Medical History and Preoperative Coagulation Profile as Predictors of Outcomes in Elective Spinal Surgery: A Meta-Analysis.

BACKGROUND: In patients with unremarkable medical history, comprehensive preoperative hemostasis screening in elective neurosurgery remains debated. Comprehensive medical history has shown to be noninferior to coagulation profile to evaluate surgical outcomes. This study aims to evaluate the predictiveness of preoperative coagulation screening and medical history for surgical outcomes. METHODS: Databases were searched until April 2023 for observational cohort studies that reported preoperative hemostasis screening and clinical history prior to elective neurosurgical procedures. Outcomes of interest included postoperative transfusion, mortality, and complications. Pooled relative risk ratios (RRs) were analyzed using random-effects models. RESULTS: Out of 604 studies, 3 cohort studies met our inclusion criteria, adding a patient population of 83,076. Prolonged partial thromboplastin time (PTT; RR=1.42, 95% confidence interval [CI] =1.14, 1.77, P=0.002), elevated international normalized ratio (INR; RR=2.01, 95% CI=1.14, 3.55, P=0.02), low platelet count (RR=1.58, 95% CI=1.34, 1.86, P<0.00001), and positive bleeding history (RR=2.14, 95% CI=1.16, 3.93, P=0.01) were associated with postoperative transfusion risk. High PTT (RR=2.42, 95% CI=1.24, 4.73, P=0.010), High INR (RR=8.15, 95% CI=5.97, 11.13; P<0.00001), low platelet count (RR=4.89, 95% CI=3.73, 6.41, P<0.00001), and bleeding history (RR=7.59, 95% CI=5.84, 9.86, P<0.00001) were predictive of mortality. Prolonged PTT (RR=1.53, 95% CI=1.25, 1.86, P=<0.0001), a high INR (RR=3.41, 95% CI=2.63, 4.42, P=< 0.00001), low platelets (RR=1.63, 95% CI=1.40, 1.90, P=<0.00001), and medical history (RR=2.15, 95% CI=1.71, 2.71, P=<0.00001) were predictive of complications. CONCLUSIONS: Medical history was a noninferior predictor to coagulation profile for postoperative transfusion, mortality, and complications. However, our findings are mostly representative of elective spinal procedures. Cost-effective alternatives should be explored to promote affordable patient care in patients with unremarkable history.

The visual perception of long outdoor distances.

Many previous studies have investigated visual distance perception, especially for small to moderate distances. Few experiments, however, have evaluated the perception of large distances (e.g., 100 m or more). The studies that have been conducted have found conflicting results (diametrically opposite conclusions). In the current experiment, the functions relating actual and perceived distance were obtained for sixteen adult observers using the method of equal appearing intervals. These functions relating perceived and actual distance were obtained for outdoor viewing in a typical University environment-the experiment was conducted along a sidewalk adjacent to a typical street where campus buildings, trees, street signs, etc., were visible. The overall results indicated perceptual compression of distances in depth so that the stimulus distance intervals appeared significantly shorter than the actual (physical) distance intervals. It is important to note, however, that there were sizeable individual differences-the judgments of half of the observers were relatively accurate, whereas the judgments of the remaining half were inaccurate to varying degrees. The results of the experiment demonstrate that there is no single function that describes how human observers visually perceive large distance intervals in outdoor environments.

Generation of Non-Alloreactive Antiviral Central Memory CD8 Human Veto T Cells for Cell Therapy.

