Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea.

Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.

Severe acute respiratory syndrome coronavirus 2 infection in hematopoietic stem cell transplant recipients in Mexico City.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are among patients with highest risk of adverse coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: We compared clinical outcomes in post-HSCT patients with COVID-19 before and during the Omicron period. STUDY DESIGN: This was a retrospective study including patients post-HSCT with severe acute respiratory syndrome coronavirus 2 infection from April 2020 to March 2023 at Instituto Nacional de Cancerología, Mexico City. We describe their clinical characteristics and report the variables associated with severe clinical disease, hospitalization, and death. RESULTS: Fifty-three patients were included; 31 (58.5%) from the pre-Omicron period and 22 (41.5%) from the Omicron period. Median age was 42-years old (interquartile range 26-53), and 31 patients (59%) were men. Only four patients (16%) had received a vaccine prior to COVID-19 diagnosis in the pre-Omicron period versus 20 (91%) in the Omicron period (p < 0.001). COVID-19 severe cases were more common before Omicron: seven patients (23%) versus two patients (9%). Only one patient (3%) received an antiviral in the pre-Omicron period compared to 11 patients (50%) during the Omicron period (p < 0.01). COVID-19-associated mortality was almost double in the pre-Omicron period (16% vs. 9%, p = 0.6). CONCLUSIONS: This study reports patients with a high proportion of severe outcomes during the first 2 years of the pandemic. Outcomes improved during Omicron with better access to vaccines and antivirals and no in-hospital cases. Variables associated with worse outcomes were similar to other reports. Strengthening infection control measures in the hospital and better access to preventive strategies and therapeutic options are mandatory in these high-risk patients.

Effectiveness of diaphragmatic ultrasound as a predictor of successful weaning from mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Several measurements have been used to predict the success of weaning from mechanical ventilation; however, their efficacy varies in different studies. In recent years, diaphragmatic ultrasound has been used for this purpose. We conducted a systematic review and meta-analysis to evaluate the effectiveness of diaphragmatic ultrasound in predicting the success of weaning from mechanical ventilation. METHODS: Two investigators independently searched PUBMED, TRIP, EMBASE, COCHRANE, SCIENCE DIRECT, and LILACS for articles published between January 2016 and July 2022. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool; additionally, the certainty of the evidence is evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. Sensitivity and specificity analysis was performed for diaphragmatic excursion and diaphragmatic thickening fraction; positive and negative likelihood ratios and diagnostic odds ratios (DOR) with their confidence intervals (95% CI) were calculated by random effects analysis, summary receiver operating characteristic curve was estimated. Sources of heterogeneity were explored by subgroup analysis and bivariate meta-regression. RESULTS: Twenty-six studies were included, of which 19 were included in the meta-analysis (1204 patients). For diaphragmatic excursion, sensitivity was 0.80 (95% CI 0.77-0.83), specificity 0.80 (95% CI 0.75-0.84), area under the summary receiver operating characteristic curve 0.87 and DOR 17.1 (95% CI 10.2-28.6). For the thickening fraction, sensitivity was 0.85 (95% CI 0.82-0.87), specificity 0.75 (95% CI 0.69-0.80), area under the summary receiver operating characteristic curve 0.87 and DOR 17.2 (95% CI 9.16-32.3). There was heterogeneity among the included studies. When performing a subgroup analysis and excluding studies with atypical cutoff values, sensitivity and specificity increased for diaphragmatic thickening fraction; sensitivity increased and specificity decreased for diaphragmatic excursion; when comparing studies using pressure support (PS) versus T-tube, there was no significant difference in sensitivity and specificity; bivariate meta-regression analysis shows that patient position at the time of testing was a factor of heterogeneity in the included studies. CONCLUSIONS: Measurement of diaphragmatic excursion and diaphragmatic thickening fraction predict the probability of successful weaning from mechanical ventilation with satisfactory diagnostic accuracy; however, significant heterogeneity was evident in the different included studies. Studies of high methodological quality in specific subgroups of patients in intensive care units are needed to evaluate the role of diaphragmatic ultrasound as a predictor of weaning from mechanical ventilation.

The effect of dispersal on asymptotic total population size in discrete- and continuous-time two-patch models.

