Urea-Comprising Single Core Diketopyrrolopyrrole Derivatives: Exploring the Synthesis, Self-Assembly and Charge Transport Properties.

Supramolecular electronics exploits the distinctive features stemming from noncovalent interactions, guiding the self-assembly of molecules to craft materials endowed with customized electronic functionalities. Hydrogen-bonded materials, characterized by their capacity to establish dynamic and stable networks, introduce an extra dimension to the development of supramolecular electronic systems. This study presents a comparative analysis of two remarkably small semiconductors utilizing diketopyrrolopyrrole functionalized with urea units as hydrogen-bonding motifs, strategically positioned at opposing ends of the conjugated core. We show how the subtle distinction in functionalization not only influences morphology and self-assembly dynamics via hydrogen-bonding and π-π stacking formation, but also holds significant consequences for ultimate charge transport properties. Our observations into the interplay of noncovalent interactions provide valuable insights and strategic pathways for the design of novel materials with enhanced electronic characteristics.

Daisy chain architectures: from discrete molecular entities to polymer materials.

Daisy chain architectures, made by the self-complementary threading of an axle covalently linked to a macrocycle, represent a particularly intriguing family of supramolecular and mechanically interlocked (macro)molecules. In this review, we discuss their recent history, their modular chemical structures, and the various synthetic strategies to access them. We also detail how their internal sliding motions can be controlled and how their integration within polymers can amplify that motions up to the macroscopic scale. This overview of the literature demonstrates that the peculiar structure and dynamics of daisy chains have already strongly influenced the research on artificial molecular machines, with the potential to be implemented from nanometric switchable devices to mechanically active soft-matter materials.

Complete genome sequence of Pediococcus acidilactici A40, a bacterium with biocontrol and plant growth-promoting properties.

We report the complete genome assembly of Pediococcus acidilactici A40, a bacterium with biocontrol and plant growth-promoting properties, obtained from Colombia.

Concordancia entre cinco criterios de síndrome metabólico en adolescentes de una zona altoandina del Perú / Concordance between five criteria of metabolic syndrome in teenagers from a Peruvian high andes region

RESUMEN Objetivo. Determinar la concordancia entre cinco criterios diagnósticos de síndrome metabólico (SM) entre adolescentes residentes de una zona altoandina del Perú. Materiales y métodos. Se realizó un estudio transversal con datos secundarios de un estudio de intervención en dos escuelas públicas en el año 2019. Participaron 397 adolescentes que residen en la ciudad de Cajamarca ubicada en la región andina del Perú. Se aplicaron cinco criterios diagnósticos: Third Adult Treatment Panel (ATP-III) modificados por Cook, de la Federación Internacional de Diabetes (IDF), de la American Heart Association (AHA), de Ferranti, y de la Organización Mundial de Salud (OMS). Se estimaron las prevalencias puntuales y de intervalo con los cinco criterios. Se estimó el coeficiente de concordancia de Kappa con su respectivo intervalo de confianza al 95% (IC 95%). Resultados. El criterio de Ferranti identificó un 17,1% (IC 95%: 13,4 a 20,8) de adolescentes con SM, seguido del criterio de la ATP-III con 4,3% (IC 95%: 2,3 a 6,3); los demás criterios identificaron una menor frecuencia. La mejor concordancia fue encontrada entre los criterios de la AHA y la ATP-III (k = 0,905), los criterios de la OMS e IDF tuvieron un coeficiente de 0,628. Los cinco criterios coincidieron en clasificar como SM a seis adolescentes (1,5%). Conclusiones. Los criterios de la AHA y la ATP-III modificados por Cook tuvieron una concordancia casi perfecta, que se mantuvo en ambos sexos. Los criterios ATP-III, de Ferranti, IDF, AHA y OMS concuerdan en menos del 2% en identificar SM en el mismo grupo de adolescentes.

