The Impact of Liquid Biopsy in Advanced Ovarian Cancer Care.

INTRODUCTION: Ovarian cancer is the third most common gynaecological cancer and has a very high mortality rate. The cornerstone of treatment is complete debulking surgery plus chemotherapy. Even with treatment, 80% of patients have a recurrence. Circulating tumour DNA (ctDNA) has been shown to be useful in the control and follow-up of some tumours. It could be an option to define complete cytoreduction and for the early diagnosis of recurrence. OBJECTIVE: We aimed to demonstrate the usefulness of ctDNA and cell-free DNA (cfDNA) as a marker of complete cytoreduction and during follow-up in patients with advanced ovarian cancer. MATERIAL AND METHODS: We selected 22 women diagnosed with advanced high-grade serous ovarian cancer, of which only 4 had complete records. We detected cfDNA by polymerase chain reaction (PCR), presented as ng/mL, and detected ctDNA with droplet digital PCR (ddPCR). We calculated Pearson correlation coefficients to evaluate correlations among cfDNA, ctDNA, and cancer antigen 125 (CA125), a biomarker. RESULTS: The results obtained in the evaluation of cfDNA and ctDNA and their correlation with tumour markers and the radiology of patients with complete follow-up show disease progression during the disease, stable disease, or signs of recurrence. cfDNA and ctDNA correlated significantly with CA125. Following cfDNA and ctDNA over time indicated a recurrence several months earlier than computed tomography and CA125 changes. CONCLUSION: An analysis of cfDNA and ctDNA offers a non-invasive clinical tool for monitoring the primary tumour to establish a complete cytoreduction and to diagnose recurrence early.

Oxidation of 5-hydroxymethylfurfural into 2,5-diformylfuran on alkali doped Ru/C catalysts. Electron properties of Ruthenium species as descriptor of catalytic activity.

Selective aerobic oxidation of 5-hydroxymethylfurfural into 2,5-diformylfuran has been achieved on alkali doped Ru/C catalyst. Optimization of Ru metal nanoparticles, as well as the nature and amount of the alkali dopant have been performed. The results showed that doping the Ru/C catalyst with controlled amount of potassium increases the catalytic activity, 2.5 fold with respect to the non-doped sample. Spectroscopic studies showed that these differences in activity can be attributed to a different oxidation reaction mechanism associated to the presence of electron rich Ru species in the promoted sample that facilitate the dissociation of O2, while prevents the oxidation of the metal. The Ru/C-K doped catalyst resulted very stable against leaching and metal sintering, being possible the reuse over several consecutive runs. Moreover, the catalyst could be successfully applied to the oxidation of different alcohols.

First Evidence of Leishmania infantum Antibodies in Sheep (Ovis aries) from Southern Germany.

In Europe, Leishmania infantum is the most prevalent Leishmania species, and this protozoan is transmitted by phlebotomine sandflies. A recent publication has shown that sheep harbor L. infantum antibodies. This raises questions about the epidemiological role of small ruminants. Therefore, sera from small ruminants located in two southern German federal states, Baden-Wuerttemberg (BW) and Bavaria (BAV), were analyzed with an ELISA to determine the presence of L. infantum antibodies. The species, sex and age (gimmer vs. ewe) were recorded, and a univariate analysis was conducted to determine possible associations. In total, seven sheep flocks (274 sheep/10 goats) from BW and seven sheep flocks (277 sheep/78 goats) from BAV were examined. In BW, four sheep from three flocks tested positive for L. infantum antibodies. In BAV, the same number of positive sheep were detected but in four flocks. The total seropositivity rate in sheep was 1.45%. All goats tested negative. No significant association (p > 0.05) was detected between Leishmania seropositivity and the variables evaluated. Our study reveals the exposure of sheep to L. infantum in a non-endemic area. Further investigation is needed to determine whether sheep can be used as sentinels to identify new phlebotomine habitats and Leishmania risk areas.

Dentate gyrus is needed for memory retrieval.

