The Relative Contribution of Glycine-GABA Cotransmission in the Core of the Respiratory Network.

The preBötzinger complex (preBötC) and the Bötzinger complex (BötC) are interconnected neural circuits that are involved in the regulation of breathing in mammals. Fast inhibitory neurotransmission is known to play an important role in the interaction of these two regions. Moreover, the corelease of glycine and GABA has been described in the respiratory network, but the contribution of the individual neurotransmitter in different pathways remains elusive. In sagittal brainstem slices of neonatal mice, we employed a laser point illumination system to activate glycinergic neurons expressing channelrhodopsin-2 (ChR2). This approach allowed us to discern the contribution of glycine and GABA to postsynaptic currents of individual whole-cell clamped neurons in the preBötC and BötC through the application of glycine and GABA receptor-specific antagonists. In more than 90% of the recordings, both transmitters contributed to the evoked IPSCs, with the glycinergic component being larger than the GABAergic component. The GABAergic component appeared to be most prominent when stimulation and recording were both performed within the preBötC. Taken together, our data suggest that GABA-glycine cotransmission is the default mode in the respiratory network of neonatal mice with regional differences that may be important in tuning the network activity.

Superior Hypogastric Nerve Blockade for Uterine Artery Embolization: A Systematic Review.

Superior hypogastric nerve block (SHNB) has potential to reduce pain following uterine artery embolization (UAE). However, existing studies are limited by design, sample size, or conflicting results. A systematic review of the literature was performed. Outcomes included technical success, time to complete SHNB, time under fluoroscopy, procedure time, time to recovery, needle repositioning, same-day discharge, readmission, pain, analgesic consumption, and adverse events. Of 15 included studies, the same-day discharge rate was 98.8%, and readmission rate was 6.9%. The mean pain score was 3.4 in patients who received SHNB compared to 4.3 among controls. Of patients who received SHNB, 46.7% did not require further pain medication. Major adverse events occurred in 0.4% of patients. Early clinical studies suggest that SHNB appears to reduce pain and analgesic consumption in patients undergoing UAE. Additional randomized trials are needed to confirm these findings.

Quantifying odour impacts from aged organic waste to be considered as a priority constraint in route optimization for waste collection trucks.

Route optimization has been used for years to plan the routes for municipal solid waste (MSW) collection trucks to achieve cost reductions. Historically, optimized routes had overlooked a number of aspects and parameters in their design. This study aims to consider MSW odour detection as a performance indicator and a priority constraint in the optimization process by quantifying the impact of objectionable odours from uncollected aged MSW that contains a high percentage of food waste (typically called wet garbage). Odours from 48 aged food waste samples were rated on a scale from 0 to 3 to mark the beginning of the critical time of objectionable odour detection. The critical time was found to take place approximately at the hour 13.6, which was then used, along with the estimated food waste weight in the bin, to define the beginning of a time window that puts the bin on a high priority status for collection over the other, less odoriferous bins. Three optimization scenarios for collection of 100 MSW bins in the city of Madaba, Jordan, were conducted under different constraints: least travelled distance, maximum collected volume and least odour impact. Without the application of the odour consideration, a total travelled distance of 143 km was the shortest travelled distance achieved, with 53 bins emitting odours and leaving 81 m3 of uncollected waste. However, when odour impact was the main routing constraint, a total travelled distance of 161 km was needed and 13 m3 of waste was left uncollected.

Resistance to critically important antimicrobials in Australian silver gulls (Chroicocephalus novaehollandiae) and evidence of anthropogenic origins.

