Machine perfusion preservation highlights from the Congress of the European Society of Organ Transplantation 2023.

The 21st Congress of the European Society of Organ Transplantation (ESOT), held on September 17-20th, 2023, in Athens, Greece, was a pivotal event in transplantation, focusing on the theme "Disruptive Innovation, Trusted Care." The congress attracted a global audience of 2 826 participants from 82 countries, emphasizing its international significance. Machine perfusion, as a groundbreaking technology in organ transplantation, was one of the central focuses of the conference. This year's meeting had a remarkable increase in accepted abstracts on machine perfusion, evidencing its growing prominence in the field. The collective findings from these abstracts highlighted the efficacy of machine perfusion in improving organ viability and transplant outcomes. Studies demonstrated improvements in graft survival and reduction in complications, as well as novel uses and techniques. Furthermore, the integration of machine perfusion with regenerative medicine and its application across multiple organ types were significant discussion points. The congress also highlighted the challenges and solutions in implementing machine perfusion in clinical settings, emphasizing the importance of practical training and international collaboration for advancing this technology. ESOT 2023 served as a crucial platform for disseminating scientific advancements, fostering practical learning, and facilitating international collaborations in organ transplantation. The congress underscored the evolution and importance of machine perfusion technology, marking a significant step forward in enhancing patient outcomes in the field of organ transplantation.

Demand-only patient-controlled analgesia for treatment of acute vaso-occlusive pain in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic illness that is associated with frequent admissions for vaso-occlusive episodes (VOE). Opioids are frequently utilized in pain management, but dosing is often provider dependent. Opioids cause both short-term and long-term side effects, so the minimal effective dose is desired. This study examined demand-only patient-controlled analgesia (PCA) in pediatric patients. METHODS: A new clinical practice guideline (CPG) for a single institution was implemented, which eliminated basal infusion dosing for PCAs on hospital admission. The primary aim of this retrospective study was to evaluate length of stay (LOS) before and after implementation of a CPG of demand-only PCA and, in a selected subpopulation, addition of short-term methadone. Secondary aims included opioid utilization, acute chest syndrome (ACS), and hypoxia. Inclusion criteria included SCD, ≤21 years of age, uncomplicated VOE admission, and ≥ 3 and ≤ 8 hospital admissions for SCD pain control within one calendar year. RESULTS: LOS decreased postintervention (7.2 ± 5.1 vs 4.5 ± 3.8 days, P < 0.001). Mean total opioid utilization in morphine equivalents mg/kg markedly decreased between the cohorts (13.3 ± 33.8 vs 3.6 ± 3.0, P < 0.001). ACS (21.9% vs 2.8%, P = 0.004) and hypoxia (28% vs 6.9%, P< 0.001) decreased significantly as well. CONCLUSION: Bolus PCA dosing of opioids resulted in decreased LOS and reductions in opioid utilization, hypoxia, and ACS.

Overexpression of chalcone isomerase in apple reduces phloridzin accumulation and increases susceptibility to herbivory by two-spotted mites.

Apples (Malus spp.) accumulate significant quantities of the dihydrochalcone glycoside, phloridzin, whilst pears (Pyrus spp.) do not. To explain this difference, we hypothesized that a metabolic bottleneck in the phenylpropanoid pathway might exist in apple. Expression analysis indicated that transcript levels of early phenylpropanoid pathway genes in apple and pear leaves were similar, except for chalcone isomerase (CHI), which was much lower in apple. Apples also showed very low CHI activity compared with pear. To relieve the bottleneck at CHI, transgenic apple plants overexpressing the Arabidopsis AtCHI gene were produced. Unlike other transgenic apples where phenylpropanoid flux was manipulated, AtCHI overexpression (CHIox) plants were phenotypically indistinguishable from wild-type, except for an increase in red pigmentation in expanding leaves. CHIox plants accumulated slightly increased levels of flavanols and flavan-3-ols in the leaves, but the major change was a 2.8- to 19-fold drop in phloridzin concentrations compared with wild-type. The impact of these phytochemical changes on insect preference was studied using a two-choice leaf assay with the polyphagous apple pest, the two-spotted spider mite (Tetranychus urticae Koch). Transgenic CHIox leaves were more susceptible to herbivory, an effect that could be reversed (complemented) by application of phloridzin to transgenic leaves. Taken together, these findings shed new light on phenylpropanoid biosynthesis in apple and suggest a new physiological role for phloridzin as an antifeedant in leaves.

