Recent advances and challenges in temperature monitoring and control in microfluidic devices.

Temperature is a critical-yet sometimes overlooked-parameter in microfluidics. Microfluidic devices can experience heating inside their channels during operation due to underlying physicochemical phenomena occurring therein. Such heating, whether required or not, must be monitored to ensure adequate device operation. Therefore, different techniques have been developed to measure and control temperature in microfluidic devices. In this contribution, the operating principles and applications of these techniques are reviewed. Temperature-monitoring instruments revised herein include thermocouples, thermistors, and custom-built temperature sensors. Of these, thermocouples exhibit the widest operating range; thermistors feature the highest accuracy; and custom-built temperature sensors demonstrate the best transduction. On the other hand, temperature control methods can be classified as external- or integrated-methods. Within the external methods, microheaters are shown to be the most adequate when working with biological samples, whereas Peltier elements are most useful in applications that require the development of temperature gradients. In contrast, integrated methods are based on chemical and physical properties, structural arrangements, which are characterized by their low fabrication cost and a wide range of applications. The potential integration of these platforms with the Internet of Things technology is discussed as a potential new trend in the field.

In vitro and in vivo evaluation of two combined ß-lactamase inhibitors against carbapenem-resistant Acinetobacter baumannii.

The objective of this study was to evaluate the in vitro and in vivo efficacy of clavulanic acid (C/A) in combination with tazobactam against clinical strains of carbapenem-resistant Acinetobacter baumannii. The MIC of 24 clinical strains of A. baumannii was determined, and a checkerboard assay and time-kill curve analysis were performed in selected strains to determine the synergy between C/A and tazobactam. The efficacy of C/A in monotherapy and in combination with tazobactam was evaluated in vitro in cell culture experiments and in a murine peritoneal sepsis model. The C/A and C/A plus tazobactam MIC50 were 128 and <1 mg/L, respectively. The checkerboard assay showed that tazobactam (4 and 8 mg/L) demonstrated synergy with C/A against A. baumannii Ab40, an OXA-24 producer strain, and Ab293, a lacking OXA ß-lactamase strain. The time-kill curve assay showed both bactericidal and synergistic effects against Ab40 and Ab293, with C/A 1xMIC and tazobactam (4 and 8 mg/L) at 24 h. In the murine peritoneal sepsis model with Ab293 strain, the combination of C/A and tazobactam reduced bacterial loads in tissues and blood by 2 and 4 log10 CFU/g or mL compared with C/A alone. Combining C/A with tazobactam could be considered as a potential alternative strategy to treat A. baumannii in some cases, and future work with more strains is needed to confirm this possibility.

XAANTAL1 Reveals an Additional Level of Flowering Regulation in the Shoot Apical Meristem in Response to Light and Increased Temperature in Arabidopsis.

Light and photoperiod are environmental signals that regulate flowering transition. In plants like Arabidopsis thaliana, this regulation relies on CONSTANS, a transcription factor that is negatively posttranslational regulated by phytochrome B during the morning, while it is stabilized by PHYA and cryptochromes 1/2 at the end of daylight hours. CO induces the expression of FT, whose protein travels from the leaves to the apical meristem, where it binds to FD to regulate some flowering genes. Although PHYB delays flowering, we show that light and PHYB positively regulate XAANTAL1 and other flowering genes in the shoot apices. Also, the genetic data indicate that XAL1 and FD participate in the same signaling pathway in flowering promotion when plants are grown under a long-day photoperiod at 22 °C. By contrast, XAL1 functions independently of FD or PIF4 to induce flowering at higher temperatures (27 °C), even under long days. Furthermore, XAL1 directly binds to FD, SOC1, LFY, and AP1 promoters. Our findings lead us to propose that light and temperature influence the floral network at the meristem level in a partially independent way of the signaling generated from the leaves.

Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells.