Previous studies in mice demonstrated that CD8 T cells exhibit marked veto activity enhancing engraftment in several models for T cell-depleted bone marrow (TDBM) allografting. To reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic CD8 veto T cells, these studies made use of naive CD8 T cells stimulated against third-party stimulators under cytokine deprivation and subsequent expansion in the presence of IL-15. More recently, it was shown that mouse CD8 veto T cells can be generated by stimulating CD8 memory T cells from ovalbumin immunized mice under cytokine deprivation, using ovalbumin as a third-party antigen. These cells also exhibited substantial enhancement of BM allografting without GVHD. In this study, we tested the hypothesis that stimulation and expansion of human CD8 memory T cells under IL-15 and IL-7 deprivation during the early phase of activation against recall viral antigens can lead to substantial loss of alloreactive T clones while retaining marked veto activity. Memory CD8 T cells were enriched by removal of CD45RA+, CD4+, and CD56+ cells from peripheral blood of cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-positive donors. In parallel, CD14+ monocytes were isolated; differentiated into mature dendritic cells (mDCs); pulsed with a library of CMV, EBV, adenovirus, and BK virus peptides; and irradiated. The CD8 T cell-enriched fraction was then cultured with the pulsed mDCs in the presence of IL-21 for 3 days, after which IL-15 and IL-7 were added. After 12 days of culture, the cells were tested by limiting dilution analysis for the frequency of alloreactive T cell clones and their veto activity. In preclinical runs using GMP reagents, we established that within 12 days of culture, a large number of highly homogenous CD8 T cells, predominantly expressing a central memory phenotype, could be harvested. These cells exhibited marked veto activity in vitro and >3-log depletion of alloreactivity. Based on these preclinical data, a phase 1-2 clinical trial was initiated to test the safety and efficacy of these antiviral CD8 central memory veto cells in the context of nonmyeloablative (NMA) T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT). In 2 validation runs and 11 clinical runs using GMP reagents, >1 × 1010 cells were generated from a single leukapheresis in 12 out of 13 experiments. At the end of 12 days of culture, there were 97 ± 2.5% CD3+CD8+ T cells, of which 84 ± 9.0% (range, 71.5% to 95.1%) exhibited the CD45RO+CD62L+ CM phenotype. Antiviral activity tested by intracellular expression of INF-γ and TNF-α and showed an average of 38.8 ± 19.6% positive cells on 6 hours of stimulation against the viral peptide mixture. Our results demonstrate a novel approach for depleting alloreactive T cell clones from preparations of antiviral CD8 veto cells. Based on these results, a phase 1-2 clinical trial is currently in progress to test the safety and efficacy of these veto cells in the context of NMA haploidentical T cell-depleted HSCT. Studies testing the hypothesis that these non-alloreactive CD8 T cells could potentially offer a platform for off-the-shelf veto chimeric antigen receptor T cell therapy in allogenic recipients, are warranted.

Brain transcriptomic, metabolic and mitohormesis properties associated with N-propargylglycine treatment: A prevention strategy against neurodegeneration.

INTRODUCTION: There is an urgent need for new or repurposed therapeutics that protect against or significantly delay the clinical progression of neurodegenerative diseases, such as Huntington's disease (HD), Parkinson's disease and Alzheimer's disease. In particular, preclinical studies are needed for well tolerated and brain-penetrating small molecules capable of mitigating the proteotoxic mitochondrial processes that are hallmarks of these diseases. We identified a unique suicide inhibitor of mitochondrial proline dehydrogenase (Prodh), N-propargylglycine (N-PPG), which has anticancer and brain-enhancing mitohormesis properties, and we hypothesize that induction of mitohormesis by N-PPG protects against neurodegenerative diseases. We carried out a series of mouse studies designed to: i) compare brain and metabolic responses while on oral N-PPG treatment (50 mg/kg, 9-14 days) of B6CBA wildtype (WT) and short-lived transgenic R6/2 (HD) mice; and ii) evaluate potential brain and systemwide stress rebound responses in WT mice 2 months after cessation of extended mitohormesis induction by well-tolerated higher doses of N-PPG (100-200 mg/kg x 60 days). WT and HD mice showed comparable global evidence of N-PPG induced brain mitohormesis characterized by Prodh protein decay and increased mitochondrial expression of chaperone and Yme1l1 protease proteins. Interestingly, transcriptional analysis (RNAseq) showed partial normalization of HD whole brain transcriptomes toward those of WT mice. Comprehensive metabolomic profiles performed on control and N-PPG treated blood, brain, and kidney samples revealed expected N-PPG-induced tissue increases in proline levels in both WT and HD mice, accompanied by surprising parallel increases in hydroxyproline and sarcosine. Two months after cessation of the higher dose N-PPG stress treatments, WT mouse brains showed robust rebound increases in Prodh protein levels and mitochondrial transcriptome responses, as well as altered profiles of blood amino acid-related metabolites. Our HD and WT mouse preclinical findings point to the brain penetrating and mitohormesis-inducing potential of the drug candidate, N-PPG, and provide new rationale and application insights supporting its further preclinical testing in various models of neurodegenerative diseases characterized by loss of mitochondrial proteostasis.

