- Image-guided phenotyping of ovariectomized mice: altered functional connectivity, cognition, myelination, and dopaminergic functionality. [Journal Article]
- NANeurobiol Aging 2018 Oct 17; 74:77-89
- A large proportion of the population suffers from endocrine disruption, e.g., menopausal women, which might result in accelerated aging and a higher risk for developing cognitive disorders. Therefore...
A large proportion of the population suffers from endocrine disruption, e.g., menopausal women, which might result in accelerated aging and a higher risk for developing cognitive disorders. Therefore, it is crucial to fully understand the impact of such disruptions on the brain to identify potential therapeutic strategies. Here, we show using resting-state functional magnetic resonance imaging that ovariectomy and consequent hypothalamus-pituitary-gonadal disruption result in the selective dysconnectivity of 2 discrete brain regions in mice. This effect coincided with cognitive deficits and an underlying pathological molecular phenotype involving an imbalance of neurodevelopmental/neurodegenerative signaling. Furthermore, this quantitative mass spectrometry proteomics-based analysis of molecular signaling patterns further identified a strong involvement of altered dopaminergic functionality (e.g., DAT and predicted upstream regulators DRD3, NR4A2), reproductive signaling (e.g., Srd5a2), rotatin expression (rttn), cellular aging (e.g., Rxfp3, Git2), myelination, and axogenesis (e.g., Nefl, Mag). With this, we have provided an improved understanding of the impact of hypothalamus-pituitary-gonadal dysfunction and highlighted the potential of using a highly translational magnetic resonance imaging technique for monitoring these effects on the brain.
- Continuous activity tracking using a wrist-mounted device in adult spinal deformity: A proof of concept study. [Journal Article]
- WNWorld Neurosurg 2018 Nov 12
- CONCLUSIONS: Wrist-mounted devices are a non-invasive and effective measure to track daily activity and ambulatory capacity of spinal deformity patients. In a single case, progressive deformity correlated with worsening activity levels, while deformity correction improved step count and activity level. These results support remote activity monitoring as an exploratory outcome for future studies.
- Cellular brain edema induced by water intoxication in rat experimental model. [Journal Article]
- NENeuro Endocrinol Lett 2018 Sep 15; 39(3)
- CONCLUSIONS: Our experimental model can help the future studies of pathophysiology of cellular brain edema and is suitable for testing neuroprotective agents.
- The Influence of TGF-β3, EGF, and BGN on SOX9 and RUNX2 Expression in Human Chondrogenic Progenitor Cells. [Journal Article]
- JHJ Histochem Cytochem 2018 Nov 15; :22155418811645
- Osteoarthritis (OA) is the most common chronic joint disease and leads to the degradation of the extracellular matrix by an imbalance between anabolic and catabolic processes. TGF-β3 (transforming gr...
Osteoarthritis (OA) is the most common chronic joint disease and leads to the degradation of the extracellular matrix by an imbalance between anabolic and catabolic processes. TGF-β3 (transforming growth factor beta-3) and epidermal growth factor (EGF) influence the osteochondrogenic potential of chondrocytes. In this study, we compared the expression of mediators and receptors in the TGF-β3 and EGF pathways, as well as biglycan (BGN), in healthy and diseased chondrocytes. Furthermore, we used chondrogenic progenitor cells (CPCs) for in vitro stimulation and knockdown experiments to elucidate the effects of TGF-β3 and EGF on the chondrogenic potential. Our results demonstrate that the expression of TGF-beta receptor type-1 (TGFBRI) and epidermal growth factor receptor (EGFR) is altered in diseased chondrocytes as well as in CPCs. Moreover, TGF-β3 and EGF stimulation influenced the expression levels of BGN, SRY (sex determining region Y)-box 9 (SOX9), and Runt-related transcription factor 2 (RUNX2) in CPCs. Therefore, changes in TGFBRI and EGFR expression likely contribute to the degenerative and regenerative effects seen in late stages of OA.
- Robotic distal pancreatectomy with selective closure of pancreatic duct: surgical outcomes. [Journal Article]
- USUpdates Surg 2018 Nov 14
- Pancreatic fistula is the main post-operative complication of distal pancreatectomy associated with other further complications, such as intra-abdominal abscesses, wound infection, sepsis, electrolyt...
