Point-of-Care and Label-Free Detection of Porcine Reproductive and Respiratory Syndrome and Swine Influenza Viruses Using a Microfluidic Device with Photonic Integrated Circuits

Swine viral diseases challenge the sector’s sustainability by affecting productivity and the health and welfare of the animals. The lack of antiviral drugs and/or effective vaccines renders early and reliable diagnosis the basis of viral disease management, underlining the importance of point-of-care (POC) diagnostics. A novel POC diagnostic device utilizing photonic integrated circuits (PICs), microfluidics, and information and communication technologies for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza A (SIV) was validated using spiked and clinical oral fluid samples. Metrics including sensitivity, specificity, accuracy, precision, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the performance of the device. For PRRSV, the device achieved a sensitivity of 83.5%, specificity of 77.8%, and DOR values of 17.66, whereas the values for SIV were 81.8%, 82.2%, and 20.81, respectively. The POC device and PICs can be used for the detection of PRRSV and SIV in the field, paving the way for the introduction of novel technologies in the field of animal POC diagnostics to further optimize livestock biosecurity.     

Centredness in health care: A systematic overview of reviews

IntroductionThe introduction of effective, evidence‐based approaches to centredness in health care is hindered by the fact that research results are not easily accessible. This is partly due to the large volume of publications available and because the field is closely linked to and in some ways encompasses adjoining fields of research, for example, shared decision making and narrative medicine. In an attempt to survey the field of centredness in health care, a systematic overview of reviews was conducted with the purpose of illuminating how centredness in health care is presented in current reviews.MethodsSearches for relevant reviews were conducted in the databases PubMed, Scopus, Cinahl, PsychINFO, Web of Science and EMBASE using terms connected to centredness in health care. Filters specific to review studies of all types and for inclusion of only English language results as well as a time frame of January 2017–December 2018, were applied.ResultsThe search strategy identified 3697 unique reviews, of which 31 were included in the study. The synthesis of the results from the 31 reviews identified three interrelated main themes: Attributes of centredness (what centredness is), Translation from theory into practice (how centredness is done) and Evaluation of effects (possible ways of measuring effects of centredness). Three main attributes of centeredness found were: being unique, being heard and shared responsibility. Aspects involved in translating theory into practice were sufficient prerequisites, strategies for action and tools used in safeguarding practice. Further, a variety and breadth of measures of effects were found in the included reviews.ConclusionsOur synthesis demonstrates that current synthesized research literature on centredness in health care is broad, as it focuses both on explorations of the conceptual basis and the practice, as well as measures of effects. This study provides an understanding of the commonalities identified in the reviews on centredness in healthcare overall, ranging from theory to practice and from practice to evaluation.Patient or Public ContributionPatient representatives were involved during the initiation of the project and in decisions about its focus, although no patient or public representatives made direct contributions to the review process.     

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.     

The space-time profiles of sleep spindles and their coordination with slow oscillations on the electrode manifold

Sleep spindles are important for sleep quality and cognitive functions, with their coordination with slow oscillations (SOs) potentially organizing cross-region reactivation of memory traces. Here, we describe the organization of spindles on the electrode manifold and their relation to SOs. We analyzed the sleep night EEG of 34 subjects and detected spindles and SOs separately at each electrode. We compared spindle properties (frequency, duration, and amplitude) in slow wave sleep (SWS) and Stage 2 sleep (S2); and in spindles that coordinate with SOs or are uncoupled. We identified different topographical spindle types using clustering analysis that grouped together spindles co-detected across electrodes within a short delay (±300 ms). We then analyzed the properties of spindles of each type, and coordination to SOs. We found that SWS spindles are shorter than S2 spindles, and spindles at frontal electrodes have higher frequencies in S2 compared to SWS. Furthermore, S2 spindles closely following an SO (about 10% of all spindles) show faster frequency, shorter duration, and larger amplitude than uncoupled ones. Clustering identified Global, Local, Posterior, Frontal-Right and Left spindle types. At centro-parietal locations, Posterior spindles show faster frequencies compared to other types. Furthermore, the infrequent SO-spindle complexes are preferentially recruiting Global SO waves coupled with fast Posterior spindles. Our results suggest a non-uniform participation of spindles to complexes, especially evident in S2. This suggests the possibility that different mechanisms could initiate an SO-spindle complex compared to SOs and spindles separately. This has implications for understanding the role of SOs-spindle complexes in memory reactivation.     