ABSTRACT Objective. To determine the concordance between five diagnostic criteria for metabolic syndrome (MS) among teenagers from a Peruvian high Andes region. Materials and methods. A cross-sectional study was carried out with secondary data from an intervention study in two public schools in 2019. We included 397 teenagers who lived in the city of Cajamarca, in the Andean region of Peru. We applied the criteria from the Adult Treatment Panel III (ATP-III) modified by Cook, the International Diabetes Federation (IDF), the American Heart Association (AHA), Ferranti, and the World Health Organization (WHO). The point prevalence and interval prevalence were estimated with the five criteria. The Kappa concordance coefficient with an 95% confidence interval (95%CI) was estimated. Results. The Ferranti criterion identified 17.1% (95%CI: 13.4 to 20.8) of teenagers with MS, followed by the ATP-III criterion with 4.3% (95%CI: 2.3 to 6.3); the other criteria identified a lower frequency. The best concordance was found between the AHA and ATP-III criteria (k = 0.905); the WHO and IDF criteria had a coefficient of 0.628. The five criteria coincided in classifying six adolescents (1.5%) as MS. Conclusions. The AHA and ATP-III criteria modified by Cook had almost perfect concordance, which was also found for both sexes. The ATP-III, Ferranti, IDF, AHA and WHO criteria agree in less than 2% when identifying MS in the same group of adolescents.

Conservative Surgery for Diabetic Foot Osteomyelitis is not Associated With Longer Survival Time Without Recurrence of Foot Ulcer When Compared With Amputation.

Conservative surgery of diabetic foot osteomyelitis (DFO) in which bone infection is removed without amputation could minimize the biomechanical changes associated with foot surgery. We hypothesize that patients who undergo conservative surgery will have a longer survival time without recurrence of foot ulcers and further amputations than those who undergo any type of amputation to treat DFO. We assessed a retrospective cohort of 108 patients who underwent surgery for DFO from January 2011 to December 2012. Patients were followed-up until May 2020. Reulceration and reamputation-free survival times were plotted using the Kaplan-Meier method and were calculated from the date of first surgery to recurrence, new amputation, or end of the study. A stratified log rank was used to study differences among groups. Cumulative survival without recurrences at 1, 5, and 8 years was 95%, 36%, and 29%, respectively, in patients who underwent conservative surgery and 95%, 43%, and 30%, respectively, in those undergoing amputation. Cumulative survival without a new amputation at 1, 5, and 8 years was 100%, 80%, and 80%, respectively, in patients who underwent conservative surgery and 98%, 82%, and 69%, respectively, in those undergoing amputation. No differences were found regarding either recurrence (log rank, P = .98) or new amputations (log rank, P = .64). In conclusion, conservative surgery is as safe as amputation to arrest bone infection in the feet of patients with diabetes. Conservative surgery was not associated with a lower rate of recurrence and new amputations than those patients who underwent amputations.

Long-term Mortality of a Cohort of Patients Undergoing Surgical Treatment for Diabetic Foot Infections. An 8-year Follow-up Study.

We analyzed a retrospective cohort of 150 patients with diabetic foot infections (DFIs) who underwent surgical treatment to determine long-term outcomes. The median follow-up of the series was 7.6 years. Cox's proportional hazards model for survival time was performed and hazard ratios (HRs) were estimated. Survival times were plotted using the Kaplan-Meier method. Fifteen patients (10%) required readmission after discharge from the hospital for a recurrence of the infection. Ninety patients (60%) had re-ulcerations. Forty-nine (54.4% of those re-ulcerated) required new admission and 24 of them (26.6% of those re-ulcerated) finally required a new amputation. Overall cumulative survival rates at 1, 5, and 8 years were 95%, 78%, and 64%, respectively. Predictive variables of long-term mortality were insulin treatment (HR: 2.0, 95% CI: 1.1-3.6, P = .01), female sex (HR: 3.1, 95% CI: 1.7-5.3, P<.01) and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (HR: 2.2, 95% CI: 1.1-4.2, P = .01). In conclusion, patients undergoing surgical treatment for DFIs had a high rate of recurrences and mortality. Women, patients who underwent treatment with insulin, and those with eGFR <60 ml/min/1.73 m2 had a higher risk of long-term mortality.

