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Enzymes are extraordinary catalysts and a preferred tool for green chemistry, but they have not evolved to tolerate the harsh conditions required in large-scale chemical processes, making the replacement of inorganic catalysts extremely expensive in most cases. However, the continuous knowledge generated by protein engineers helps to realize the promise of using biocatalysts to address critical environmental and industrial challenges. The increasing demand for food and biofuels pressures the vegetable oil industry to continuously improve its manufacturing efficiency and at the same time mitigate the environmental pollution caused by the refineries. Enzymatic degumming is a key enabling technology to obtain cleaner and more efficient methods, but advanced enzymes are needed for widespread adoption. Here, we present an enzymatic degumming process based on chPLC, a synthetic phospholipase C with remarkable thermal stability and catalytic properties. The process developed does not require modifications in current soybean oil factories, avoiding upfront investments, and is four times faster than the enzymatic processes available in the market. A techno-economic analysis predicts a ~ 60% cost reduction for a base-case scenario, establishing the largely expected conditions to promote the global adoption of enzymatic oil degumming by refineries of all sizes. To the best of our knowledge, this is the first report showing the application of a synthetic enzyme designed to address an industrial need having an impact on both the global economy and the environment, in the billion-dollar range.

RESUMEN El objetivo de la presente investigación fue determinar la influencia que ejercen los estilos de crianza en la depresión de adolescentes escolarizados peruanos. Para ello, se utilizó una muestra de 308 estudiantes de nivel secundario, entre varones (47.1 %) y mujeres (52.9 %), que tuvieron una edad promedio de 14.5 años (DE = 2.218). Tiene un diseño no experimental, empírico de estrategia asociativa, clasificado dentro de un estudio explicativo. Para medir las variables de estudio elegidas se utilizó la Escala Estilos de Crianza Familiar (ECF29) y el Patient Health Questionnaire (PHQ-9), ambos con evidencias sólidas de validez y confiabilidad. Los resultados hallados mediante el análisis del modelo de ecuaciones estructurales evidenciaron que el 42 % (r2=.42) explica la varianza de la depresión y el 65 % (r2=.65) explica la varianza de los estilos de crianza. Además, el mejor predictor de la depresión es el estilo sobreprotector (13=.43), seguido del estilo autoritario (13=.18) e indulgente (13=.17); a diferencia del estilo democrático, el cual no explica de manera relevante la depresión en los adolescentes (β= - .09). Se concluye que la depresión se explica con mayor intensidad por las características comunes del estilo de crianza sobreprotector, mientras que el estilo de crianza democrático no lo hace de forma significativa. ABSTRACT The objective of this research was to determine the influence exerted by parenting styles on the depression of Peruvian schooled adolescents. For this, a sample of 308 high school students was used, between men (47.1 %) and women (52.9 %), who had an average age of 14.5 years (SD = 2.218). It has a non-experimental, empirical design of associative strategy, classified within an explanatory study. To measure the chosen study variables, the following were used: the Family Parenting Styles Scale (ECF-29) and the Patient Health Questionnaire (PHQ-9); both with solid evidence of validity and reliability. The results of the structural equation model analysis revealed that 42 % (r2=.42) explains the variance of depression and 65 % (r2=.65) explains the variance of parenting styles. In addition, the best predictor of depression is the overprotective style (β=.43), followed by the authoritarian (β=.18) and indulgent (β=.17) style; unlike the democratic style, which does not explain depression in adolescents in a relevant way (β= - .09). It is concluded that depression is being explained with greater intensity by the common characteristics of the overprotective parenting style, while the democratic parenting style does not do so significantly.

