Stenting for Venous Sinus Stenosis in Patients With Idiopathic Intracranial Hypertension: An Updated Systematic Review and Meta-Analysis of the Literature.

BACKGROUND AND OBJECTIVES: Although venous sinus stenting (VSS) improves cerebrospinal fluid reabsorption and decreases intracranial pressure in patients with idiopathic intracranial hypertension (IIH), the underlying pathophysiology of IIH is not well understood. We present a review and meta-analysis of the literature on VSS for IIH treatment, focusing on the rates of restenosis and symptom recurrence. METHODS: We performed a systematic review of PubMed and Embase databases between January 1, 2011, and December 31, 2021. Articles including ≥5 patients with IIH and venous sinus stenosis treated with VSS and post-treatment rates of restenosis (de novo stenosis at a different anatomic location along the dural sinuses or restenosis within or adjacent to the stent) were selected. Demographic, procedural, and outcomes data were collected and analyzed. Mean values for variables collected were pooled, and a mean value was calculated with a 95% CI. RESULTS: Twenty-four articles were included, comprising 694 patients and 781 VSS cases. The mean age was 33.9 (CI, 31.5-36.2) years. The mean body mass index was 35.3 (CI, 32.9-37.7) kg/m 2 . Before VSS, 98.8% (CI, 96.8%-100.0%) of patients experienced headaches, 87.7% (CI, 80.6%-95.5%) had visual acuity issues, 78.7% (CI, 69.9%-88.5%) had papilledema, 58.3% (CI, 46.0%-73.9%) had tinnitus, and 98.8% (96.4%-100.0%) had symptoms refractory to previous therapies. After VSS, 77.7% (CI, 71.1%-84.95%) experienced symptom improvement and 22.3% (CI, 15.1%-29.0%) had persistent or worsened symptoms. Pooled restenosis rate was 17.7% (CI, 14.9%-20.9%). CONCLUSION: VSS is effective in alleviating IIH signs and symptoms, but the associated high rates of restenosis and persistent symptoms highlight the need for further investigation of this procedure and other adjunctive treatments for IIH.

Comparison of the Accuracy of a Mounting Fixture for Dental Implants for Implant Position Transfer and Open-Tray Implant Level Impression-An In Vitro Study.

The accuracy for the implant position transfer of a mounting fixture and a standardized open-tray implant level impression was compared. Ten aluminum master models with four implant analogs placed in different angulations were fabricated. By performing an open-tray implant level impression stone casts were produced. The master models and stone casts were scanned (comparison group one) using a laboratory scanner. Deviations in the scan body surface were determined in the form of mean (absolute) point distances and (signed) surface distances. The same procedure was performed with a screwed transfer and by fixing the posts of the mounting fixture (comparison group two). The mounting device was applied to each master model and scanned in a fixed and detached state (comparison group three). In a point comparison, the open-tray implant level impression showed mean deviations of 43.6 µm and a mounting fixture of 44.6 µm with no significant differences (p < 0.05). There were significant differences between groups two and three. The angulation of the implants had no effect on the accuracy. In a surface comparison, the open-tray implant level impression showed mean deviations of 36.0 µm and a mounting fixture of 2.0 µm (p > 0.05). Within the limits of this study, the mounting fixture transferred the implant position with the same accuracy as the open-tray implant level impression with respect to point deviations.

NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme.

In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I and from HLA-G contributes to inhibition of natural killer (NK) cells with expression of the inhibitory receptor CD94/NKG2A. We investigated whether NK cells expressing the activating CD94/NKG2C receptor counterpart were able to exert anti-glioma effects. NKG2C+ subsets were preferentially expanded by a feeder cell line engineered to express an artificial disulfide-stabilized trimeric HLA-E ligand (HLA-E*spG). NK cells expanded by a feeder cell line, which facilitates outgrowth of conventional NKG2A+, and fresh NK cells, were included for comparison. Expansion via the HLA-E*spG feeder cells selectively increased the fraction of NKG2C+ NK cells, which displayed a higher frequency of KIR2DL2/L3/S2 and CD16 when compared to expanded NKG2A+ NK cells. NKG2C+ NK cells exhibited increased cytotoxicity against K562 and KIR:HLA-matched and -mismatched primary glioblastoma multiforme (GBM) cells when compared to NKG2A+ NK cells and corresponding fresh NK cells. Cytotoxic responses of NKG2C+ NK cells were even more pronounced when utilizing target cells engineered with HLA-E*spG. These findings support the notion that NKG2C+ NK cells have potential therapeutic value for treating gliomas.