Many populations occupy spatially fragmented landscapes. How dispersal affects the asymptotic total population size is a key question for conservation management and the design of ecological corridors. Here, we provide a comprehensive overview of two-patch models with symmetric dispersal and two standard density-dependent population growth functions, one in discrete and one in continuous time. A complete analysis of the discrete-time model reveals four response scenarios of the asymptotic total population size to increasing dispersal rate: (1) monotonically beneficial, (2) unimodally beneficial, (3) beneficial turning detrimental, and (4) monotonically detrimental. The same response scenarios exist for the continuous-time model, and we show that the parameter conditions are analogous between the discrete- and continuous-time setting. A detailed biological interpretation offers insight into the mechanisms underlying the response scenarios that thus improve our general understanding how potential conservation efforts affect population size.

Association between ventilatory ratio and mortality in patients with acute respiratory distress syndrome and COVID 19: A multicenter, retrospective cohort study.

BACKGROUND: Mortality rates in patients with COVID-19 undergoing mechanical ventilation in the intensive care unit are high. The causes of this mortality have been rigorously investigated. The aim of the present study is to establish mortality risk factors related to lung mechanics measured at days 1 and 5 in patients with covid-19 ARDS managed with invasive mechanical ventilation in the intensive care unit. METHODS: A retrospective observational multicenter study including consecutive patients with a confirmed diagnosis of COVID-19-induced ARDS, admitted to three institutions and seven intensive care units in the city of Bogota between May 20, 2020 and May 30, 2022 who required mechanical ventilation for at least five days. Data were collected from the medical records of patients who met the inclusion criteria on day 1 and day 5 of mechanical ventilation. The primary outcome assessed was mortality at day 30. RESULTS: A total of 533 consecutive patients admitted with ARDS with COVID-19 were included. Ventilatory ratio, plateau pressure and driving pressure measured on day 5 were significantly higher in non-survivors (p < 0.05). Overall, 30-day follow-up mortality was 48.8%. The increases between day 1 and day 5 in the ventilatory ratio (OR 1.42, 95%CI 1.03-2.01, p = 0.04), driving pressure (OR 1.56, 95%CI 1.10-2.22, p = 0.01); and finally plateau pressure (OR 1.9, 95%CI 1.34-2.69, p = 0.001) were associated with an increased risk of death. There was no association between deterioration of PaO2/FIO2 index and mortality (OR 1.34, 95%CI 0.96-1.56, p = 0.053). CONCLUSIONS: Ventilatory ratio, plateau pressure, driving pressure, and age were identified as independent risk factors for 30-day mortality in patients with ARDS due to COVID-19 on day 5 of invasive mechanical ventilation.

Exoscope improves visualization and extent of hippocampal resection in temporal lobectomy.

INTRODUCTION: Anterior temporal lobectomy (ATL) is a safe and well-validated procedure in the treatment of temporal lobe epilepsy (TLE), but is a challenging technique to master and still confers a risk of morbidity and mortality due to the complex anatomy of the mesial temporal lobe structures. Automated robotic 3D exoscopes have been developed to address limitations traditionally associated with microscopic visualization, allowing for ergonomic, high-definition 3D visualization with hands-free control of the robot. Given the potential advantages of using such a system for visualization of complex anatomy seen during mesial structure resection in ATL, this group sought to investigate impact on the percentage of hippocampal resection in both exoscope and microscope guided procedures. METHODS: We conducted a retrospective analysis of 20 consecutive patients undergoing standard ATL for treatment of medically refractory TLE at our institution. Using pre-operative and post-operative imaging, the coronal plane cuts in which either the head, body, or tail of the hippocampus appeared were counted. The number of cuts in which the hippocampus appeared were multiplied by slice thickness to estimate hippocampal length. RESULTS: Mean percentage of hippocampal resection was 61.1 (SD 13.1) and 76.5 (SD 6.5) for microscope and exoscope visualization, respectively (p = 0.0037). CONCLUSION: Use of exoscope for mesial resection during ATL has provided good visualization for those in the operating room and the potential for a safe increase in hippocampal resection in our series. Further investigation of its applications should be evaluated to see if it will improve outcomes.