Pancreatic fistula is the main post-operative complication of distal pancreatectomy associated with other further complications, such as intra-abdominal abscesses, wound infection, sepsis, electrolyte imbalance, malabsorption and hemorrhage. Surgeons have tried various techniques to close the stump of the remaining pancreas, but the controversy regarding the impact of stapler closure and suture closure of the pancreatic stump is far from resolved. In this study, we reported our technique and results of robotic assisted distal pancreatectomy with ultrasound identification and consequent selective closure of pancreatic duct. Twenty-one patients underwent consecutive robotic-assisted distal pancreatectomy were included in our study. We describe our technique and analyzed the operative and peri-operative data including mean operative time, intra-operative bleeding, blood transfusions necessity, conversion rate, mortality and morbidity rate, pancreatic fistula rate and grade, time of refeeding and canalization, length of hospital stay and readmission. Median operative time was 260 min. No conversion occurred. Estimated blood loss was 100 mL (range 50-200). No blood transfusions were performed. Mortality rate was 0%. One (5%) patient had a major complication, while 9 (43%) patients had minor complications (grade I). Three (14%) patients developed pancreatic fistula (grade B), while two (10%) patients had a biochemical leak. No late pancreatic fistula and re-operation occurred. The refeeding was started at second day (range 1^-6^) and the median canalization time was 4 days (range 2-7). The median hospital stay was 6 days (range 3-25) with a readmission rate of 0%. Robotic distal pancreatectomy can be considered safe and feasible. Our technique is easily reproducible, with good surgical results.
- Prediction of Incident Delirium Using a Random Forest classifier. [Journal Article]
- JMJ Med Syst 2018 Nov 14; 42(12):261
- Delirium is a serious medical complication associated with poor outcomes. Given the complexity of the syndrome, prevention and early detection are critical in mitigating its effects. We used Confusio...
Delirium is a serious medical complication associated with poor outcomes. Given the complexity of the syndrome, prevention and early detection are critical in mitigating its effects. We used Confusion Assessment Method (CAM) screening and Electronic Health Record (EHR) data for 64,038 inpatient visits to train and test a model predicting delirium arising in hospital. Incident delirium was defined as the first instance of a positive CAM occurring at least 48 h into a hospital stay. A Random Forest machine learning algorithm was used with demographic data, comorbidities, medications, procedures, and physiological measures. The data set was randomly partitioned 80% / 20% for training and validating the predictive model, respectively. Of the 51,240 patients in the training set, 2774 (5.4%) experienced delirium during their hospital stay; and of the 12,798 patients in the validation set, 701 (5.5%) experienced delirium. Under-sampling of the delirium negative population was used to address the class imbalance. The Random Forest predictive model yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.909 (95% CI 0.898 to 0.921). Important variables in the model included previously identified predisposing and precipitating risk factors. This machine learning approach displayed a high degree of accuracy and has the potential to provide a clinically useful predictive model for earlier intervention in those patients at greatest risk of developing delirium.
- Two-photon imaging of the endoplasmic reticulum thiol flux in the brains of mice with depression phenotypes. [Journal Article]
- AAnalyst 2018 Nov 15
- Depression is a common mental illness with high morbidity and mortality. Mounting evidence suggests that an imbalance of the oxidant-antioxidant defence system is strongly correlated with depression ...
Depression is a common mental illness with high morbidity and mortality. Mounting evidence suggests that an imbalance of the oxidant-antioxidant defence system is strongly correlated with depression and the dysfunction of the endoplasmic reticulum (ER) is strongly related to the oxidative stress. Therefore, as vital and abundant antioxidants in the ER, biothiols may contribute to the etiology of depression. However, ideal two-photon (TP) fluorescent probes for in vivo imaging of ER-associated thiols in the brains of mice with depression phenotypes are still lacking. Hence, we describe a fluorescent probe (ER-SH) to visualize thiols in living systems. ER-SH displays high sensitivity, excellent ER-targeting ability, outstanding TP properties and low cytotoxicity. Using this ER-SH probe, we succeeded in revealing an increase in the endogenous thiol levels under ER stress induced by DTT. Significantly, TP in vivo imaging showed for the first time that the thiol levels are reduced in brains of mice with depression phenotypes. Collectively, this work can assist in further understanding the molecular mechanism of depression and offers a crucial dimension for diagnosis and anti-depression treatments.
- Mal de Debarquement Syndrome: A Case Report. [Journal Article]
- CCureus 2018 Sep 07; 10(9):e3270
- Mal de Debarquement syndrome (MdDS) is an uncommon neurological disorder seen in women, mostly in their fourth decade of life. It is characterized by a constant sensation of swaying or motion after o...
