No inflammatory effects after acute inhalation of barium sulfate particles in human volunteers

$\bf Background:$ Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles ($BaSO_{4}$), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for $BaSO_{4}$ to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out. $\bf Methods:$ Sixteen healthy volunteers were exposed to filtered air and $BaSO_{4}$ particles ($4.0 mg/m^{3}$) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of $BaSO_{4}$ was investigated with regard to mode of action and differences between in vivo and in vitro effects. $\bf Results:$ No local or systemic clinical signs were observed after acute $BaSO_{4}$ inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by $BaSO_{4}$ particles was minimal and 15-fold lower compared to ZnO. $\bf Conclusion:$ The results of this study indicate that $BaSO_{4}$ as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied

Maggot extract interrupts bacterial biofilm formation and maturation in combination with antibiotics by reducing the expression of virulence genes

Biofilms are aggregates of bacteria encased in an extracellular polymer matrix that acts as a diffusion barrier protecting the microbial community. Bacterial communication occurs by small signaling molecules called quorum sensing (QS) factors, which are involved in the activation of virulence genes and formation of biofilms. Larvae of the green bottle blowfly $\textit {Lucilia sericata}$ remove necrotic tissue by mechanical action (debridement) and proteolytic digestion. We produced a freeze-dried storable powder from larval extract and investigated its therapeutic effect on biofilms. Larval extract in concentrations of 6 and 12 mg/mL in combination with 0.5% antibiotics (≙50 U/mL penicillin and 50 $\mu$g/mL streptomycin) diminished free-floating (planktonic) $\textit {Pseudomonas aeruginosa}$ maintenance, while it showed no effect on $\textit {Staphylococcus aureus}$ and was not toxic to dermal cells. We established an ex vivo human dermal wound model. Larval extract in concentrations of 24 and 75 mg/mL in the presence of antibiotics (0.5%) significantly destroyed the biofilm stability of both $\textit {P. aeruginosa}$ and $\textit {S. aureus}$ biofilms. Furthermore, SEM analyses revealed crack and gap formations on $\textit {P. aeruginosa}$. biofilm surface and decreased expression of $\textit {P. aeruginosa}$ biofilm maturation and virulence genes ($\it lasR$, $\it rhlR$ and $\it rhlA$) was observed after treatment by larval extract in combination with antibiotics

Health effects after inhalation of micro- and nano-sized zinc oxide particles in human volunteers

Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of $0.5 mg/m^{3}$. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles ($2.0 mg/m^{3}$) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions

Improved physiological gait in acute and chronic SCI patients after training with wearable cyborg hybrid assistive limb

In recent years robotic devices became part of rehabilitation offers for patients suffering from Spinal Cord Injury (SCI) and other diseases. Most scientific publications about such devices focus on functional outcome. The aim of this study was to verify whether an improvement in physiological gait can be demonstrated in addition to the functional parameters after treatment with neurological controlled HAL® Robot Suit. Fifteen subjects with acute (12 months since injury, $\it n$ = 10) incomplete paraplegia (AIS B, $\it n$ = 0/AIS C, $\it n$ = 2/AIS D, $\it n$ = 8) or complete paraplegia (AIS A, $\it n$ = 5) with zones of partial preservation participated. Subjects underwent a body weight supported treadmill training for five times a week over 12 weeks using HAL®. At baseline and at the end of the study a gait analysis was performed and additional functional parameters such as 10-Meter-Walk-Test, Timed-Up-and-Go-Test, 6-Minutes-Walk-Test, and WISCI II score were collected. Results were evaluated for whole group and individually for acute and chronic subgroups. All functional parameters improved. Differences were also found in physiological parameters such as phases of gait cycle and accompanied by significant improvement in all spatiotemporal and gait phase parameters. The presented study shows signs that an improvement in physiological gait can be achieved in addition to improved functional parameters in patients with SCI after completing 12-week training with HAL®

Effects of wearing different face masks on cardiopulmonary performance at rest and exercise in a partially double-blinded randomized cross-over study

The use of face masks became mandatory during SARS-CoV-2 pandemic. Wearing masks may lead to complaints about laboured breathing and stress. The influence of different masks on cardiopulmonary performance was investigated in a partially double-blinded randomized cross-over design. Forty subjects (19–65 years) underwent body plethysmography, ergometry, cardiopulmonary exercise test and a 4-h wearing period without a mask, with a surgical mask (SM), a community mask (CM), and an FFP2 respirator (FFP2). Cardiopulmonary, physical, capnometric, and blood gas related parameters were recorded. Breathing resistance and work of breathing were significantly increased while wearing a mask. During exercise the increase in minute ventilation tended to be lower and breathing time was significantly longer with mask than without mask. Wearing a mask caused significant minimal decreases in blood oxygen pressure, oxygen saturation, an initial increase in blood and inspiratory carbon dioxide pressure, and a higher perceived physical exertion and temperature and humidity behind the mask under very heavy exercise. All effects were stronger when wearing an FFP2. Wearing face masks at rest and under exercise, changed breathing patterns in the sense of physiological compensation without representing a health risk. Wearing a mask for 4-h during light work had no effect on blood gases

Influence of face masks on the subjective impairment at different physical workloads