The hippocampus is crucial for acquiring and retrieving episodic and contextual memories. In previous studies, the inactivation of dentate gyrus (DG) neurons by chemogenetic- and optogenetic-mediated hyperpolarization led to opposing conclusions about DG's role in memory retrieval. One study used Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-mediated clozapine N-oxide (CNO)-induced hyperpolarization and reported that the previously formed memory was erased, thus concluding that denate gyrus is needed for memory maintenance. The other study used optogenetic with halorhodopsin induced hyperpolarization and reported and dentate gyrus is needed for memory retrieval. We hypothesized that this apparent discrepancy could be due to the length of hyperpolarization in previous studies; minutes by optogenetics and several hours by DREADD/CNO. Since hyperpolarization interferes with anterograde and retrograde neuronal signaling, it is possible that the memory engram in the dentate gyrus and the entorhinal to hippocampus trisynaptic circuit was erased by long-term, but not with short-term hyperpolarization. We developed and applied an advanced chemogenetic technology to selectively silence synaptic output by blocking neurotransmitter release without hyperpolarizing DG neurons to explore this apparent discrepancy. We performed in vivo electrophysiology during trace eyeblink in a rabbit model of associative learning. Our work shows that the DG output is required for memory retrieval. Based on previous and recent findings, we propose that the actively functional anterograde and retrograde neuronal signaling is necessary to preserve synaptic memory engrams along the entorhinal cortex to the hippocampal trisynaptic circuit.

Temporo-Parieto-Occipital Disconnection by Robot-Assisted Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for Refractory Epilepsy in a Pediatric Patient: Proof-of-Principle Case Report and Surgical Nuances.

OBJECTIVE: Magnetic resonance imaging-guided laser interstitial thermal therapy (MRIgLITT) has been proven safe and effective for the treatment of focal epilepsy of different etiologies. It has also been used to disconnect brain tissue in more extensive or diffuse epilepsy, such as corpus callosotomy and hemispherotomy. METHODS: In this study, we report a case of temporo-parieto-occipital disconnection surgery performed using MRIgLITT assisted by a robotic arm for refractory epilepsy of the posterior quadrant. A highly realistic cadaver simulation was performed before the actual surgery. RESULTS: The patient was a 14-year-old boy whose seizures began at the age of 8. The epilepsy was a result of a left perinatal ischemic event that caused a porencephalic cyst, and despite receiving multiple antiepileptic drugs, the patient continued to experience daily seizures which led to the recommendation of surgery. CONCLUSIONS: A Wada test lateralized language in the right hemisphere. Motor and sensory function was confirmed in the left hemisphere through magnetic resonance imaging functional studies and NexStim. The left MRIgLITT temporo-parieto-occipital disconnection disconnection was achieved using 5 laser fibers. The patient followed an excellent postoperative course and was seizure-free, with no additional neurological deficits 24 months after the surgery.

Serum protein electrophoresis in European mink (Mustela lutreola): reference intervals and comparison of agarose gel electrophoresis and capillary zone electrophoresis.

BACKGROUND: Knowledge of reference intervals for blood analytes, including serum protein fractions, is of great importance for the identification of infectious and inflammatory diseases and is often lacking in wild animal species. MATERIAL AND METHODS: Serum samples were obtained from European minks enrolled in the breeding program (n = 55). Agarose gel electrophoresis (AGE) and capillary zone electrophoresis (CZE) were used to separate and identify protein fractions. Albumin, α1, α2, ß, and γ-globulins fractions were identified in all mink sera by both electrophoresis methods. Reference intervals (90% CI) were determined following the 2008 guidelines of the Clinical Laboratory Standard Institute. The methods were compared using Passing-Bablok regression, Bland-Altman analysis, and Lin's concordance correlation. RESULTS: A significant bias was found between methods for α1, α2, and γ-globulin. Lin's concordance correlation was considered unacceptable for α1, α2, and ß-globulins. Differences for gender between methods were found for albumin and α2-globuins, which were higher for males than females. γ-globulins were higher for adults than young minks using both methods; however, α1 and α2-globulins were lower. CONCLUSION: Both methods are adequate for identifying serum protein disorders, but the AGE and CZE methods are not equivalent. Therefore, reference intervals for each technique are required.