Durante la molienda de los sulfuros minerales en molinos de acero se llevan a cabo reacciones galvánicas entre el hierro de las bolas de molienda y las especies sulfurosas provocando la oxidación superficial de los elementos que constituyen los sulfuros, afectando el éxito de la siguiente etapa. Por tal razón se estudió y caracterizó el efecto de los medios de acero, el pH inicial y el tiempo, en la fisicoquímica de la pulpa de molienda de arsenopirita (FeAsS). Los resultados experimentales muestran la variación del potencial de iones hidrógeno con el tiempo, resultado del contacto galvánico entre el hierro y las partículas de arsenopirita, provocando la oxidación de los elementos que constituyen el mineral tal como; hierro (Fe), arsénico (As) y el azufre (S), este conlleva a la formación de ion sulfato acidificando la pulpa, además, tiende a aumentar la conductividad eléctrica k (µS) de la pulpa. Por otro lado, la concentración de oxígeno disuelto disminuye significativamente desde un valor de alrededor de 8 mg/L hasta prácticamente cero a valores de pH más alcalinos y tiempos de 20 minutos, junto a esto el ambiente químico de la pulpa muestra potenciales óxido reducción negativos y disminuye continuamente con el progreso de la molienda.

Background Efficient DNA repair in response to standard chemo and radiation therapies often contributes to glioblastoma (GBM) therapy resistance. Understanding the mechanisms of therapy resistance and identifying the drugs that enhance the therapeutic efficacy of standard therapies may extend the survival of GBM patients. In this study, we investigated the role of KDM1A/LSD1 in DNA double-strand break (DSB) repair and a combination of KDM1A inhibitor and temozolomide (TMZ) in vitro and in vivo using patient-derived glioma stem cells (GSCs). Methods Brain bioavailability of the KDM1A inhibitor (NCD38) was established using LS-MS/MS. The effect of a combination of KDM1A knockdown or inhibition with TMZ was studied using cell viability and self-renewal assays. Mechanistic studies were conducted using CUT&Tag-seq, RNA-seq, RT-qPCR, western blot, homologous recombination (HR) and non-homologous end joining (NHEJ) reporter, immunofluorescence, and comet assays. Orthotopic murine models were used to study efficacy in vivo. Results TCGA analysis showed KDM1A is highly expressed in TMZ-treated GBM patients. Knockdown or knockout or inhibition of KDM1A enhanced TMZ efficacy in reducing the viability and self-renewal of GSCs. Pharmacokinetic studies established that NCD38 readily crosses the blood-brain barrier. CUT&Tag-seq studies showed that KDM1A is enriched at the promoters of DNA repair genes and RNA-seq studies confirmed that KDM1A inhibition reduced their expression. Knockdown or inhibition of KDM1A attenuated HR and NHEJ-mediated DNA repair capacity and enhanced TMZ-mediated DNA damage. A combination of KDM1A knockdown or inhibition and TMZ treatment significantly enhanced the survival of tumor-bearing mice. Conclusions Our results provide evidence that KDM1A inhibition sensitizes GBM to TMZ via attenuation of DNA DSB repair pathways.

Recent data suggest that interactions between systems involved in higher order knowledge and associative learning drive responses during value-based learning. However, it is unknown how these systems impact subjective responses, such as pain. We tested how instructions and reversal learning influence pain and pain-evoked brain activation. Healthy volunteers (n=40) were either instructed about contingencies between cues and aversive outcomes or learned through experience in a paradigm where contingencies reversed three times. We measured predictive cue effects on pain and heat-evoked brain responses using functional magnetic resonance imaging. Predictive cues dynamically modulated pain perception as contingencies changed, regardless of whether participants received contingency instructions. Heat-evoked responses in the insula, anterior cingulate, and other regions updated as contingencies changed, and responses in the prefrontal cortex mediated dynamic cue effects on pain, whereas responses in the brainstem’s rostroventral medulla (RVM) were shaped by initial contingencies throughout the task. Quantitative modeling revealed that expected value was shaped purely by instructions in the Instructed Group, whereas expected value updated dynamically in the Uninstructed Group as a function of error-based learning. These differences were accompanied by dissociations in the neural correlates of value-based learning in the rostral anterior cingulate, thalamus, and posterior insula, among other regions. These results show how predictions dynamically impact subjective pain. Moreover, imaging data delineate three types of networks involved in pain generation and value-based learning: those that respond to initial contingencies, those that update dynamically during feedback-driven learning as contingencies change, and those that are sensitive to instruction. Together, these findings provide multiple points of entry for therapies designs to impact pain.

