Biophysical mechanisms of myocardium sodium channelopathies.

Genetic variants of gene SCN5A encoding the alpha-subunit of cardiac voltage-gated sodium channel Nav1.5 are associated with various diseases, including long QT syndrome (LQT3), Brugada syndrome (BrS1), and progressive cardiac conduction disease (PCCD). In the last decades, the great progress in understanding molecular and biophysical mechanisms of these diseases has been achieved. The LQT3 syndrome is associated with gain-of-function of sodium channels Nav1.5 due to impaired inactivation, enhanced activation, accelerated recovery from inactivation or the late current appearance. In contrast, BrS1 and PCCD are associated with the Nav1.5 loss-of-function, which in electrophysiological experiments can be manifested as reduced current density, enhanced fast or slow inactivation, impaired activation, or decelerated recovery from inactivation. Genetic variants associated with congenital arrhythmias can also disturb interactions of the Nav1.5 channel with different proteins or drugs and cause unexpected reactions to drug administration. Furthermore, mutations can affect post-translational modifications of the channels and their sensitivity to pH and temperature. Here we briefly review the current knowledge on biophysical mechanisms of LQT3, BrS1 and PCCD. We focus on limitations of studies that use heterologous expression systems and induced pluripotent stem cells (iPSC) derived cardiac myocytes and summarize our understanding of genotype-phenotype relations of SCN5A mutations.

Performance Assessment of Out-of-Hospital Use of Pelvic Circumferential Compression Devices for Severely Injured Patients in Switzerland: A Nationwide Retrospective Cross-Sectional Study.

BACKGROUND: Patients with severe pelvic fractures carry a greater risk of severe bleeding, and pelvic compression devices (PCCD) are used to stabilize the pelvis on the pre-hospital scene. The aim of this study was to describe the use of PCCD in the pre-hospital setting on a nationwide scale (Switzerland) and determine the sensitivity, specificity and rates of over- and under-triage of the current application practices. The secondary objective was to identify pre-hospital factors associated with unstable pelvic fractures. METHODS: Retrospective cross-sectional study using anonymized patient data (1 January 2015-31 December 2020) from the Swiss Trauma Registry (STR). Based on AIS scores, patients were assigned a unique principal diagnosis among three categories (unstable pelvic fracture-stable pelvic fracture-other) and assessed for use or not of PCCD. Secondarily, patient characteristics, initial pre-hospital vital signs, means of pre-hospital transport and trauma mechanism were also extracted from the database. RESULTS: 2790 patients were included for analysis. A PCCD was used in 387 (13.9%) patients. In the PCCD group, 176 (45.5%) had an unstable pelvic fracture, 52 (13.4%) a stable pelvic fracture and 159 (41.1%) an injury unrelated to the pelvic region. In the group who did not receive a PCCD, 214 (8.9%) had an unstable pelvic fracture, 182 (7.6%) a stable pelvic fracture and 2007 (83.5%) an injury unrelated to the pelvic region. The nationwide sensitivity of PCCD application was 45.1% (95% CI 40.1-50.2), the specificity 91.2% (95% CI 90-92.3), with both over- and under-triage rates of 55%. The prevalence of unstable fractures in our population was 14% (390/2790). We identified female sex, younger age, lower systolic blood pressure, higher shock index, pedestrian hit and fall ≥3 m as possible risk factors for an unstable pelvic fracture. CONCLUSIONS: Our results demonstrate a nationwide both over- and under-triage rate of 55% for out-of-hospital PCCD application. Female gender, younger age, lower blood pressure, higher shock index, pedestrian hit and fall >3 m are possible risk factors for unstable pelvic fracture, but it remains unclear if those parameters are relevant clinically to perform pre-hospital triage.

Benefits of early application of pelvic circumferential compression device to reduce bleeding in pelvic fractures.