Plant metabolic response to stress in an arid ecosystem is mediated by the presence of neighbors.

Plant neighbors in arid environments can ameliorate abiotic stress by reducing insolation, but they also attract herbivores and pathogens, especially when neighbors are close relatives that share similar antagonists. Plants' metabolic profiles provide a chemical fingerprint of the physiological processes behind plant responses to different environmental stresses. For example, abscisic acid and proline, mainly involved in stomatal closure and osmotic adjustment, can induce plant responses to abiotic stress, while jasmonic acid and salicylic acid primarily regulate plant defense to herbivory or pathogens. Neighbor plants can generate contrasting ecological contexts, modulating plant responses to abiotic and biotic stresses. We hypothesize that plant metabolic profile is modulated by its neighbors in a vegetation patch, expecting a higher investment in metabolites related to biotic-stress tolerance (i.e., herbivory or pathogens) when growing associated with other plants, especially to phylogenetically close relatives, compared to plants growing alone. We show that plants from five species growing with neighbors invest more in biotic-stress tolerance while their conspecifics, growing alone, invest more in abiotic-stress tolerance. This tendency in plants' metabolic profiles was not affected by the phylogenetic diversity of their neighborhood. Linking physiological snapshots with community processes can contribute to elucidating metabolic profiles derived from plant-plant interactions.

Noble-Metal-Free Carbon Encapsulated CoNi Alloy Catalyst for the Hydrogenation of 5-(Hydroxymethyl) Furfural to Tetrahydrofurandiol in Aqueous Media.

The selective hydrogenation of 5-(hydroxymethyl)furfural (HMF) into 2,5-bis-(hydroxymethyl)tetrahydrofuran (BHMTHF) in flow reactor using water as a green solvent, has been achieved on a non-noble metal catalyst based on monodispersed CoNi alloy nanoparticles covered by a thin carbon layer. The alloyed catalyst containing CoNi (molar ratio 1 : 1) was prepared in a one-step synthesis following a hydrothermal method. Total conversion of HMF with 91 % selectivity to BHMTHF was achieved. The reaction network has been stablished, in which the carbonyl group of HMF is first reduced to alcohol giving the 2,5-bis-(hydroxymethyl)furan (BHMF) with an apparent activation energy of 25 KJ/mol, and then the double bonds of the furan ring are hydrogenated (apparent Ea=31 KJ/mol). Formation of byproducts, mainly proceed from furan ring opening and ring rearrangement processes of BHMF, promoted by water. BHMTHF resulted a compound highly stable under reaction conditions. The fixed bed flow reactor was maintained operational for 65 h without observing any loss of catalytic activity and selectivity.

Should We Abandon Intraperitoneal Chemotherapy in the Treatment of Advanced Ovarian Cancer? A Meta-Analysis.

BACKGROUND: Ovarian cancer is the gynaecological malignancy with the highest mortality and diagnosis often occurs in its advanced stages. Standard treatment in these cases is based on complete cytoreductive surgery with adjuvant intravenous chemotherapy. Other types of treatment are being evaluated to improve the prognosis of these patients, including intraperitoneal chemotherapy and antiangiogenic therapy. These may improve survival or time to relapse in addition to intravenous chemotherapy. OBJECTIVE: The aim of this meta-analysis is to determine whether treatment with intravenous chemotherapy remains the gold standard, or whether the addition of intraperitoneal chemotherapy has a benefit in overall survival (OS) and disease-free interval (DFS). MATERIALS AND METHODS: A literature search was carried out in Pubmed and Cochrane, selecting clinical studies and systematic reviews published in the last 10 years. Statistical analysis was performed using the hazard ratio measure in the RevMan tool. RESULTS: Intraperitoneal chemotherapy shows a benefit in OS and DFS compared with standard intravenous chemotherapy. The significant differences in OS (HR: 0.81 CI 95% 0.74-0.88) and in DFS (HR: 0.81 CI 95% 0.75-0.87) are statistically significant (p < 0.00001). There were no clinical differences in toxicity and side-effects. CONCLUSION: Intraperitoneal chemotherapy is an option that improves OS and DFS without significant toxicity regarding the use of intravenous chemotherapy alone. However, prospective studies are needed to determine the optimal dose and treatment regimen that will maintain the benefits while minimising side effects and toxicity and the profile of patients who will benefit most from this treatment.

