Neutral or detrimental effects of TREM2 agonist antibodies in preclinical models of Alzheimer's Disease and Multiple Sclerosis.

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's Disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia. For mice bearing amyloid-ß (Aß) pathology (PS2APP) or combined Aß and tau pathology (TauPS2APP), chronic TREM2 agonist antibody treatment had limited impact on microglia engagement with pathology, overall pathology burden, or downstream neuronal damage. For mice with demyelinating injuries triggered acutely with lysolecithin, TREM2 agonist antibodies unexpectedly disrupted injury resolution. Likewise, TREM2 agonist antibodies limited myelin recovery for mice experiencing chronic demyelination from cuprizone. We highlight the contributions of dose timing and frequency across models. These results introduce important considerations for future TREM2-targeting approaches.Significance Statement Multiple TREM2 agonist antibodies are investigated in mouse models of Alzheimer's Disease and Multiple Sclerosis. Despite agonism in culture models and after acute dosing in mice, antibodies do not show benefit in overall AD pathology and worsen recovery after demyelination.

Hope for vascular cognitive impairment: Ac-YVAD-cmk as a novel treatment against white matter rarefaction.

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear. To address this, we performed BCAS on C57/BL6 mice to study the effects of Ac-YVAD-cmk, a caspase-1 inhibitor, on the subcortical and cortical regions. Cerebral blood flow (CBF), WMR, neuroinflammation and the expression of tight junction-related proteins associated with blood-brain barrier integrity were assessed 15 days post BCAS. We observed that Ac-YVAD-cmk restored CBF, attenuated BCAS-induced WMR and restored subcortical myelin expression. Within the subcortical region, BCAS activated the NLRP3/caspase-1/interleukin-1beta axis only within the subcortical region, which was attenuated by Ac-YVAD-cmk. Although we observed that BCAS induced significant increases in VCAM-1 expression in both brain regions that were attenuated with Ac-YVAD-cmk, only ZO-1 and occludin were observed to be significantly altered in the subcortical region. Here we show that caspase-1 may contribute to subcortical regional susceptibility in a mouse model of VCI. In addition, our results support further investigations into the potential of Ac-YVAD-cmk as a novel treatment strategy against subcortical VCI and other conditions exhibiting cerebral hypoperfusion-induced WMR.

The Role of Wait Time During the Questioning of Children: A Systematic Review.

The benefits of wait time in classroom discourses have been well documented in the field of education since the 1970s. While current forensic interview guidelines recognize the importance of pauses, whether there is sufficient empirical evidence to inform wait time guidelines in the legal context remains unanswered. This systematic review aimed to synthesize and provide a holistic update on the available research on the role of wait time when questioning children and recommended future direction to develop wait time guidelines specific to child forensic interviews. Systematic searches were conducted using four databases (PsycINFO, MedLine, ERIC, and Scopus). A total of 3,953 unique articles were returned, following a title and abstract screening, 68 full texts were reviewed, and 26 (including five additional studies identified through a hand search) were included. Inclusion criteria were the study sample included children under 18, published a measure of wait time in a questioning context, and in English. Overall, most knowledge of wait time remains in the field of education. Natural wait time is short, but with training, extended wait time yields significant benefits for both child and adult talk. Only one study examined the role of wait time in the forensic interviewing setting where a 10-s wait time appears to be more productive than shorter pauses. Extended wait time is a promising and simple interviewing practice with the potential to facilitate children's disclosure. The current review is a call for research in the area as it pertains to forensic interviewing of children and youth.

Multiplexed multicolor antiviral assay amenable for high-throughput research.

To curb viral epidemics and pandemics, antiviral drugs are needed with activity against entire genera or families of viruses. Here, we develop a cell-based multiplex antiviral assay for high-throughput screening against multiple viruses at once, as demonstrated by using three distantly related orthoflaviviruses: dengue, Japanese encephalitis and yellow fever virus. Each virus is tagged with a distinct fluorescent protein, enabling individual monitoring in cell culture through high-content imaging. Specific antisera and small-molecule inhibitors are employed to validate that multiplexing approach yields comparable inhibition profiles to single-virus infection assays. To facilitate downstream analysis, a kernel is developed to deconvolute and reduce the multidimensional quantitative data to three cartesian coordinates. The methodology is applicable to viruses from different families as exemplified by co-infections with chikungunya, parainfluenza and Bunyamwera viruses. The multiplex approach is expected to facilitate the discovery of broader-spectrum antivirals, as shown in a pilot screen of approximately 1200 drug-like small-molecules.