Control of TRPM3 Ion Channels by Protein Kinase CK2-Mediated Phosphorylation in Pancreatic ß-Cells of the Line INS-1.

In pancreatic ß-cells of the line INS-1, glucose uptake and metabolism induce the openings of Ca2+-permeable TRPM3 channels that contribute to the elevation of the intracellular Ca2+ concentration and the fusion of insulin granules with the plasma membrane. Conversely, glucose-induced Ca2+ signals and insulin release are reduced by the activity of the serine/threonine kinase CK2. Therefore, we hypothesized that TRPM3 channels might be regulated by CK2 phosphorylation. We used recombinant TRPM3α2 proteins, native TRPM3 proteins from INS-1 ß-cells, and TRPM3-derived oligopeptides to analyze and localize CK2-dependent phosphorylation of TRPM3 channels. The functional consequences of CK2 phosphorylation upon TRPM3-mediated Ca2+ entry were investigated in Fura-2 Ca2+-imaging experiments. Recombinant TRPM3α2 channels expressed in HEK293 cells displayed enhanced Ca2+ entry in the presence of the CK2 inhibitor CX-4945 and their activity was strongly reduced after CK2 overexpression. TRPM3α2 channels were phosphorylated by CK2 in vitro at serine residue 1172. Accordingly, a TRPM3α2 S1172A mutant displayed enhanced Ca2+ entry. The TRPM3-mediated Ca2+ entry in INS-1 ß-cells was also strongly increased in the presence of CX-4945 and reduced after overexpression of CK2. Our study shows that CK2-mediated phosphorylation controls TRPM3 channel activity in INS-1 ß-cells.

The impact of long-term non-pharmaceutical interventions on COVID-19 epidemic dynamics and control: the value and limitations of early models.

Mathematical models of epidemics are important tools for predicting epidemic dynamics and evaluating interventions. Yet, because early models are built on limited information, it is unclear how long they will accurately capture epidemic dynamics. Using a stochastic SEIR model of COVID-19 fitted to reported deaths, we estimated transmission parameters at different time points during the first wave of the epidemic (March-June, 2020) in Santa Clara County, California. Although our estimated basic reproduction number ([Formula: see text]) remained stable from early April to late June (with an overall median of 3.76), our estimated effective reproduction number ([Formula: see text]) varied from 0.18 to 1.02 in April before stabilizing at 0.64 on 27 May. Between 22 April and 27 May, our model accurately predicted dynamics through June; however, the model did not predict rising summer cases after shelter-in-place orders were relaxed in June, which, in early July, was reflected in cases but not yet in deaths. While models are critical for informing intervention policy early in an epidemic, their performance will be limited as epidemic dynamics evolve. This paper is one of the first to evaluate the accuracy of an early epidemiological compartment model over time to understand the value and limitations of models during unfolding epidemics.

Increased Pericardial Adipose Tissue in Smokers.

BACKGROUND: Pericardial adipose tissue (PAT), a visceral fat depot directly located to the heart, is associated with atherosclerotic and inflammatory processes. The extent of PAT is related to the prevalence of coronary heart disease and might be used for cardiovascular risk prediction. This study aimed to determine the effect of smoking on the extent of PAT. METHODS: We retrospectively examined 1217 asymptomatic patients (490 females, age 58.3 ± 8.3 years, smoker n = 573, non-smoker n = 644) with a multislice CT scanner and determined the PAT volume. Coronary risk factors were determined at inclusion, and a multivariate analysis was performed to evaluate the influence of smoking on PAT independent from accompanying risk factors. RESULTS: The mean PAT volume was 215 ± 107 mL in all patients. The PAT volume in smokers was significantly higher compared to PAT volume in non-smokers (231 ± 104 mL vs. 201 ± 99 mL, p = 0.03). Patients without cardiovascular risk factors showed a significantly lower PAT volume (153 ± 155 mL, p < 0.05) compared to patients with more than 1 risk factor. Odds ratio was 2.92 [2.31, 3.61; p < 0.001] for elevated PAT in smokers. CONCLUSION: PAT as an individual marker of atherosclerotic activity and inflammatory burden was elevated in smokers. The finding was independent from metabolic risk factors and might therefore illustrate the increased inflammatory activity in smokers in comparison to non-smokers.