The role of salicylic acid on glutathione metabolism under endoplasmic reticulum stress in tomato.

The endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are highly dependent on phytohormones such as salicylic acid (SA). In this study, the effect of SA supplementation and the lack of endogenous SA on glutathione metabolism were investigated under ER stress in wild-type (WT) and transgenic SA-deficient NahG tomato (Solanum lycopersicum L.) plants. The expression of the UPR marker gene SlBiP was dependent on SA levels and remained lower in NahG plants. Exogenous application of the chemical chaperone 4-phenylbutyrate (PBA) also reduced tunicamycin (Tm)-induced SlBiP transcript accumulation. At the same time, Tm-induced superoxide and hydrogen peroxide production were independent of SA, whereas the accumulation of reduced form of glutathione (GSH) and the oxidised glutathione (GSSG) was regulated by SA. Tm increased the activity of glutathione reductase (GR; EC 1.6.4.2) independently of SA, but the activities of dehydroascorbate reductase (DHAR; EC 1.8.5.1) and glutathione S-transferases (GSTs; EC 2.5.1.18) were increased by Tm in a SA-dependent manner. SlGR2, SlGGT and SlGSTT2 expression was activated in a SA-dependent way upon Tm. Although expression of SlGSH1, SlGSTF2, SlGSTU5 and SlGTT3 did not change upon Tm treatment in leaves, SlGR1 and SlDHAR2 transcription decreased. PBA significantly increased the expression of SlGR1, SlGR2, SlGSTT2, and SlGSTT3, which contributed to the amelioration of Tm-induced ER stress based on the changes in lipid peroxidation and cell viability. Malondialdehyde accumulation and electrolyte leakage were significantly higher in WT as compared to NahG tomato leaves under ER stress, further confirming the key role of SA in this process.

Analysis of Intraoperative Variables Responsible for the Increase in Lactic Acid in Patients Undergoing Debulking Surgery.

Background: Cytoreductive surgery (CRS) is a complex procedure with a high incidence of perioperative complications. Elevated lactacidaemia levels have been associated with complications and perioperative morbidity and mortality. This study aims to analyse the intraoperative variables of patients undergoing CRS and their relationship with lactacidaemia levels. Methods: This retrospective, observational study included 51 patients with peritoneal carcinomatosis who underwent CRS between 2014 and 2016 at the Abdomino-Pelvic Oncological Surgery Reference Unit (URCOAP) of the General University Hospital of Castellón (HGUCS). The main variable of interest was the level of lactic acid at the end of surgery. Intraoperative variables, including preoperative haemoglobin, duration of surgery, intraoperative bleeding, fluid therapy administered, administration of blood products, and intraoperative peritoneal cancer index (PCI), were analysed. Results: Positive correlations were found between lactic acid levels and PCI, duration of intervention, fluid therapy, intraoperative bleeding, and transfusion of blood products. Additionally, a negative correlation was observed between haemoglobin levels and lactic acid levels. Notably, the strongest correlations were found with operative PCI (ρ = 0.532; p-value < 0.001) and duration of surgery (ρ = 0.518; p-value < 0.001). Conclusions: PCI and duration of surgery are decisive variables in determining the prognosis of patients undergoing debulking surgery. This study suggests that, for each minute of surgery, lactic acid levels increase by 0.005 mmol/L, and for each unit increase in PCI, lactic acid levels increase by 0.060 mmol/L.