OBJECTIVES: Antimicrobial resistance (AMR) to critically important antimicrobials (CIAs) amongst Gram-negative bacteria can feasibly be transferred amongst wildlife, humans and domestic animals. This study investigated the ecology, epidemiology and origins of CIA-resistant Escherichia coli carried by Australian silver gulls (Chroicocephalus novaehollandiae), a gregarious avian wildlife species that is a common inhabitant of coastal areas with high levels of human contact. METHODS: Sampling locations were widely dispersed around the perimeter of the Australian continent, with sites separated by up to 3500 km. WGS was used to study the diversity and molecular characteristics of resistant isolates to ascertain their epidemiological origin. RESULTS: Investigation of 562 faecal samples revealed widespread occurrence of extended-spectrum cephalosporin-resistant (21.7%) and fluoroquinolone-resistant (23.8%) E. coli. Genome sequencing revealed that CIA-resistant E. coli isolates (n = 284) from gulls predominantly belonged to human-associated extra-intestinal pathogenic E. coli (ExPEC) clones, including ST131 (17%), ST10 (8%), ST1193 (6%), ST69 (5%) and ST38 (4%). Genomic analysis revealed that gulls carry pandemic ExPEC-ST131 clades (O25:H4 H30-R and H30-Rx) and globally emerging fluoroquinolone-resistant ST1193 identified among humans worldwide. Comparative analysis revealed that ST131 and ST1193 isolates from gulls overlapped extensively with human clinical isolates from Australia and overseas. The present study also detected single isolates of carbapenem-resistant E. coli (ST410-blaOXA-48) and colistin-resistant E. coli (ST345-mcr-1). CONCLUSIONS: The carriage of diverse CIA-resistant E. coli clones that strongly resemble pathogenic clones from humans suggests that gulls can act as ecological sponges indiscriminately accumulating and disseminating CIA-resistant bacteria over vast distances.

Low Prevalence of Hypomagnesemia in Long-term Recipients of Proton Pump Inhibitors in a Managed Care Cohort.

BACKGROUND & AIMS: Chronic intake of proton pump inhibitors (PPI) has been associated with hypomagnesemia, but prevalence of PPI-associated hypomagnesemia is not known. METHODS: We examined the prevalence of hypomagnesemia among long-term PPI recipients by using a large health maintenance organization database. We collected data on 10,167 participants eligible for chronic drug prescriptions from 2008 through 2013. Adult subjects receiving continuous PPI therapy for ≥ 6 months between 2008 and 2013 and ≥ 1 serum magnesium determination(s) were identified. Patients with any magnesium levels less than 1.6 mg/dL were selected for analysis; those with recognizable causes of altered magnesium homeostasis were excluded. RESULTS: Five hundred ninety participants received long-term PPIs, and 414 (70.2%) met the inclusion criteria for a total exposure of 2293 PPI-years (average, 5.7 years/subject). Of these patients, 57 (13.8%) had ≥ 1 low serum magnesium; 5 were no longer on PPIs, and 44 had other recognizable causes for hypomagnesemia (25 receiving diuretics, 8 with chronic diarrhea, 8 with chronic kidney disease, and 3 with malignancies). Of the 8 remaining patients (7 female; mean age, 71.2 ± 13.4 years; mean daily medications, 5.4 ± 1.1), mild hypomagnesemia (range, 1.2-1.5 mg/dL) was noted in 13.9% of 289 measurements. All 8 patients had normal serum levels of magnesium at their final measurement. CONCLUSIONS: In the absence of known precipitating factors, chronic PPI use does not appear to be associated with hypomagnesemia.

Oropharyngeal Reflux Monitoring and Atypical Gastroesophageal Reflux Disease.

The prevalence of gastroesophageal reflux disease (GERD) has been increasing since the 1990 s, with up to 27.8 % of people in North America affected by this disorder. The healthcare burden of patients who primarily have extra-esophageal manifestations of GERD (atypical GERD) is estimated to be 5 times that of patients with primarily heartburn and regurgitation due to lack of a gold standard diagnostic test, poor responsiveness to PPI therapy, and delay in recognition. Empiric twice daily PPI therapy for 1-2 months is currently considered the best diagnostic test, but due to poor responsiveness to PPIs in patients with atypical GERD in multiple randomized controlled trials, newer modes of diagnostic procedures such as oropharyngeal pH monitoring have gained significantly more traction. The utility of oropharyngeal pH monitoring systems such as Restech Dx-pH is currently limited due to lack of consensus on normal and abnormal cutoff values. Recent studies suggest its utility as a prognostic tool and its ability to predict responsiveness to medical and surgical therapy. However, routine use of oropharyngeal pH monitoring is still not widespread due to the lack of well-controlled prospective studies.

Radiation enteritis.

Radiation enteritis continues to be a major health concern in recipients of radiation therapy. The incidence of radiation enteritis is expected to continue to rise during the coming years paralleling the unprecedented use of radiotherapy in pelvic cancers. Radiation enteritis can present as either an acute or chronic syndrome. The acute form presents within hours to days of radiation exposure and typically resolves within few weeks. The chronic form may present as early as 2 months or as long as 30 years after exposure. Risk factors can be divided into patient and treatment-related factors. Chronic radiation enteritis is characterized by progressive obliterative endarteritis with exaggerated submucosal fibrosis and can manifest by stricturing, formation of fistulae, local abscesses, perforation, and bleeding. In the right clinical context, diagnosis can be confirmed by cross-sectional imaging, flexible or video capsule endoscopy. Present treatment strategies are directed primarily towards symptom relief and management of emerging complications. Recently, however, there has been a shift towards rational drug design based on improved understanding of the molecular basis of disease in an effort to limit the fibrotic process and prevent organ damage.