Cavß3 Regulates Ca2+ Signaling and Insulin Expression in Pancreatic ß-Cells in a Cell-Autonomous Manner.

Voltage-gated Ca2+ (Cav) channels consist of a pore-forming Cavα1 subunit and auxiliary Cavα2-δ and Cavß subunits. In fibroblasts, Cavß3, independent of its role as a Cav subunit, reduces the sensitivity to low concentrations of inositol-1,4,5-trisphosphate (IP3). Similarly, Cavß3 could affect cytosolic calcium concentration ([Ca2 +]) in pancreatic ß-cells. In this study, we deleted the Cavß3-encoding gene Cacnb3 in insulin-secreting rat ß-(Ins-1) cells using CRISPR/Cas9. These cells were used as controls to investigate the role of Cavß3 on Ca2+ signaling, glucose-induced insulin secretion (GIIS), Cav channel activity, and gene expression in wild-type cells in which Cavß3 and the IP3 receptor were coimmunoprecipitated. Transcript and protein profiling revealed significantly increased levels of insulin transcription factor Mafa, CaMKIV, proprotein convertase subtilisin/kexin type-1, and nitric oxide synthase-1 in Cavß3-knockout cells. In the absence of Cavß3, Cav currents were not altered. In contrast, CREB activity, the amount of MAFA protein and GIIS, the extent of IP3-dependent Ca2+ release and the frequency of Ca2+ oscillations were increased. These processes were decreased by the Cavß3 protein in a concentration-dependent manner. Our study shows that Cavß3 interacts with the IP3 receptor in isolated ß-cells, controls IP3-dependent Ca2+-signaling independently of Cav channel functions, and thereby regulates insulin expression and its glucose-dependent release in a cell-autonomous manner.

In Situ Characterization of Polycaprolactone Fiber Response to Quasi-Static Tensile Loading in Scanning Electron Microscopy.

Microstructural responses to the mechanical load of polymers used in tissue engineering is notably important for qualification at in vivo testing, although insufficiently studied, especially regarding promising polycaprolactone (PCL). For further investigations, electrospun PCL scaffolds with different degrees of fiber alignment were produced, using two discrete relative drum collector velocities. Development and preparation of an adjusted sample geometry enabled in situ tensile testing in scanning electron microscopy. By analyzing the microstructure and the use of selected tracking techniques, it was possible to visualize and quantify fiber/fiber area displacements as well as local fractures of single PCL fibers, considering quasi-static tensile load and fiber alignment. The possibility of displacement determination using in situ scanning electron microscopy techniques for testing fibrous PCL scaffolds was introduced and quantified.

CT as a first-line modality in elderly patients with stable blunt chest trauma.

PURPOSE: Blunt thoracic injuries are common among elderly patients and may be a common cause of morbidity and death from blunt trauma injuries. We aimed to examine the impact of chest CT on the diagnosis and change of management plan in elderly patients with stable blunt chest trauma. We hypothesized that chest CT may play an important role in providing optimal management to this subgroup of trauma patients. METHODS: A retrospective analysis was performed on all the admitted adult blunt trauma patients between January 2014 and December 2018. Stable blunt chest trauma patients with abbreviated injury severity (AIS) < 3 for extra-thoracic injuries confirmed with chest X-ray (CXR) and chest CT on admission or during hospitalization were included in the study. The AIS is an international scale for grading the severity of anatomic injury following blunt trauma. Primary outcome variables were occult injuries, change in management, need for surgical procedures, missed injuries, readmission rate, intensive care unit (ICU) and length of hospital stay. RESULTS: There are 473 patients with blunt chest trauma included in the study. The study patients were divided into two groups according to the age range: group 1: 289 patients were included and aged 18-64 years; group 2: 184 patients were included and aged 65-99 years . Elderly patients in group 2 more often required ICU admission (11.4% vs. 5.2%), had a longer length of ICU stay (days) (median 11 vs. 6, p = 0.01), and the length of hospital stay (days) (median 14 vs. 6, p = 0.04). Injuries identified on chest CT has led to a change of management in 4.4% of young patients in group 1 and in 10.9% of elderly patients in group 2 with initially normal CXR. Chest CT resulted in a change of management in 12.8% of young patients in group 1 and in 25.7% of elderly patients in group 2 with initially abnormal CXR. CONCLUSION: Chest CT led to a change of management in a substantial proportion of elderly patients. Therefore, we recommend chest CT as a first-line imaging modality in patients aged over 65 years with isolated blunt chest trauma.