The aim of this study was to analyse the association between human immunodeficiency virus (HIV) related clinical and analytical parameters and the presence of subclinical atherosclerosis as well as endothelial dysfunction. This was a prospective cohort study of HIV-positive patients who underwent intima media thickness (IMT) determination and coronary artery calcium scoring to determine subclinical atherosclerosis. To detect endothelial dysfunction, the breath holding index, flow-mediated dilation and the concentration of endothelial progenitor cells (EPCs) were measured. Patients with an IMT ≥ 0.9 mm had an average of 559.3 ± 283.34 CD4/μl, and those with an IMT 4 ± 5 × 104 copies/ml vs 23.4 × 104 ± 19 × 104 copies/ml (p = 0.02)). The number of early EPCs in patients with a CD4 nadir

OBJECTIVES: The purposes of this study were to analyze Latino/a immigrant mushroom workers’ perceptions of how the workplace environment shapes occupational safety and health, examine whether and how those perceptions differ by gender, and identify future areas for research on occupational safety and health in the mushroom industry. METHODS: Researchers conducted structured interviews with fifteen women and forty-five men on six Pennsylvania mushroom farms to obtain their descriptions and perspectives of safety and health risk factors in their workplaces. RESULTS: Approximately one-third of respondents had suffered an injury at work and nearly half felt there are workplace factors that affect their health and safety. The study found that Latino/a mushroom farmworkers perceive that risks are posed by the indoor infrastructure of mushroom production houses, including poorly maintained wooden walkways and cool indoor temperatures, and by the organization of mushroom production work, including the application of chemicals including pesticides, physical demands of the job, use of small knives, contact with compost, and the piece rate payment system. Workers commonly discussed back pain and believed it was associated with the organization of work. Women in the sample were more likely to be concerned about slips and falls than men and less likely to be concerned about aches and pains. CONCLUSION: Mushroom farm infrastructure and the specific demands of the jobs pose occupational safety and health risks to Latino/a farmworkers that merit further study in order to develop adequate public health interventions. Future research should obtain gender-disaggregated objective reports of injury, aches and pains, and discomfort and test for relationships between these reports and the indoor infrastructure and conditions of mushroom production work.

Rising temperatures and severe heat, as a result of climate change, have led to a significant number of heat-related deaths and injuries among correctional populations in the United States. This article analyzes cases from the U.S. Circuit Courts of Appeals in which inmates challenged the constitutionality of their conditions of confinement in extremely hot facilities pursuant Title 42 U.S. Code Section 1983. An inductive analysis of caselaw revealed two themes: inmates with heat-sensitive health conditions and reasonable staff responses to inmate's heat exposure. The article concludes by offering policy guidance to prison officials based on the themes revealed in the circuit court decisions and by providing recommendations for future research.

Thirteen shorebird species and 5683 individuals were recorded at Estero Punta Banda from October 1988 to April 1989 in three soft-bottom habitats bordering the northern tip of the sand bar (open beach; terminal beach; mud-flats) and a semi-protected seasonal pond at the southwest comer of the estuary. The open beach (seven species; 1310 individuals), mud-flats (13 species; 3958 individuals) and the pond (two species; 146 individuals) harbored distinctive species assemblages while the terminal beach (five species; 239 individuals) acted as an extension of the open beach and mud flats. Most species where exclusive of a single habitat, or almost exclusive (species that occur in more that one habitat but exhibit strong quantitative differences among them). Seasonal changes were rather neat, although the study period missed the first part of the autumn migration towards the south. Seasonal movements were not synchronic in the different habitats. We estimated that about 14,000 shorebirds visit the lagoon each season (3,000 in the open beach; 11,000 in mud-flats). Although most species had been recorded for the site, quantitative data and evidence of the role of estero Punta Banda along the Pacific Flyway are offered in this study for the first time. Distinctive species assemblages in the different habitats, and asynchronism of migration in each, show that patchiness of habitats is important for the maintenance of species richness and for the conservation of the migratory process as well.