Neoadjuvant Chemotherapy plus Interval Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy (NIHIPEC) in the Treatment of Advanced Ovarian Cancer: A Multicentric Propensity Score Study.

INTRODUCTION: Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). MATERIALS AND METHODS: A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. RESULTS: A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58-0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64-1.20; p = 0.44). There was no increase in complications in the CRSH group. CONCLUSION: The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients.

Surgery in Recurrent Ovarian Cancer: A Meta-Analysis.

Background: The second cytoreductive surgery performed for a patient who has recurrent ovarian cancer remains controversial. Our study analyzes overall survival (OS) and disease-free survival (DFS) for cytoreductive surgery in addition to chemotherapy in recurrent ovarian cancer instead of chemotherapy alone. Methods: A meta-analysis was conducted using PubMed and the Cochrane database of systematic reviews to select randomized controlled studies. In total, three randomized studies were used, employing a total of 1249 patients. Results: The results of our meta-analysis of these randomized controlled trials identified significant differences in OS (HR = 0.83, IC 95% 0.70-0.99, p < 0.04) and DFS (HR = 0.63, IC 95% 0.55-0.72, p < 0.000001). A subgroup analysis comparing complete cytoreductive surgery and surgery with residual tumor achieved better results for both OS (HR = 0.65, IC 95% 0.49-0.86, p = 0.002) and DFS (HR = 0.67, IC 95% 0.53-0.82, p = 0.0008), with statistical significance. Conclusions: A complete secondary cytoreductive surgery (SCS) in recurrent ovarian cancer (ROC) demonstrates an improvement in the OS and DFS, and this benefit is most evident in cases where complete cytoreductive surgery is achieved. The challenge is the correct patient selection for secondary cytoreductive surgery to improve the results of this approach.

Morphological, physiological, and molecular scion traits are determinant for salt-stress tolerance of grafted citrus plants.

Introduction: Citrus productivity has been decreasing in the last decade in the Mediterranean basin as a consequence of climate change and the high levels of salinity found in the aquifers. Citrus varieties are cultivated grafted onto a rootstock, which has been reported as responsible for plant tolerance to adverse situations. However, other important factors for stress tolerance relying in the scion have been less studied. The aim of this study was to evaluate the effect of the grafted scion on citrus tolerance to salt stress. Methods: Four different citrus rootstock/scion combinations were subjected to salt stress for 30 days, using Carrizo citrange (CC) or Citrus macrophylla (CM) as rootstocks, and Navelina orange (NA) or Oronules mandarin (OR) as scions. CM-OR was the most tolerant combination, whereas CC-NA was the most sensitive one. Results and discussion: Our results support the idea that the rootstock plays an important role in salt stress tolerance, but scion is also crucial. Thus, photosynthesis and transpiration, processes regulated by abscisic acid and jasmonic acid, are determinant of plant performance. These photosynthetic parameters were not affected in plants of the salt-tolerant combination CM-OR, probably due to the lower intoxication with Cl- ions, allowing a better performance of the photosynthetic machinery under stress conditions. The different stomatal density of the two citrus scions used in this work (higher in the sensitive NA in comparison to the tolerant OR) also contributes to the different tolerance of the grafted plants to this adverse condition. Additionally, CsDTX35.1 and CsDTX35.2, genes codifying for Cl- tonoplast transporters, were exclusively overexpressed in plants of the salt-tolerant combination CM-OR, suggesting that these transporters involved in Cl- compartmentalization could be crucial for salt stress tolerance. It is concluded that to improve citrus tolerance to high salinity, it is important that scions have a versatile photosynthetic system, an adequate stomatal density, and a proper modulation of genes coding for Cl- transporters in the tonoplast.

Exogenous spermine alleviates the negative effects of combined salinity and paraquat in tomato plants by decreasing stress-induced oxidative damage.