Smartphone-based human fatigue level detection using machine learning approaches.

Human muscle fatigue is the main result of diminishing muscle capability, leading to reduced performance and increased risk of falls and injury. This study provides a classification model to identify the human fatigue level based on the motion signals collected by a smartphone. 24 participants were recruited and performed the fatiguing exercise (i.e. squatting). Upon completing each set of squatting, they walked for a fixed distance while the smartphone attached to their right shank and the gait data were associated with the Borg's Rating of Perceived Exertion (i.e. data label). Our machine-learning model of two (no- vs. strong-fatigue), three (no-, medium-, and strong-fatigue) and four (no-, low-, medium-, and strong-fatigue) levels of fatigue reached the accuracy of 91, 78, and 64%, respectively. The outcomes of this study may facilitate the accessibility of a fatigue-monitoring tool in the workplace, which improves the workers' performance and reduce the risk of falls and injury. Practitioner Summary: This study aimed to develop a machine-learning model to identify human fatigue level using motion data captured by a smartphone attached to the shank. Our results can facilitate the development of an accessible fatigue-monitoring system that may improve the workers' performance and reduce the risk of falls and injury. Abbreviations: WMSD: work-related musculoskeletal disorders; IMU: inertial measurement unit; RPE: rating of perceived exertion; SVM: support vector machine; IRB: institutional review board; SOM: self-organizing map; LDA: linear discriminant analysis; PCA: principal component analysis; FT: fourier transformation; RBF: radial basis function; CUSUM: cumulative sum; ROM: range of motion; MVC: maximum voluntary contractions.

Maternal postpartum depression is a risk factor for infant emotional variability at 4 months.

Maternal postpartum depression (PPD) is a risk for disruption of mother-infant interaction. Infants of depressed mothers have been found to display less positive, more negative, and neutral affect. Other studies have found that infants of mothers with PPD inhibit both positive and negative affect. In a sample of 28 infants of mothers with PPD and 52 infants of nonclinical mothers, we examined the role of PPD diagnosis and symptoms for infants' emotional variability, measured as facial expressions, vocal protest, and gaze using microanalysis, during a mother-infant face-to-face interaction. PPD symptoms and diagnosis were associated with (a) infants displaying fewer high negative, but more neutral/interest facial affect events, and (b) fewer gaze off events.  PPD diagnosis, but not symptoms, was associated with less infant vocal protest. Total duration of seconds of infant facial affective displays and gaze off was not related to PPD diagnosis or symptoms, suggesting that when infants of depressed mothers display high negative facial affect or gaze off, these expressions are more sustained, indicating lower infant ability to calm down and re-engage, interpreted as a disturbance in self-regulation. The findings highlight the importance of not only examining durations, but also frequencies, as the latter may inform infant emotional variability.