Health equity, care access and quality in headache - part 2.

BACKGROUND: Headache disorders are a global public health concern affecting diverse populations. This review examines headache service organizations in low-, middle-, and high-income countries. It addresses global challenges in pharmacological headache treatment, with a focus on safety, tolerability, reproductive and child health, and outlines disparities in accessing innovative treatments worldwide. MAIN BODY: Organized headache services are essential due to the wide prevalence and varying severity of headache disorders. The tiered headache service model is globally recognized, although its implementation varies based on financial and workforce considerations. Headache burden affects well-being, causing disability, economic challenges, and work limitations, irrespective of location or income. All nations still require improved diagnosis and treatment, and the majority of countries face obstacles including limited access, awareness, economic barriers, and inadequate health policies. Provided adequate internet availability, telemedicine could help improve health equity by expanding access to headache care, since it can offer patients access to services without lengthy waiting times or extensive travel and can provide healthcare unavailable in underserved areas due to staff shortages. Numerous health disparities restrict global access to many headache medications, especially impacting individuals historically excluded from randomized controlled trials, such as those with cardiovascular and cerebrovascular conditions, as well as pregnant women. Furthermore, despite advancements in researching migraine treatments for young patients, the options for treatment remain limited. Access to headache treatment relies on factors like medication availability, approval, financial coverage, and healthcare provider expertise. Inadequate public awareness leads to neglect by policymakers and undertreatment by patients and healthcare providers. Global access discrepancies are exacerbated by the introduction of novel disease-specific medications, particularly impacting Asian, African, and Latin American nations excluded from clinical trials. While North America and Europe experience broad availability of migraine treatments, the majority of countries worldwide lack access to these therapies. CONCLUSIONS: Healthcare disparities, treatment access, and medication availability are concerning issues in headache medicine. Variations in national healthcare systems impact headache management, and costly innovative drugs are widening these gaps. Healthcare practitioners and experts should acknowledge these challenges and work towards minimizing access barriers for equitable global headache care in the future.

Mode and site of action of therapies targeting CGRP signaling.

Targeting CGRP has proved to be efficacious, tolerable, and safe to treat migraine; however, many patients with migraine do not benefit from drugs that antagonize the CGRPergic system. Therefore, this review focuses on summarizing the general pharmacology of the different types of treatments currently available, which target directly or indirectly the CGRP receptor or its ligand. Moreover, the latest evidence regarding the selectivity and site of action of CGRP small molecule antagonists (gepants) and monoclonal antibodies is critically discussed. Finally, the reasons behind non-responders to anti-CGRP drugs and rationale for combining and/or switching between these therapies are addressed.

Difference in ketone bodies levels between diurnal and nocturnal fasting in children: observational study

Introduction Children are susceptible to developing preoperative ketonemia, which can be affected by changes in the circadian rhythm and counter-regulatory hormones. It is unclear whether ketonemia depends on the timing of fasting. Objective To assess the effect of preoperative fasting time (diurnal vs. night) on the preoperative concentration of ketone bodies in children. Methods We conducted a prospective-observational clinical study between September 2020 and March 2021, including children under 48 months of age scheduled for elective surgery. Two groups were identified based on fasting time, as follows: diurnal fasting (group A, n = 40) and nocturnal fasting (group B, n = 52). Demographic data, duration of fasting, time of excess fasting, type of food intake, the concentration of ketone bodies and capillary blood glucose, level of anxiety, and dehydration were analyzed in both groups. Results Diurnal fasting was associated with higher incidence of ketonemia compared with nocturnal fasting (Group A: 62.5% (95% CI 48.1-82.0); group B: 38,5% (95% CI 26.5-52.5), P=0.02). Most of the patients exceeded the duration of fasting recommended by preoperative fasting guidelines (95.6%). The type of food eaten before surgery was significantly associated with the presence of ketonemia (P=0.01). Conclusions Preoperative ketonemia is relatively common in patients under 48 months of age, especially among those who undergo diurnal fasting compared to nocturnal fasting.