Circuit mechanism for suppression of frontal cortical ignition during NREM sleep.

Conscious perception is greatly diminished during sleep, but the underlying circuit mechanism is poorly understood. We show that cortical ignition-a brain process shown to be associated with conscious awareness in humans and non-human primates-is strongly suppressed during non-rapid-eye-movement (NREM) sleep in mice due to reduced cholinergic modulation and rapid inhibition of cortical responses. Brain-wide functional ultrasound imaging and cell-type-specific calcium imaging combined with optogenetics showed that activity propagation from visual to frontal cortex is markedly reduced during NREM sleep due to strong inhibition of frontal pyramidal neurons. Chemogenetic activation and inactivation of basal forebrain cholinergic neurons powerfully increased and decreased visual-to-frontal activity propagation, respectively. Furthermore, although multiple subtypes of dendrite-targeting GABAergic interneurons in the frontal cortex are more active during wakefulness, soma-targeting parvalbumin-expressing interneurons are more active during sleep. Chemogenetic manipulation of parvalbumin interneurons showed that sleep/wake-dependent cortical ignition is strongly modulated by perisomatic inhibition of pyramidal neurons.

Assessing Left Ventricular Systolic Function in Patients with Pregnancy-Induced Hypertension Using Three-Dimensional Speckle Tracking Technology.

Objective: This study investigates the clinical utility of three-dimensional speckle tracking technology in assessing left ventricular systolic function in pregnancy-induced hypertension syndrome (PIH). Methods: We retrospectively enrolled 70 patients with diagnosed PIH treated at our institution between July 2019 and August 2021 as the study group. A total of 70 healthy pregnant women undergoing routine antenatal examinations at the same institution during the same period were included in the control group. Two-dimensional conventional echocardiography measured left ventricular parameters in both groups. Three-dimensional speckle tracking technology analyzed Left Ventricular Global Longitudinal Peak Strain (LVGLS), Left Ventricular Global Radial Peak Strain (LVGRS), and Left Ventricular Global Circumferential Peak Strain (LVGCS). Differences in left ventricular systolic function and pregnancy outcomes were compared. Results: In the study group, LVEDD, LVPWTd, and IVSTd (47.67±4.88, 10.68±1.21, 11.24±1.03) exceeded those in the control group (45.21±5.65, 8.17±0.98, 8.91±0.37). LVEF (62.12±5.63) was lower than the control group (65.25±5.17) (all P < .05). LVGLS, LVGCS, and LVGAS in the study group (-15.66±1.07, -20.17±2.89, -23.17±3.43) were higher than the control group (-20.14±1.27, -25.17±1.36, -37.68±3.29), while LVGRS (30.29±3.61) was lower than the control group (34.18±4.08) (all P < .05). The study group had 72.86% natural deliveries and 27.14% cesarean sections; the control group had 31.43% natural deliveries and 68.57% cesarean sections (all P < .05). Weeks of delivery and birth weight in the study group (36.87±1.23, 2.71±0.41) were lower than the control group (38.96±1.54, 3.41±0.78) (both P < .05). Conclusions: Compared to traditional methods, three-dimensional speckle tracking technology more sensitively detects left ventricular strain and rotation in PIH patients. It holds clinical relevance in early left ventricular dysfunction detection, effectively mitigating adverse pregnancy outcomes and warranting clinical adoption and application.

Endotracheal tube forces exerted on the larynx and a novel support device to reduce it.