Image guided preoperative abdominal wall botox injection for large ventral hernia repair: A case series.

This case series aims to explore the application of preoperative CT guided Botox injections in three different cases of abdominal wall reconstructions. Each of the three cases highlights the role of chemical component separation in achieving myofascial release and contributing to a successful surgical repair. The use of Botox in the preoperative planning of abdominal wall repair aims at creating a tension-free environment for midline closure and promoting an overall positive postoperative course for the patient. This case series presents as a valuable contribution to the different surgical approaches in abdominal wall reconstruction and the collaboration between Interventional Radiology and Surgery in treating such patients.

In-vivo optogenetic identification and electrophysiology of glycinergic neurons in pre-Bötzinger complex of mice.

Breathing requires distinct patterns of neuronal activity in the brainstem. The most critical part of the neuronal network responsible for respiratory rhythm generation is the preBötzinger Complex (preBötC), located in the ventrolateral medulla. This area contains both rhythmogenic glutamatergic neurons and also a high number of inhibitory neurons. Here, we aimed to analyze the activity of glycinergic neurons in the preBötC in anesthetized mice. To identify inhibitory neurons, we used a transgenic mouse line that allows expression of Channelrhodopsin 2 in glycinergic neurons. Using juxtacellular recordings and optogenetic activation via a single recording electrode, we were able to identify neurons as inhibitory and define their activity pattern in relation to the breathing rhythm. We could show that the activity pattern of glycinergic respiratory neurons in the preBötC was heterogeneous. Interestingly, only a minority of the identified glycinergic neurons showed a clear phase-locked activity pattern in every respiratory cycle. Taken together, we could show that neuron identification is possible by a combination of juxtacellular recordings and optogenetic activation via a single recording electrode.

Tooth loss and periodontitis by socio-economic status and inflammation in a longitudinal population-based study.

AIM: To examine the associations between factors of socio-economic status (SES), systemic inflammation and the progression of periodontitis and incidence of tooth loss. MATERIAL AND METHODS: Data of 2566 participants from the Study of Health in Pomerania (SHIP) with a 5-year follow-up were analysed. We evaluated attachment loss and tooth loss with regard to social variables including education, income, marital status and related risks such as smoking and obesity. RESULTS: Socio-economic factors were associated with the progression of attachment level and tooth loss during the follow-up period. Low education and low income were associated with tooth loss (incidence risk ratio IRR 1.63, p < 0.001 and 1.25, p < 0.001 respectively) and also progression of mean clinical attachment level (p < 0.010 and p = 0.046 respectively). SES as well as smoking and obesity were also associated with increased levels of C-reactive protein (CRP) with effect modifications between SES factors and CRP, also between gender and marital status. Tooth loss was associated with disadvantageous SES, particularly under conditions of high CRP levels (p < 0.001). CONCLUSIONS: The progression of periodontal disease is influenced by socio-economic factors. Effect modifications of socio-behavioural factors by CRP indicate that under conditions of systemic inflammation adverse SES effects may be aggravated.

Role of failed renal allograft embolization in the treatment of graft intolerance syndrome.

Nearly, 20% of renal allografts fail after 5 years resulting in a return to hemodialysis. These patients subsequently undergo withdrawal of immunosuppressant therapy, and the failed allograft is left in situ. However, many patients (40%) develop graft intolerance syndrome, characterized by fever, pain, and hematuria. Conventionally, this is managed with low-dose maintenance immunosuppressant therapy, however, that is not without notable adverse risk. In refractory patients, transplant nephrectomy is the treatment of choice; however, this caries significant morbidity and mortality. Interventional radiology plays a substantial role of treating graft intolerance syndrome while delivering improved patient outcomes.

Fiber optical imaging of astroglial calcium signaling in the respiratory network in the working heart brainstem preparation.

The neuronal activity in the respiratory network strongly depends on a variety of different neuromodulators. Given the essential role of astrocytes in stabilizing respiratory network activity generated by neurons in the preBötzinger complex (preBötC), our aim was to investigate astrocytic calcium signaling in the working heart brainstem preparation using fiber-optical imaging. By using transgenic mice that express GCaMP6s specifically in astrocytes, we successfully recorded astrocytic calcium signals in response to norepinephrine from individual astrocytes.