Introducción Los niños son susceptibles a desarrollar cetonemia preoperatoria que puede verse afectada por cambios en el ritmo circadiano y las hormonas contrarreguladoras. No está claro si la cetonemia depende de la hora del ayuno. Objetivo Evaluar el efecto del momento del ayuno preoperatorio (diurno vs. nocturno) sobre la concentración preoperatoria de los cuerpos cetónicos en niños. Métodos Llevamos a cabo un estudio clínico observacional entre septiembre de 2020 y marzo de 2021, en niños menores de 48 meses, programados para cirugía electiva. Se identificaron dos grupos basados en la hora del ayuno, como sigue: ayuno diurno (grupo A, n = 40) y ayuno nocturno (grupo B, n = 52). En ambos grupos se analizaron los datos demográficos, la duración del ayuno, el tiempo excesivo de ayuno, el tipo de ingesta de alimentos, la concentración de cuerpos cetónicos, la glicemia capilar, el nivel de ansiedad y la deshidratación. Resultados El ayuno diurno se asocio con una mayor incidencia de cenotemia en comparación con el ayuno nocturno (Grupo A: 62,5% (IC 95% 48,1-82,0); grupo B: 38,5% (95% CI 26.5-52.5), P=0.02). La mayoría de los pacientes excedieron el tiempo de ayuno recomendado según las guías de ayuno preoperatorio (95,6%). El tipo de alimentos ingeridos antes de la cirugía se asoció de manera importante con la presencia de cetonemia (P=0,01). Conclusiones La cetonemia preoperatoria es relativamente común en pacientes menores de 48 meses de edad, especialmente entre quienes se someten a ayuno diurno en comparación con ayuno nocturno.

Calcitonin/PAC1 receptor splice variants: a blind spot in migraine research.

The neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) and their receptors are linked to migraine neurobiology. Recent antimigraine therapeutics targeting the signaling of these neuropeptides are effective; however, some patients respond suboptimally, indicating an incomplete understanding of migraine pathophysiology. The CGRP- and PACAP-responsive receptors can be differentially spliced. It is known that receptor splice variants can have different pathophysiological effects in other receptor-mediated pain pathways. Despite considerable knowledge on the structural and pharmacological differences of the CGRP- and PACAP-responsive receptor splice variants and their expression in migraine-relevant tissues, their role in migraine is rarely considered. Here we shine a spotlight on the calcitonin and PACAP (PAC1) receptor splice variants and examine what implications they may have for drug activity and design.

Antioxidants in Traditional Mexican Medicine and Their Applications as Antitumor Treatments.

Traditional medicine in Latin America and mainly in Mexico represents an essential alternative for treating different diseases. The use of plants as medicine is the product of a rich cultural tradition of the indigenous peoples, in which a great variety of species are used for the treatment of gastrointestinal, respiratory, and mental diseases and some other sicknesses; the therapeutic efficacy that they possess is due to the properties that derive from the active ingredients of plants principally antioxidants, such as phenolic compounds, flavonoids, terpenes, and tannins. An antioxidant is a substance that, at low concentrations, delays or prevents substrate oxidation through the exchange of electrons. Different methods are used to determine the antioxidant activity and the most commonly used are described in the review. Cancer is a disease in which some cells multiply uncontrollably and spread to other parts of the body, a process known as metastasis. These cells can lead to the formation of tumors, which are lumps of tissue that can be cancerous (malignant) or noncancerous (benign). Generally, the treatment of this disease consists of surgery, radiotherapy, or chemotherapy, which have side effects that decrease the quality of life of patients, so new treatments, focusing on natural resources such as plants, can be developed. This review aims to gather scientific evidence on the antioxidant compounds present in plants used in traditional Mexican medicine, specifically as antitumor treatment in the most common cancer types worldwide (e.g., breast, liver, and colorectal cancer).