Mast cells (MCs) play pivotal roles in many inflammatory conditions including infections, anaphylaxis, and asthma. MCs store immunoregulatory compounds in their large cytoplasmic granules and, upon stimulation, secrete them via regulated exocytosis. Exocytosis in many cells requires the participation of Munc18 proteins (also known as syntaxin-binding proteins), and we found that mature MCs express all three mammalian isoforms: Munc18-1, -2, and -3. To study their functions in MC effector responses and test the role of MC degranulation in anaphylaxis, we used conditional knockout (cKO) mice in which each Munc18 protein was deleted exclusively in MCs. Using recordings of plasma membrane capacitance for high-resolution analysis of exocytosis in individual MCs, we observed an almost complete absence of exocytosis in Munc18-2-deficient MCs but intact exocytosis in MCs lacking Munc18-1 or Munc18-3. Stereological analysis of EM images of stimulated MCs revealed that the deletion of Munc18-2 also abolishes the homotypic membrane fusion required for compound exocytosis. We confirmed the severe defect in regulated exocytosis in the absence of Munc18-2 by measuring the secretion of mediators stored in MC granules. Munc18-2 cKO mice had normal morphology, development, and distribution of their MCs, indicating that Munc18-2 is not essential for the migration, retention, and maturation of MC-committed progenitors. Despite that, we found that Munc18-2 cKO mice were significantly protected from anaphylaxis. In conclusion, MC-regulated exocytosis is required for the anaphylactic response, and Munc18-2 is the sole Munc18 isoform that mediates membrane fusion during MC degranulation.

A century of climate and land-use change cause species turnover without loss of beta diversity in California's Central Valley.

Climate and land-use changes are thought to be the greatest threats to biodiversity, but few studies have directly measured their simultaneous impacts on species distributions. We used a unique historic resource-early 20th-century bird surveys conducted by Joseph Grinnell and colleagues-paired with contemporary resurveys a century later to examine changes in bird distributions in California's Central Valley, one of the most intensively modified agricultural zones in the world and a region of heterogeneous climate change. We analyzed species- and community-level occupancy using multispecies occupancy models that explicitly accounted for imperfect detection probability, and developed a novel, simulation-based method to compare the relative influences of climate and land-use covariates on site-level species richness and beta diversity (measured by Jaccard similarity). Surprisingly, we show that mean occupancy, species richness and between-site similarity have remained remarkably stable over the past century. Stability in community-level metrics masked substantial changes in species composition; occupancy declines of some species were equally matched by increases in others, predominantly species with generalist or human-associated habitat preferences. Bird occupancy, richness and diversity within each era were driven most strongly by water availability (precipitation and percent water cover), indicating that both climate and land-use are important drivers of species distributions. Water availability had much stronger effects than temperature, urbanization and agricultural cover, which are typically thought to drive biodiversity decline.

Clinical outcomes of trochanteric syndrome endoscopically treated.

BACKGROUND: Greater trochanteric pain syndrome (GTPS) is clinically defined as greater trochanter pain with mechanical characteristics. Most cases of GTPS are resolved with conservative treatment. Surgical techniques are reserved for those who had unsatisfactory results with conservative treatment. PURPOSE: The aim of the present paper is to describe the outcomes observed within endoscopic treatment of peritrochanteric pathology. METHODS: Twenty-three patients were included in the present study, undergoing surgery between January 2010 and December 2011, diagnosed with GTPS and surgically treated with endoscopy. All patients were evaluated with Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) Modified Harris Hip Score (mHHS) and Hip Outcome Score (HOS). The Scales were assessed before surgery and at 3, 6 and 12 months postoperatively. RESULTS: All scores showed statistically significant differences (p < 0.001) within all periods. CONCLUSION: The endoscopic technique has proven to be safe and reproducible with good and excellent results, thus being an additional surgical procedure to consider within therapeutic management of greater trochanteric pain syndrome. LEVEL OF EVIDENCE: IV. Case series.

Evaluation of the presence and severity of menopausal symptoms among postmenopausal women screened for the metabolic syndrome.

BACKGROUND: The prevalence of the metabolic syndrome (METS) increases after the menopause. Reports indicate that the METS and its components, especially obesity, enhance the intensity of menopausal symptoms. OBJECTIVE: Assess the frequency and severity of menopausal symptoms in postmenopausal women. Factors related to the symptom severity were also analyzed including depressive and metabolic status. METHODS: A total of 204 natural postmenopausal women (40-65 years) participating in a METS screening program were asked to fill out the Menopause Rating Scale (MRS), the Hospital Anxiety and Depression Scale (HADS), and a general socio-demographic questionnaire containing personal and partner data. Criteria of the American Heart Association were used to define the METS. RESULTS: Median age of the whole sample was 56 years. A 52.9% presented the METS, with 37.3% presenting hyperglycemia, 51.5% hypertension, 58.3% abdominal obesity, 45.6% high triglyceride and 56.4% low HDL-C levels. Total and subscale MRS scores did not differ in accordance to the presence or not of the METS. The three top prevalent menopausal symptoms were muscle and joint problems (87.2%), physical and mental exhaustion (72%) and depressive mood (64.7%). A 19.6% of women presented total MRS scores above 16 defined as severe. Multivariate linear regression analysis determined that anxiety (higher HADS anxiety subscale scores) was significantly and positively correlated with all components of the MRS (Total and subscale scores). Higher total MRS scores correlated positively with abdominal perimeter and higher parity. Somatic scores correlated inversely with female education and positively with psychotropic drug use; and psychological MRS scores positively correlated depressed mood (higher HADS depressive subscale scores) and abdominal perimeter. CONCLUSION: In this postmenopausal sample, severity of menopausal symptoms correlated to abdominal obesity, mood and other personal aspects.