Angiotensin II increases respiratory rhythmic activity in the preBötzinger complex without inducing astroglial calcium signaling.

Angiotensin II (Ang II) is the primary modulator of the renin-angiotensin system and has been widely studied for its effect on the cardiovascular system. While a few studies have also indicated an involvement of Ang II in the regulation of breathing, very little is known in this regard and its effect on brainstem respiratory regions such as the preBötzinger complex (preBötC), the kernel for inspiratory rhythm generation, has not been investigated yet. This study reports that Ang II temporarily increases phrenic nerve activity in the working heart-brainstem preparation, indicating higher central respiratory drive. Previous studies have shown that the carotid body is involved in mediating this effect and we revealed that the preBötC also plays a part, using acute slices of the brainstem. It appears that Ang II is increasing the respiratory drive in an AT1R-dependent manner by optimizing the interaction of inhibitory and excitatory neurons of the preBötC. Thus, Ang II-mediated effects on the preBötC are potentially involved in dysregulating breathing in patients with acute lung injury.

Increase of breathing rate mediated by unilateral optogenetic inactivation of inhibitory neurons in the preBötzinger Complex in vivo.

Brainstem neural circuits located in the preBötzinger complex (preBötC) and Bötzinger complex (BötC) play a critical role in the control of breathing. In this study, glycinergic preBötC and BötC neurons were inactivated with optogenetics in vivo using mice with Cre inducible expression of eNpHR3.0-EYFP. Unilateral inhibition of glycinergic neurons in the preBötC, and to a lower extend also in the BötC, led to a higher respiratory rate. It can be concluded that functional inactivation of inhibitory neurons leads to a disinhibition of preBötC excitatory neurons and thus an increase in the respiratory drive of the network.

Acute presentation of renal pseudoaneurysms in a patient with systemic lupus erythematosus after percutaneous renal biopsy.

The development of renal pseudoaneurysms following percutaneous kidney biopsy is a rare but potentially dangerous complication due to the risk of rupture with subsequent hemorrhage. We describe a female patient in her 20s with long-standing lupus nephritis who presented to the hospital for elective CT-guided left renal biopsy that was complicated by pseudoaneurysms in the bilateral kidneys. Post-biopsy, she developed a perinephric hematoma that extended to the upper pelvis with resultant superior displacement and diminished blood flow to the left kidney. Successful endovascular coil embolization was performed after left renal artery angiography confirmed contrast extravasation in one of the branches that supplied the inferior pole of the left kidney. Despite the embolization, her hemoglobin continued to decline, and a subsequent CT-scan demonstrated a persistent loculated hyperdense fluid collection in the beforementioned area. Repeat angiography revealed multiple left renal pseudoaneurysms and a single pseudoaneurysm in the upper pole of the right kidney, neither of which were previously visualized. The acute development of pseudoaneurysms due to accidental or non-accidental trauma is a well-established entity. Here we present a patient that acutely developed numerous arterial pseudoaneurysms after renal biopsy and has never been reported in the literature. Special caution should be undertaken in the case of high-risk patients predisposed to these pseudoaneurysms.

Embolization of Renal Cell Carcinoma Skeletal Metastases Preceding Orthopedic Surgery.

Renal cell carcinoma (RCC) is the most common type of renal malignancy in adults. Bone is a major site of metastatic disease from RCC. Osseous metastatic disease from RCC is often seen in the spine, pelvis, and femur, and is usually hypervascular in nature like its primary tumor source. This can cause significant pain, reduced function, pathological fracture, nerve compression, and decreased quality of life during cancer treatment and disease course. Surgical treatments for pathological fracture of the femur include resection, reconstruction, and stabilization with arthroplasty or placement of an intramedullary nail. This series looks at three cases of renal cell carcinoma metastases to the hip with pre-procedural embolization and orthopedic stabilization. Interventional radiology embolization of the arterial supply to the metastatic hypervascular bone lesions can reduce intraoperative blood loss and associated complications.

Norepinephrine regulates calcium signals and fate of oligodendrocyte precursor cells in the mouse cerebral cortex.