Plants are frequently exposed to different combinations of soil constraints including salinity and different herbicides. These abiotic conditions negatively affect photosynthesis, growth and plant development resulting in limitations in agriculture production. To respond to these conditions, plants accumulate different metabolites that restore cellular homeostasis and are key for stress acclimation processes. In this work, we analyzed the role of exogenous spermine (Spm), a polyamine involved in plant tolerance to abiotic stress, in tomato responses to the combination of salinity (S) and the herbicide paraquat (PQ). Our findings showed that application of Spm reduced leaf damage and enhanced survival, growth, photosystem II function and photosynthetic rate of tomato plants subjected to the combination of S and PQ. In addition, we revealed that exogenous Spm reduced H2O2 and malondialdehyde (MDA) accumulation in plants subjected to S+PQ, suggesting that the role of exogenous Spm in alleviating the negative effects of this stress combination could be attributed to a decrease in stress-induced oxidative damage in tomato plants. Taken together, our results identify a key role for Spm in improving plant tolerance to combined stress.

Effectiveness of Hyperthermic Intraperitoneal Chemotherapy Associated with Cytoreductive Surgery in the Treatment of Advanced Ovarian Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment for epithelial ovarian cancer remains controversial. Our study aims to analyze the overall survival and disease-free survival for the use of HIPEC as a treatment for advanced epithelial ovarian cancer after neoadjuvant chemotherapy. METHODS: A systematic review and meta-analysis was carried out using PubMed, Cochrane, Web of Science, and ClinicalTrials.gov. A total of six studies were used, comprising a total of 674 patients. RESULTS: The results of our meta-analysis of all studies analyzed together (observational and randomized controlled trials (RCT)) did not achieve significant results. Contrary to the OS (HR = 0.56, 95% IC = 0.33-0.95, p = 0.03) and DFS (HR = 0.61, 95% IC = 0.43-0.86, p < 0.01) of the RCT analyzed separately, a clear impact on survival was suggested. The subgroup analysis showed that studies making use of higher temperatures (≥42 °C) for a shorter period of time (≤60 min) achieved better results for both OS and DFS, as well as the use of cisplatin as the form of chemotherapy in HIPEC. Moreover, the use of HIPEC did not increase high-grade complications. CONCLUSIONS: The addition of HIPEC to cytoreductive surgery demonstrates an improvement in OS and DFS for patients with epithelial ovarian cancer in advanced stages, without an increase in the number of complications. The use of cisplatin as chemotherapy in HIPEC obtained better results.

Peripheral neuropathy caused by fenugreek (Trigonella foenum-graecum) straw intoxication in cattle and experimental reproduction in sheep and goats.

Trigonella foenum-graecum (fenugreek) is a legume widely used as a food supplement in humans and less frequently in ruminants. Toxicity has been described sporadically in ruminants grazing mature fenugreek plants or stubble; however, the pathological features are unclear. This report describes a natural outbreak of intoxication in cattle fed fenugreek straw and the experimental reproduction using 8 sheep and 8 goats. Affected cattle presented clinical signs approximately 1 month after consuming the straw and 100 of 400 cattle (25%) were affected, of which 60 of 100 (60%) died or were euthanized. Clinical signs were characterized by proprioceptive positioning defects with abnormal postures and weakness of hindlimbs. Forelimbs were also affected in severely affected animals, and cattle became recumbent. Locomotion was characterized by trembling, and some cattle showed high-stepping movements of their forelimbs and knuckled over in their fetlocks. Experimental intoxication induced clinical signs only in sheep and were similar to cattle, although with signs starting in the forelegs. Gross and microscopic lesions were similar in spontaneous and experimental intoxications. Macroscopic changes corresponded with muscular hemorrhages and edema, mainly surrounding the peripheral nerves. Microscopic examination only demonstrated lesions in the distal peripheral nerves, which included edema, hemorrhages, and Wallerian degeneration. Neurofilament immunohistochemistry revealed altered axon labeling and S100 showed a decrease in myelin intensity and loss of its typical compact arrangement around axons. Biochemical and hematological abnormalities included elevated levels of muscle and liver enzymes and thrombocytopenia. These findings indicate that fenugreek straw induces peripheral neuropathy in cattle and sheep, but not in goats.