Objective: Endotracheal tubes (ETTs) are commonly associated with laryngeal injury that may be short lasting and temporary or more severe and life altering. Injury is believed to result from forces that these ETTs exert on the larynx. Here we quantify the forces of ETTs of various sizes on the laryngotracheal complex to gain a more quantitative understanding of these potential damaging forces. Here we also perform preclinical testing of a novel support device to offload these forces. Methods: Endotracheal intubation was performed on a fresh human cadaver using various ETT sizes. A strain-sensitive graphene nanosheet sensor and a commercially available force sensing resistor were secured behind the larynx, anterior to the prevertebral fascia. The forces exerted on the larynx were measured for each of the commonly used ETTs. A novel support device, ETT clip (Endo Clip), was attached to the ETTs and changes in these forces were observed. Results: Forces exerted on the laryngotracheal complex by various ETTs were observed to increase with increasing tube size. This pressure can be significantly reduced with a novel ETT clip. Conclusion: Here we demonstrate the first quantitative measurement of forces that ETTs exert on the larynx. We demonstrate a novel device that can easily clip onto an ETT reducing pressure on the laryngotracheal complex. This preclinical test paves the way for a human clinical trial. Level of evidence: 5.

Development and validation of a predictive model for low cardiac output syndrome after surgical repair of tetralogy of Fallot.

Background: Low cardiac output syndrome (LCOS) remains a serious postoperative complication for children with tetralogy of Fallot (TOF), which often leads to increased morbidity and mortality. Early identification of LCOS and timely management are critical for better outcomes. This study aimed to develop a prediction model incorporating pre- and intraoperative characteristics for LCOS within 24 hours after surgical repair of TOF in children. Methods: The training dataset consisted of patients with TOF who underwent surgical repair in 2021, while the validation dataset consisted of patients in 2022. The univariable and multivariable logistic regression analyses were performed to recognize the risk factors of postoperative LCOS and a predictive model was established based on multivariable logistic regression analysis in the training dataset. Model predictive power was assessed using the area under the receiver operating characteristic curve (AUC). The calibration of the nomogram was evaluated and the Hosmer-Lemeshow test was used to assess the good fit. Decision curve analysis (DCA) was used to estimate the net benefits of the prediction model at different threshold probabilities. Results: In the multivariable logistic analysis, peripheral oxygen saturation, mean blood pressure, and central venous pressure were independent risk factors for postoperative LCOS. The AUC of the predictive model for postoperative LCOS was 0.84 (95% CI: 0.77-0.91) and 0.80 (95% CI: 0.70-0.90) in the training and validation datasets, respectively. The calibration curve for the probability of LCOS showed good agreement between the prediction by nomogram and actual observation both in the training and validation datasets. The Hosmer-Lemeshow test yielded nonsignificant statistics both in the training and validation datasets (P=0.69 and 0.54, respectively), indicating a good fit. The DCA revealed that more net benefits would be obtained by using the nomogram to predict LCOS than that achieved in either the treat-all-patient scheme or the treat-none scheme both in the training and validation datasets. Conclusions: This study is the first to incorporate pre- and intraoperative characteristics to develop a predictive model for LCOS after surgical repair of TOF in children. This model showed good discrimination, good fit and clinical benefits.

Number of segments with motion abnormalities is better correlated with infarct size in acute myocardial infarction.

BACKGROUND: The relationship between the number of segments with motion abnormalities (SMA) on the bull's-eye plots of speckle-tracking echocardiography (STE) and myocardial infarct size (MIS) on late gadolinium-enhanced cardiac MRI (LGE-cMRI) has not been well characterized. This study aimed to determine MIS using the number of SMA in patients with acute myocardial infarction (MI). METHODS: Left ventricular two-dimensional STE and LGE-cMRI were performed in 380 patients with ST-segment elevation MI within 48 h and 5-6 days after primary percutaneous intervention, respectively. RESULTS: Patients with impaired global and regional myocardial strain, work and greater number of SMA had significantly larger infarcts ( P  < 0.05). Multivariate logistic regression analysis that included myocardial strain, work, and number of SMA showed that total number of SMA [odds ratio (OR) = 1.976; 95% confidence interval (CI): 1.539-2.538, P  < 0.0001], the number of segments with paradoxalic systolic movements (SPSM, OR = 3.703; 95% CI: 2.112-6.493, P  < 0.0001) were independent risk factors of large MIS (>19%). The area under receiver operating characteristic curve (AUC) of 0.904 (0.866~0.942) for total number of SMA was superior to that for global longitudinal strain (GLS, AUC = 0.813, 0.761~0.865), global work efficiency (GWE, AUC = 0.794, 0.730~0.857) and number of SPSM (AUC = 0.851, 0.804-0.899) to predict a large MIS ( P  < 0.05). The optimal cutoff value of total number of SMA was 7, with a sensitivity of 85.31%, a specificity of 81.48%, and an accuracy of 83.27%. CONCLUSION: Total number of SMA is better associated with infarct size, which provided an incremental prognostic value above established prognostic parameters such as GLS and GWE.