Vitrectomy for optic disc pit maculopathy: a long-term follow-up study

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the clinical outcomes of vitrectomy with induction of posterior vitreous detachment for the treatment of optic disc...     

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.     

Coaxial Drainage versus Standard Chest Tube after Pulmonary Lobectomy: A Randomized Controlled Study

Chest tubes are routinely inserted after thoracic surgery procedures in different sizes and numbers. The aim of this study is to assess the efficacy of Smart Drain Coaxial drainage compared with two standard chest tubes in patients undergoing thoracotomy for pulmonary lobectomy. Ninety-eight patients (57 males and 41 females, mean age 68.3 ± 7.4 years) with lung cancer undergoing open pulmonary lobectomy were randomized in two groups: 50 received one upper 28-Fr and one lower 32-Fr standard chest tube (ST group) and 48 received one 28-Fr Smart Drain Coaxial tube (SDC group). Hospitalization, quantity of fluid output, air leaks, radiograph findings, pain control and costs were assessed. SDC group showed shorter hospitalization (7.3 vs. 6.1 days, p = 0.02), lower pain in postoperative day-1 (p = 0.02) and a lower use of analgesic drugs (p = 0.04). Pleural effusion drainage was lower in SDC group in the first postoperative day (median 400.0 ± 200.0 mL vs. 450.0 ± 193.8 mL, p = 0.04) and as a mean of first three PODs (median 325.0 ± 137.5 mL vs. 362.5 ± 96.7 mL, p = 0.01). No difference in terms of fluid retention, residual pleural space, subcutaneous emphysema and complications after chest tubes removal was found. In conclusion, Smart Drain Coaxial chest tube seems a feasible option after thoracotomy for pulmonary lobectomy. The SDC group showed a shorter hospitalization and decreased analgesic drugs use and, thus, a reduction of costs.     

Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice

Rationale In rodents, serotonin 1B (5-HT_1B) agonists specifically reduce aggressive behaviors, including several forms of escalated aggression. One form of escalated aggression is seen in mice that seek the opportunity to attack another mouse by accelerating their responding during a fixed interval (FI) schedule. Responses preceding the opportunity to attack may reflect aggressive motivation. Objective This study investigated the effects of two 5-HT_1B receptor agonists on the motivation to fight and the performance of heightened aggression. Materials and methods Male mice were housed as “residents” and performed nose-poke responses on an FI 10-min schedule with the opportunity to briefly attack an “intruder” serving as the reinforcer. In the first experiment, the 5-HT_1B receptor agonist, CP-94,253 (0–10 mg/kg, IP), was given 30 min before the FI 10 schedule. To confirm that CP-94,253 achieved its effects via 5-HT_1B receptors, the 5HT_1B/1D receptor antagonist, GR 127935 (10 mg/kg, IP) was administrated before the agonist injection. In the second experiment, the 5-HT_1B agonist CP-93,129 (0–1.0 μg) was microinjected into the dorsal raphe 10 min before the FI 10 schedule. Results The agonists had similar effects on all behaviors. CP-94,253 and CP-93,129 significantly reduced the escalated aggression towards the intruder at doses lower than those required to affect operant responding. The highest doses of CP-94,253 (10 mg/kg) and CP-93,129 (1.0 μg) decreased the rate and accelerating pattern of responding during the FI 10 schedule; lower doses were less effective. GR 127935 antagonized CP-94,253’s effects on all other behaviors, except response rate. Conclusions These data extend the anti-aggressive effects of 5-HT_1B agonists to a type of escalated aggression that is rewarding and further suggest that these effects are associated with actions at 5-HT_1B receptors in the dorsal raphe.