Impact and Sustainability of Foreign Medical Aid: A Qualitative Study with Honduran Healthcare Providers.

Background: There is growing concern about the sustainability and long-term impact of short-term medical missions (STMMs)-an increasingly common form of foreign medical aid-given that brief engagements do little to address the underlying poverty and fragmented healthcare system that plagues many low- and middle-income countries (LMICs). In the absence of formal evaluations, unintended but serious consequences for patients and local communities may arise, including a lack of continuity of patient care, poor alignment with community needs, and cultural and language barriers. Objective: We conducted semi-structured interviews with Honduran healthcare providers (n = 88) in 2015 to explore local providers' perceptions of the impact and sustainability of foreign medical aid on patient needs, community health, and the country's healthcare system. Methods: Respondents represented a random sample of Honduran healthcare providers (physicians, dentists, nurses) who worked for either a government-run rural clinic or non-governmental organization (NGO) in Honduras. Findings: Honduran healthcare providers largely framed foreign medical teams as being assets that help to advance community health through the provision of medical personnel and supplies. Nonetheless, most respondents identified strategies to improve implementation of STMMs and reduce negative impacts. Many respondents emphasized a need for culturally- and linguistically-tailored medical care and health education interventions. Participants also recommended strengthening local partnerships to mitigate the risk of dependence, including on-going training and support of community health workers to promote sustainable change. Conclusions: Guidelines informed by local Honduran expertise are needed to increase accountability for more robust training of foreign physicians in the provision of context-appropriate care. These findings provide valuable local perspectives from Honduran healthcare providers to improve the development and implementation of STMMs, informing strategies that can complement and strengthen healthcare systems in LMICs.

Proteomic Analysis of Huntington's Disease Medium Spiny Neurons Identifies Alterations in Lipid Droplets.

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin (HTT) gene. The resulting polyglutamine (polyQ) tract alters the function of the HTT protein. Although HTT is expressed in different tissues, the medium-spiny projection neurons (MSNs) in the striatum are particularly vulnerable in HD. Thus, we sought to define the proteome of human HD patient-derived MSNs. We differentiated HD72-induced pluripotent stem cells and isogenic controls into MSNs and carried out quantitative proteomic analysis. Using data-dependent acquisitions with FAIMS for label-free quantification on the Orbitrap Lumos mass spectrometer, we identified 6323 proteins with at least two unique peptides. Of these, 901 proteins were altered significantly more in the HD72-MSNs than in isogenic controls. Functional enrichment analysis of upregulated proteins demonstrated extracellular matrix and DNA signaling (DNA replication pathway, double-strand break repair, G1/S transition) with the highest significance. Conversely, processes associated with the downregulated proteins included neurogenesis-axogenesis, the brain-derived neurotrophic factor-signaling pathway, Ephrin-A:EphA pathway, regulation of synaptic plasticity, triglyceride homeostasis cholesterol, plasmid lipoprotein particle immune response, interferon-γ signaling, immune system major histocompatibility complex, lipid metabolism, and cellular response to stimulus. Moreover, proteins involved in the formation and maintenance of axons, dendrites, and synapses (e.g., septin protein members) were dysregulated in HD72-MSNs. Importantly, lipid metabolism pathways were altered, and using quantitative image analysis, we found that lipid droplets accumulated in the HD72-MSN, suggesting a deficit in the turnover of lipids possibly through lipophagy. Our proteomics analysis of HD72-MSNs identified relevant pathways that are altered in MSNs and confirm current and new therapeutic targets for HD.