La depresión maternal posterior al parto (PPD) representa un riesgo para la alteración en la interacción madre-infante. Se ha encontrado que los infantes de madres depresivas muestran un afecto menos positivo, más negativo y neutral. Otros estudios han concluido con que los infantes de madres con PPD inhiben tanto el afecto positivo como el negativo. En un grupo muestra de 28 infantes de madres con PPD y 52 infantes de un grupo de madres no clínico, examinamos el papel de la diagnosis y síntomas de PPD en la variabilidad emocional de los infantes, medida como expresiones faciales, protesta verbal y mirada, usando microanálisis, durante una interacción cara a cara entre madre e infante. Se asociaron los síntomas y la diagnosis de PPD con 1) los infantes mostrando momentos afectuosos faciales menos negativos altos, pero más neutrales/de interés, y 2) menos momentos de miradas hacia otro lado. Se asoció la diagnosis de PPD, aunque no así los síntomas, con menos protesta verbal del infante. La duración total de segundos de las muestras afectivas faciales y las miradas hacia otro lado por parte del infante no estuvo relacionada con la diagnosis o síntomas de PPD, lo cual sugiere que cuando los infantes de madres depresivas muestran afectos faciales negativos altos o miradas hacia otro lado, estas expresiones son más sostenidas, indicando así la más baja habilidad del infante de calmarse y volver a establecer contacto, interpretado esto como una disrupción en la auto-regulación. Los resultados subrayan la importancia no sólo de examinar las duraciones sino también las frecuencias, ya que estas últimas pudieran informar sobre la variabilidad emocional del infante.

La dépression postpartum maternelle (abrégé ici dans le texte DPM) pose un risque de bouleversement de l'interaction mère-bébé. Les recherches ont montré que les bébés de mères déprimées font preuve d'un affect moins positif, plus négatif, et neutre. D'autres études ont prouvé que les bébés de mères avec DPM inhibent à la fois l'affect positif et négatif. Chez un échantillon de 28 bébés de mères avec DPM et 52 bébés de mères non-cliniques, nous avons examiné le rôle du diagnostic de la DPM et les symptômes de la variabilité émotionnelle des bébés, mesurés par les expressions faciales, la réaction vocale, et le regard en utilisant une microanalyse, durant une interaction de face-à-face mère-bébé. Les symptômes de la DPM et le diagnostic ont été liés 1) aux bébés faisant preuve de moins d'instances d'affect facial hautement négatifs mais de plus de neutre/intéressé, et 2) à moins d'instances de regard se perdant. Le diagnostic de DPM, mais non les symptômes, était lié à réaction vocale de protestation du bébé. La durée totale de secondes de démonstration affectives faciales du bébé et du regard se perdant n'était pas liée au diagnostic ou aux symptômes de DPM, suggérant que quand les bébés de mères déprimées font preuve d'un affect très fortement négatif ou d'un regard se perdant, ces expressions sont plus soutenues, indiquant une moindre capacité du bébé à se calmer et à se réengager, interprété comme une perturbation de l'auto-régulation. Les résultats mettent en lumière l'importance qu'il y a à non seulement examiner les durées mais aussi les fréquences, puisque ces dernières peuvent informer la variabilité émotionnelle du bébé.

Getting the Balance Right: Medical Futility, Scientific Advancement, and the Role of Law.

The concept of medical futility as an applied ethical framework has seen a rise and fall in its popularity over the last 30 years. It is a term used in relation to the assessment of a patient's health condition that is deemed untreatable, irreversible, and unresolvable. In four recent cases, Gard, Evans, Haastrup, and Raqeeb, the concept has been brought to the fore once again. These cases highlight a mounting tension between clinicians and families. Parental desires to see their child's treatment continued, while understandable, should not dominate treatment planning. This article analyses judicial interpretation of the factors which determine an assessment of futility and in doing so, argues that the role of medical futility in judicial decisions of this kind is gaining prominence and will continue to do so as scientific advancement blurs the limits of medicine even further.

Managing conflicts between economic activities and threatened migratory marine species toward creating a multiobjective blue economy.

