Association between estradiol levels in early pregnancy and risk of preeclampsia after frozen embryo transfer.

Introduction: The failure of remodeling the spiral arteries is associated with the pathogenesis of preeclampsia. Estradiol (E2) plays a crucial role in placentation and may be involved in the development of preeclampsia. However, there is a lack of data in this area. This study aims to assess the association between serum estradiol levels in early pregnancy and the risk of preeclampsia. Methods: We conducted a retrospective cohort study on patients who conceived after frozen embryo transfer (FET) using data from a database at a university-affiliated in vitro fertilization center. The study period spanned from January 1, 2010, to December 31, 2020. Multivariable logistic regression analyses were performed to determine the adjusted effect of E2 levels on the risk of preeclampsia. We compared the odds ratios of preeclampsia across quartiles of E2 levels and assessed their significance. Results: Serum E2 levels at the fifth gestational week were significantly different between women with and without preeclampsia after FET programmed cycles (607.5 ± 245.4 vs. 545.6 ± 294.4 pg/ml, p=0.009). A multivariable logistic regression model demonstrated that E2 levels in early pregnancy were independent risk factors for preeclampsia. We observed an increased odds ratio of preeclampsia with increasing quartiles of estradiol levels after adjusting for potential confounders in FET programmed cycles. When comparing quartiles 3 and 4 (E2 > 493 pg/ml at the fifth gestational week) to quartiles 1 and 2, the odds ratios of preeclampsia were significantly higher. Conclusion: We found that serum E2 levels in early pregnancy may impact the risk of preeclampsia, particularly following FET programmed cycles. The association between E2 levels in early pregnancy and preeclampsia deserves further investigation.

The value of LH maximum level in predicting optimal oocyte yield following GnRH agonist trigger.

Background: Risk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone. Methods: We retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle. Results: Following confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035-47.274). Group 1 (b = -12.72; 95% CI -20.9 to -4.55) and BMI (b = -0.25; 95% CI -0.5 to -0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS. Conclusions: The maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes.

Stress-related reduction of hippocampal subfield volumes in major depressive disorder: A 7-Tesla study.

Background: Major depressive disorder (MDD) is a prevalent health problem with complex pathophysiology that is not clearly understood. Prior work has implicated the hippocampus in MDD, but how hippocampal subfields influence or are affected by MDD requires further characterization with high-resolution data. This will help ascertain the accuracy and reproducibility of previous subfield findings in depression as well as correlate subfield volumes with MDD symptom scores. The objective of this study was to assess volumetric differences in hippocampal subfields between MDD patients globally and healthy controls (HC) as well as between a subset of treatment-resistant depression (TRD) patients and HC using automatic segmentation of hippocampal subfields (ASHS) software and ultra-high field MRI. Methods: Thirty-five MDD patients and 28 HC underwent imaging using 7-Tesla MRI. ASHS software was applied to the imaging data to perform automated hippocampal segmentation and provide volumetrics for analysis. An exploratory analysis was also performed on associations between symptom scores for diagnostic testing and hippocampal subfield volumes. Results: Compared to HC, MDD and TRD patients showed reduced right-hemisphere CA2/3 subfield volume (p = 0.01, η 2 = 0.31 and p = 0.3, η 2 = 0.44, respectively). Additionally, negative associations were found between subfield volumes and life-stressor checklist scores, including left CA1 (p = 0.041, f 2 = 0.419), left CA4/DG (p = 0.010, f 2 = 0.584), right subiculum total (p = 0.038, f 2 = 0.354), left hippocampus total (p = 0.015, f 2 = 0.134), and right hippocampus total (p = 0.034, f 2 = 0.110). Caution should be exercised in interpreting these results due to the small sample size and low power. Conclusion: Determining biomarkers for MDD and TRD pathophysiology through segmentation on high-resolution MRI data and understanding the effects of stress on these regions can enable better assessment of biological response to treatment selection and may elucidate the underlying mechanisms of depression.

Clinical use of aqueous subcutaneous progesterone compared with vaginal progesterone as luteal support in in vitro fertilization: A randomized controlled study in Taiwan.