Public parks and the pandemic: How park usage has been affected by COVID-19 policies.

Public parks serve an important societal function as recreational spaces for diverse communities of people, with well documented physical and mental health benefits. As such, parks may be crucial for how people have handled effects of the COVID-19 pandemic, particularly the increasingly limited recreational opportunities, widespread financial uncertainty, and consequent heightened anxiety. Despite the documented benefits of parks, however, many states have instituted park shutdown orders due to fears that public parks could facilitate SARS-CoV-2 transmission. Here we use geotagged social media data from state, county, and local parks throughout New Jersey to examine whether park visitation increased when the COVID-19 pandemic began and whether park shutdown orders were effective at deterring park usage. We compare park usage during four discrete stages of spring 2020: (1) before the pandemic began, (2) during the beginning of the pandemic, (3) during the New Jersey governor's state-wide park shutdown order, and (4) following the lifting of the shutdown. We find that park visitation increased by 63.4% with the onset of the pandemic. The subsequent park shutdown order caused visitation in closed parks to decline by 76.1% while parks that remained open continued to experience elevated visitation levels. Visitation then returned to elevated pre-shutdown levels when closed parks were allowed to reopen. Altogether, our results indicate that parks continue to provide crucial services to society, particularly in stressful times when opportunities for recreation are limited. Furthermore, our results suggest that policies targeting human behavior can be effective and are largely reversible. As such, we should continue to invest in public parks and to explore the role of parks in managing public health and psychological well-being.

Dual Microcatheter Technique for Coiling of Intracranial Aneurysms: 2-Dimensional Operative Video.

Primary coiling of large intracranial aneurysms with complex morphology, such as multiple lobes and a wide neck, is challenging. In these aneurysms, achieving adequate intra-aneurysmal packing density while preventing coil herniation into the parent vessel may be difficult with traditional coiling technique. In the setting of acute aneurysm rupture, alternative treatment options such as stent-assisted coiling or flow diversion may not be feasible due to the need for dual antiplatelets. In this video, we demonstrate the use of a dual microcatheter technique to achieve adequate packing density within a wide-necked, bilobed saccular aneurysm. The patient presented with a ruptured posterior communicating artery aneurysm with Hunt and Hess grade 2 and Fisher grade 4 subarachnoid hemorrhage. A biaxial catheter system was used for primary coiling of the aneurysm. Two .017-inch microcatheters were strategically positioned in the aneurysm lobes. The first coil was deployed through the distal catheter, which created a basket for the second coil to be deployed through the proximal microcatheter. Subsequent simultaneously deployed coils were weaved into each other to form a stable coil mass that prevented coil herniation into the parent vessel. Complete obliteration of the aneurysm was achieved. The patient gave informed consent for the procedures and video recording. Institutional review board approval was deemed unnecessary. Video. ©University at Buffalo Neurosurgery, Inc., January 2020. With permission. 10.1093/ons/opab074 VIDEO 1 Dual Microcatheter Technique for Coiling of Intracranial Aneurysms: 2-Dimensional Operative Video opab074Media1 6236960343001.

Development and dissemination of infectious disease dynamic transmission models during the COVID-19 pandemic: what can we learn from other pathogens and how can we move forward?