Harnessing the economic potential of the oceans is key to combating poverty, enhancing food security, and strengthening economies. But the concomitant risk of intensified resource extraction to migratory species is worrying given these species contribute to important ecological processes, often underpin alternative livelihoods, and are mostly already threatened. We thus sought to quantify the potential conflict between key economic activities (5 fisheries and hydrocarbon exploitation) and sea turtle migration corridors in a region with rapid economic development: southern and eastern Africa. We satellite tracked the movement of 20 loggerhead (Caretta caretta) and 14 leatherback (Dermochelys coriacea) turtles during their postnesting migrations. We used movement-based kernel density estimation to identify migration corridors for each species. We overlaid these corridors on maps of the distribution and intensity of economic activities, quantified the extent of overlap and threat posed by each activity on each species, and compared the effects of activities. These results were compared with annual bycatch rates in the respective fisheries. Both species' 3 corridors overlapped most with longline fishing, but the effect was worse for leatherbacks: their bycatch rates of approximately 1500/year were substantial relative to the regional population size of <100 nesting females/annum. This bycatch rate is likely slowing population growth. Artisanal fisheries may be of greater concern for loggerheads than for leatherbacks, but the population appears to be withstanding the high bycatch rates because it is increasing exponentially. The hydrocarbon industry currently has a moderately low impact on both species, but mining in key areas (e.g., Southern Mozambique) may undermine >50 years of conservation, potentially affecting >80% of loggerheads, 33% of the (critically endangered) leatherbacks, and their nesting beaches. We support establishing blue economies (i.e., generating wealth from the ocean), but oceans need to be carefully zoned and responsibly managed in both space and time to achieve economic (resource extraction), ecological (conservation, maintenance of processes), and social (maintenance of alternative livelihood opportunities, alleviate poverty) objectives.

Antenatal haemoglobin A1c centiles: does one size fit all?

BACKGROUND: In New Zealand, haemoglobin A1c measurements are routinely offered at booking, preferably before 20 weeks gestation, to detect pre-existing hyperglycaemia. A haemoglobin A1c <5.9% (41 mmol/mol) is considered normal based on the reference range for the non-pregnant population. AIMS: To determine pregnancy-specific haemoglobin A1c centiles by gestation and ethnicity. MATERIALS AND METHODS: This is a population-based observational study of pregnancies uncomplicated by diabetes (pre-existing or gestational) with ≥1 haemoglobin A1c measurement. Haemoglobin A1c centiles were calculated from data extracted from electronic laboratory and clinical records for pregnancies during 2008-2010. RESULTS: Included were 6800 pregnancies, European 80% (5462), Maori 6% (415), Pacific Islander 3% (196) and 11% (727) 'Others' (mostly Asian). Haemoglobin A1c levels fell with increasing gestation, reaching a nadir at 24 weeks, a trend verified by longitudinal data from 112 women. The 97.5th centile for haemoglobin A1c in European women was 5.76% (39.5 mmol/mol) at 8+0  weeks, 5.70% (38.8 mmol/mol) at 16+0  weeks, and 5.65% (38.3 mmol/mol) at 24+0  weeks. Non-European women had both higher plasma glucose levels (although within the range considered normal) and higher mean haemoglobin A1c levels compared with Europeans; mean (SD) difference in haemoglobin A1c in Maori +0.13% (0.05) (+1.4 mmol/mol (0.5)), Pacific +0.20% (0.03) (+2.2 mmol/mol (0.3)), 'Others' +0.10% (0.03) (+1.1 mmol/mol (0.3)). CONCLUSIONS: The New Zealand haemoglobin A1c cut-point ≥5.9% (41 mmol/mol) for identifying hyperglycaemia in early pregnancy is greater than the 97.5th centile in European and 'Other' women. Utilising population haemoglobin A1c centiles adjusted by gestation may thus better guide management decisions.

The Thorny Relation Between Measurement Quality and Fit Index Cutoffs in Latent Variable Models.

Latent variable modeling is a popular and flexible statistical framework. Concomitant with fitting latent variable models is assessment of how well the theoretical model fits the observed data. Although firm cutoffs for these fit indexes are often cited, recent statistical proofs and simulations have shown that these fit indexes are highly susceptible to measurement quality. For instance, a root mean square error of approximation (RMSEA) value of 0.06 (conventionally thought to indicate good fit) can actually indicate poor fit with poor measurement quality (e.g., standardized factors loadings of around 0.40). Conversely, an RMSEA value of 0.20 (conventionally thought to indicate very poor fit) can indicate acceptable fit with very high measurement quality (standardized factor loadings around 0.90). Despite the wide-ranging effect on applications of latent variable models, the high level of technical detail involved with this phenomenon has curtailed the exposure of these important findings to empirical researchers who are employing these methods. This article briefly reviews these methodological studies in minimal technical detail and provides a demonstration to easily quantify the large influence measurement quality has on fit index values and how greatly the cutoffs would change if they were derived under an alternative level of measurement quality. Recommendations for best practice are also discussed.