Oligodendrocyte precursor cells (OPCs) generate oligodendrocytes, contributing to myelination and myelin repair. OPCs contact axons and respond to neuronal activity, but how the information relayed by the neuronal activity translates into OPC Ca2+ signals, which in turn influence their fate, remains unknown. We generated transgenic mice for concomitant monitoring of OPCs Ca2+ signals and cell fate using 2-photon microscopy in the somatosensory cortex of awake-behaving mice. Ca2+ signals in OPCs mainly occur within processes and confine to Ca2+ microdomains. A subpopulation of OPCs enhances Ca2+ transients while mice engaged in exploratory locomotion. We found that OPCs responsive to locomotion preferentially differentiate into oligodendrocytes, and locomotion-non-responsive OPCs divide. Norepinephrine mediates locomotion-evoked Ca2+ increases in OPCs by activating α1 adrenergic receptors, and chemogenetic activation of OPCs or noradrenergic neurons promotes OPC differentiation. Hence, we uncovered that for fate decisions OPCs integrate Ca2+ signals, and norepinephrine is a potent regulator of OPC fate.

Association between the insulin-like growth factor axis in serum and periodontitis in the Study of Health in Pomerania: an exploratory study.

AIM: To evaluate the association of Insulin-like Growth Factor (IGF) I-related variables with periodontitis in the population-based Study of Health in Pomerania (SHIP). MATERIAL AND METHODS: From the cross-sectional SHIP, 2293 subjects with clinical attachment loss (CAL) data and 2398 subjects with tooth count data aged 20-59 years were analysed. Serum IGF-I and IGF-binding protein (BP)-3 levels were determined by chemiluminescence immunoassays. Linear and logistic regressions with fractional polynomials were used to study associations between IGF-related variables and mean CAL or high tooth loss. For non-linear relations between IGFBP-3 and mean CAL, graphical presentations of fractional polynomials were used to deduce knots for linear splines. RESULTS: In fully adjusted models, for serum IGFBP-3 values ≤1200 ng/ml, mean CAL increased significantly for decreasing serum IGFBP-3 levels [B = -0.027 (95% CI, -0.049; -0.005), p = 0.02]. The odds for high tooth loss decreased significantly for high serum IGFBP-3 values [OR = 0.97 (0.95; 0.99), p = 0.02]. Serum IGF-I levels and the IGF-I/IGFBP-3 ratio were not related to mean CAL or tooth loss after full adjustment. CONCLUSIONS: Low serum IGFBP-3 levels might be associated with higher levels of periodontal disease. Neither serum IGF-I nor IGF-I/IGFBP-3 ratios were associated with periodontitis.

Auxiliary Subunits Regulate the Dendritic Turnover of AMPA Receptors in Mouse Hippocampal Neurons.

Different families of auxiliary subunits regulate the function and trafficking of native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the central nervous system. While a facilitatory role of auxiliary subunits in ER export and forward trafficking of newly synthesized AMPA receptors is firmly established, it is unclear whether auxiliary subunits also control endosomal receptor turnover in dendrites. Here, we manipulated the composition of AMPA receptor complexes in cultured hippocampal neurons by overexpression of two auxiliary subunits, transmembrane AMPAR regulatory protein (TARP) γ-8 or cysteine knot AMPAR-modulating protein (CKAMP) 44a, and monitored dendritic receptor cycling in live-cell imaging experiments. Receptor surface delivery was assayed using a modified AMPA receptor subunit carrying the pH-dependent fluorophore superecliptic pHluorin (SEP-GluA1), which regains its fluorescence during receptor exocytosis, when transiting from the acidic lumen of transport organelles to the neutral extracellular medium. Strikingly, we observed a dramatic reduction in the spontaneous fusion rate of AMPA receptor-containing organelles in neurons overexpressing either type of auxiliary subunit. An analysis of intracellular receptor distribution also revealed a decreased receptor pool in dendritic recycling endosomes, suggesting that incorporation of TARPγ-8 or CKAMP44a in receptor complexes generally diminishes cycling through the endosomal compartment. To directly analyze dendritic receptor turnover, we also generated a new reporter by N-terminal fusion of a self-labeling HaloTag to an AMPA receptor subunit (HaloTag-GluA1), which allows for selective, irreversible staining of surface receptors. Pulse chase-experiments with HaloTag-GluA1 indeed demonstrated that overexpression of TARPγ-8 or CKAMP44a reduces the constitutive internalization rate of surface receptors at extrasynaptic but not synaptic sites. Thus, our data point to a yet unrecognized regulatory function of TARPγ-8 and CKAMP44a, by which these structurally unrelated auxiliary subunits delay local recycling and increase surface lifetime of extrasynaptic AMPA receptors.