Jasmonic acid is required for tomato acclimation to multifactorial stress combination.

As a result of global warming and climate change, the number and intensity of weather events such as droughts, heat waves, and floods are increasing, resulting in major losses in crop yield worldwide. Combined with the accumulation of different pollutants, this situation is leading to a gradual increase in the complexity of environmental factors affecting plants. We recently used the term 'multifactorial stress combination' (MFSC) to describe the impact of three or more stressors occurring simultaneously or sequentially on plants. Here, we show that a MFSC of six different abiotic stressors (high light, heat, nitrogen deficiency, paraquat, cadmium, and salinity) has a negative impact on the growth, photosystem II function, and photosynthetic activity of mature tomato plants. We further reveal a negative correlation between proline accumulation and the increasing number of stress factors combined, suggesting that proline could have an adverse effect on plants during MFSC. Our findings further indicate that alterations in hormonal levels and stomatal responses are stress/stress combination-dependent, and that a tomato mutant deficient in jasmonic acid accumulation is more sensitive to high light and its combinations with salinity and/or paraquat. Taken together, our study reveals that the effects of MFSC on tomato plants are broad, that photosynthesis and proline accumulation are especially vulnerable to MFSC, and that jasmonic acid is required for tomato acclimation to MFSCs involving high light, salinity and paraquat.

Enzymatic and chemo-enzymatic strategies to produce highly valuable chiral amines from biomass with ω-transaminases on 2D zeolites.

Amino transaminases (ATAs) have been supported on a 2D ITQ-2 zeolite through electrostatic interactions, resulting in a highly stable active biocatalyst to obtain a variety of valuable chiral amines starting from prochiral ketones derived from biomass. We have extended the biocatalyst applications by designing a chemo-enzymatic process that allows, as the first step, prochiral ketones to be obtained from biomass-derived compounds through an aldol condensation-reduction step using a bifunctional metal/base catalyst. The prochiral ketone is subsequently converted into the chiral amine using the immobilized ATA. We show that it is feasible to couple both steps in a semi-continuous process to produce industrially relevant chiral amines with yields of >95% and ∼100% enantiomer excess.

Fertility-Sparing Surgery versus Radical Hysterectomy in Early Cervical Cancer: A Propensity Score Matching Analysis and Noninferiority Study.

OBJECTIVE: Fertility-sparing surgery (FSS) is the treatment of choice for patients with early cervical cancer (ECC) and fertility desire, but survival rates compared to radical hysterectomy (RH) have been scarcely reported. The aim of this study was to analyse the oncological outcomes of FSS compared to a balanced group of standard RH. METHODS: A retrospective multicentre study of ECC patients who underwent FSS or RH was carried out in 12 tertiary hospitals in Spain between January 2005 and January 2019. The experimental group included patients who underwent a simple and radical trachelectomy, and the control group included patients who underwent RH. Optimal 1:1 propensity score (PS) matching analysis was performed to balance the series. RESULTS: The study included 222 patients with ECC; 111 (50%) were treated with FSS, and 111 (50%) were treated with RH. After PS matching, a total of 38 patients in the FSS group and 38 patients in the RH group were analysed. In both groups, the overall survival (HR 2.5; CI 0.89, 7.41) and recurrence rates (28.9% in the FSS group vs. 13.2% in RH group) were similar. The rate of disease-free survival at 5 years was 68.99% in the FSS group and 88.01% in the RH group (difference of -19.02 percentage points; 95% CI -32.08 to -5.96 for noninferiority). In the univariate analysis, only tumour size reached statistical significance. CONCLUSION: FSS offers excellent disease-free and overall survival in women with ECC with fertility desire and is not inferior compared to RH.