Antibiotic resistance patterns in infections associated with health care in a Third Level Center with hospital reconversion in the COVID-19 pandemic / Patrones de resistencia a antibióticos en infecciones asociadas a la atención de salud en un centro de tercer nivel con reconversión hospitalaria en la pandemia por COVID-19

Objetive: Description of the different isolated microorganisms and their prevalence in infections associated with health care, in addition to determining their patterns of resistance to antibiotics in patients admitted with a confirmed or suspected diagnosis of COVID-19 in the Intensive Care Unit, during a third-level medical center with hospital reconversion.Method: Patient demographic data was obtained from the clinical record, with defined criteria. Antibiotic resistance patterns were evaluated as well as the identification of isolated bacteria in cultures of expectoration, pleural fluid, catheter tips. For bacterial identification and resistance mechanisms, automated equipment and phenotypic tests were used, following the CLSI (Clinical & Laboratory Standards Institute) criteria.Results: A total of 100 patients with bacterial infection added to the main COVID-19 picture were obtained, representing pneumonia, urinary tract infection, catheter infections and bacteremia. A total of 100 strains were isolated, of which 84 are Extremely Drug Resistant, 12 Multidrug Resistant and only 4 variable sensitivity. The bacteria with the highest prevalence is Staphylococcus aureus with, followed by Pseudonomas aeruginosa and Stenotrophomonas maltophilia. 100% of the patients admitted to the ICU (Intensive Care Unit) had death.Conclusion: The increase in resistance to antibiotics in the COVID-19 pandemic has set off alarms due to the complication that this brings, and the improper use of drugs as prophylaxis or attempted treatment only generates selective pressure that leads to an increase in resistance as observed in the isolated strains in this study, where the vast majority present enzymes as well as other resistance mechanisms that confer them to be XDR (Extremely Drug Resistant). (AU)

Objetivo: Descripción de los diferentes microorganismos aislados y su prevalencia en infecciones asociadas a la atención de la salud, además de determinar sus patrones de resistencia a antibióticos en pacientes ingresados con diagnóstico confirmado o sospechado de COVID-19 en la Unidad de Cuidados Intensivos, en Centro médico de tercer nivel con reconversión hospitalaria.Método: Los datos demográficos de los pacientes se obtuvieron de la historia clínica, con criterios definidos. Se evaluaron patrones de resistencia a antibióticos, así como la identificación de bacterias aisladas en cultivos de expectoración, líquido pleural, puntas de catéter. Para la identificación bacteriana y los mecanismos de resistencia se utilizaron equipos automatizados y pruebas fenotípicas, siguiendo los criterios del CLSI (Clinical & Laboratory Standards Institute).Resultados: Se estudió un total de 100 pacientes con infección bacteriana sumado al cuadro principal de COVID-19, de los cuales representó neumonía, infección de vías urinarias, infecciones de catéter y bacteriemia. Se aislaron un total de 100 cepas, de las cuales 84 son Extremadamente Resistentes, 12 Multirresistentes y solo 4 de sensibilidad variable. La bacteria con mayor prevalencia es Staphylococcus aureus, seguida de Pseudonomas aeruginosa y Stenotrophomonas maltophilia. El 100% de los pacientes ingresados en UCI (Unidad de Cuidados Intensivos) tuvieron muerte.Conclusión: El aumento de las resistencias a los antibióticos en la pandemia de COVID-19 ha hecho saltar las alarmas por la complicación que esto trae consigo, y el uso inadecuado de fármacos como profilaxis o intento de tratamiento solo genera una presión selectiva que conduce a un aumento de las resistencias como se observa en las cepas aisladas en este estudio, donde la gran mayoría presenta enzimas así como otros mecanismos de resistencia que les confieren ser XDR (Extremadamente Resistente). (AU)

Comparative Study between Two Simple Synthesis Methods for Obtaining Green Gold Nanoparticles Decorating Silica Particles with Antibacterial Activity.

The SiO2 particles system is one of the most common ways to protect colloidal metal systems, such as gold nanoparticles, from aggregation and activity loss due to their high chemical stability and low reactivity. In this study, silica green gold nanoparticles (AuNPs synthesized with mullein extract) were fabricated using two different sol-gel methods. The nanoparticles were characterized by Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Fourier Transformed Infrared (FTIR), and the antibacterial activity against pathogens (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella enterica). Synthesis-1 nanoparticles had a kidney-shaped form and uniform distribution, while synthesis-2 nanoparticles had a spherical and non-uniform form. Characterization showed that temperature is an important factor in the distribution of AuNPs in silica; a decrease allowed the formation of Janus-type, and an increase showed a higher concentration of gold in energy-dispersive spectroscopy (EDS) analysis. Overall, similar bands of the two synthesis silica nanoparticles were observed in FTIR, while XRD spectra showed differences in the preferential growth in AuNPs depending on the synthesis. Higher antibacterial activity was observed against S. aureus, which was followed by L. monocytogenes. No differences were observed in the antibacterial activity between the two different sol-gel methods.