Does Metabolic Control Have Any Influence on the Clinical Presentation and Short-Term Outcomes of Diabetic Foot Infections?

Objective: We hypothesized that patients with poor glycemic control undergoing treatment for diabetic foot infections (DFIs) would have a poorer prognosis than those with better metabolic control assessed by glycated hemoglobin (HbA1c). Approach: We analyzed a retrospective cohort of 245 patients with moderate and severe DFIs. HbA1c values were dichotomized (<7% or ≥7% and ≤75th percentile (P75) and >P75) to analyze patient outcomes regarding metabolic control. The present study adhered to the STROBE guidelines for cohort studies. Results: One hundred sixty-nine patients (69%) were men. Their mean age was 60.7 years (10.8). HbA1c ≥7% was detected in 203 patients (82.9%). P75 HbA1c was 10.9%. After performing univariate analysis, we found an association of HbA1c <7% with major amputations and mortality. However, after applying the logistic regression model, we did not find HbA1c <7% to be a predictive factor of major amputation. The risk factors for mortality following application of Cox's proportional hazards model were osteomyelitis (HR: 0.2, 95% CI: 0.07-0.62, p < 0.01), eGFR <60 mL/min/1.73 m2 (HR: 2.7, 95% CI: 1.0-7.5, p = 0.04), and HbA1c <7% (HR: 4.9, 95% CI: 1.8-13.2, p < 0.01). Innovation: The group with optimal glycemic control (HbA1c <7%) had a shorter survival time than those with worse metabolic control. Conclusions: We did not find a longer duration of hospitalization, a higher rate of amputations, or longer healing times in the groups with worse metabolic control. HbA1c <7% was a risk factor for mid-term mortality.

Surgical Diabetic Foot Infections: Is Osteomyelitis Associated With a Worse Prognosis?

It has been reported that patients with diabetes and foot ulcers complicated with osteomyelitis (OM) have a worse prognosis than those complicated with soft tissue infections (STI). Our study aimed to determine whether OM is associated with a worse prognosis in cases of moderate and severe diabetic foot infections requiring surgery. A retrospective series consisted of 150 patients who underwent surgery for diabetic foot infections. We studied the differences between OM versus STI. Furthermore, diabetic foot infections were reclassified into four groups: moderate STI (M-STI), moderate OM (M-OM), severe STI (S-STI), and severe OM (S-OM). The variables associated with prognosis were limb loss, length of hospital stay, duration of antibiotic treatment, recurrence of the infection, and time to healing (both the initial ulcer and the postoperative wound). No differences in limb salvage, hospital stay, duration of antibiotic treatment, recurrence of the infection, and time to healing were found when comparing OM with STI. Patients with M-O had a higher rate of recurrences after initial treatment and a longer time to healing when comparing with M-STI. We didn't find any differences between severe infections with or without OM. In conclusion, we have found in our surgical series of diabetic foot infections that OM is not associated with worse prognosis when comparing with STI regarding limb loss rate, length of hospital stays, duration of antibiotic treatment, recurrence of the infection, and time to healing. The results of the present series should further be confirmed by other authors.

Concordance between five criteria of metabolic syndrome in teenagers from a Peruvian high andes region. / Concordancia entre cinco criterios de síndrome metabólico en adolescentes de una zona altoandina del Perú.