Aortic thrombosis and acute kidney injury due to atherosclerosis in a dog.

OBJECTIVE: Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Due to its cardiovascular ischemic complications, it is one of the most common causes of death in people. However, atherosclerosis is seldomly reported in dogs. ANIMAL: A 10-year-old male mixed-breed dog. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: Severe acute kidney injury associated with thrombosis of the abdominal aorta. TREATMENT AND OUTCOME: Treatment included renal replacement therapy, antithrombotic therapy, and supportive care. However, the dog developed neurological and respiratory complications and was euthanized due to worsening kidney function and lack of improvement of the thrombosis. Postmortem examination confirmed the presence of aortic thromboembolism and renal infarcts. Histology revealed severe chronic-active atherosclerosis of the distal aorta and renal arteries. CLINICAL RELEVANCE: Aortic thrombosis is uncommon in dogs, and it is often associated with underlying conditions such as protein-losing nephropathy, endocrine disorders, cardiac disease, or hypercoagulability. In this case, no specific underlying cause was identified and atherosclerosis was considered the primary cause of the thrombosis.

Efficacy of Tamoxifen Metabolites in Combination with Colistin and Tigecycline in Experimental Murine Models of Escherichia coli and Acinetobacter baumannii.

This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant Escherichia coli and Acinetobacter baumannii, using a repurposing approach to shorten the time required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and virulence studies were conducted on E. coli (colistin-susceptible C1-7-LE and colistin-resistant MCR-1+) and A. baumannii (tigecycline-susceptible Ab#9 and tigecycline-resistant Ab#186) strains. The efficacy of the metabolite mix (33.3% each) and N-desmethyltamoxifen in combination with colistimethate sodium (CMS) or tigecycline was evaluated in experimental models in mice. In the pneumonia model, N-desmethyltamoxifen exhibited significant efficacy against Ab#9 and both E. coli strains, especially E. coli MCR-1+ (-2.86 log10 CFU/g lungs, -5.88 log10 CFU/mL blood, and -50% mortality), and against the Ab#186 strain when combined with CMS (-2.27 log10 CFU/g lungs, -2.73 log10 CFU/mL blood, and -40% mortality) or tigecycline (-3.27 log10 CFU/g lungs, -4.95 log10 CFU/mL blood, and -50% mortality). Moreover, the metabolite mix in combination with both antibiotics decreased the bacterial concentrations in the lungs and blood for both A. baumannii strains. In the sepsis model, the significant efficacy of the metabolite mix was restricted to the colistin-susceptible E. coli C1-7-LE strain (-3.32 log10 CFU/g lung, -6.06 log10 CFU/mL blood, and -79% mortality). N-desmethyltamoxifen could be a new therapeutic option in combination with CMS or tigecycline for combating multidrug-resistant GNB, specifically A. baumannii.

The Impact of the COVID-19 Pandemic on Incidence and Short-Term Survival for Common Solid Tumours in the United Kingdom: A Cohort Analysis.

Purpose: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreatic, prostate, and stomach cancer in the UK. Methods: This was a population-based cohort study of electronic health records from the UK primary care Clinical Practice Research Datalink GOLD database. In sum, 12,259,744 eligible patients aged ≥18 years with ≥1 year's history identified from January 2000 to December 2022 were included. We estimated age-standardised incidence and short-term (one- and two-year) survival for several common cancers from 2000 to 2019 (in five-year strata) and compared these to 2020-2022 using the Kaplan-Meier method. Results: Incidence decreased for most cancers in 2020 and recovered to different extents in 2021-2022. Short-term survival improved for most cancers between 2000 and 2019, but then declined, albeit minimally, for those diagnosed in 2020-2022. This was most pronounced for colorectal cancer, with one-year survival falling from 78.8% (95% CI 78%-79.6%) in 2015-2019 to 77% (95% CI 75.6-78.3%) for those diagnosed in 2020-2022. Conclusion: Short-term survival for many cancers was impacted, albeit minimally, by the pandemic in the UK, with reductions in survivorship from colorectal cancer equivalent to returning to the mortality seen in the first decade of the 2000s. While data on longer-term survival are needed to fully comprehend the impact of COVID-19 on cancer care, our findings illustrate the need for an urgent and substantial commitment from the UK National Health Service to address the existing backlog in cancer screening and diagnostic procedures to improve cancer care and mortality.