Do the test results of cognitive function and activities of daily life of seniors correlate with the state of vitamin D supply to the organism?

INTRODUCTION: Till recently, the main effect of Vitamin D (calcitriol) was accounted for its role in regulation of calcium levels. But at the present time several other important functions of this vitamin have been unfolding in human organism, which currently ascribe to the properties of hormone. It also effects among other functions such as cognitive functions, immune system and muscle mass. In the resent past there are rising number of scientific publications on possible consequences of the long term deficit of Calcitriol, not only in the older generation. AIM: The aim of our study was to establish the relationship between the supply of Vitamin D to the organism and basic parameters of self-sufficiency, which are cognitive functions stipulated in the Mini Mental State Examination (MMSE) test and Barthels test for Activities of Daily Living (ADL) among seniors. MATERIALS AND METHODS: In our study we evaluated, 244 patients (65 men and 179 women) of average age 80,1 ± 7,4 (min. 65, max. 99) hospitalized at Department of Internal Medicine, Geriatrics, and General Practice of Faculty of Medicine, Masaryk University and Faculty Hospital Brno, from March 2012 to September 2012. The state of Vitamin D supply to the organism was evaluated with the help of serum Vitamin D total [1.25(OH)2D + 25(OH)D], the values of MMSE and ADL were taken from the third day of hospitalization till overcoming the acute stage. The characteristics of the patients were drawn with multimorbidity index CIRS - CI (cumulative Illness Rating Scale - Comorbidity Index). Furthermore, we observed the correlation of Serum Vitamin D levels to the season of the year. RESULTS:   In our patients average concentration of vitamin D levels, MMSE, and ADL was 37.9 ± 26.1 (8-142 nmol/l), 23.36 ± 6.91 (0-30 points), 80.66 ± 25.13 (0-100 points), and CIRS CI 4.7 + 1.9 points, respectively. The correlation of vitamin D serum level with MMSE was r = 0,289 (p 0.01), with ADL r = 0,292 (p 0.01), and CIRS CI r = -0.22 (p < 0.05). Using multivariation analysis proved the significance of correlations obtained, even after the exclusion of multimorbidity. There was no statistically significant correlation between seasons of the year and serum vitamin D total level. However, nonsignificant decreasing trend of serum vitamin D total level with rising age of patients was found (r = -0.149, NS). CONCLUSIONS: The values obtained for MMSE and ADL demonstrated a significant correlation with serum vitamin D total levels. Attention paid to maintain an adequate supply of serum vitamin D in the organism, helps to maintain quality bone remodeling and functioning of other processes with which it takes part. For supplementing elderly sick patients, apart from diet, it is suitable to choose partially or fully hydroxylated supplements and adequate exposure to sunlight. Key words:  ADL - cognitive function - MMSE - vitamin D.

Current possibilities of dural reconstruction in neurosurgery.

An integral part of intracranial neurosurgery is the opening of the subdural space and its subsequent closure or reconstruction after the surgery. The optimal goal is a primary watertight suture, although that is often unfeasible for various reasons. Cerebrospinal fluid leakage in postoperative care is an undesirable and potentially dangerous complication of most of the surgical interventions. The aim of this article is to present the current possibilities of dural reconstruction in neurosurgery. Key words:  mater cerebrospinal fluid leakage dural defect craniectomy.

Branched pedal bypass in the treatment of critical limb ischemia - a single center experience.