OBJECTIVE.: Motivation for the study. There are several criteria for metabolic syndrome in adolescents, each reporting different prevalence rates and not necessarily coinciding with each other. Main findings. We studied school children from the city of Cajamarca at 2750 meters above sea level. The five criteria for metabolic syndrome coincided in six of the 397 (1.5%) adolescents. The criteria generated prevalence rates ranging from 3.0% to 17.1%. The criteria with near perfect concordance were those from the American Heart Association criteria and those modified by Cook. Implications. The diagnosis of metabolic syndrome in adolescents is complex, even more so among those residing at high altitudes. . To determine the concordance between five diagnostic criteria for metabolic syndrome (MS) among teenagers from a Peruvian high Andes region. MATERIALS AND METHODS.: A cross-sectional study was carried out with secondary data from an intervention study in two public schools in 2019. We included 397 teenagers who lived in the city of Cajamarca, in the Andean region of Peru. We applied the criteria from the Adult Treatment Panel III (ATP-III) modified by Cook, the International Diabetes Federation (IDF), the American Heart Association (AHA), Ferranti, and the World Health Organization (WHO). The point prevalence and interval prevalence were estimated with the five criteria. The Kappa concordance coefficient with an 95% confidence interval (95%CI) was estimated. RESULTS.: The Ferranti criterion identified 17.1% (95%CI: 13.4 to 20.8) of teenagers with MS, followed by the ATP-III criterion with 4.3% (95%CI: 2.3 to 6.3); the other criteria identified a lower frequency. The best concordance was found between the AHA and ATP-III criteria (k = 0.905); the WHO and IDF criteria had a coefficient of 0.628. The five criteria coincided in classifying six adolescents (1.5%) as MS. CONCLUSIONS.: The AHA and ATP-III criteria modified by Cook had almost perfect concordance, which was also found for both sexes. The ATP-III, Ferranti, IDF, AHA and WHO criteria agree in less than 2% when identifying MS in the same group of adolescents.

OBJETIVO.: Determinar la concordancia entre cinco criterios diagnósticos de síndrome metabólico (SM) entre adolescentes residentes de una zona altoandina del Perú. MATERIALES Y MÉTODOS.: Se realizó un estudio transversal con datos secundarios de un estudio de intervención en dos escuelas públicas en el año 2019. Participaron 397 adolescentes que residen en la ciudad de Cajamarca ubicada en la región andina del Perú. Se aplicaron cinco criterios diagnósticos: Third Adult Treatment Panel (ATP-III) modificados por Cook, de la Federación Internacional de Diabetes (IDF), de la American Heart Association (AHA), de Ferranti, y de la Organización Mundial de Salud (OMS). Se estimaron las prevalencias puntuales y de intervalo con los cinco criterios. Se estimó el coeficiente de concordancia de Kappa con su respectivo intervalo de confianza al 95% (IC 95%). RESULTADOS.: El criterio de Ferranti identificó un 17,1% (IC 95%: 13,4 a 20,8) de adolescentes con SM, seguido del criterio de la ATP-III con 4,3% (IC 95%: 2,3 a 6,3); los demás criterios identificaron una menor frecuencia. La mejor concordancia fue encontrada entre los criterios de la AHA y la ATP-III (k = 0,905), los criterios de la OMS e IDF tuvieron un coeficiente de 0,628. Los cinco criterios coincidieron en clasificar como SM a seis adolescentes (1,5%). CONCLUSIONES.: Los criterios de la AHA y la ATP-III modificados por Cook tuvieron una concordancia casi perfecta, que se mantuvo en ambos sexos. Los criterios ATP-III, de Ferranti, IDF, AHA y OMS concuerdan en menos del 2% en identificar SM en el mismo grupo de adolescentes.

Loss of G0/G1 switch gene 2 (G0S2) promotes disease progression and drug resistance in chronic myeloid leukaemia (CML) by disrupting glycerophospholipid metabolism.