BACKGROUND: To study of efficacy of early pelvic circumferential compression device using in patients with suspected pelvic trauma, compared with conventional stepwise approach. METHODS: Traumatic injury and at least one of the following criteria are required for inclusion: loss of consciousness or a Glasgow coma score (GCS) of less than 13; systolic blood pressure less than 90 mmHg; falling from more than 6 m; injury to several important organs; and a positive pelvic compression test. Patients who satisfied the inclusion criteria for the experimental group were given an early application of a commercial pelvic sling beginning in July 2019. The control group consisted of cases who got the device after clinical or radiological confirmation of a pelvic fracture in the previous year. Gender, age, mechanism of injury, GCS, hospital stay, amount of packed red blood cell transfusion, hematocrit in emergency room, and hematocrit 24 h after application of pelvic binder were all assessed and compared. RESULTS: The study had a total of 30 participants, with 15 in each group. The number of packed red blood cell transfusions in the early pelvic binder group (0.80 ± 1.42) is considerably lower than in the control group (2.4 ± 2.32) (P = 0.008), although the hematocrit change is not statistically different between the groups (2.1 VS 0.7) (P = 0.191). The time it took to install a pelvic binder was considerably shorter in the early pelvic binder group (16.40 ± 5.45) than in the control group (40.40 ± 13.64) (P = 0.001). There were no problems associated to soft tissue and skin necrosis in either group of patients. CONCLUSIONS: The use of the PCCD for 24 h prior to clinical and radiographic confirmation has significantly reduced the rate of packed red blood cell transfusion in any pelvic fracture patient without device-related complications. TRIAL REGISTRATION: The study was entered into the Thai Clinical Trials Registry ( TCTR20210809007 ).

Application of Pelvic Circumferential Compression Devices in Pelvic Ring Fractures-Are Guidelines Followed in Daily Practice?

Early administration of a pelvic circumferential compression device (PCCD) is recommended for suspected pelvic trauma. This study was conducted to evaluate the prevalence of PCCD in patients with pelvic fractures assigned to the resuscitation room (RR) of a Level I trauma center. Furthermore, correct application of the PCCD as well as associated injuries with potential clinical sequelae were assessed. All patients with pelvic fractures assigned to the RR of a level one trauma center between 2016 and 2017 were evaluated retrospectively. Presence and position of the PCCD on the initial trauma scan were assessed and rated. Associated injuries with potential adverse effects on clinical outcome were analysed. Seventy-seven patients were included, of which 26 (34%) had a PCCD in place. Eighteen (23%) patients had an unstable fracture pattern of whom ten (56%) had received a PCCD. The PCCD was correctly placed in four (15%) cases, acceptable in 12 (46%) and incorrectly in ten (39%). Of all patients with pelvic fractures (n = 77, 100%) treated in the RR, only one third (n = 26, 34%) had a PCCD. In addition, 39% of PCCDs were positioned incorrectly. Of the patients with unstable pelvic fractures (n = 18, 100%), more than half either did not receive any PCCD (n = 8, 44%) or had one which was inadequately positioned (n = 2, 11 %). These results underline that preclinical and clinical education programs on PCCD indication and application should be critically reassessed.

Evaluation of the concentration of the toxic 2,3,6,7-tetrachlorobiphenylene in air after an electrical material fire.

It is known that when fires or explosions involve electrical systems, along with PCDDs and PCDFs, polychlorinated biphenylenes (PCBPs) are also produced. These chlorinated tricyclic aromatic pollutants were noticed in fire rubbles and after the World Trade Center destruction. However, the analytical difficulties in developing an efficient method have limited the knowledge of their environmental distribution. In light of the equipotency of 2,3,6,7-TeCBP and 2,3,7,8-TeCDD, PCBPs call for more accurate investigations. In this paper, for the first time, the level and persistence of 2,3,6,7-TeCBP have been investigated in air samples (both indoor and outdoor) after a fire broke out in an industrial building. GC-MS/MS analysis revealed that 2,3,6,7-TeCBP concentrations after the fire (3046 fg/m3 at the "epicentre") were remarkably higher than that of the 2,3,7,8-TeCDD. Moreover, the monitoring for over two years has demonstrated the persistent nature of this compound. 2,3,6,7-TeCBP was also analyzed in two different ambient air scenario: industrial and periurban areas and in both cases its concentrations were no matter of concern, confirming the correlation of 2,3,6,7-TeCBP with fire episodes. Collectively, 2,3,6,7-TeCBP, because of its toxicity, concentration and persistence, is a crucial compound in the evaluation of the health effects correlated with fires of electrical systems.

Influence of organic and inorganic flocculants on the formation of PCDD/Fs during sewage sludge incineration.