Flow cytometry analysis of CD11c-positive peripheral blood mononuclear cells in horses.

Horses have played a prominent role in shaping our modern world, with important effects on health. Unfortunately, better characterization of the horse immune system is still needed. In this report, using flow cytometry techniques, four monoclonal antibodies against horse CD11c integrin were characterized and described for their ability to provide a positive recognition signal in peripheral blood mononuclear cells. Further immune cell phenotype experiments were performed using MHC-II, CD14, TLR4 and the specific anti-horse CD11c monoclonal antibody (1C4). With this staining panel, it was possible to detect a cell population defined by CD11c+MHC-II+TLR4+CD14low, which could be considered as putative dendritic cells. This manuscript shows that a new monoclonal antibody (1C4) can be used for the characterization of dendritic cells and their different lineages, opening the possibility of better understanding the mechanisms of immunity in horses.

Gold Nanoparticles Synthesized with Common Mullein (Verbascum thapsus) and Castor Bean (Ricinus communis) Ethanolic Extracts Displayed Antiproliferative Effects and Induced Caspase 3 Activity in Human HT29 and SW480 Cancer Cells.

Gold nanoparticles (AuNPs) are promising nanomaterials exhibiting anti-cancer effects. Green AuNPs synthesis using plant extracts can be used to achieve stable and beneficial nanoparticles due to their content of bioactive compounds. This research aimed to synthesize and evaluate the antiproliferative and caspase-3 activity induction of green AuNPs synthesized with common mullein (V. thapsus) flowers (AuNPsME) and castor bean (R. communis) leaves (AuNPsCE) ethanolic extracts in human HT29 and SW480 colorectal cancer cells. Their effect was compared with chemically synthesized AuNPs (AuNPsCS). The extracts mainly contained p-coumaric acid (71.88-79.93 µg/g), ferulic acid (19.07-310.71 µg/g), and rutin (8.14-13.31 µg/g). The obtained nanoparticles presented typical FT-IR bands confirming the inclusion of polyphenols from V. thapsus and R. communis and spherical/quasi-spherical morphologies with diameters in the 20.06-37.14 nm range. The nanoparticles (20-200 µg/mL) showed antiproliferative effects in both cell lines, with AuNPsCE being the most potent (IC50 HT29: 110.10 and IC50SW480: 64.57 µg/mL). The AuNPsCS showed the lowest intracellular reactive oxygen species (ROS) generation in SW480 cells. All treatments induced caspase 3/7 activity to a similar or greater extent than 30 mM H2O2-treated cells. Results indicated the suitability of V. thapsus and R. communis extracts to synthesize AuNPs, displaying a stronger antiproliferative effect than AuNPsCS.

Chitosan-G-Glycidyl Methacrylate/Au Nanocomposites Promote Accelerated Skin Wound Healing.

Herein, we report the synthesis of Au nanoparticles (AuNPs) in chitosan (CTS) solution by chemically reducing HAuCl4. CTS was further functionalized with glycidyl methacrylate (chitosan-g-glycidyl methacrylate/AuNP, CTS-g-GMA/AuNP) to improve the mechanical properties for cellular regeneration requirements of CTS-g-GMA/AuNP. Our nanocomposites promote excellent cellular viability and have a positive effect on cytokine regulation in the inflammatory and anti-inflammatory response of skin cells. After 40 days of nanocomposite exposure to a skin wound, we showed that our films have a greater skin wound healing capacity than a commercial film (TheraForm®), and the presence of the collagen allows better cosmetic ave aspects in skin regeneration in comparison with a nanocomposite with an absence of this protein. Electrical percolation phenomena in such nanocomposites were used as guiding tools for the best nanocomposite performance. Our results suggest that chitosan-based Au nanocomposites show great potential for skin wound repair.