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have turned chronic myeloid leukaemia (CML) from a fatal disease into a manageable condition for most patients. Despite improved survival, targeting drug-resistant leukaemia stem cells (LSCs) remains a challenge for curative CML therapy. Aberrant lipid metabolism can have a large impact on membrane dynamics, cell survival and therapeutic responses in cancer. While ceramide and sphingolipid levels were previously correlated with TKI response in CML, the role of lipid metabolism in TKI resistance is not well understood. We have identified downregulation of a critical regulator of lipid metabolism, G0/G1 switch gene 2 (G0S2), in multiple scenarios of TKI resistance, including (1) BCR::ABL1 kinase-independent TKI resistance, (2) progression of CML from the chronic to the blast phase of the disease, and (3) in CML versus normal myeloid progenitors. Accordingly, CML patients with low G0S2 expression levels had a worse overall survival. G0S2 downregulation in CML was not a result of promoter hypermethylation or BCR::ABL1 kinase activity, but was rather due to transcriptional repression by MYC. Using CML cell lines, patient samples and G0s2 knockout (G0s2-/- ) mice, we demonstrate a tumour suppressor role for G0S2 in CML and TKI resistance. Our data suggest that reduced G0S2 protein expression in CML disrupts glycerophospholipid metabolism, correlating with a block of differentiation that renders CML cells resistant to therapy. Altogether, our data unravel a new role for G0S2 in regulating myeloid differentiation and TKI response in CML, and suggest that restoring G0S2 may have clinical utility.

Co-Inoculation of Plant-Growth-Promoting Bacteria Modulates Physiological and Biochemical Responses of Perennial Ryegrass to Water Deficit.

Perennial ryegrass is a forage commonly used in temperate regions for livestock feeding; however, its yield is affected by reduced biomass production under water deficit. In a previous study, three co-inoculations of beneficial bacteria were selected based on their ability to promote plant growth under reduced water availability. The aim of this work was to elucidate some mechanisms by which the selected bacteria can help improve the response of perennial ryegrass to water deficit. Ryegrass plants were inoculated with each of the co-inoculations (Herbaspirillum sp. AP02−Herbaspirillum sp. AP21; Herbaspirillum sp. AP02−Pseudomonas sp. N7; Herbaspirillum sp. AP21−Azospirillum brasilense D7) and subjected to water deficit for 10 days. Physiological and biochemical measurements were taken 10 days after stress and shortly after rehydration. The results showed that bacteria had a positive effect on shoot biomass production, dissipation of excess energy, and proline and chlorophyll pigments during the days of water deficit (p < 0.05). The leaf water status of the inoculated plants was 12% higher than that of the uninoculated control after rehydration. Two Herbaspirillum strains showed greater potential for use as biofertilizers that help ameliorate the effects of water deficit.

Effect of a 16-Session Qigong Program in Non-Hodgkin Lymphoma Survivors: A Randomized Clinical Trial.

Background: The treatment associated with non-Hodgkin lymphoma patients may cause adverse effects on their physical and psychological condition. The aim of this study is to detect the response to an eight-week, 16-session, 60-min presential Qigong program in anxiety, depression and vagal nerve activity alongside a control group. Methods: A randomized controlled clinical trial was managed. Randomization was carried out by generating a numerical sequence of three cycles through the software EPIDAT 4.1. Numbers were placed in sealed opaque envelopes for assignment to the different groups. Results: Anxiety levels were substantially decreased in the experimental group, with a large effect size (F = 30.38, p < 0.00). Depression levels had an improvement in the experimental group in contrast to the control group, reaching statistical significance (F = 19.19, p < 0.00). Heart Rate Variability unveiled significant results in terms of between-group differences, with a large effect size in the HRV Index (F = 15.80, p < 0.00), SDNN (F = 8.82, p < 0.00), and RMSSD (F = 6.72, p < 0.01) in the time domain, and a medium effect size in the HF (F = 9.78, p < 0.003), LF (F = 9.78, p < 0.00), and LF/HF Ratio (F = 18.44, p < 0.00) in the frequency domain, which were all bettered in the experimental group, after the Qigong program. Conclusions: Qigong therapy can be an effective therapeutic activity in consonance with traditional medicine to improve psychological health and autonomic nervous system balance in non-Hodgkin lymphoma survivors.

Clinical, microbiological and inflammatory markers of severe diabetic foot infections.