Antioxidant and Antidiabetic Properties of Phlorotannins from Ascophyllum nodosum Seaweed Extracts.

Seaweeds have gained considerable attention in recent years due to their potential health benefits and high contents of bioactive compounds. This review focuses on the exploration of seaweed's health-promoting properties, with particular emphasis on phlorotannins, a class of bioactive compounds known for their antioxidant and antidiabetic properties. Various novel and ecofriendly extraction methods, including solid-liquid extraction, ultrasound-assisted extraction, and microwave-assisted extraction are examined for their effectiveness in isolating phlorotannins. The chemical structure and isolation of phlorotannins are discussed, along with methods for their characterization, such as spectrophotometry, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and chromatography. Special attention is given to the antioxidant activity of phlorotannins. The inhibitory capacities of polyphenols, specifically phlorotannins from Ascophyllum nodosum against digestive enzymes, such as α-amylase and α-glucosidase, are explored. The results suggest that polyphenols from Ascophyllum nodosum seaweed hold significant potential as enzyme inhibitors, although the inhibitory activity may vary depending on the extraction conditions and the specific enzyme involved. In conclusion, seaweed exhibits great potential as a functional food ingredient for promoting health and preventing chronic diseases. Overall, this review aims to condense a comprehensive collection of high-yield, low-cost, and ecofriendly extraction methods for obtaining phlorotannins with remarkable antioxidant and antidiabetic capacities.

A Review of Endoscopic Spine Surgery: Decompression for Radiculopathy.

PURPOSE OF REVIEW: With this manuscript the authors sought to write a succinct review of the origins, as well as the latest advancements in endoscopic spine surgery to serve as a reference frame for physicians looking to learn this approach. RECENT FINDINGS: At its infancy, the indications for posterolateral and transforaminal endoscopic decompression remained narrow, which prevented the procedure from gaining rapid traction during those days. However, more recently the tides have turned and an increasing number of surgeons are starting to adopt this technique given all its advantages. With the advent of higher quality camera systems and instruments, indications to use a minimally invasive option have gotten significantly broader. The most basic indication for the use of this technology is a soft disc herniation causing compromise of a neural structure that has failed to be managed successfully with non-surgical therapies. The use of endoscopic techniques provides significant advantages to patient outcomes and patient recovery. Endoscopic procedures should not be used as a blanket approach to nerve root decompression, as they certainly have limitations. Most contraindications to this procedure are relative and serve mostly as points to consider when selecting the methods to address neural compression. As these techniques become more widely accepted, we expect its reach and indications to continue to broaden and diversify. The full integration of navigation technologies will likely leapfrog this procedure into the mainstream use.

First report of Xanthomonas prunicola causing bacterial leaf streaks on wheat in Argentina.