INTRODUCTION: Pedal bypass is a therapeutic option for limb salvage in critical limb ischemia. METHOD: Retrospective analysis of 20 patients who underwent either simple (14 patients) or branched (6 patients) pedal bypass in a single center and had at least one postoperative follow-up. In patients with branched pedal bypass, the main trunk was connected to the pedal artery of better quality and the side branch to an artery on the opposite side of the foot. The main trunk was constructed as a reverse saphenous bypass in all patients with branched bypass. From patients with simple bypass, nine had reverse saphenous graft, three had an allograft, one patient had in situ saphenous graft, and one PTFE prosthesis. RESULTS: The difference in the operation time was not significant. One patient with simple bypass required reoperation for wound bleeding and there was one case of perioperative mortality in the same group. The difference between the groups in the primary or secondary patency rates, limb salvage and overall survival was not significant. CONCLUSIONS: We did not find any significant difference in patency rates, limb salvage, or perioperative complications between patients with simple and branched pedal bypass in our cohort. We believe that the anticipated benefits of constructing an additional branch are masked by the disadvantageous presence of an additional anastomosis. Adoption of a branched pedal bypass may therefore require further improvements - perhaps the utilization of a branched saphenous graft. Key words:  critical limb ischemia - peripheral arterial disease - bypass - revascularization - amputation.

Serum Monitoring and Phenotype Identification of Stage I Non-Small Cell Lung Cancer Patients.

A stage I non-small cell lung cancer (NSCLC) serum profiling platform is presented which is highly efficient and accurate. Test sensitivity (0.95) for stage I NSCLC is the highest reported so far. Test metrics are reported for discriminating stage I adenocarcinoma vs squamous cell carcinoma subtypes. Blinded analysis identified 23 out of 24 stage I NSCLC and control serum samples. Group-discriminating mass peaks were targeted for tandem mass spectrometry peptide/protein identification, and yielded a lung cancer phenotype. Bioinformatic analysis revealed a novel lymphocyte adhesion pathway involved with early-stage lung cancer.

Recent Trends in Marine Phycotoxins from Australian Coastal Waters.

Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the  marine food web, are of growing concern for Australia. These harmful algae pose a threat to  ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest  growing food sectors in the world. With better monitoring, advanced analytical skills and an  increase in microalgal expertise, many phycotoxins have been identified in Australian coastal  waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish  toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The  potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern,  warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012  resulted in an estimated total economic loss of~AUD$23M, indicating that there is an imperative to  improve  toxin  and  organism  detection  methods,  clarify  the  toxin  profiles  of  species  of  phytoplankton and carry out both intra- and inter-species toxicity comparisons. Future work also  includes the application of rapid, real-time molecular assays for the detection of harmful species  and toxin genes. This information, in conjunction with a better understanding of the life histories  and  ecology  of  harmful  bloom  species,  may  lead  to  more  appropriate  management  of  environmental, health and economic resources.

Smoking-Related Interstitial Fibrosis: Evidence of Radiologic Regression with Advancing Age and Smoking Cessation.

More data are needed regarding the radiology, co-morbidities and natural history of smoking-related interstitial fibrosis (SRIF), a common pathological finding, mainly described heretofore in association with lung cancer, where respiratory bronchiolitis (RB) usually co-exists. We prospectively acquired high resolution CT scan data (edge-enhancing lung reconstructions) to detect any radiologic interstitial lung abnormality (ILA) in individuals who ultimately underwent surgical lobectomy for lung cancer (n = 20), for radiologic/pathologic correlation. We also re-examined other smoking-related benign histologic cases: chronic obstructive pulmonary disease (COPD lung explants, n = 20), alpha 1-antitrypsin deficiency (A1AT, explanted lungs n = 20), combined pulmonary fibrosis and emphysema (CPFE, n = 8) and idiopathic pulmonary fibrosis (IPF, n = 10). Finally, we pooled our data with all peer-reviewed published data describing histologic SRIF of known ILA status. SRIF was observed in 40% of cancer lobectomies, mean (±SD) age 65.8 ± 8.7 years, none of whom had ILA. SRIF was observed in other smoking-related benign diseases (COPD 35%, A1AT 20%, CPFE 25%, and IPF 10%). 71.4% of benign SRIF cases had no RB (nearly all ex-smokers) versus 0% of cancer-associated SRIF cases (P = 1.7 × 10-3). Pooled data showed that those SRIF subjects without ILA were 15.05 years older than those with ILA (95% confidence interval 8.99 to 21.11, P = 2.5 × 10-5) and more likely to be former smokers (P = 7.2 × 10-3). SRIF is frequently found without lung cancer, and mostly without RB in former smokers. SRIF is less likely to have ILA in older subjects and with smoking cessation, which could represent RB+/-SRIF regression.