AIMS: In addition to systemic inflammatory response syndrome (SIRS), various clinical signs, microbiological findings and inflammatory markers could be associated with severe diabetic foot infections (DFI). METHODS: This study included a retrospective cohort of 245 patients with DFI treated at San Juan de Dios Hospital in San José de Costa Rica. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CRP/albumin ratio, peripheral blood leucocyte ratios and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scoring system were evaluated. Univariate analysis was carried out between moderate and severe infections. ROC curves were plotted. Cut-off value of inflammatory markers for diagnosing severe infections was established and then dichotomized to be included in a logistic regression model. A score was designed based on its results. RESULTS: Skin necrosis (p < 0.01, OR = 8.5, 95% CI = 3.5-20.9), ESR > 94 mm/h (p < 0.01, OR = 2.5, 95% CI = 1.2-5.1), albumin < 2.8 g/dl (p = 0.04, OR = 2.0, 95% CI = 1.0-4.1) and neutrophil-to-lymphocyte ratio (NLR) > 4.52 (p < 0.01, OR = 3.3, 95% CI = 1.6-6.5) were found to be predictive of severe infections. Score >5 had a good diagnosis performance for classifying severe infections. Moderate infections with a score >5 had a worse prognosis than moderate ones. CONCLUSIONS: We found an association of necrosis, serum albumin, ESR and NLR values with severe DFI. The presence of these predictive factors of severity in cases of moderate infections was significantly associated with a higher rate of amputations and recurrences, longer duration of antibiotic treatment and longer hospital stays. DFI could be classified as mild, moderate, severe without SIRS and severe.

Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B.

Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 have revolutionized therapy for chronic myeloid leukemia (CML), paving the way for clinical development in other diseases. Despite success, targeting leukemic stem cells and overcoming drug resistance remain challenges for curative cancer therapy. To identify drivers of kinase-independent TKI resistance in CML, we performed genome-wide expression analyses on TKI-resistant versus sensitive CML cell lines, revealing a nuclear factor-kappa B (NF-κB) expression signature. Nucleocytoplasmic fractionation and luciferase reporter assays confirmed increased NF-κB activity in the nucleus of TKI-resistant versus sensitive CML cell lines and CD34+ patient samples. Two genes that were upregulated in TKI-resistant CML cells were proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), both members of the 19S regulatory complex in the 26S proteasome. PSMD1 and PSMD3 were also identified as survival-critical genes in a published small hairpin RNA library screen of TKI resistance. We observed markedly higher levels of PSMD1 and PSMD3 mRNA in CML patients who had progressed to the blast phase compared with the chronic phase of the disease. Knockdown of PSMD1 or PSMD3 protein correlated with reduced survival and increased apoptosis in CML cells, but not in normal cord blood CD34+ progenitors. Luciferase reporter assays and immunoblot analyses demonstrated that PSMD1 and PSMD3 promote NF-κB protein expression in CML, and that signal transducer and activator of transcription 3 (STAT3) further activates NF-κB in scenarios of TKI resistance. Our data identify NF-κB as a transcriptional driver in TKI resistance, and implicate PSMD1 and PSMD3 as plausible therapeutic targets worthy of future investigation in CML and possibly other malignancies.

Potential of Herbaspirillum and Azospirillum Consortium to Promote Growth of Perennial Ryegrass under Water Deficit.

Plant growth-promoting bacteria (PGPB) can mitigate the effect of abiotic stresses on plant growth and development; however, the degree of plant response is host-specific. The present study aimed to assess the growth-promoting effect of Herbaspirillum (AP21, AP02), Azospirillum (D7), and Pseudomonas (N7) strains (single and co-inoculated) in perennial ryegrass plants subjected to drought. The plants were grown under controlled conditions and subjected to water deficit for 10 days. A significant increase of approximately 30% in dry biomass production was observed using three co-inoculation combinations (p < 0.01). Genomic analysis enabled the detection of representative genes associated with plant colonization and growth promotion. In vitro tests revealed that all the strains could produce indolic compounds and exopolysaccharides and suggested that they could promote plant growth via volatile organic compounds. Co-inoculations mostly decreased the in vitro-tested growth-promoting traits; however, the co-inoculation of Herbaspirillum sp. AP21 and Azospirillum brasilense D7 resulted in the highest indolic compound production (p < 0.05). Although the Azospirillum strain showed the highest potential in the in vitro and in silico tests, the plants responded better when PGPB were co-inoculated, demonstrating the importance of integrating in silico, in vitro, and in vivo assessment results when selecting PGPB to mitigate drought stress.