The current COVID-19 pandemic has resulted in the unprecedented development and integration of infectious disease dynamic transmission models into policy making and public health practice. Models offer a systematic way to investigate transmission dynamics and produce short-term and long-term predictions that explicitly integrate assumptions about biological, behavioural, and epidemiological processes that affect disease transmission, burden, and surveillance. Models have been valuable tools during the COVID-19 pandemic and other infectious disease outbreaks, able to generate possible trajectories of disease burden, evaluate the effectiveness of intervention strategies, and estimate key transmission variables. Particularly given the rapid pace of model development, evaluation, and integration with decision making in emergency situations, it is necessary to understand the benefits and pitfalls of transmission models. We review and highlight key aspects of the history of infectious disease dynamic models, the role of rigorous testing and evaluation, the integration with data, and the successful application of models to guide public health. Rather than being an expansive history of infectious disease models, this Review focuses on how the integration of modelling can continue to be advanced through policy and practice in appropriate and conscientious ways to support the current pandemic response.

Performance of the Edwards Sapien 3 Ultra Transcatheter Aortic Valve System in Patients With Aortic Stenosis and Annulus Diameter in Proximity to Valve Size.

OBJECTIVES: The new Sapien 3 Ultra (S3U) transcatheter heart valve (Edwards Lifesciences) was designed with the intention to improve paravalvular sealing. In patients with an annulus size in proximity to the prosthesis size, little or no oversizing of the transcatheter aortic valve implantation (TAVI) prosthesis may lead to paravalvular regurgitation. Thus, this study was designed to assess valve performance in such patients. METHODS: We retrospectively enrolled 30 consecutive patients with symptomatic high-grade aortic stenosis scheduled for transfemoral TAVI between October 2019 and May 2020. Comprehensive computed tomography angiography for TAVI planning included standard measurements and quantification of calcification of the aortic valve. All patients had an aortic annular size in proximity to the valve size (maximum <15%) and received an S3U valve. Before discharge, paravalvular leakage was assessed via transthoracic echocardiography with an operator blinded to the TAVI results. In addition, 30-day outcome was assessed. RESULTS: The S3U was implanted in all patients without any procedural complications. One patient received a 20 mm S3U valve, 18 received 23 mm S3U valves, and 11 received 26 mm S3U valves; the annular sizes were 19.7 mm, 22.9 ± 0.2 mm, and 25.8 ± 0.2 mm, respectively. Quantification of calcification of the aortic valve revealed significant calcifications with a median Agatston score of 2571 AU (interquartile range, 1685-3467 AU). Postprocedural transthoracic echocardiography showed an excellent result in all but 2 patients. In the latter, aortic insufficiency grade I was seen. Thirty-day survival was 96.7%. CONCLUSIONS: The new S3U valve shows excellent performance in patients with high-grade aortic stenosis and annular size in proximity to the valve size, even in presence of significant valvular calcification.

Is Endovascular Therapy for Stroke Cost-Effective Globally? A Systematic Review of the Literature.

OBJECTIVES: Cost-effectiveness of endovascular therapy (EVT) is a key consideration for broad use of this approach for emergent large vessel occlusion stroke. We evaluated the evidence on cost-effectiveness of EVT in comparison with best medical management from a global perspective. MATERIALS AND METHODS: This systematic review of studies published between January 2010 and May 2020 evaluated the cost effectiveness of EVT for patients with large vessel occlusion acute ischemic stroke. The gain in quality adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER), expressed as cost per QALY resulting from EVT, were recorded. The study setting (country, economic perspective), decision model, and data sources used in economic models of EVT cost-effectiveness were recorded. RESULTS: Twenty-five original studies from 12 different countries were included in our review. Five of these studies were reported from a societal perspective; 18 were reported from a healthcare system perspective. Two studies used real-world data. The time horizon varied from 1 year to a lifetime; however, 18 studies reported a time horizon of >10 years. Twenty studies reported using outcome data from randomized, controlled clinical trials for their models. Nineteen studies reported using a Markov model. Incremental QALYs ranged from 0.09-3.5. All studies but 1 reported that EVT was cost-effective. CONCLUSIONS: Evidence from different countries and economic perspectives suggests that EVT for stroke treatment is cost-effective. Most cost-effectiveness studies are based on outcome data from randomized clinical trials. However, there is a need to study the cost-effectiveness of EVT based solely on real-world outcome data.

Systemic stress test model for shared portfolio networks.

