divergent diffuser optimization.

Enabling laser white-lighting at a correlated color temperature (CCT) of 6500K with the use of only red/green/blue (RGB) tri-color laser diodes (LDs) is demonstrated, which can further perform wavelength division multiplexing (WDM) communication with a high-spectral-usage 16 QAM-OFDM data stream at 11.2 Gbps over 0.5 m. The sampling rate of encoded data is optimized to avoid the aliasing effect and to effectively amplify the signal with high on/off extinction and modulation depth. Proper oversampling can decrease the peak-to-average power ratio (PAPR) of the OFDM data and filter out unwanted noise. There are also six different diffusers used to diverge the white-light mixed by the RGB LD beam. By analyzing the color-casting transmittance, surface roughness, CCT uniformity, divergent angle of the diffuser, and the data transmission capacity, the frosted glass (FG2.8) diffuser with high transmittance diverges the white light with the divergent angle of ± 20° and supports the highest data rate of 14 Gbps over 0.5 m. To fit the day-light CCT, the blue LD power at an optimized bias current is further attenuated with a 0.6-optical density filter for reducing CCT from 100000K to 6500K; however, such an adjustment also degrades the SNR ratio to sacrifice the achievable data rate of the blue LD. The polycarbonate (PC1.5) diffuser with proper surface roughness diverged white-light exhibits the best CCT uniformity and a divergent angle of ± 30° but supports a data rate of only 6.4 Gbps over 0.5 m. The poly (methyl methacrylate) PMMA1.5 diffuser scatters the white light with the largest angle of ± 40°; however, the data rate also decreases to 4.8 Gbps over 0.5 m.

Sonographic median nerve change after steroid injection for carpal tunnel syndrome.

INTRODUCTION: The sonographic changes of the median nerve after steroid injection for carpal tunnel syndrome (CTS) still require investigation. METHODS: Sixty-two patients with CTS were included. The Boston Carpal Tunnel Questionnaire was administered, and ultrasonographic examinations were performed before and at 2, 6, and 12 weeks after steroid injection. At 12 weeks, general improvement was scored on a 6-point Likert scale. RESULTS: After treatment, the cross-sectional area (CSA) of the median nerve was significantly reduced at 2-, 6-, and 12-week follow-ups (for each, P < 0.001, analysis of variance). The "significant improvement" group (n = 39) had a significantly greater reduction in the CSA at the carpal tunnel inlet (P = 0.014) and CSA in the proximal carpal tunnel (P = 0.003) compared with the "little/no improvement" group (n = 23). DISCUSSION: Sonographic measurement of CSA may be considered complementary to the standard clinical evaluation in monitoring of treatment response in patients with CTS. Muscle Nerve 58: 402-406, 2018.

Interactive effects of nonylphenol and bisphenol A exposure with oxidative stress on fetal reproductive indices.

Nonylphenol (NP) and/or bisphenol A (BPA) may have reproductive effects. Although the mechanisms of action remain unclear, steroid hormones biosynthesis, hypothalamus pituitary adrenal axis activity, oxidative stress, and crosstalk interaction of NP and BPA mixture and its pathways may play a contributory role. This cross-sectional study examined whether the interactive effects of NP/BPA and oxidative stress biomarkers played a role in reproductive indices (penis length and anogenital distance (AGD)) in 244 mother-fetus pairs. Four biomarkers of oxidative stress, (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 8-iso-prostaglandin F2α (8-isoPF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were simultaneously analyzed using the high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method. No significant associations were found between reproductive indices and NP/BPA or oxidative stress biomarkers. Maternal exposure to a mixture of NP and BPA may enhance 8-OHdG. Interactive effects were found in the high 8-isoPF2α group, and prenatal NP exposure was inversely associated with penis length (ß = -3.68 mm; p = 0.01). Similar results were noted among boys who were born to mothers in the high 8-isoPF2α group, in which BPA was inversely associated with penis length (ß = -4.43 mm; p = 0.005). Our findings suggest important implications for prenatal exposure to oxidative stress, as evidenced by the 8-isoPF2α level. Thus, NP and BPA may interact to shape fetal reproductive tract development, particularly in boys. The interactive effects of NP/BPA, oxidative stress, and reproductive indices should be considered.

Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF-κB-mediated IKKß expression.

We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we demonstrate how COL11A1 regulates twist family basic helix-loop-helix transcription factor 1-related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA-mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression. TWIST1 messenger RNA levels positively associated with COL11A1 messenger RNA expression levels in ovarian tumors. High TWIST1 expression levels were significantly associated with a progression-free interval of ≤ 6 months (p = 0.001) and death (p = 0.040). In addition, patients with high TWIST1 mRNA levels had significantly shorter 5-year overall-survival (p = 0.004) and progression-free survival (p = 0.009) rates, compared to patients with low TWIST1 levels. Increased TWIST1 expression caused by COL11A1-induced transcription of the inhibitor of nuclear factor kappa B kinase subunit beta (IKKß) gene occurred via increased SP1 phosphorylation and binding to the IKKß promoter. COL11A1-mediated nuclear factor-kappa B activation, via transcriptional activation of IKKß, promoted TWIST1, Mcl-1, and GAS6 expression, which were associated with chemoresistance and anti-apoptosis in ovarian cancer cells. We suggest that IKKß and TWIST1 can potentially be targeted in patients with COL11A1-positive ovarian cancer.

Prenatal Nonylphenol and Bisphenol A Exposures and Inflammation Are Determinants of Oxidative/Nitrative Stress: A Taiwanese Cohort Study.

Prenatal exposure to nonylphenol (NP) and/or bisphenol A (BPA) has been reported to be associated with adverse birth outcomes; however, the underlying mechanisms remain unclear. The primary mechanism is endocrine disruption of the binding affinity for the estrogen receptor, but oxidative stress and inflammation might also play a contributory role. We aimed to investigate urinary NP and BPA levels in relation to biomarkers of oxidative/nitrative stress and inflammation and to explore whether changes in oxidative/nitrative stress are a function of prenatal exposure to NP/BPA and inflammation in 241 mother-fetus pairs. Third-trimester urinary biomarkers of oxidative/nitrative stress were simultaneously measured, including products of oxidatively and nitratively damaged DNA (8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua)) as well as products of lipid peroxidation (8-iso-prostaglandin F2α (8-isoPF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)). The antioxidant glutathione peroxidase (GPx) and inflammation biomarkers, including C-reactive protein (CRP) and a panel of cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)), were analyzed in maternal and umbilical cord plasma samples. In adjusted models, we observed significant positive associations between NP exposure and 8-OHdG and 8-NO2Gua levels, between BPA and 8-isoPF2α levels, and between maternal CRP levels and HNE-MA levels. Additionally, BPA and TNF-α levels in cord blood were inversely associated with maternal and GPx levels in cord blood as well as maternal TNF-α levels were inversely associated with maternal GPx levels. These results support a role for exposure to NP and BPA and possibly inflammation in increasing oxidative/nitrative stress and decreasing antioxidant activity during pregnancy.

Case report: term birth after fertility-sparing treatments for stage IB1 small cell neuroendocrine carcinoma of the cervix.

BACKGROUND: Advances in cervical cancer management for childbearing women have led to less radical approaches. Use of fertility-sparing treatment to treat small cell neuroendocrine carcinoma (SCNEC) is challenging owing to the aggressive nature of the disease, even in early stage disease. CASE PRESENTATION: A 25-year-old nulligravida woman presented with malodorous vaginal discharge and was diagnosed to have an exophytic cervical SCNEC. A magnetic resonance image scan showed no evidence of parametrial invasion or distant metastasis. Clinical staging allocated her to stage IB1 disease. She underwent radical abdominal trachelectomy for reproductive purpose. Preoperative and postoperative chemotherapy with ifosfamide/etoposide/cisplatin combining gonadotropin-releasing hormone agonist were administered. She had a spontaneous, uneventful pregnancy and successfully delivered a term baby via cesarean section 7 years after treatment. CONCLUSION: To our knowledge, we describe the first success in offering a fertility-preserving multimodality strategy to present favorable oncologic, reproductive, and obstetric outcomes in a fertile woman of stage I SCNEC. Individualized multimodality therapy may be utilized in specific patients with early-stage cervical cancer to preserve their fertility.