Brain-derived neurotrophic factor contributes to neurogenesis after intracerebral hemorrhage: a rodent model and human study.

Background and purpose: Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF). Methods: A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA). Results: In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume. Conclusion: BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH.

Effect of interactive, multimedia-based home-initiated education on preoperative anxiety inchildren and their parents: a single-center randomized controlled trial.

BACKGROUND: Anesthesiologists need to appreciate the impact of preoperative anxiety in children. The present study aimed to explore whether interactive multimedia-based home-initiated interventions could effectively relieve preoperative anxiety in pediatric patients. METHODS: In this prospective study, we compared preoperative anxiety between two groups of children aged 4-9 years. Children in the control group received a question-and-answer (Q&A) introduction, and children in the intervention group received multimedia-based home-initiated preoperative education using comic booklets, videos, and coloring game books. Differences in anxiety between the two groups were evaluated by the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) at four time points: in the ophthalmology outpatient clinic before intervention as the baseline (T0); in the preoperative waiting area (T1); at the time of separating from their parents and moving to the operating room (T2); and at the time of anesthesia induction (T3). Parental anxiety was assessed by the Self-rating Anxiety Scale (SAS) and Visual Analog Scale (VAS) at T0 and T2. Other related information was collected by questionnaire. RESULTS: Eighty-four children who underwent pediatric strabismus in our center between November 2020 and July 2021 were included in this study. An intention-to-treat (ITT) analysis was performed on data from 78 enrolled children. Children in the intervention group exhibited lower m-YPAS-SF scores at T1, T2, and T3 than those in the control group (all p < 0.001). By using a mixed-effect model with repeated measurement (MMRM) after adjusting the m-YPAS score at T0 as a covariate, the interventional effect in terms of themYPAS-SF score was also significant over time (p < 0.001). The percentage of children with perfect induction compliance (ICC = 0) in the intervention group was significantly higher than that in the control group [18.4% vs. 7.5%], and poor induction compliance (ICC>4) was lower (2.6% vs. 17.5%, p = 0.048). The mean parental VAS score at T2 in the intervention group was significantly lower than that in the control group (p = 0.021). CONCLUSIONS: Interactive multimedia-based home-initiated intervention could reduce preoperative anxiety in children and improve the quality of anesthesia induction based on ICC scores, which may in turn impose a positive impact on parental anxiety.

Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial.

BACKGROUND: Bihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients. METHODS: We enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2-56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke. RESULTS: Twenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect size η2 = 0.211; responder rate: 77% vs. 36%, p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01). CONCLUSIONS: Bihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov: (ID: NCT02731508).

Chronic treatment with baicalein alleviates behavioural disorders and improves cerebral blood flow via reverting metabolic abnormalities in a J20 transgenic mouse model of Alzheimer's disease.

Baicalein (BE) has both antioxidant and anti-inflammatory effects. It has also been reported able to improve cerebral blood circulation in brain ischemic injury. However, its chronic efficacy and metabolomics in Alzheimer's disease (AD) remain unknown. In this study, BE at 80 mg/kg was administrated through the oral route in J20 AD transgenic mice aged from aged 4 months to aged 10 months. Metabolic- and neurobehavioural phenotyping was done before and after 6 months' treatment to evaluate the drug efficacy and the relevant mechanisms. Meanwhile, molecular docking was used to study the binding affinity of BE and poly (ADP-ribose) polymerase-1 (PARP-1) which is related to neuronal injury. The open field test showed that BE could suppress hyperactivity in J20 mice and increase the frequency of the target quadrant crossing in the Morris Water Maze test. More importantly, BE restored cerebral blood flow back to the normal level after the chronic treatment. A 1H NMR-based metabolomics study showed that BE treatment could restore the tricarboxylic acid cycle in plasma. And such a treatment could suppress oxidative stress, inhibit neuroinflammation, alleviate mitochondrial dysfunction, improve neurotransmission, and restore amino homeostasis via starch and sucrose metabolism and glycolipid metabolism in the cortex and hippocampus, which could affect the behavioural and cerebral blood flow. These findings showed that BE is a potential therapeutic agent for AD.