The role of TiO2 as an additive in the Pt/WO3-ZrO2 catalyst system over the catalytic activity in the hydroisomerization of n-hexane was investigated. The Pt/WO3-ZrO2-TiO2 catalysts were synthesized by two steps: the first step consisted in the WOx-ZrO2-TiO2 mixed oxides synthesis by the coprecipitation technique, and in a second step the Pt was incorporated by impregnation. The mixed oxides were characterized by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), nitrogen physisorption, scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM). The results showed that the synthesis method could promote a higher interaction among TiO2, WOx species and ZrO2 at 700 °C, producing WOx clusters that improve the n-hexane hydroisomerization conversion, TOR values and yields to bi-ramified components compared to the blank catalysts. The results confirmed the relationship among the surface area, tungsten content, and calcination temperature necessary to reach the formation of WOx species with the adequate domain size to stabilize the proton and form Bronsted acid sites. The incorporation of TiO2 mainly promotes the stabilization of these active sites.

Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there are no disease modifying therapies that prevent the loss of myelin or promote remyelination. This review aims to summarize studies in the field that highlight the importance of nuclear hormone receptors in the promotion and maintenance of myelination and the relevance of nuclear hormone receptors as potential therapeutic targets for demyelinating diseases. These nuclear hormone receptors include the estrogen receptor, progesterone receptor, androgen receptor, vitamin D receptor, thyroid hormone receptor, peroxisome proliferator-activated receptor, liver X receptor, and retinoid X receptor. Pre-clinical studies in well-established animal models of demyelination have shown a prominent role of these nuclear hormone receptors in myelination through their promotion of oligodendrocyte maturation and development. The activation of the nuclear hormone receptors by their ligands also promotes the synthesis of myelin proteins and lipids in mouse models of demyelination. There are limited clinical studies that focus on how the activation of these nuclear hormone receptors could alleviate demyelination in patients with diseases such as multiple sclerosis (MS). However, the completed clinical trials have reported improved clinical outcome in MS patients treated with the ligands of some of these nuclear hormone receptors. Together, the positive results from both clinical and pre-clinical studies point to nuclear hormone receptors as promising therapeutic targets to counter demyelination.

To investigate post-treatment relapse and remission rates 3, 6 and 9 months after completion of an acute phase of a clinician-supported internet-delivered cognitive-behavioural therapy (iCBT) for anxiety and depressive symptoms, within a routine care setting.Secondary analysis from a 12-month pragmatic randomized-controlled trial delivered within the Improving Access to Psychological Therapies (IAPT) programme in England. Participants in the intervention arm were included if they met criteria for reliable recovery from depression (PHQ-9) and anxiety (GAD-7) at post-treatment assessment. Survival analysis was used to assess durability of treatment effects and determine predictors to relapse at 3-, 6- and 9-month follow-up. Hazard ratios predicting time-to-relapse were estimated with semi-parametric Cox proportional hazards model.Of the 241 participants in the intervention arm, 89 participants met the criteria for reliable recovery from depression and anxiety at the post-treatment assessment. Of these 89 eligible cases, 29.2% relapsed within the 9-month period, with 70.8% remaining in remission at 9 months post-treatment. Of those who relapsed, 53.8% experienced a relapse of depression and anxiety; 7.7% experienced a relapse of depression only; and 38.4% experienced a relapse of anxiety only. Younger age, having a long-term condition, and residual symptoms of anxiety at end-of-treatment were all significant predictors of relapse.This study is the first to explore the remission and relapse rates after an acute phase of iCBT treatment, within a routine, stepped-care setting. The results add to the scarce literature on the durability of the effects of iCBT treatment in routine care settings, where patients are not typically followed up after receiving a completed course of treatment.

Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative.We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated.During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours).Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

Cancer stem cells (CSCs) are highly tumorigenic, spared by chemotherapy, sustain tumor growth, and are implicated in tumor recurrence after conventional therapies in triple negative breast cancer (TNBC). Lysine-specific histone demethylase 1A (KDM1A) is highly expressed in several human malignancies and CSCs including TNBC. However, the precise mechanistic role of KDM1A in CSC functions and therapeutic utility of KDM1A inhibitor for treating TNBC is poorly understood. The effect of KDM1A inhibition on cell viability, apoptosis, and invasion were examined by Cell Titer Glo, Caspase 3/7 Glo, and matrigel invasion assays, respectively. Stemness and self-renewal of CSCs were examined using mammosphere formation and extreme limiting dilution assays. Mechanistic studies were conducted using RNA-sequencing, RT-qPCR, Western blotting and reporter gene assays. Mouse xenograft and patient derived xenograft models were used for preclinical evaluation of KDM1A inhibitor. TCGA data sets indicated that KDM1A is highly expressed in TNBC. CSCs express high levels of KDM1A and inhibition of KDM1A reduced the CSCs enrichment in TNBC cells. KDM1A inhibition reduced cell viability, mammosphere formation, self-renewal and promoted apoptosis of CSCs. Mechanistic studies suggested that IL6-JAK-STAT3 and EMT pathways were downregulated in KDM1A knockdown and KDM1A inhibitor treated cells. Importantly, doxycycline inducible knockout of KDM1A reduced tumor progression in orthotopic xenograft models and KDM1A inhibitor NCD38 treatment significantly reduced tumor growth in patient derived xenograft (PDX) models. Our results establish that KDM1A inhibition mitigates CSCs functions via inhibition of STAT3 and EMT signaling, and KDM1A inhibitor NCD38 may represent a novel class of drug for treating TNBC.

Stable and sufficient food supplies are increasingly threatened by climatic variability, in particular extreme heat events. Intraspecific crop diversity may be an important biological resource to both understand and maintain crop resilience to extreme conditions. Here using data from a mass field experiment screening for heat tolerance in sweet potato (Ipomoea batatas), we identify 132 heat-tolerant cultivars and breeding lines (6.7%) out of 1,973 investigated. Sweet potato is the world's fifth most important food crop, and mean conditions experienced by sweet potato by 2070 are predicted to be 1 to 6 °C warmer, negatively impacting most genotypes. We identify canopy temperature depression, chlorophyll content and storage root-flesh colour as predictors of heat tolerance and, therefore, as potential traits for breeding consideration. These results highlight the role of intraspecific biodiversity for the productivity and resilience of food and agricultural systems in the face of climate change.

Highlights • Pneumatosis cystoides intestinalis is a rare condition with a broad spectrum of clinical symptoms. • Images are typically striking, which can confuse the medical team and lead to unnecessary procedures. • Close follow up is needed as complications can lead to a troublesome outcome., Background Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by gas infiltration into the intestine wall. When gas is seen in the intestinal wall, it is usually a sign of bowel wall infarction and a surgical emergency; therefore, an adequate differentiation of benign and urgent conditions of pneumatosis intestinalis is necessary to prevent misdiagnosis and inadequate therapies. Case presentation We present the case of a 79-year-old male with past medical history of Alzheimer’s, cholecystectomy, and umbilical hernia. PCI was identified, and conservative therapy was started. Since the patient's pain persisted, a complication was suspected, and surgery was decided. After successful treatment, the patient completely recovered. Conclusion There are many benign and life-threatening causes of pneumatosis intestinalis, the imaging appearance of both may look very similar. Therefore, clinical history, physical examination, and laboratory test results are the best indicators of whether it is due to a benign or life-threatening cause. PCI must be managed with a multidisciplinary team of clinicians, radiologists, and surgeons to achieve better results for our patients.