OBJECTIVE: This study aims to compare the efficacy, tolerability and patient satisfaction between aqueous subcutaneous progesterone (Prolutex, 25 mg/vial; IBSA) and vaginal progesterone (Crinone, 90 mg/tube; Merck) as luteal support for fresh embryo transfers in in-vitro fertilization (IVF). MATERIALS & METHODS: In this prospective randomized study, 65 patients who underwent IVF were recruited and randomly assigned to either the Prolutex (25 mg daily, n = 33) or Crinone (90 mg daily, n = 32) group. The luteal support regimens were given daily, starting from two days after oocyte pickup. If the serum pregnancy test was positive, luteal support was continued until 7 weeks of gestation. Primary outcomes were clinical pregnancy rate and serum progesterone level at the mid-luteal phase and at 4 weeks of gestation. Secondary outcomes were drug tolerability and patient satisfaction assessed by questionnaire. RESULTS: There were no significant differences in clinical pregnancy rates (Prolutex 25.0% versus Crinone 33.3%, p = 0.699), serum progesterone levels and patient satisfaction between Prolutex and Crinone group. Although the patients that had received Prolutex complained of more local pain at the injection sites, they also had less annoying vaginal discharges and vulvar discomforts. CONCLUSION: Prolutex is of comparable efficacy and patient satisfaction to Crinone, and its availability means patients have more options in regards to the routes of progesterone administration as luteal phase support during IVF.

Usage and cost-effectiveness of elective oocyte freezing: a retrospective observational study.

BACKGROUND: The previous model-based cost-effectiveness analyses regarding elective oocyte cryopreservation remained debatable, while the usage rate may influence the cost per live birth. The aim of this study is to disclose the usage and cost-effectiveness of the planned cryopreserved oocytes after oocyte thawing in real-world situations. METHODS: This was a retrospective single-center observational study. Women who electively cryopreserved oocytes and returned to thaw the oocytes were categorized as thawed group. The oocytes were fertilized at our center and the sperm samples for each individual was retrieved from their respective husbands. Clinical outcomes were traced and the cumulative live birth rate per thawed case was calculated. The costs from oocyte freezing cycles to oocyte thawing, and embryo transfer cycles were accordingly estimated. The cumulative cost per live birth was defined by the cumulative cost divided by the live births per thawed case. RESULTS: We recruited 645 women with 840 oocyte retrieval cycles for elective oocyte freezing from November 2002 to December 2020. The overall usage rate was 8.4% (54/645). After the storage duration exceeded ten years, the probabilities of thawing oocytes were 10.6%, 26.6%, and 12.7% from women who cryopreserved their oocytes at the age ≤ 35 years, 36-39 years, and ≥ 40 years, respectively (P = 0.304). Among women who thawed their oocytes, 31.5% (17/54) of women achieved at least one live birth. For the age groups of ≤ 35 years, 36-39 years, and ≥ 40 years, the cumulative live birth rates per thawed case were 63.6%, 42.3%, and 17.6%, respectively (P = 0.045), and the cumulative costs for one live birth were $11,704, $17,189, and $35,642, respectively (P < 0.001). CONCLUSIONS: The overall usage rate was 8.4% in our cohort. The cumulative live birth rate was greatest in the youngest group and the cumulative cost per live birth was highest in the oldest group, which was threefold greater than that in the group aged ≤ 35 years. The findings added to the limited evidence of the usage rate in real-world situations, which could hopefully aid future analysis and decision-making in public health policy and for women willing to preserve fertility. TRIAL REGISTRATION: None.

Vaginal birth after cesarean section: Experience from a regional hospital.