TREM2-dependent microglial function is essential for remyelination and subsequent neuroprotection.

Disability in multiple sclerosis (MS) is driven in part by the failure of remyelination and progressive neurodegeneration. Microglia, and specifically triggering receptor expressed on myeloid cells 2 (TREM2), a factor highly expressed in microglia, have been shown to play an important role in remyelination. Here, using a focal demyelination model in the brain, we demonstrate that demyelination is persistent in TREM2 knockout mice, lasting more than 6 weeks after lysolecithin injection and resulting in substantial neurodegeneration. We also find that TREM2 knockout mice exhibit an altered glial response following demyelination. TREM2 knockout microglia demonstrate defects in migration and phagocytosis of myelin debris. In addition, human monocyte-derived macrophages from subjects with a TREM2 mutation prevalent in human disease also show a defect in myelin debris phagocytosis. Together, we highlight the central role of TREM2 signaling in remyelination and neuroprotection. These findings provide insights into how chronic demyelination might lead to axonal damage and could help identify novel neuroprotective therapeutic targets for MS.

A paleo-neurologic investigation of the social brain hypothesis in frontotemporal dementia.

The social brain hypothesis posits that a disproportionate encephalization in primates enabled to adapt behavior to a social context. Also, it has been proposed that phylogenetically recent brain areas are disproportionally affected by neurodegeneration. Using structural and functional magnetic resonance imaging, the present study investigates brain-behavior associations and neural integrity of hyperspecialized and domain-general cortical social brain areas in behavioral variant frontotemporal dementia (bvFTD). The results revealed that both structure and function of hyperspecialized social areas in the middle portion of the superior temporal sulcus (STS) are compromised in bvFTD, while no deterioration was observed in domain general social areas in the posterior STS. While the structural findings adhered to an anterior-posterior gradient, the functional group differences only occurred in the hyperspecialized locations. Activity in specialized regions was associated with structural integrity of the amygdala and with social deficits in bvFTD. In conclusion, the results are in line with the paleo-neurology hypothesis positing that neurodegeneration primarily hits cortical areas showing increased specialization, but also with the compatible alternative explanation that anterior STS regions degenerate earlier, based on stronger connections to and trans-neuronal spreading from regions affected early in bvFTD.

The diagnostic utility of trichorhinophalangeal syndrome type 1 immunohistochemistry for metastatic breast carcinoma in effusion cytology specimens.

BACKGROUND: Trichorhinophalangeal syndrome type 1 (TRPS1) is a novel immunohistochemical marker with excellent performance in distinguishing breast carcinoma from other cancers in surgical specimens. The aim of this study was to evaluate the diagnostic utility of TRPS1 compared with GATA3 for metastatic breast carcinoma in effusion cytology specimens. METHODS: In total, 91 cell blocks of malignant effusion specimens, including 47 metastatic breast carcinomas (nine triple-negative breast carcinomas [TNBCs] and 38 non-TNBCs) and 44 nonmammary malignancies, were selected for TRPS1 and GATA3 immunohistochemistry. Modified H scores ≥ 200 were considered positive staining. RESULTS: The positive rate of TRPS1 was similar between TNBC and non-TNBC (77.8% vs 73.3%, p = .802), whereas the positive rate of GATA3 was lower in TNBC than in non-TNBC (66.7% vs 89.5%, p = .087). The positive rate of TRPS1 was significantly higher in breast carcinoma than in urothelial carcinoma (74.5% vs 0%, p < .001), whereas the positive rate of GATA3 showed no difference between these two (85.1% vs 85.7%, p = .956). Notably, diffuse and strong aberrant expression of TRPS1 was observed in one lung adenocarcinoma and one serous adenocarcinoma in this series. The overall sensitivity, specificity, positive predictive value, and negative predictive value of TRPS1 immunohistochemistry for breast carcinoma were 74.5%, 95.5%, 94.6%, and 77.8%, respectively. CONCLUSION: TRPS1 is a sensitive and specific marker for metastatic breast cancer in serous effusion cell-block specimens. It shows superior sensitivity and specificity compared with GATA3, especially in the TNBC setting and for excluding urothelial carcinoma.