We propose a dynamic model for systemic risk using a bipartite network of banks and assets in which the weight of links and node attributes vary over time. Using market data and bank asset holdings, we are able to estimate a single parameter as an indicator of the stability of the financial system. We apply the model to the European sovereign debt crisis and observe that the results closely match real-world events (e.g., the high risk of Greek sovereign bonds and the distress of Greek banks). Our model could become complementary to existing stress tests, incorporating the contribution of interconnectivity of the banks to systemic risk in time-dependent networks. Additionally, we propose an institutional systemic importance ranking, BankRank, for the financial institutions analyzed in this study to assess the contribution of individual banks to the overall systemic risk.

Assessment of Rod Material Types in Spine Surgery Outcomes: A Systematic Review.

BACKGROUND: Lumbar spine fusion surgery is traditionally performed with rigid fixation. Because the rigidity is often supraphysiologic, semirigid rods were developed. To the best of our knowledge, a comprehensive evaluation of rod material type on surgical outcomes has yet to be conducted. METHODS: A systematic review based on PRISMA guidelines was conducted across 3 electronic databases. After examination for inclusion and exclusion criteria, data were extracted from the studies. RESULTS: Seventeen studies, including 1399 patients, were included in this review. The mean rigid rod fusion rate is 92.2% and 95.5% for semirigid rods (P = 0.129). The mean improvement in back pain was 60.6% in rigid rods and 71.6% in semirigid rods. The improvement in leg pain was 81.9% and 77.2%, respectively. There were no differences in visual analog scale back pain score (P = 0.098), visual analog scale leg pain score (P = 0.136), or in functional improvement between rigid and semirigid rods (P = 0.143). There was no difference (P = 0.209) in the reoperation rate between rigid rods (13.1%) and semirigid rods (6.5%). There was a comparable incidence of adjacent segment disease (3%), screw fracture (1.7%), and wound infection (1.9%) between rod material types. CONCLUSIONS: There is a moderate level of evidence supporting that surgical intervention results in high fusion rates regardless of rod material type. Surgical intervention improves back pain, leg pain, and function, with neither material type showing clear superiority. There are comparable rates of reoperation, development of adjacent segment disease, development of mechanical complications, and incidence of infection in both rigid and semirigid rods. Further studies regarding rod material type are warranted.

Chopping the tail: How preventing superspreading can help to maintain COVID-19 control.

Disease transmission is notoriously heterogeneous, and SARS-CoV-2 is no exception. A skewed distribution where few individuals or events are responsible for the majority of transmission can result in explosive, superspreading events, which produce rapid and volatile epidemic dynamics, especially early or late in epidemics. Anticipating and preventing superspreading events can produce large reductions in overall transmission rates. Here, we present a stochastic compartmental (SEIR) epidemiological model framework for estimating transmission parameters from multiple imperfectly observed data streams, including reported cases, deaths, and mobile phone-based mobility that incorporates individual-level heterogeneity in transmission using previous estimates for SARS-CoV-1 and SARS-CoV-2. We parameterize the model for COVID-19 epidemic dynamics by estimating a time-varying transmission rate that incorporates the impact of non-pharmaceutical intervention strategies that change over time, in five epidemiologically distinct settings-Los Angeles and Santa Clara Counties, California; Seattle (King County), Washington; Atlanta (Dekalb and Fulton Counties), Georgia; and Miami (Miami-Dade County), Florida. We find that the effective reproduction number (RE) dropped below 1 rapidly in all five locations following social distancing orders in mid-March, 2020, but that gradually increasing mobility starting around mid-April led to an RE once again above 1 in late May (Los Angeles, Miami, and Atlanta) or early June (Santa Clara County and Seattle). However, we find that increased social distancing starting in mid-July in response to epidemic resurgence once again dropped RE below 1 in all locations by August 14. We next used the fitted model to ask: how does truncating the individual-level transmission rate distribution (which removes periods of time with especially high individual transmission rates and thus models superspreading events) affect epidemic dynamics and control? We find that interventions that truncate the transmission rate distribution while partially relaxing social distancing are broadly effective, with impacts on epidemic growth on par with the strongest population-wide social distancing observed in April, 2020. Given that social distancing interventions will be needed to maintain epidemic control until a vaccine becomes widely available, "chopping off the tail" to reduce the probability of superspreading events presents a promising option to alleviate the need for extreme general social distancing.

Control of Insulin Release by Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels.