Considerations in the use of processing fluids for the detection of PRRSV RNA and antibody.

Surveillance is mandatory for tracking the progress of porcine reproductive and respiratory syndrome virus (PRRSV) control and elimination efforts in breeding herds. Processing fluids, the fluid recovered from tissues collected at castration and/or tail docking, are used for breeding herd surveillance by large segments of the industry, but the basic diagnostic characteristics of processing fluids are largely undescribed. We undertook 3 studies to address this information gap. In study 1, we found no differences among the PRRSV RT-rtPCR results obtained with 4 commercial RNA extraction kits. In study 2, we found that PRRSV RNA was highly stable in processing fluid samples at -20°C or 4°C, but detrimental effects were observed at ≥22°C within 24 h. In study 3, using a modified PRRSV ELISA at a sample:positive cutoff of ≥0.5, we found excellent discrimination in the detection of PRRSV antibody (IgM, IgA, IgG) in processing fluids from herds of known PRRSV status. Judicious handling of processing fluid samples from sow herds, and the use of methods available in veterinary diagnostic laboratories, can provide a foundation for reliable PRRSV surveillance.

Long COVID headache.

Headache is among the most frequent symptoms persisting or newly developing after coronavirus disease 2019 (COVID-19) as part of the so-called long COVID syndrome. The knowledge on long COVID headache is still limited, however growing evidence is defining the features of this novel condition, in particular regarding clinical characteristics, some pathophysiological mechanisms and first treatment recommendations. Long COVID headache can present in the form of worsening of a preexisting primary headache, or, more specifically, in the form of a new (intermittent or daily) headache starting during the acute infection or after a delay. It often presents together with other long COVID symptoms, most frequently with hyposmia. It can manifest with a migrainous or, more frequently, with a tension-type-like phenotype. Persistent activation of the immune system and trigeminovascular activation are thought to play a role. As there are virtually no treatment studies, treatment currently is largely guided by the existing guidelines for primary headaches with the corresponding phenotype. The present report, a collaborative work of the international group of the Junior Editorial Board of The Journal of Headache and Pain aims to summarize the most recent evidence about long COVID headache and suggests approaches to the diagnosis and treatment of this disorder.

Invited review: strategic adoption of antibiotic-free pork production: the importance of a holistic approach.

The discovery of the use of antibiotics to enhance growth in the 1950s proved to be one of the most dramatic and influential in the history of animal agriculture. Antibiotics have served animal agriculture, as well as human and animal medicine, well for more than seven decades, but emerging from this tremendous success has been the phenomenon of antimicrobial resistance. Consequently, human medicine and animal agriculture are being called upon, through legislation and/or marketplace demands, to reduce or eliminate antibiotics as growth promotants and even as therapeutics. As explained in this review, adoption of antibiotic-free (ABF) pork production would represent a sea change. By identifying key areas requiring attention, the clear message of this review is that success with ABF production, also referred to as "no antibiotics ever," demands a multifaceted and multidisciplinary approach. Too frequently, the topic has been approached in a piecemeal fashion by considering only one aspect of production, such as the use of certain feed additives or the adjustment in health management. Based on the literature and on practical experience, a more holistic approach is essential. It will require the modification of diet formulations to not only provide essential nutrients and energy, but to also maximize the effectiveness of normal immunological and physiological capabilities that support good health. It must also include the selection of effective non-antibiotic feed additives along with functional ingredients that have been shown to improve the utility and architecture of the gastrointestinal tract, to improve the microbiome, and to support the immune system. This holistic approach will require refining animal management strategies, including selection for more robust genetics, greater focus on care during the particularly sensitive perinatal and post-weaning periods, and practices that minimize social and environmental stressors. A clear strategy is needed to reduce pathogen load in the barn, such as greater emphasis on hygiene and biosecurity, adoption of a strategic vaccine program and the universal adoption of all-in-all-out housing. Of course, overall health management of the herd, as well as the details of animal flows, cannot be ignored. These management areas will support the basic biology of the pig in avoiding or, where necessary, overcoming pathogen challenges without the need for antibiotics, or at least with reduced usage.