Neuroprotective Effects of Probiotic Lactobacillus reuteri GMNL-263 in the Hippocampus of Streptozotocin-Induced Diabetic Rats.

Diabetes-related brain complications have been reported in clinical patients and experimental models. The objective of the present study was to investigate the neuroprotective mechanisms of Lactobacillus reuteri GMNL-263 in streptozotocin (STZ)-induced diabetic rats. In this study, three different groups, namely control group, STZ-induced (55 mg/kg streptozotocin intraperitoneally) diabetic rats (DM), and DM rats treated with Lactobacillus reuteri GMNL-263 (1 × 109 CFU/rat/day), were utilized to study the protective effect of GMNL-263 in the hippocampus of STZ-induced diabetic rats. The results demonstrated that GMNL-263 attenuated diabetes-induced hippocampal damage by enhancing the cell survival pathways and repressing both inflammatory and apoptotic pathways. Histopathological analysis revealed that GMNL-263 prevented structural changes in the hippocampus in the DM group and decreased the level of inflammation and apoptosis in the hippocampus of DM rats. The IGF1R cell survival signaling pathway also improved after GMNL-263 treatment. These results indicate that probiotic GMNL-263 exerts beneficial effects in the brain of diabetic rats and has potential ability for clinical application.

Muscle Engagement Monitoring Using Self-Adhesive Elastic Nanocomposite Fabrics.

Insight into, and measurements of, muscle contraction during movement may help improve the assessment of muscle function, quantification of athletic performance, and understanding of muscle behavior, prior to and during rehabilitation following neuromusculoskeletal injury. A self-adhesive, elastic fabric, nanocomposite, skin-strain sensor was developed and validated for human movement monitoring. We hypothesized that skin-strain measurements from these wearables would reveal different degrees of muscle engagement during functional movements. To test this hypothesis, the strain sensing properties of the elastic fabric sensors, especially their linearity, stability, repeatability, and sensitivity, were first verified using load frame tests. Human subject tests conducted in parallel with optical motion capture confirmed that they can reliably measure tensile and compressive skin-strains across the calf and tibialis anterior. Then, a pilot study was conducted to assess the correlation of skin-strain measurements with surface electromyography (sEMG) signals. Subjects did biceps curls with different weights, and the responses of the elastic fabric sensors worn over the biceps brachii and flexor carpi radialis (i.e., forearm) were well-correlated with sEMG muscle engagement measures. These nanocomposite fabric sensors were validated for monitoring muscle engagement during functional activities and did not suffer from the motion artifacts typically observed when using sEMGs in free-living community settings.

Case Report: Myomatous erythrocytosis syndrome presenting as rapid growth of an extra-uterine mass.

Objective: To report a case of myomatous erythrocytosis syndrome (MES) with an extra-uterine manifestation. Case report: A 43-year-old woman presented with progressive abdominal distension and rapid enlargement of a pelvic mass. Upon survey, a high-level of hemoglobin (19.0 g/dl) was documented. The initial impression was an ovarian malignancy, but uterine sarcoma could not be ruled out because of its rapid growth. However, during exploratory laparotomy, the pelvic mass was found to be a 31 cm broad ligament leiomyoma; which is extremely rare for its size and location. The specimen was further studied immunohistochemically, which revealed excessive expressions of erythropoietin and erythropoietin receptors in addition to the diffusely matured blood vessels in the myoma tissue. The patient's hemoglobin level resumed to normal three months post-surgery. The diagnosis of MES was confirmed both clinically and histologically. Conclusion: A correct preoperative diagnosis is challenging when MES manifests as an extrauterine mass. The coexistence of MES should be considered in the management of all leiomyoma with polycythemia, regardless of locations.