Since 2018, bacterial-like symptoms, such as leaf streaks were observed on wheat plants (Triticum aestivum L.) in Córdoba province in Argentina, with 1 to 5% of disease incidence. Samples of wheat stem and spike collected in a trial of varieties for summer/autumn sowing in the experimental field of the INTA Marcos Juárez were disinfected, washed and macerated in mortars with sterile distilled water and extracts were streaked on Luria-Bertani (LB) agar. After 48 h incubation at 28 °C, circular, mucoid, convex, and cream colonies were observed and pure cultures were transferred to LB medium for further identification tests. Biochemical tests corroborated the detection of a Gram-negative bacillus. Conventional PCR was performed using DNA isolate from pure cultures and general primers for various species of genera Xanthomonas (Maes 1993) and Pseudomonas (Mulet et al. 2010). An isolate (Arg-1), with cream colored colonies was positive using general primers for Xanthomonas sp (amplified fragment of 444 bp). A bacterial suspension containing 108 CFU mL-1 grown for 48 h on LB medium at 28 °C was injected into three-week-old leaves of wheat plants to fulfill Koch's postulates. After 5 days, plants showed symptoms of chlorosis, streaks and then necrosis on the leaves. The bacteria were re-isolated from the inoculated plants, showing same symptoms observed in the original plants. Negative control plants, inoculated with sterile water remained without symptoms. The amplified 444 bp fragment described above was sequenced by the Sanger method (GenBank accession OM972662), as well as another 757 bp fragment amplified with universal primers that amplify the partial 16S rDNA gene (GenBank accession OM972661). Analyses of these sequences, as well as the protein profile of the isolate obtained by matrix assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF MS) Bruker Biotyper, allowed to identify only the genus Xanthomonas. With the purpose of determine the species status, the complete genome of isolate Arg-1 was sequenced using Oxford Nanopore Technologies (ONT). Total gDNA was isolate from pure cultures using a commercial kit (Wizard Genomic DNA Purification Kit, Promega). gDNA library was constructed using Ligation Sequencing Kit (SQK-LSK109) and sequenced using ONT platform on a MinION 1kb device. Raw basecalled sequences were filtered using Filtlong and assembled using Trycycler. The genome was assembled in a single contig comprising 5.410.641 bp with 4740 predicted CDSs and 63.9% GC content. Genome sequence was deposited in GenBank under accession number CP094827 and SRA data SRX14635308. Whole-genome Average Nucleotide Identity (ANI) analysis showed values of ~ 97% against the reference genomes of Xanthomonas prunicola (PHKX01.1, PHKV01.1 and PHKW01.1) and 100% in complete 16S rRNA gene sequences (1547 bp). These findings suggest that a new wheat pathogen within the genus Xanthomonas is present in Argentina, as well as was reported in Uruguay and USA (Clavijo et al. 2021). To our knowledge, this is the first report of X. prunicola affecting wheat in Argentina and the first complete genome registered for this specie. Accurate and specific diagnostics are required for the detection of X. prunicola in wheat crops to implement correct prevention and control strategies to this disease, avoiding the dissemination in lots where it has not yet been found.

Towards Building a Sustainable Future: Positioning Ecological Modelling for Impact in Ecosystems Management.

As many ecosystems worldwide are in peril, efforts to manage them sustainably require scientific advice. While numerous researchers around the world use a great variety of models to understand ecological dynamics and their responses to disturbances, only a small fraction of these models are ever used to inform ecosystem management. There seems to be a perception that ecological models are not useful for management, even though mathematical models are indispensable in many other fields. We were curious about this mismatch, its roots, and potential ways to overcome it. We searched the literature on recommendations and best practices for how to make ecological models useful to the management of ecosystems and we searched for 'success stories' from the past. We selected and examined several cases where models were instrumental in ecosystem management. We documented their success and asked whether and to what extent they followed recommended best practices. We found that there is not a unique way to conduct a research project that is useful in management decisions. While research is more likely to have impact when conducted with many stakeholders involved and specific to a situation for which data are available, there are great examples of small groups or individuals conducting highly influential research even in the absence of detailed data. We put the question of modelling for ecosystem management into a socio-economic and national context and give our perspectives on how the discipline could move forward.

Proteomic Advances in Milk and Dairy Products.

Proteomics is a new area of study that in recent decades has provided great advances in the field of medicine. However, its enormous potential for the study of proteomes makes it also applicable to other areas of science. Milk is a highly heterogeneous and complex fluid, where there are numerous genetic variants and isoforms with post-translational modifications (PTMs). Due to the vast number of proteins and peptides existing in its matrix, proteomics is presented as a powerful tool for the characterization of milk samples and their products. The technology developed to date for the separation and characterization of the milk proteome, such as two-dimensional gel electrophoresis (2DE) technology and especially mass spectrometry (MS) have allowed an exhaustive characterization of the proteins and peptides present in milk and dairy products with enormous applications in the industry for the control of fundamental parameters, such as microbiological safety, the guarantee of authenticity, or the control of the transformations carried out, aimed to increase the quality of the final product.

Proteomic Advances in Cereal and Vegetable Crops.