WNT7A Expression is Downregulated in T Lymphocytes after T-Cell Receptor Activation Due to Histone Modifications and in T-ALL by DNA Methylation.

WNT signaling pathway regulates several processes involved in the homeostasis of normal cells. Its dysregulation is associated with pathological outcomes like cancer. We previously demonstrated that downregulation of WNT7A correlates with higher proliferation rates in acute lymphoblastic leukemia. However, the regulation of this gene in pathological and normal conditions remains unexplored. In this work, we aimed to analyze the transcriptional regulation of WNT7A in leukemic cells and in normal T lymphocytes after a proliferative stimulus. WNT7A expression was measured in blood cells and in T lymphocytes after phytohemagglutinin-L (PHA-L) treatment or T-cell receptor (TCR) activation by qPCR and Western blot. Promoter methylation was assessed using methylation-sensitive restriction enzymes, and histone modifications were determined by chromatin immunoprecipitation and qPCR. In T-cell acute lymphoblastic leukemia (T-ALL), WNT7A expression is silenced through DNA methylation of CpG island in the promoter region. In normal peripheral blood cells, WNT7A is mainly expressed by monocytes and T lymphocytes. TCR activation induces the downregulation of WNT7A in normal T lymphocytes by changes in histone methylation marks (H3K4me2/3) and histone deacetylases. A proliferative stimulus mediated by IL-2 keeps WNT7A expression at low levels but in the absence of IL-2, the expression of this gene tends to be restored. Furthermore, after TCR activation and WNT7A downregulation, target genes associated with the WNT canonical pathway were upregulated indicating an independent activity of WNT7A from the WNT canonical pathway. WNT7A expression is silenced by long-term DNA methylation in T-ALL-derived cells and downregulated by histone modifications after TCR activation in normal T lymphocytes.

Exogenous Expression of WNT7A in Leukemia-Derived Cell Lines Induces Resistance to Chemotherapeutic Agents.

BACKGROUND: Dysregulations of the WNT pathway are implicated in the malignant transformation of different types of neoplasia. WNT7A is expressed in normal peripheral lymphocytes, but is decreased in the tumoral counterpart. Furthermore, the treatment of leukemic cells with recombinant WNT7A decreases proliferation, suggesting its possible use as a therapeutic biomolecule. This study aimed to evaluate the concomitant action of WNT7A and different chemotherapeutic agents over proliferation and cell death of leukemia/ lymphoma derived cell lines. METHODS: Ectopic expression of WNT7A was induced in CEM and BJAB cell lines by using a lentiviral system. RNA expression was analyzed by microarrays and qPCR, and protein expression was determined by Western Blot. Cell proliferation was measured by cell counting, metabolic activity by WST-1 assay, cell death and DNA content by flow cytometry. RESULTS: WNT7A ectopic expression was shown to decrease cell proliferation, but the apoptosis rate of leukemic cells was not altered. Moreover, these cells acquired resistance to doxorubicin, vincristine and MG-132. Cell cycle analysis reveals a decrease in G1 and an increase in S and G2 phases with a further upregulation of senescence- associated genes. Microarray analysis reveals that most gene expression changes were related to cancer and metabolic associated pathways. All those changes appear to be independent of the WNT canonical pathway regulation. CONCLUSION: WNT7A negatively regulates cell proliferation in leukemic cell lines and promotes resistance to chemotherapeutic agents by inducing a senescence-like phenotype independently of the WNT canonical pathway.

From Molecular Machines to Stimuli-Responsive Materials.