Despite considerable change in inmate rights over the past several decades, researchers, practitioners, and policymakers know little about the current state of prisoner litigation. The purpose of t...

We synthesized a series of new Ni catalysts supported on mesoporous silica KIT-5. The metal loading on this support was varied (0.9–7.0 wt% NiO). The catalysts were characterized by N2 physisorption, powder XRD, XRF spectrometry, UV-vis DRS, H2-TPR, HRTEM and FT-IR with CO. The mesoporous structure is maintained in all the catalytic materials. The increase in the Ni loading resulted in the formation of crystalline phases at the KIT-5 surface. The catalysts were tested in hydrodeoxygenation (HDO) of palmitic acid. The catalytic activity increased with the metal loading, reaching a maximum by using the catalyst with 1.8 wt% NiO. On the other hand, calculation of kinetic parameters indicated the effective utilization of catalytically active Ni particles in the HDO process. Formation of oxygen-free products was higher for the catalyst with higher metal loading in this series. These catalytic materials were compared with a series of Ni catalysts supported on carbon, finding that the Ni/KIT-5 catalysts were much more active in the HDO reaction. These new catalysts supported on the mesoporous silica KIT-5 exhibited high activity with low metal loadings. This feature makes them attractive for their application in the HDO of fatty acids.

Each year a rising number of infections can not be successfully treated owing to the increasing pandemic of antibiotic resistant pathogens. The global shortage of innovative antibiotics fuels the emergence and spread of drug resistant microbes. Basic research, development, and applications of alternative therapies are urgently needed. Since the 90´s, light-mediated therapies have promised to be the next frontier combating multidrug-resistance microbes. These platforms have demonstrated to be a reliable, rapid, and efficient alternative to eliminate tenacious pathogens while avoiding the emergence of resistance mechanisms. Among the materials showing antimicrobial activity triggered by light, conjugated polymers (CPs) have risen as the most promising option to tackle this complex situation. These materials present outstanding characteristics such as high absorption coefficients, great photostability, easy processability, low cytotoxicity, among others, turning them into a powerful class of photosensitizer (PS)/photothermal agent (PTA) materials. Herein, we summarize and discuss the advances in the field of CPs with applications in photodynamic inactivation and photothermal therapy towards bacteria elimination. Additionally, a section of current challenges and needs in terms of well-defined benchmark experiments and conditions to evaluate the efficiency of phototherapies is presented.

Background: The antibiotic of choice for methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is antistaphylococcal penicillins, such as oxacillin, but cefazolin has also risen as an equally effective alternative. Murine models have suggested that clindamycin is a therapeutic alternative for Staphylococcus aureus bacteremia (SAB). Methods: In this retrospective cohort study, patients from the Hospital Universitario San Vicente Fundación (HUSVF) in Medellín, Colombia, were recruited from January 2013 and December 2019. Patients with positive blood culture for MSSA, with at least one follow-up blood culture, and those with more than 72 hours of parenteral antibiotic therapy for SAB were selected. The main objective was to determine the efficacy of clindamycin compared to other antibiotics to achieve a microbiologic cure. Secondary results included in-hospital mortality and hospital stay. Results: A total of 486 patients were included (clindamycin = 50 and other anti-MSSA = 436). The patients in the clindamycin group had a lower rate of microbiological cure (n = 41 [84%]) compared to other antibiotics (n = 367 [84%]) (OR 1.08 IC 95% 0.74-1.58). In secondary outcomes, no statistically significant differences were observed in the in-hospital mortality. The main source of SAB was a central or peripheral catheter (58%). Conclusions: Our study found no differences in the rate of microbiological cure, in-hospital mortality, and hospital stay on the clindamycin group compared to other anti-MSSA antibiotics. However, in patients with metastatic complications, the rate of microbiological cure is reduced, and the in-hospital mortality is higher in patients with more severe disease.