Flocculants are widely used to improve the properties of sludge dewatering in industrial wastewater treatment. However, there have been no studies conducted on the influence of flocculants on the formation of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) during sewage sludge incineration. This paper selected three typical kinds of flocculants, including polyacrylamide (PAM), poly-ferric chloride (PFC), and polyaluminum chloride (PAC) flocculant, to study their influences on the formation of PCDD/Fs during sewage sludge incineration. The results indicated that PAM flocculant, which is an organic flocculant, inhibited the formation of PCDD/Fs in sewage sludge incineration, while inorganic flocculant, such as PFC and PAC flocculant, promoted the formation. The most probable explanation is that the amino content in the PAM flocculant acted as an inhibitor in the formation of PCDD/Fs, while the chlorine content, especially the metal catalyst in the PFC and PAC flocculants, increased the formation rate. The addition of flocculants nearly did not change the distribution of PCDD/F homologues. The PCDFs contributed the most toxic equivalent (TEQ) value, especially 2, 3, 4, 7, 8-PeCDF. Therefore, the use of inorganic flocculants in industrial wastewater treatment should be further assessed and possibly needs to be strictly regulated if the sludge is incinerated. From this aspect, a priority to the use of organic flocculants should be given.

Flotability and flotation separation of polymer materials modulated by wetting agents.

The surface free energy, surface tension and contact angles were performed to investigate the properties of wetting agents. Adsorption of wetting agents changes wetting behavior of polymer resins. Flotability of polymer materials modulated by wetting agents was studied, and wetting agents change significantly flotability of polymer materials. The flotability decreases with increasing the concentration of wetting agents, and the wetting ability is lignin sulfonate (LS)>tannic acid (TA)>methylcellulose (MC)>triton X-100 (TX-100) (from strong to weak). There is significant difference in the flotability between polymer resins and plastics due to the presence of additives in the plastics. Flotation separation of two-component and multicomponent plastics was conducted based on the flotability modulated by wetting agents. The two-component mixtures can be efficiently separated using proper wetting agent through simple flotation flowsheet. The multicomponent plastic mixtures can be separated efficiently through multi-stage flotation using TA and LS as wetting agents, and the purity of separated component was above 94%, and the recovery was more than 93%.

Regulation of the MIR155 host gene in physiological and pathological processes.

MicroRNAs (miRNAs), a family of small nonprotein-coding RNAs, play a critical role in posttranscriptional gene regulation by acting as adaptors for the miRNA-induced silencing complex to inhibit gene expression by targeting mRNAs for translational repression and/or cleavage. miR-155-5p and miR-155-3p are processed from the B-cell Integration Cluster (BIC) gene (now designated, MIR155 host gene or MIR155HG). MiR-155-5p is highly expressed in both activated B- and T-cells and in monocytes/macrophages. MiR-155-5p is one of the best characterized miRNAs and recent data indicate that miR-155-5p plays a critical role in various physiological and pathological processes such as hematopoietic lineage differentiation, immunity, inflammation, viral infections, cancer, cardiovascular disease, and Down syndrome. In this review we summarize the mechanisms by which MIR155HG expression can be regulated. Given that the pathologies mediated by miR-155-5p result from the over-expression of this miRNA it may be possible to therapeutically attenuate miR-155-5p levels in the treatment of several pathological processes.

Measurements of the exerted pressure by pelvic circumferential compression devices.

BACKGROUND: Data on the efficacy and safety of non-invasive Pelvic Circumferential Compression Devices (PCCDs) is limited. Tissue damage may occur if a continuous pressure on the skin exceeding 9.3 kPa is sustained for more than two or three hours. The aim of this study was to gain insight into the pressure build-up at the interface, by measuring the PCCD-induced pressure when applying pulling forces to three different PCCDs (Pelvic Binder((R)) , SAM-Sling ((R)) and T-POD((R)) ) in a simplified model. METHODS: The resulting exerted pressures were measured at four 'anatomical' locations (right, left, posterior and anterior) in a model using a pressure measurement system consisting of pressure cuffs. RESULTS: The exerted pressure varied substantially between the locations as well as between the PCCDs. Maximum pressures ranged from 18.9-23.3 kPa and from 19.2-27.5 kPa at the right location and left location, respectively. Pressures at the posterior location stayed below 18 kPa. At the anterior location pressures varied markedly between the different PCCDs. CONCLUSION: The circumferential compression by the different PCCDs showed high pressures measured at the four locations using a simplified model. Difference in design and functional characteristics of the PCCDs resulted in different pressure build-up at the four locations. When following the manufacturer's instructions, the exerted pressure of all three PCCDs tested exceeded the tissue damaging level (9.3 kPa). In case of prolonged use in a clinical situation this might put patients at risk for developing tissue damage.