The importance of vegetables in human nutrition, such as cereals, which in many cases represent the main source of daily energy for humans, added to the impact that the incessant increase in demographic pressure has on the demand for these plant foods, entails the search for new technologies that can alleviate this pressure on markets while reducing the carbon footprint of related activities. Plant proteomics arises as a response to these problems, and through research and the application of new technologies, it attempts to enhance areas of food science that are fundamental for the optimization of processes. This review aims to present the different approaches and tools of proteomics in the investigation of new methods for the development of vegetable crops. In the last two decades, different studies in the control of the quality of crops have reported very interesting results that can help us to verify parameters as important as food safety, the authenticity of the products, or the increase in the yield by early detection of diseases. A strategic plan that encourages the incorporation of these new methods into the industry will be essential to promote the use of proteomics and all the advantages it offers in the optimization of processes and the solution of problems.

Biochemical characterization of a partially purified protease from Aspergillus terreus 7461 and its application as an environmentally friendly dehairing agent for leather industry.

Proteases can be used in several biotechnological processes including detergent, food and leather industries. In the leather industry, dehairing is carried out by chemicals, which pollute the environment. Therefore, to make the hair removal process environmentally friendly, a protease produced by Aspergillus terreus has been purified, biochemically characterized and had an efficient ability to remove hair from bovine leather. The protease was produced using 1% wheat bran and was purified 2.3-fold using two chromatographic steps showing a molecular weight of 90 kDa. Optimal temperature and pH were 50 °C and 6.5, respectively. Thermal stability was up to 1 h at 50 °C. Protease was stable to detergents like Tween 80 and to organic solvents. The activity was activated by Ca2+ and inhibited by Hg2+ and Cu2+. The enzyme was classified as serine protease, by the inhibition by PMSF and was stable to reducing agents. It hydrolyzed casein, azocasein, BSA, egg albumin and BTpNA. The Km and Vmax values were 0.65 ± 0.03 mg/mL and 3.66 ± 0.18 µmol/min, respectively. Remarkable properties about temperature, pH, stability to detergents and reducing agents ensure that the protease from A. terreus can be an excellent candidate for industrial applications, particularly in the leather industry.

Caspase activity in post mortem muscle and its relation to cattle handling practices.

BACKGROUND: Animal handling practices are one of the factors majorly affecting animal metabolism prior to slaughter. This phenomenon increases the occurrence of meat quality defects such as dark cutting-beef, causing high economical losses in the meat industry. Under this framework, the assessment of apoptosis onset in post mortem muscle was proposed as a novel approach to reveal biochemical characteristics in several Spanish bovine breeds (Asturiana de los Valles, Retinta and Rubia Gallega) managed under different production systems (intensive versus semi-extensive) and transport/lairage conditions (mixing versus not mixing with unfamiliar animals). To do so, the activities of initiator caspase 9 and executioner caspases 3/7 were determined in Longissimus thoracis et lumborum muscle at three early post mortem times (2, 8, and 24 h). RESULTS: Breed effect and transport/lairage conditions were the most relevant factors that influenced both caspase activities over post mortem time, showing Rubia Gallega breed a completely different behavior compared to Asturiana de los Valles and Retinta breeds. Moreover, it is postulated that apoptosis cascade is initiated via the activation of caspase 9 under hypoxic or metabolic stress followed by the activation of executioner caspases 3/7. CONCLUSIONS: Assessment of apoptosis on post mortem muscle can be a novel approach to study the influence of animal handling on muscle metabolism and post mortem cell death and its consequences on meat quality traits. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Dual targeting of EZH2 and androgen receptor as a novel therapy for castration-resistant prostate cancer.

Castration-resistant prostate cancer (CRPC) emerges after androgen withdrawal therapy and remains incurable due to the lack of effective treatment protocols. Treatment with enzalutamide, a second generation androgen receptor (AR) antagonist, offers an initial response followed by drug resistance and tumor relapse. Enhancer of zeste homolog 2 (EZH2), a member of PRC2 complex, is an important target that acts as a coactivator of AR-mediated gene suppression whose oncogenic activity increases during castration. We hypothesize that dual targeting of EZH2 and AR could be highly effective in CRPC treatment. The present study aimed to examine the effectiveness of combination using EZH2 inhibitor GSK126 with antiandrogen enzalutamide in the treatment of CRPC cells. Treatment of 22Rv1 and C42B CRPC cells with a combination of GSK126 and enzalutamide led to synergistic inhibition of cell proliferation, cell cycle arrest and marked increase in cell death. Mechanistically, this combination treatment significantly reduced expression of AR and AR-v7, decrease in PSA and Akt activity, diminution of EZH2 and other members of PCR2 complex including SUZ12 and EED, with simultaneous loss of H3K27 trimethylation and dissociation between AR and PRC2 complex members compared to individual treatment. This study provides preclinical proof-of-concept that combined treatment of EZH2 inhibitor with AR antagonist results in synergistic anticancer effects opening new possibilities for treatment of CRPC tumors.