Retrospective evaluation of hematological ratios in canine parvovirosis: 401 cases.

BACKGROUND: The utility of neutrophil-to-lymphocyte ratio (NLR), platelet to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) as prognostic indicators has not been investigated in canine parvovirosis (CPV). HYPOTHESIS: To evaluate whether these hematological ratios obtained at hospital admission in CPV are associated with outcome or duration of hospitalization. ANIMALS: Four hundred one client-owned dogs presented with CPV. Methods-Retrospective multicenter cohort study. Medical records were reviewed to identify dogs with CPV. Data regarding signalment, complete blood count at admission, duration of hospitalization and outcome were collected. RESULTS: Of the 401 dogs included in the study, 336 (83.8%) survived to discharge. The median (25th and 75th percentiles) PLR in nonsurvivors (336.56 [159.84-635.77]) was significantly higher than in survivors (217.65 [117.67-389.65]) (P = .003). The area under the receiver-operating characteristic curve for nonsurvival was 0.615 (95% CI [0.593-0.691], P = .003). A cut off of 700 showed a 21.5% sensitivity and 90% specificity for nonsurvival. No association was observed between hospitalization duration and either hematological ratios or total WBC counts. The median (25th and 75th percentiles) lymphocyte count was below reference interval in all dogs and was significantly lower in the dogs which died (0.82 × 109 /L [0.5-1.87]) than in survivors (1.27 × 109 /L [0.73-2.22]) (P = .005). The median (25th and 75th percentiles) monocyte count however was lower in survivors (0.38 × 109 /L [0.29-1.59]), than in nonsurvivors (0.73 × 109 /L [0.1-2]) (P = .002). CONCLUSIONS: Evaluation of PLR at hospital admission might be a useful marker of disease severity and could have prognostic value in dogs with CPV.

The metabolic syndrome and its components in postmenopausal women.

BACKGROUND: Prevalence of the metabolic syndrome (METS) increases significantly after the menopause. OBJECTIVE: To assess the prevalence of the METS and its components in postmenopausal women. Factors relating to each of the composing items of the METS were also analyzed. METHODS: Natural postmenopausal women (40-65 years) were invited to participate in this cross-sectional study in order to assess the presence of the METS using modified Adult Treatment Panel III (ATP-III) criteria. Participants were also requested to fill out a general socio-demographic questionnaire. RESULTS: A total of 204 women were surveyed with a median age of 56 years. A 52.9% presented the METS according to modified ATP-III criteria, with 37.3% presenting hyperglycemia, 51.5% hypertension, 58.3% abdominal obesity, 45.6% high triglyceride levels and 56.4% low HDL-C levels. Women with the METS presented a higher rate of dyslipidemia (high triglyceride and low HDL-C levels), hyperglycemia, hypertension and abdominal obesity than those without the syndrome. Those with abdominal obesity and hyperglycemia significantly displayed higher rates of low HDL-C levels (bivariate analysis). Multiple linear regression analysis found a positive correlation between glucose and triglyceride levels. Systolic blood pressure significantly and positively correlated to age and abdominal circumference. Abdominal circumference displayed an inverse correlation with educational level. CONCLUSION: Prevalence of the METS in this postmenopausal female sample was high and associated to metabolic and lipid derangements. As abdominal obesity was significantly associated to lower education, there is an urgent need of implementing educational programs directed to high-risk populations in order to increase awareness of the problem.

In Vitro and In Vivo Virulence Study of Listeria monocytogenes Isolated from the Andalusian Outbreak in 2019.