OBJECTIVE: Trial of labor after cesarean section (TOLAC) is an option for women with previous cesarean section. However, few women choose this option because of safety concerns. We evaluate the safety and risks associated with TOLAC and the success rate of vaginal birth after cesarean delivery (VBAC). MATERIAL AND METHODS: We reviewed all patients with a history of previous cesarean section that underwent elective repeat cesarean section (ERCS) or TOLAC in a regional teaching hospital from Nov, 2013 to May, 2018. Maternal basic clinical information, intrapartum management, postpartum complications, and neonatal outcomes were analyzed. RESULTS: 199 pregnant women with a history of at least one previous cesarean section were enrolled. 156 women received ERCS and 43 women (21.6%) underwent TOLAC, with 37 (86.0%) who underwent successful VBAC. The VBAC rate was 18.6%. Higher success rate was found in women with previous vaginal birth than in women without vaginal birth (100% vs. 81.8%). One case (2.3%) in the VBAC group was complicated with uterine rupture and inevitable neonatal death during second stage of labor. The uterus was repaired without maternal complications. In another case, the newborn's condition was complicated with low APGAR score (<7) at birth due to maternal chorioamnionitis. Among indications for previous cesarean section, cephalo-pelvic disproportion (CPD) was associated with TOLAC failure and uterine rupture after VBAC. CONCLUSION: VBAC is a feasible and safe option. Modes of delivery should be thoroughly discussed when considering TOLAC for women with history of previous cesarean section due to CPD, considering its association with TOLAC failure in second stage of labor.

Experience in different modes of delivery in twin pregnancy.

BACKGROUND/PURPOSE: Vaginal delivery, compared with Cesarean delivery, remains a less chosen mode of delivery for twin pregnancy. We studied the maternal and perinatal outcomes of twin pregnancy with different modes of delivery. METHODS: A retrospective study with data collected from a regional hospital, including vital twin pregnancies delivered at gestational age of 32 weeks and above. Medical charts were reviewed for prenatal conditions and postpartum outcomes. RESULTS: Ninety-eight pairs of twins were included and 44.9% were delivered via vaginal delivery. Women in the vaginal delivery group were significantly younger (32.5 ±4.3 years versus 34.8 ±4.6 years, p < 0.01), multiparous (34.1% versus 18.5%) and with more twins in vertex-vertex presentation (70.5% versus 33.3%) compared with women in the Cesarean delivery group. There were no differences between maternal postpartum complications and neonatal outcomes in both groups. The outcomes showed longer inter-twin delivery time interval (5.7 ± 5.6 versus 1.5 ± 0.9 min, p < 0.01), less estimated blood loss (198.7 ± 144.1 versus 763.2 ± 332.3 mL, p < 0.01), and shorter maternal hospital stay (3.0 ± 0.5 versus 5.7 ± 0.5 days, p< 0.01) in the vaginal delivery group. Twenty newborns had Apgar score below seven at birth. Logistic regression analysis revealed that low Apgar score was independently related to younger maternal age, maternal obstetric diseases and fetal non-vertex presentation. Gestational weeks and mode of delivery were not related to low Apgar score. CONCLUSION: With careful case selection, vaginal delivery could be safely performed in twin pregnancies with less estimated blood loss and better recovery than Cesarean delivery.

Lateralisation of subcortical functional connectivity during and after general anaesthesia.

BACKGROUND: Arousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. METHODS: Resting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left-right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. RESULTS: Functional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left-right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. CONCLUSIONS: Functional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. CLINICAL TRIAL REGISTRATION: NCT02275026.

Diagnosis of Peritoneal Tuberculosis from Primary Peritoneal Cancer.

Peritoneal tuberculosis (PTB) is an uncommon extrapulmonary infection mimickng primary peritoneal cancer (PPC). We retrospectively included 23 women with PTB and 47 women with PPC treated in a medical center to study the clinical and radiological features that differentiate PTB from PPC. Body temperature above 38 °C was a unique feature of PTB (34.7% versus 0%, p < 0.001). Body Mass Index (BMI) was lower (21.9 ± 3.7 versus 25.2 ± 4.1, p = 0.003), white blood cell (WBC) count was lower (5179.6 ± 1502.2 versus 7716.2 ± 2741.8, p < 0.001), and CA-125 level was lower (508.0 ± 266.1 versus 2130.1 ± 2367.2 U/mL, p < 0.001) in PTB compared with PPC. Imaging detected more pulmonary infiltration and consolidation (52.2% versus 6.4%, p < 0.001), and less omental/mesentery changes (52% versus 83%, p < 0.001) in PTB compared with PPC. The operated patients received earlier treatment compared to patients without operation (7.9 ± 5.3 days versus 17.2 ± 11.0 days, p = 0.010). In conclusion, fever above 38 °C, lower BMI, lower WBC count, less elevated CA-125 level, and imaging of less omental involvement were features of PTB differentiated from PPC.

Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia.

BACKGROUND: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls. METHODS: Thirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1-weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls. RESULTS: CSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75 mm2) compared with side-matched controls (5.77 mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347 mm3) was reduced on the symptomatic side compared with controls (0.401 mm3, p = 0.025) and the paralaminar subnucleus volume (0.04 mm3) was also reduced on the symptomatic side compared with controls (0.05 mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033 mm3) and asymptomatic side (0.035 mm3), compared with the corresponding sides in controls (0.025 mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2 mm3 and 0.17 mm3 respectively) compared to controls (0.23 mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed. CONCLUSIONS: These findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing.

Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress.

Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner.

Fully automated prediction of liver fibrosis using deep learning analysis of gadoxetic acid-enhanced MRI.

OBJECTIVES: To (1) develop a fully automated deep learning (DL) algorithm based on gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and (2) compare the diagnostic performance of DL vs. MR elastography (MRE) for noninvasive staging of liver fibrosis. METHODS: This single-center retrospective study included 355 patients (M/F 238/117, mean age 60 years; training, n = 178; validation, n = 123; test, n = 54) who underwent gadoxetic acid-enhanced abdominal MRI, including HBP and MRE, and pathological evaluation of the liver within 1 year of MRI. Cropped liver HBP images from a custom-written fully automated liver segmentation were used as input for DL. A transfer learning approach based on the ImageNet VGG16 model was used. Different DL models were built for the prediction of fibrosis stages F1-4, F2-4, F3-4, and F4. ROC analysis was performed to evaluate the performance of DL in training, validation, and test sets and of MRE liver stiffness in the test set. RESULTS: AUC values of DL were 0.99/0.70/0.77 (F1-4), 0.92/0.71/0.91 (F2-4), 0.91/0.78/0.90 (F3-4), and 0.98/0.83/0.85 (F4) for training/validation/test sets, respectively. The AUCs of MRE liver stiffness in the test set were 0.86 (F1-4), 0.87 (F2-4), 0.92 (F3-4), and 0.86 (F4). AUCs of MRE and DL were not significantly different for any of the fibrosis stages (p > 0.134). CONCLUSIONS: The fully automated DL models based on HBP gadoxetic acid MRI showed good-to-excellent diagnostic performance for staging of liver fibrosis, with similar diagnostic performance to MRE. After validation in independent sets, the DL algorithm may allow for noninvasive liver fibrosis assessment without the need for additional MRI hardware. KEY POINTS: • The developed deep learning algorithm, based on routine standard-of-care gadoxetic acid-enhanced MRI data, showed good-to-excellent diagnostic performance for noninvasive staging of liver fibrosis. • The diagnostic performance of the deep learning algorithm was equivalent to that of MR elastography in a separate test set.

Resting-state functional connectivity in early postanaesthesia recovery is characterised by globally reduced anticorrelations.

BACKGROUND: A growing body of literature addresses the possible long-term cognitive effects of anaesthetics, but no study has delineated the normal trajectory of neural recovery attributable to anaesthesia alone in adults. We obtained resting-state functional MRI scans on 72 healthy human volunteers between ages 40 and 80 (median: 59) yr before, during, and after general anaesthesia with sevoflurane, in the absence of surgery, as part of a larger study on cognitive function postanaesthesia. METHODS: Region-of-interest analysis, independent component analysis, and seed-to-voxel analysis were used to characterise resting-state functional connectivity and to differentiate between correlated and anticorrelated connectivity before, during, and after general anaesthesia. RESULTS: Whilst positively correlated functional connectivity remained essentially unchanged across these perianaesthetic states, anticorrelated functional connectivity decreased globally by 35% 1 h after emergence from general anaesthesia compared with baseline, as seen by the region-of-interest analysis. This decrease corresponded to a consistent reduction in expression of canonical resting-state networks, as seen by independent component analysis. All measures returned to baseline 1 day later. CONCLUSIONS: The normal perianaesthesia trajectory of resting-state connectivity in healthy adults is characterised by a transient global reduction in anticorrelated activity shortly after emergence from anaesthesia that returns to baseline by the following day. CLINICAL TRIAL REGISTRATION: NCT02275026.