Neurosurgical Evaluation for Patients with Chronic Lower Back Pain.

PURPOSE OF REVIEW: Chronic low back pain (CLBP) is a major cause of disability in the USA, and it affects approximately 1 in 4 Americans. CLBP patients are commonly referred to or seek out neurosurgical evaluations and opinions for treatment and management. RECENT FINDINGS: Literature shows that only a minority of patients with CLBP may benefit from a surgical procedure. These patients that present to clinic often have been ailing for a considerable amount of time and are eager for effective treatment to alleviate pain. However, determining if a patient with CLBP is a surgical candidate is predicated upon having no success of pain relief with non-operative management. Patients with CLBP require thorough and adequate imaging, clinical exam, and diagnostic evaluation. When adequate non-operative management was provided, and proven fruitless, the patient may be considered an operative candidate. In this manuscript, a framework is presented for workup and evaluation of patients with CLBP.

Evaluation of linseed oil oleogels to partially replace pork backfat in fermented sausages.

BACKGROUND: Nowadays, fat replacement in meat products is a matter of concern in the meat industry. The objective of this study was to evaluate the replacement of pork backfat with two oleogels of linseed in dry-cured sausages. RESULTS: Five batches of dry-cured sausages were prepared with two oleogels, a mixture of γ-oryzanol and ß-sitosterol (SO) and beeswax (B), at two levels of replacement (20% and 40%) (SO-20, SO-40, B-20, and B-40, respectively) and a control batch. The fatty acid profile improved in terms of nutrition: the polyunsaturated fatty acid / saturated fatty acid (PUFA/SFA) and n-6/n-3 ratio was about 1.41 and 0.93 for the higher levels of replacement, SO-40 and B-40, respectively. Quality parameters such as pH and color also changed with the inclusion of oleogels, resulting in changes in the sensory quality. CONCLUSION: Oleogels based on linseed enabled the replacement of pork backfat in fermented sausages. Depending on the level of fat substitution, such oleogels could replace fat in dry-cured sausages at the industrial level. © 2019 Society of Chemical Industry.

The first evidence of global meat phosphoproteome changes in response to pre-slaughter stress.

BACKGROUND: Pre-slaughter stress (PSS) impairs animal welfare and meat quality. Dark, firm and dry (DFD) are terms used to designate poor quality meats induced by PSS. Protein phosphorylation can be a potentially significant mechanism to explain rapid and multiple physiological and biochemical changes linked to PSS-dependent muscle-to-meat conversion. However, the role of reversible phosphorylation in the response to PSS is still little known. In this study, we report a comparative phosphoproteomic analysis of DFD and normal meats at 24 h post-mortem from the longissimus thoracis (LT) bovine muscle of male calves of the Rubia Gallega breed. For this purpose, two-dimensional gel electrophoresis (2-DE), in-gel multiplex identification of phosphoproteins with PRO-Q Diamond phosphoprotein-specific stain, tandem (MALDI-TOF/TOF) mass spectrometry (MS), novel quantitative phosphoproteomic statistics and bioinformatic tools were used. RESULTS: Noticeable and statistically significant differences in the extent of protein phosphorylation were detected between sample groups at the qualitative and quantitative levels. Overall phosphorylation rates across significantly changed phosphoproteins were about three times higher in DFD than in normal meat. Significantly changed phosphoproteins involved a variable number of isoforms of 13 myofibrillar and sarcoplasmic nonredundant proteins. However, fast skeletal myosin light chain 2 followed by troponin T, F-actin-capping and small heat shock proteins showed the greatest phosphorylation change, and therefore they were the most important phosphoproteins underlying LT muscle conversion to DFD meat in the Rubia Gallega breed. CONCLUSIONS: This is the first study reporting global meat phosphoproteome changes in response to PSS. The results show that reversible phosphorylation is a relevant mechanism underlying PSS response and downstream effects on meat quality. This research opens up novel horizons to unravel the complex molecular puzzle underlying muscle-to-meat conversion in response to PSS.