In 2019, the biggest listeriosis outbreak by Listeria monocytogenes (Lm) in the South of Spain was reported, resulting in the death of three patients from 207 confirmed cases. One strain, belonging to clonal complex 388 (Lm CC388), has been isolated. We aimed to determine the Lm CC388 virulence in comparison with other highly virulent clones such as Lm CC1 and Lm CC4, in vitro and in vivo. Four L. monocytogenes strains (Lm CC388, Lm CC1, Lm CC4 and ATCC 19115) were used. Attachment to human lung epithelial cells (A549 cells) by these strains was characterized by adherence and invasion assays. Their cytotoxicities to A549 cells were evaluated by determining the cells viability. Their hemolysis activity was determined also. A murine intravenous infection model using these was performed to determine the concentration of bacteria in tissues and blood. Lm CC388 interaction with A549 cells is non-significantly higher than that of ATCC 19115 and Lm CC1, and lower than that of Lm CC4. Lm CC388 cytotoxicity is higher than that of ATCC 19115 and Lm CC1, and lower than that of Lm CC4. Moreover, Lm CC388 hemolysis activity is lower than that of the Lm CC4 strain, and higher than that of Lm CC1. Finally, in the murine intravenous infection model by Lm CC388, higher bacterial loads in tissues and at similar levels of Lm CC4 were observed. Although a lower rate of mortality of patients during the listeriosis outbreak in Spain in 2019 has been reported, the Lm CC388 strain has shown a greater or similar pathogenicity level in vitro and in an animal model, like Lm CC1 and Lm CC4.

A surge in obsidian exploitation more than 1.2 million years ago at Simbiro III (Melka Kunture, Upper Awash, Ethiopia).

Pleistocene archaeology records the changing behaviour and capacities of early hominins. These behavioural changes, for example, to stone tools, are commonly linked to environmental constraints. It has been argued that, in earlier times, multiple activities of everyday life were all uniformly conducted at the same spot. The separation of focused activities across different localities, which indicates a degree of planning, according to this mindset characterizes later hominins since only 500,000 years ago. Simbiro III level C, in the upper Awash valley of Ethiopia, allows us to test this assumption in its assemblage of stone tools made only with obsidian, dated to more than 1.2 million years (Myr) old. Here we first reconstruct the palaeoenvironment, showing that the landscape was seasonally flooded. Following the deposition of an accumulation of obsidian cobbles by a meandering river, hominins began to exploit these in new ways, producing large tools with sharp cutting edges. We show through statistical analysis that this was a focused activity, that very standardized handaxes were produced and that this was a stone-tool workshop. We argue that at Simbiro III, hominins were doing much more than simply reacting to environmental changes; they were taking advantage of new opportunities, and developing new techniques and new skills according to them.

Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.

Background: Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease. Methods: We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome. Participants: Patients admitted due to COVID-19 infection with mild disease. Results: Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy. Conclusions: Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration. Trial registration: https://clinicaltrials.gov/, identifier NCT04348695.

Hematological Composite Scores in Patients with Inflammatory Bowel Disease.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been identified as potential inflammatory biomarkers. In this work we aimed to analyze whether the hematological composite scores differ between inflammatory bowel disease (IBD) patients and healthy controls, and if they are related to disease activity. A total of 197 IBD patients-130 Crohn's (CD) disease and 67 ulcerative colitis (UC)-and 208 age- and sex-matched healthy controls were enrolled. C-reactive protein and fecal calprotectin were assessed. Multivariable linear regression analysis was executed. After adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls. C-reactive protein and SIRI and NLR were correlated in IBD patients. However, fecal calprotectin was not related to any of these blood scores. Furthermore, disease activity parameters were not associated with any of the blood composite scores in both CD and UC patients. In conclusion, NLR and PLR, but not SIRI and MLR, are independently higher in IBD patients compared to controls. However, the four hematological scores are not related to disease activity in either CD or UC patients. Based on these results, blood-based inflammatory scores may not serve as subrogated biomarkers of disease activity in IBD.

Ultrasensitive and rapid identification of ESRI developer- and piperacillin/tazobactam-resistant Escherichia coli by the MALDIpiptaz test.