Methanol Extract of Usnea barbata Induces Cell Killing, Apoptosis, and DNA Damage against Oral Cancer Cells through Oxidative Stress.

Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially for oral cancer cells. The aim of this study was to investigate the cell killing function of methanol extracts of U. barbata (MEUB) against oral cancer cells. MEUB shows preferential killing against a number of oral cancer cell lines (Ca9-22, OECM-1, CAL 27, HSC3, and SCC9) but rarely affects normal oral cell lines (HGF-1). Ca9-22 and OECM-1 cells display the highest sensitivity to MEUB and were chosen for concentration effect and time course experiments to address its cytotoxic mechanisms. MEUB induces apoptosis of oral cancer cells in terms of the findings from flow cytometric assays and Western blotting, such as subG1 accumulation, annexin V detection, and pancaspase activation as well as poly (ADP-ribose) polymerase (PARP) cleavage. MEUB induces oxidative stress and DNA damage of oral cancer cells following flow cytometric assays, such as reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) production, mitochondrial membrane potential (MMP) depletion as well as overexpression of γH2AX and 8-oxo-2'deoxyguanosine (8-oxodG). All MEUB-induced changes in oral cancer cells were triggered by oxidative stress which was validated by pretreatment with antioxidant N-acetylcysteine (NAC). In conclusion, MEUB causes preferential killing of oral cancer cells and is associated with oxidative stress, apoptosis, and DNA damage.

Neural correlates of rumination in major depressive disorder: A brain network analysis.

Patients with major depressive disorder (MDD) exhibit higher levels of rumination, i.e., repetitive thinking patterns and exaggerated focus on negative states. Rumination is known to be associated with the cortical midline structures / default mode network (DMN) region activity, although the brain network topological organization underlying rumination remains unclear. Implementing a graph theoretical analysis based on ultra-high field 7-Tesla functional MRI data, we tested whether whole brain network connectivity hierarchies during resting state are associated with rumination in a dimensional manner across 20 patients with MDD and 20 healthy controls. Applying this data-driven approach we found a significant correlation between rumination tendency and connectivity strength degree of the right precuneus, a key node of the DMN. In order to interrogate this region further, we then applied the Dependency Network Analysis (DEPNA), a recently developed method used to quantify the connectivity influence of network nodes. This revealed that rumination was associated with lower connectivity influence of the left medial orbito-frontal cortex (MOFC) cortex on the right precuneus. Lastly, we used an information theory entropy measure that quantifies the cohesion of a network's correlation matrix. We show that subjects with higher rumination scores exhibit higher entropy levels within the DMN i.e. decreased overall connectivity within the DMN. These results emphasize the general DMN involvement during self-reflective processing related to maladaptive rumination in MDD. This work specifically highlights the impact of the MOFC on the precuneus, which might serve as a target for clinical neuromodulation treatment.

Neuroanatomical Determinants of Secondary Trigeminal Neuralgia: Application of 7T Ultra-High-Field Multimodal Magnetic Resonance Imaging.

BACKGROUND: Seven-Tesla (7T) magnetic resonance imaging (MRI) has demonstrated value for evaluating a variety of intracranial diseases. However, its utility in trigeminal neuralgia has received limited attention. The authors of the present study applied ultra-high field multimodal MRI to two representative patients with secondary trigeminal neuralgia due to epidermoid tumors to illustrate the possible clinical and surgical advantages of 7T compared with standard clinical strength imaging. Techniques included co-registration of multiple 7T sequences to optimize the detection of potential concurrent neurovascular and neoplasm-derived compression. METHODS: 7T MRI studies were performed using a whole body scanner. Two- and three-dimensional renderings of potential neurovascular conflict were created by co-registering time-of-flight angiography and T2-weighted turbo spin echo images in MATLAB and GE software. Detailed comparisons of the various field strength images were provided by a collaborating neuroradiologist (B.D.). RESULTS: 7T MRI clearly illustrated minute tumor-adjacent vasculature. In contrast, conventional, low-field imaging did not consistently provide adequate details to distinguish cerebrospinal fluid pulsatility from vessels. The tumor margins, although distinct from the trigeminal nerve fibers at 7T, blended with those of the surrounding structures at 3T. Two- and three-dimensional co-registration of time-of-flight angiography with T2-weighted MRI suggested that delicate, intervening vasculature may have contributed to these illustrative patients' symptomatology. CONCLUSIONS: 7T provided superior visualization of vital landmarks and subtle nerve and vessel features. Co-registration of various advanced 7T modalities may help to resolve complex disease etiologies. Future studies should explore the extent to which this dual etiology might persist across tumor types and utilize diffusion-based techniques to quantify what microstructural differences might exist between patients with trigeminal neuralgia from varying etiologies.