Mal de Debarquement syndrome (MdDS) is an uncommon neurological disorder seen in women, mostly in their fourth decade of life. It is characterized by a constant sensation of swaying or motion after one disembarks from a vehicle such as a ship or plane following a lengthy trip. These symptoms temporarily subside when the patient is subjected again to passive motion like driving a car. There are no definitive diagnostic tests for Mal de Débarquement syndrome. It is a diagnosis of exclusion and does not have an effective treatment. The symptoms usually resolve spontaneously in about a year. We report a case of a 47-year-old female who presented with a feeling of imbalance following about a four-week cruise, which temporarily subsides during a bicycle ride or a car drive. We report this case, as this condition may not be well-known and probably under-reported. Prospective travelers should be warned and patients can perhaps be cautiously reassured.
- Towards personalized medicine in Ménière's disease. [Review]
- FF1000Res 2018; 7
- Ménière's disease (MD) represents a heterogeneous group of relatively rare disorders with three core symptoms: episodic vertigo, tinnitus, and sensorineural hearing loss involving 125 to 2,000 Hz fre...
Ménière's disease (MD) represents a heterogeneous group of relatively rare disorders with three core symptoms: episodic vertigo, tinnitus, and sensorineural hearing loss involving 125 to 2,000 Hz frequencies. The majority of cases are considered sporadic, although familial aggregation has been recognized in European and Korean populations, and the search for familial MD genes has been elusive until the last few years. Detailed phenotyping and cluster analyses have found several clinical predictors for different subgroups of patients, which may indicate different mechanisms, including genetic and immune factors. The genes associated with familial MD are COCH, FAM136A, DTNA, PRKCB, SEMA3D, and DPT. At least two mechanisms have been involved in MD: (a) a pro-inflammatory immune response mediated by interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα), and IL-6, and (b) a nuclear factor-kappa B (NF-κB)-mediated inflammation in the carriers of the single-nucleotide variant rs4947296. It is conceivable that microbial antigens trigger inflammation with release of pro-inflammatory cytokines at different sites within the cochlea, such as the endolymphatic sac, the stria vascularis, or the spiral ligament, leading to fluid imbalance with an accumulation of endolymph. Computational integration of clinical and "omics" data eventually should transform the management of MD from "one pill fits all" to precise patient stratification and a personalized approach. This article lays out a proposal for an algorithm for the genetic diagnosis of MD. This approach will facilitate the identification of new molecular targets for individualized treatment, including immunosuppressant and gene therapy, in the near future.
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- Mice With Decreased Number of Interneurons Exhibit Aberrant Spontaneous and Oscillatory Activity in the Cortex. [Journal Article]
- FNFront Neural Circuits 2018; 12:96
- GABAergic (γ-aminobutyric acid) neurons are inhibitory neurons and protect neural tissue from excessive excitation. Cortical GABAergic neurons play a pivotal role for the generation of synchronized c...
GABAergic (γ-aminobutyric acid) neurons are inhibitory neurons and protect neural tissue from excessive excitation. Cortical GABAergic neurons play a pivotal role for the generation of synchronized cortical network oscillations. Imbalance between excitatory and inhibitory mechanisms underlies many neuropsychiatric disorders and is correlated with abnormalities in oscillatory activity, especially in the gamma frequency range (30-80 Hz). We investigated the functional changes in cortical network activity in response to developmentally reduced inhibition in the adult mouse barrel cortex (BC). We used a mouse model that displays ∼50% fewer cortical interneurons due to the loss of Rac1 protein from Nkx2.1/Cre-expressing cells [Rac1 conditional knockout (cKO) mice], to examine how this developmental loss of cortical interneurons may affect basal synaptic transmission, synaptic plasticity, spontaneous activity, and neuronal oscillations in the adult BC. The decrease in the number of interneurons increased basal synaptic transmission, as examined by recording field excitatory postsynaptic potentials (fEPSPs) from layer II networks in the Rac1 cKO mouse cortex, decreased long-term potentiation (LTP) in response to tetanic stimulation but did not alter the pair-pulse ratio (PPR). Furthermore, under spontaneous recording conditions, Rac1 cKO brain slices exhibit enhanced sensitivity and susceptibility to emergent spontaneous activity. We also find that this developmental decrease in the number of cortical interneurons results in local neuronal networks with alterations in neuronal oscillations, exhibiting decreased power in low frequencies (delta, theta, alpha) and gamma frequency range (30-80 Hz) with an extra aberrant peak in high gamma frequency range (80-150 Hz). Therefore, our data show that disruption in GABAergic inhibition alters synaptic properties and plasticity, while it additionally disrupts the cortical neuronal synchronization in the adult BC.