BACKGROUND: The excessive use of piperacillin/tazobactam (P/T) has promoted the emergence of P/T-resistant Enterobacterales. We reported that in Escherichia coli, P/T contributes to the development of extended-spectrum resistance to ß-lactam/ß-lactamase inhibitor (BL/BLI) (ESRI) in isolates that are P/T susceptible but have low-level resistance to BL/BLI. Currently, the detection of P/T resistance relying on conventional methods is time-consuming. To overcome this issue, we developed a cost-effective test based on MALDI-MS technology, called MALDIpiptaz, which aims to detect P/T resistance and ESRI developers in E. coli. METHODS: We used automated Clover MS Data Analysis software to analyse the protein profile spectra obtained by MALDI-MS from a collection of 248 E. coli isolates (91 P/T-resistant, 81 ESRI developers and 76 P/T-susceptible). This software allowed to preprocess all the spectra to build different peak matrices that were analysed by machine learning algorithms. RESULTS: We demonstrated that MALDIpiptaz can efficiently and rapidly (15 min) discriminate between P/T-resistant, ESRI developer and P/T-susceptible isolates and allowed the correct classification between ESRI developers from their isogenic resistance to P/T. CONCLUSION: The combination of excellent performance and cost-effectiveness are all desirable attributes, allowing the MALDIpiptaz test to be a useful tool for the rapid determination of P/T resistance in clinically relevant E. coli isolates.

mRNA-Based Reprogramming Under Xeno-Free and Feeder-Free Conditions.

Reprogramming somatic cells into induced pluripotent stem cells (iPSC) has provided a gateway for many novel discoveries in the field of tissue engineering, regenerative medicine and cell therapy. The need for an efficient, less laborious and fast reprogramming protocol under xeno-free, feeder-free and chemically defined conditions has never been greater. Here we describe a novel approach to reprogramming using the StemRNA 3rd Gen Reprogramming Kit (ReproCELL) which encompasses non-modified microRNAs (NM-miRNA), non-modified E3, K3, B18R RNAs (EKB NM-RNA) and non-modified mRNAs for six crucial transcription factors (OSKMNL NM-RNA).

Buprenorphine versus dexamethasone as perineural adjuvants in femoral and adductor canal nerve blocks for total knee arthroplasty: a randomized, non-inferiority clinical trial.

BACKGROUND: Optimal control of acute postoperative pain and prevention of chronic persistent pain in total knee arthroplasty (TKA) remain a challenge. METHODS: A randomized, non-inferiority clinical trial (385 patients) evaluated every hour immediate postoperative pain during 24 h, using a verbal rating 11-point scale for patient self-reporting of pain (VRS11). All patients received subarachnoid anesthesia and were randomly allocated in four groups: single shots femoral (FNB) or adductor canal blocks (ACB), both with dexamethasone (dex) and buprenorphine (bup). Patients received intravenous analgesia (metamizole magnesium, dexketoprofen) and rescue analgesia when needed: intravenous (paracetamol and morphine) and/or regional (femoral and sciatic nerve blocks). Demographics and adverse effects were also recorded. RESULTS: A 45.7% of patients had pain: bupACB 56.3%, bupFNB 50.0%, dexACB 40.6% and dexFNB 36.1% (P=0.022). Rescue analgesia was needed in 37.7% of patients (P=0.128). There were statistical differences in percentage of timepoints without pain (95.0±7.9%, P=0.014) and mean VRS11 (0.18±0.3, P=0.012) but no differences in distribution of intensity periods of pain. There were no significant differences in the need of rescue analgesia excepting the use of intravenous morphine (P=0.025). CONCLUSIONS: Buprenorphine is in the present trial inferior to dexamethasone by less than the established non-inferiority limit when used as perineural adjuvant in femoral nerve or adductor canal blocks in total knee arthroplasty analgesia. So, it could be considered an alternative in patients where dexamethasone is contraindicated, such as diabetics.

Social Science Pedagogy as a Way of Integrating Sustainable Education and Global Citizenship into the Initial Training of Pre-Primary Teachers.

The main objective of this research was to demonstrate the integration of international and national strategies in education for sustainable development and global citizenship into initial teacher training. The researchers analyzed the outcomes of a feminist teaching strategy based on family trees, focusing on the usefulness of social science pedagogy in developing critical thinking among pupils. They also attempted to enhance teachers' digital literacy and make progress in reflecting on its functioning and use. The research used mixed methods, and the research instrument was a questionnaire using Likert-type scales validated by specialists from several universities. It was deployed in the module Didáctica del Conocimiento del Medio Social y Medioambiental (Pedagogy of Knowledge of the Social and Cultural Environment) of the Bachelor's Degree in Pre-Primary Education at the University of Alicante. Using historical research with a gender perspective, the trainee teachers investigated their family trees, focusing on the women in their families. They also carried out a speculative exercise to aid reflection on their contributions as teachers in support of equal education. The results obtained showed that this was a novel and useful educational activity, which inspired participants to work for a fair and democratic global citizenship based on coeducation.