Enhancing population stability with combined adaptive limiter control and finding the optimal harvesting-restocking balance.

Fluctuations in population size may have negative consequences (e.g., an increased risk of extinction or the occurrence of repeated outbreaks), and many management strategies are aimed at avoiding them by either only restocking or only harvesting the population. Two of these strategies are adaptive limiter control (ALC) and adaptive threshold harvesting (ATH). With ALC the population is controlled by only restocking and with ATH by only harvesting. We propose the strategy of combined adaptive limiter control (CALC) as the combination of ALC and ATH and study the potential advantages of CALC over ALC and ATH. We consider two different population models, namely a stochastic overcompensatory model and a host-pathogen-predator model. For the first model, our results show that the combination of restocking and harvesting under CALC improves the constancy stability of the managed populations when the harvesting and restocking intensities are high enough. Otherwise the effect is marginal or in rare cases negative. For the second model, we show that combining harvesting with restocking reduces the outbreak risk only if the harvesting intensity is low. For medium harvesting intensities the effect is marginal and for high harvesting intensities the risk of outbreaks is increased. In addition, we study the optimal harvesting-restocking balance by considering a proxy of the benefit obtained in terms of the reduction in the outbreak risk and the harvesting and restocking costs.

Antibiotic treatment for newborns with congenital syphilis.

BACKGROUND: Congenital syphilis continues to be a substantial public health problem in many parts of the world. Since the first use of penicillin for the treatment of syphilis in 1943, which was a notable early success, it has remained the preferred and standard treatment including for congenital syphilis. However, the treatment of congenital syphilis is largely based on clinical experience and there is extremely limited evidence on the optimal dose or duration of administration of penicillin or the use of other antibiotics. OBJECTIVES: To assess the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable and possible congenital syphilis. SEARCH METHODS: We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 23 May 2018. We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotic treatment (any concentration, frequency, duration and route) with no intervention or any other antibiotic treatment for neonates with confirmed, highly probable or possible congenital syphilis. DATA COLLECTION AND ANALYSIS: All review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Two RCTs (191 participants) met our inclusion criteria and none of these trials was funded by the industry. One trial (22 participants) compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested that benzathine penicillin administration may not have decreased the rate of neonatal death due to any cause (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.06 to 11.70), and showed a possible reduction into the proportion of neonates with clinical manifestations of congenital syphilis (RR 0.12, 95% CI 0.01 to 2.09). Penicillin administration increased the serological cure at the third month (RR 2.13, 95% CI 1.06 to 4.27). These results should be taken with caution, because the trial was stopped early because there were four cases with clinical congenital syphilis in the no treatment group and none in the treatment group. Interim analysis suggested this difference was significant. This study did not report neonatal death due to congenital syphilis or the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of imprecision and risk of bias.One trial (169 participants) compared benzathine penicillin versus procaine benzylpenicillin. High- and moderate-quality evidence suggested that there were probably no differences between benzathine penicillin and procaine benzylpenicillin for the outcomes: absence of clinical manifestations of congenital syphilis (RR 1.00, 95% CI 0.97 to 1.03) and serological cure (RR 1.00, 95% CI 0.97 to 1.03). There were no cases of neonatal death due congenital syphilis; all 152 babies who followed up survived. This study did not report on the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of serious risk of bias. AUTHORS' CONCLUSIONS: At present, the evidence on the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable or possible congenital syphilis is sparse, implying that we are uncertain about the estimated effect. One trial compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested penicillin administration possibly reduce the proportion of neonates with clinical manifestations of congenital syphilis, penicillin administration increased the serological cure at the third month. These findings support the clinical use of penicillin in neonates with confirmed, highly probable or possible congenital syphilis. High- and moderate-quality evidence suggests that there are probably no differences between benzathine penicillin and procaine benzylpenicillin administration for the outcomes of absence of clinical manifestations of syphilis or serological cure.