Immobilized Lipases on Functionalized Silica Particles as Potential Biocatalysts for the Synthesis of Fructose Oleate in an Organic Solvent/Water System.

Lipases from Thermomyces lanuginosus (TLL) and Pseudomonas fluorescens (PFL) wereimmobilized on functionalized silica particles aiming their use in the synthesis of fructose oleate in a tert-butyl alcohol/water system. Silica particles were chemically modified with octyl (OS), octyl plus glutaraldehyde (OSGlu), octyl plus glyoxyl(OSGlx), and octyl plus epoxy groups(OSEpx). PFL was hyperactivated on all functionalized supports (more than 100% recovered activity) using low protein loading (1 mg/g), however, for TLL, this phenomenon was observed only using octyl-silica (OS). All prepared biocatalysts exhibited high stability by incubating in tert-butyl alcohol (half-lives around 50 h at 65 °C). The biocatalysts prepared using OS and OSGlu as supports showed excellent performance in the synthesis of fructose oleate. High estersynthesis was observed when a small amount of water (1%, v/v) was added to the organic phase, allowing an ester productivity until five times (0.88-0.96 g/L.h) higher than in the absence of water (0.18-0.34 g/L.h) under fixed enzyme concentration (0.51 IU/g of solvent). Maximum ester productivity (16.1-18.1 g/L.h) was achieved for 30 min of reaction catalyzed by immobilized lipases on OS and OSGlu at 8.4 IU/mL of solvent. Operational stability tests showed satisfactory stability after four consecutive cycles of reaction.

Hyperuricaemia, Xanthine Oxidoreductase and Ribosome-Inactivating Proteins from Plants: The Contributions of Fiorenzo Stirpe to Frontline Research.

The enzymes called ribosome-inactivating proteins (RIPs) that are able to depurinate  nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline  research field, mostly because of their promising medical applications. The contributions of Stirpe  to the development of these studies has been one of the most relevant. After a short biographical  introduction, an overview is offered of the main results obtained by his investigations during last  55 years on his main research lines: hyperuricaemia, xanthine oxidoreductase and RIPs.

Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita-Baylis-Hillman Adducts: In Vitro Screening against Leishmania donovani.

Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala-aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The Morita-Baylis-Hillman adducts (MBHAs) are being explored as drug candidates against several diseases, one of them being leishmaniasis. We present here the design, synthesis and in vitro screening against Leishmania donovani of sixteen new molecular hybrids from analgesic/antiinflammatory tetrahydropyrans derivatives and Morita-Baylis-Hillman adducts. First, acrylates were synthesized from analgesic/anti-inflammatory tetrahydropyrans using acrylic acid under TsOH as a catalyst (70-75% yields). After the 16 new MBHAs were prepared in moderate to good yields (60-95%) promoted by microwave irradiation or low temperature (0 °C) in protic and aprotic medium. The hybrids were evaluated in vitro on the promastigote stage of Leishmania donovani by determining their inhibitory concentrations 50% (IC50), 50% hemolysis concentration (HC50), selectivity index (HC50/IC50,), and comparing to Amphotericin B, chosen as the anti-leishmanial reference drug. The hybrid which presents the bromine atom in its chemical structure presents high leishmanicide activity and the high selectivity index in red blood cells (SIrb > 180.19), compared with the highly-toxic reference drug (SIrb = 33.05), indicating that the bromine hybrid is a promising compound for further biological studies.