BACKGROUND/AIMS: The release of insulin in response to increased levels of glucose in the blood strongly depends on Ca2+ influx into pancreatic beta cells by the opening of voltage-gated Ca2+ channels. Transient Receptor Potential Melastatin 3 proteins build Ca2+ permeable, non-selective cation channels serving as pain sensors of noxious heat in the peripheral nervous system. TRPM3 channels are also strongly expressed in pancreatic beta cells that respond to the TRPM3 agonist pregnenolone sulfate with Ca2+ influx and increased insulin release. Therefore, we hypothesized that in beta cells TRPM3 channels may contribute to pregnenolone sulfate- as well as to glucose-induced insulin release. METHODS: We used INS-1 cells as a beta cell model in which we analysed the occurrence of TRPM3 isoformes by immunoprecipitation and western blotting and by cloning of RT-PCR amplified cDNA fragments. We applied pharmacological as well as CRISPR/Cas9-based strategies to analyse the interplay of TRPM3 and voltage-gated Ca2+ channels in imaging experiments (FMP, Fura-2) and electrophysiological recordings. In immunoassays, we examined the contribution of TRPM3 channels to pregnenolone sulfate- and glucose-induced insulin release. To confirm our findings, we generated beta cell-specific Trpm3-deficient mice and compared their glucose clearance with the wild type in glucose tolerance tests. RESULTS: TRPM3 channels triggered the activity of voltage-gated Ca2+ channels and both channels together contributed to insulin release after TRPM3 activation. Trpm3-deficient INS-1 cells lacked pregnenolone sulfate-induced Ca2+ signals just like the pregnenolone sulfate-induced insulin release. Both, glucose-induced Ca2+ signals and the glucose-induced insulin release were strongly reduced. Accordingly, Trpm3-deficient mice displayed an impaired decrease of the blood sugar concentration after intraperitoneal or oral administration of glucose. CONCLUSION: The present study suggests an important role for TRPM3 channels in the control of glucose-dependent insulin release.

Impact of Apparatus Orientation and Gravity in Electrospinning-A Review of Empirical Evidence.

Electrospinning is a versatile fibre fabrication method with applications from textile to tissue engineering. Despite the appearance that the influencing parameters of electrospinning are fully understood, the effect of setup orientation has not been thoroughly investigated. With current burgeoning interest in modified and specialised electrospinning apparatus, it is timely to review the impact of this seldom-considered parameter. Apparatus configuration plays a major role in the morphology of the final product. The primary difference between spinning setups is the degree to which the electrical force and gravitational force contribute. Since gravity is much lower in magnitude when compared with the electrostatic force, it is thought to have no significant effect on the spinning process. But the shape of the Taylor cone, jet trajectory, fibre diameter, fibre diameter distribution, and overall spinning efficiency are all influenced by it. In this review paper, we discuss all these developments and more. Furthermore, because many research groups build their own electrospinning apparatus, it would be prudent to consider this aspect as particular orientations are more suitable for certain applications.

Hypotension on admission in patients with isolated traumatic brain injury: contemporary examination of the incidence and outcomes using a national registry.

PURPOSE: This study was primarily aimed at establishing the incidence and impact of hypotension in patients with blunt traumatic brain injury based on National Trauma Registry Database. METHODS: A retrospective cohort study using the National Trauma Registry was conducted. Patients with TBI following blunt mechanisms of injury were examined, comparing those with and without hypotension (SBP < 90 mm Hg) on arrival. RESULTS: During the period from 1998 to 2017, the registry included 437.354 blunt trauma patients. Of them, 7818 patients were hemodynamically unstable (SBP < 90 mm Hg) on admission. 513 met the inclusion criteria. Significant percentages of patients with high grade injures (ISS≥16) and low admission's GCS 3-12 (46% vs 16.4%), were found in the group of hypotensive TBI patients (p<0.0001). 323 (62.9%) patients had head AIS score 3-4 and only 190 (37.1%) patients AIS 5-6 (p<0.0001). Mortality in the hypotensive TBI group was 32.3%, whereas 6.1% patients died in the TBI hemodynamically stable group (p<0.0001). CONCLUSION: TBI patients presenting with hypotension represent an appreciable portion blunt trauma patients. Prompt brain CT, expedient efforts at optimal resuscitation and possibly early inotropic and vasopressors agents use may have an impact on final outcome in these patients.