Primary visual cortical thickness in correlation with visual field defects in patients with pituitary macroadenomas: a structural 7-Tesla retinotopic analysis.

OBJECTIVE: Vision loss remains a debilitating complication of pituitary adenomas, although there is considerable variability in visual impairment before and after decompression surgery. Growing evidence suggests secondary damage to remote visual structures may contribute to vision loss in patients with chiasmatic compression. The present study leverages ultrahigh field 7-T MRI to study the retinotopic organization of the primary visual cortex (V1), and correlates visual defects with cortical thinning in V1 to characterize consequences of pituitary adenomas on the posterior visual system. METHODS: Eight patients (4 males and 4 females, mean age 44.3 years) with pituitary adenomas who exhibited chiasmatic compression and visual field defects, as well as 8 matched healthy controls (4 males and 4 females, mean age 43.3 years), were scanned at 7-T MRI for this prospective study. Whole-brain cortical thickness was calculated using an automated algorithm. A previously published surface-based algorithm was applied to associate the eccentricity and polar angle with each position in V1. Cortical thickness was calculated at each point in the retinotopic organization, and a cortical thickness ratio was generated against matched controls for each point in the visual fields. Patients with adenoma additionally underwent neuroophthalmological examination including 24-2 Humphrey automated visual field perimetry. Pattern deviation (PD) of each point in the visual field, i.e., the deviation in point detection compared with neurologically healthy controls, was correlated with cortical thickness at corresponding polar and eccentricity angles in V1. RESULTS: Whole-brain cortical thickness was successfully derived for all patients and controls. The mean tumor volume was 19.4 cm3. The median global thickness of V1 did not differ between patients (mean ± SD 2.21 ± 0.12 cm), compared with controls (2.06 ± 0.13 cm, p > 0.05). Surface morphometry-based retinotopic maps revealed that all 8 patients with adenoma showed a significant positive correlation between PD and V1 thickness ratios (r values ranged from 0.31 to 0.53, p < 0.05). Mixed-procedure analysis revealed that PD = -8.0719 + 5.5873*[Median V1 Thickness Ratio]. CONCLUSIONS: All 8 patients showed significant positive correlations between V1 thickness and visual defect. These findings provide retinotopic maps of localized V1 cortical neurodegeneration spatially corresponding to impairments in the visual field. These results further characterize changes in the posterior visual pathway associated with chiasmatic compression, and may prove useful in the neuroophthalmological workup for patients with pituitary macroadenoma.