To quantify the subjective and cognitive impairment caused by wearing face masks at work, 20 men and 20 women (median age 47 years, range 19–65) were tested under different ergometer workloads while wearing surgical mask, community mask, FFP2 respirator or no mask in a randomized and partially double-blinded design. Masks were worn also at the workplace for four hours. Subjective impairment was recorded by questionnaires. Cognitive performance was tested before and after the workplace examination. Subjective feeling of heat, humidity, and difficult breathing increased with rising physical exertion and wearing time for all three mask types, most notably for FFP2. Even when blinded, participants with FFP2 reported difficult breathing already at rest. During physical exertion, individuals with low tolerance to discomfort reported significantly stronger impairment (OR 1.14, 95% CI 1.02 - 1.27). Regarding light work, older subjects (OR 0.95, 95% CI 0.92 - 0.98) and women (OR 0.84, 95% CI 0.72 - 0.99) showed significantly lower and atopic subjects stronger impairment (OR 1.16, 95% CI 1.06 - 1.27). No significant influence of mask wearing was detected on cognitive performance. Wearing a mask had no effect on cognitive performance, but led to discomfort which increased with physical exertion and wearing time. Individuals who tolerate discomfort poorly felt more impaired by wearing a mask during physical exertion

P2000 - a high-nitrogen austenitic steel for application in bone surgery

Optimal treatment of bone fractures with minimal complications requires implant alloys that combine high strength with high ductility. Today, TiAl6V4 titanium and 316L steel are the most applied alloys in bone surgery, whereas both share advantages and disadvantages. The nickel-free, high-nitrogen austenitic steel X13CrMnMoN18-14-3 (1.4452, brand name: P2000) exhibits high strength in combination with superior ductility. In order to compare suitable alloys for bone implants, we investigated titanium, 316L steel, CoCrMo and P2000 for their biocompatibility and hemocompatibility (according to DIN ISO 10993–5 and 10993–4), cell metabolism, mineralization of osteoblasts, electrochemical and mechanical properties. P2000 exhibited good biocompatibility of fibroblasts and osteoblasts without impairment in vitality or changing of cell morphology. Furthermore, investigation of the osteoblasts function by ALP activity and protein levels of the key transcription factor RUNX2 revealed 2x increased ALP activity and more than 4x increased RUNX2 protein levels for P2000 compared to titanium or 316 steel, respectively. Additionally, analyses of osteoblast biomineralization by Alizarin Red S staining exhibited more than 6x increased significant mineralization of osteoblasts grown on P2000 as compared to titanium. Further, P2000 showed no hemolytic effect and no significant influence on emocompatibility. Nanoindentation hardness tests of Titanium and 316L specimens exposed an indentation hardness (HIT) of about 4 GPa, whereas CoCrMo and P2000 revealed HIT of 7.5 and 5.6 GPa, respectively. Moreover, an improved corrosion resistance of P2000 compared to 316L steel was observed. In summary, we could demonstrate that the nickel-free high-nitrogen steel P2000 appears to be a promising alternative candidate for applications in bone surgery. As to nearly all aspects like biocompatibility and hemocompatibility, cell metabolism, mineralization of osteoblasts and mechanical properties, P2000 was similar to or revealed advantages against titanium, 316L or CoCrMo

Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany

The use of extracorporeal membrane oxygenation (ECMO) is discussed to improve patients’ outcome in severe COVID-19 with respiratory failure, but data on ECMO remains controversial. The aim of the study was to determine the characteristics of patients under invasive mechanical ventilation (IMV) with or without veno-venous ECMO support and to evaluate outcome parameters. Ventilated patients with COVID-19 with and without additional ECMO support were analyzed in a retrospective multicenter study regarding clinical characteristics, respiratory and laboratory parameters in day-to-day follow-up. Recruitment of patients was conducted during the first three COVID-19 waves at four German university hospitals of the Ruhr University Bochum, located in the Middle Ruhr Region. From March 1, 2020 to August 31, 2021, the charts of 149 patients who were ventilated for COVID-19 infection, were included (63.8% male, median age 67 years). Fifty patients (33.6%) received additional ECMO support. On average, ECMO therapy was initiated 15.6 $\pm$ 9.4 days after symptom onset, 10.6 $\pm$ 7.1 days after hospital admission, and 4.8 $\pm$ 6.4 days after the start of IMV. Male sex and higher SOFA and RESP scores were observed significantly more often in the high-volume ECMO center. Pre-medication with antidepressants was more often detected in survivors (22.0% vs. 6.5%; $\it p$ = 0.006). ECMO patients were 14 years younger and presented a lower rate of concomitant cardiovascular diseases (18.0% vs. 47.5%; $\it p$ = 0.0004). Additionally, cytokine-adsorption (46.0% vs. 13.1%; $\it p$ < 0.0001) and renal replacement therapy (76.0% vs. 43.4%; $\it p$ = 0.0001) were carried out more frequently; in ECMO patients thrombocytes were transfused 12-fold more often related to more than fourfold higher bleeding complications. Undulating C-reactive protein (CRP) and massive increase in bilirubin levels (at terminal stage) could be observed in deceased ECMO patients. In-hospital mortality was high (Overall: 72.5%, ECMO: 80.0%, ns). Regardless of ECMO therapy half of the study population deceased within 30 days after hospital admission. Despite being younger and with less comorbidities ECMO therapy did not improve survival in severely ill COVID-19 patients. Undulating CRP levels, a massive increase of bilirubin level and a high use of cytokine-adsorption were associated with worse outcomes. In conclusion, ECMO support might be helpful in selected severe cases of COVID-19