Artificial molecular machines are able to produce and exploit precise nanoscale actuations in response to chemical or physical triggers. Recent scientific efforts have been devoted to the integration, orientation, and interfacing of large assemblies of molecular machines in order to harness their collective actuations at larger length scale and up to the generation of macroscopic motions. Making use of such "hierarchical mechanics" represents a fundamentally new approach for the conception of stimuli-responsive materials. Furthermore, because some molecular machines can function as molecular motors-which are capable of cycling a unidirectional motion out of thermodynamic equilibrium and progressively increasing the work delivered to their environment-one can expect unique opportunities to design new kinds of mechanically active materials and devices capable of autonomous behavior when supplied by an external source of energy. Recently reported achievements are summarized, including the integration of molecular machines at surfaces and interfaces, in 3D self-assembled materials, as well as in liquid crystals and polymer materials. Their detailed functioning principles as well as their functional properties are discussed along with their potential applications in various domains such as sensing, drug delivery, electronics, optics, plasmonics, and mechanics.

El cuidado humanizado en los futuros enfermeros del sur de Chile / The humanized care in the nursing futures of south Chile

OBJETIVO: Reconocer la percepción que tienen estudiantes de enfermería, en una Universidad del sur de Chile, respecto de los cuidados humanizados que entregan durante el año 2018. MATERIAL Y MÉTODO: Estudio cuantitativo, transversal, no experimental realizado en 2018 en 197 estudiantes, entre 18 y 25 años, de segundo a quinto año de enfermería, se autoadministra instrumento validado basado en los comportamientos humanizados: Caring Efficacy Scale (CES). RESULTADOS: El 73% de los futuros enfermeros poseen un alto grado de percepción de cuidados humanizados, el 26% una percepción regular y solo el 1% posee un bajo nivel de percepción de cuidados humanizados de su atención. Además, se comprobó que no existe diferencia en el género al momento de entregar cuidados humanizados y que a mayor nivel académico la percepción de cuidados humanizados también aumenta. CONCLUSIÓN: Al analizar las variables entre los comportamientos positivos y negativos, en relación con el género, se pudo comprobar que no existe significancia; sin embargo, en relación al nivel académico, se pudo determinar que mientras mayor es el nivel académico, mayor es la percepción del cuidado humanizado que poseen los estudiantes de enfermería.

OBJECTIVE: To recognize the perception that nursing student shave, in a University of southern Chile, regarding the humanized care they deliver during 2018. MATERIAL AND METHOD: Quantitative, cross-sectional, non-experimental study conducted in 2018 in 197 students, among 18 and 25 years, from second to fifth year of nursing, validated instrument is self-administered based on humanized behaviors: Caring Efficacy Scale (CES). RESULTS: 73% of future nurses have a high degree of perception of humanized care, 26% have a regular perception and only 1% have a low level of perception of humanized care of their care. In addition, it was found that there is no difference in gender when delivering humanized care and that at a higher academic level the perception of humanized care also increases. CONCLUSION: When analyzing the variables between positive and negative behaviors, in relation to gender, it was found that there is no significance; However, in relation to the academic level, it was determined that the higher the academic level, the greater the perception of the humanized care that nursing students possess.

Sensing Biomolecular Interactions by the Luminescence of a Planar Gold Film.

We describe the operating principle and performance of a recently developed surface plasmon-enhanced optical sensor that utilizes two-photon excited luminescence of a planar gold film as the reporter signal. The sensor enables direct visualization of nanoscopic binding events near a sensing surface. Light is coupled to the Au/sample interface in an objective-based Kretschmann configuration to excite surface plasmon polariton (SPP) modes at a metal-dielectric interface. The gold luminescence induced by the confined optical field between the particle and the film is detected in the epi-direction by a far-field camera where individual binding events show up as diffraction limited bright spots against a dark background. We study the sensor's emission spectrum and the distance dependence between the target and substrate, which both suggest that the optical signal of the sensor originates from electron-hole pair excitations in the planar Au film. In addition, we show that the well-behaved pointspread function of the sensor enables a straightforward implementation of super-resolution techniques. Finally, we demonstrate the utility of the sensor for detecting DNA binding events, underlining the sensor's usefulness for label-free imaging of nanoscopic particles and biomolecular interactions.