First application of 7-T ultra-high field diffusion tensor imaging to detect altered microstructure of thalamic-somatosensory anatomy in trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia (TN) is a debilitating neurological disease that commonly results from neurovascular compression of the trigeminal nerve (CN V). Although the CN V has been extensively studied at the site of neurovascular compression, many pathophysiological factors remain obscure. For example, thalamic-somatosensory function is thought to be altered in TN, but the abnormalities are inadequately characterized. Furthermore, there are few studies using 7-T MRI to examine patients with TN. The purpose of the present study was to use 7-T MRI to assess microstructural alteration in the thalamic-somatosensory tracts of patients with TN by using ultra-high field MRI. METHODS: Ten patients with TN and 10 age- and sex-matched healthy controls underwent scanning using 7-T MRI with diffusion tensor imaging. Structural images were segmented with an automated algorithm to obtain thalamus and primary somatosensory cortex (S1). Probabilistic tractography was performed between the thalamus and S1, and the microstructure of the thalamic-somatosensory tracts was compared between patients with TN and controls. RESULTS: Fractional anisotropy of the thalamic-somatosensory tract ipsilateral to the site of neurovascular compression was reduced in patients (mean 0.43) compared with side-matched controls (mean 0.47, p = 0.01). The mean diffusivity was increased ipsilaterally in patients (mean 6.58 × 10-4 mm2/second) compared with controls (mean 6.15 × 10-4 mm2/second, p = 0.02). Radial diffusivity was increased ipsilaterally in patients (mean 4.91 × 10-4 mm2/second) compared with controls (mean 4.44 × 10-4 mm2/second, p = 0.01). Topographical analysis revealed fractional anisotropy reduction and diffusivity elevation along the entire anatomical S1 arc in patients with TN. CONCLUSIONS: The present study is the first to examine microstructural properties of the thalamic-somatosensory anatomy in patients with TN and to evaluate quantitative differences compared with healthy controls. The finding of reduced integrity of these white matter fibers provides evidence of microstructural alteration at the level of the thalamus and S1, and furthers the understanding of TN neurobiology.

The different impact of stimulation duration on oocyte maturation and pregnancy outcome in fresh cycles with GnRH antagonist protocol in poor responders and normal responders.

OBJECTIVE: To study the impact of stimulation duration on intracytoplasmic sperm injection (ICSI) - embryo transfer (ET) outcome in poor and normal responders during controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist protocol. MATERIALS AND METHODS: This is a retrospective cohort study. There were 1481 women undergoing ICSI-ET cycles. Women with ovum pick-up number ≤3 were defined as poor responders (n = 235), and those with a number ≥4 were normal responders (n = 1246). RESULTS: The mean stimulation duration was shorter in poor responders with pregnancy group as compared with normal responders with pregnancy group (7.8 ± 2.2 vs. 9.2 ± 1.6 days, p < 0.01). Poor responders with a shortest stimulation duration (≤6 days) appeared a higher live birth rate (≤6 days: 33.3%, 7-8 days: 20.0%, 9-10 days: 15.9%, and ≥11 days: 11.1%, p = 0.18). Normal responders with a shortest stimulation duration (≤6 days) appeared a lowest live birth rate (≤6 days: 28.6%, 7-8 days: 35.8%, 9-10 days: 33.6%, and ≥11 days: 29.3%, p = 0.61). Oocyte maturation rate was significantly lower at stimulation durations ≤6 days group (≤6 days: 67%, 7-8 days: 80%, 9-10 days: 85%, and ≥11 days: 87%, p = 0.02) in normal responders. CONCLUSION: In ICSI-ET cycles, stimulation duration appears to have different impact on oocyte maturation, clinical pregnancy rates and live birth rates in both poor and normal responders.

Ethyl Acetate Extract of Nepenthes ventricosa x maxima Exerts Preferential Killing to Oral Cancer Cells.

Nepenthes plants are a folk medicine in many Southeast Asia countries for curing diseases but its anticancer effect is rarely investigated. The objectives of this study were to investigate the antioral cancer ability of ethyl acetate extract of Nepenthes ventricosa x maxima (EANV). The preferential killing ability of EANV was determined by MTS-based cell viability assays. The bioactive effects were further screened by flow cytometry for apoptosis, oxidative stress, and DNA damage. At 24 h treatment, EANV dose dependently decreased six types of oral cancer cells, but the normal oral cells (HGF-1) kept a 90% viability. EANV also showed chronic antiproliferative effects and inhibited 3D sphere formation ability of oral cancer cells. Ca9-22 and CAL 27 oral cancer cells with high response to EANV increased subG1 populations and enhanced Annexin V- and pancaspase-detected apoptosis in these cells. EANV also induced the generation of reactive oxygen species (ROS) and mitochondrial superoxide and the dysfunction of mitochondrial membrane potential. Moreover, the oxidative DNA damage level such as 8-oxo-2'deoxyguanosine was increased in EANV-treated oral cancer cells. Taken together, EANV has a preferential killing effect against oral cancer cells associated with oxidative stress, apoptosis, and DNA damage, suggesting EANV as a potential antioral cancer agent.