Real-world effectiveness and safety of stereotactic body radiotherapy for liver metastases with different respiratory motion management techniques.

PURPOSE: Stereotactic body radiotherapy (SBRT) has been firmly established as a treatment choice for patients with oligometastases, as it has demonstrated both safety and efficacy by consistently achieving high rates of local control. Moreover, it offers potential survival benefits for carefully selected patients in real-world clinical settings. METHODS: Between January 2008 and May 2020, a total of 149 patients (with 414 liver metastases) received treatment. The Active Breathing Coordinator device was used for 68 patients, while respiratory gating was used for 65 and abdominal compression was used for 16 patients. The most common histological finding was colorectal adenocarcinoma, with 37.6% of patients having three or more metastases, and 18% having two metastases. The prescribed dose ranged from 36 to 60 Gy, delivered in 3-5 fractions. RESULTS: Local control rates at 2 and 3 years were 76.1% and 61.2%, respectively, with no instances of local recurrence after 3 years. Factors negatively impacting local control included colorectal histology, lower prescribed dose, and the occurrence of new liver metastases. The median overall survival from SBRT was 32 months, with the presence of metastases outside the liver and the development of new liver metastases after SBRT affecting survival. The median disease-free survival was 10 months. No substantial differences in both local control and survival were observed between the respiratory motion control techniques employed. Treatment tolerance was excellent, with only one patient experiencing acute grade IV thrombocytopenia and two patients suffering from ≥ grade II chronic toxicity. CONCLUSION: For radical management of single or multiple liver metastases, SBRT is an effective and well-tolerated treatment option. Regardless of the technology employed, experienced physicians can achieve similarly positive outcomes. However, additional studies are required to elucidate prognostic factors that can facilitate improved patient selection.

The 8-Odorant Barcelona Olfactory Test (BOT-8): Validation of a New Test in the Spanish Population During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. METHODS: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. RESULTS: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). CONCLUSION: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic.

Recycling drainage effluents using reverse osmosis powered by photovoltaic solar energy in hydroponic tomato production: Environmental footprint analysis.

Greenhouse cultivation in the Mediterranean region has undoubtedly enhanced the economic growth and has generated social benefits by making an efficient use of resources. However, these production systems caused undesirable environmental impacts. In order to move towards cleaner production in greenhouse areas, this study has assessed the potential environmental benefits and trade-offs of the integration of an on-farm reverse osmosis system powered by photovoltaic solar energy to recycle the drainage effluents from greenhouses. To that end, we compare the environmental footprint of a greenhouse tomato crop using this technology in a hydroponic system (HS), versus the conventional sanded soil 'enarenado' (CS) with free-drainage to soil. Additionally, for comparison, three independent irrigation sources (desalinated seawater with low electrical conductivity and two different mixes of underground and desalinated water, with moderate and high electrical conductivity, respectively) were evaluated. The use of desalinated seawater can help reduce the overexploitation of aquifers, although if the desalination process is not done with clean energy it also comes with a negative impact on the carbon footprint. Life Cycle Assessment (LCA) was used to analyse and evaluate six environmental impact indicators associated with these production systems and water treatments. In addition, a sensitivity analysis was conducted to explore the potential environmental benefits of increasing the use of renewable energy for desalinated water production, whilst also curbing the common over-fertilisation malpractice reported in the study area. Based on our findings, the HS with leachate treatment technology showed, compared to the CS system, a significant reduction in the eutrophication (72 %), although it did inevitably increase the depletion of fossil fuels (43 %) global warming (37 %) and acidification (32 %) impacts, due to the need for additional infrastructure and equipment. Among the inputs considered for the cultivation systems, the greenhouse structure, and the production of fertilisers and electricity for fertigation represented the highest environmental burdens. When comparing the three irrigation treatments, it was observed that the partial substitution of desalinated seawater by brackish groundwater substantially mitigated (27 %) the global warming footprint. The sensitivity analysis revealed that a significant reduction in the environmental impact is feasible.

Pediatric Barcelona Olfactory Test ̶ 6 (pBOT-6): Validation of a Combined Odor Identification and Threshold Screening Test in Healthy Spanish Children and Adolescents.

BACKGROUND AND OBJECTIVE: Few odor tests have been developed for children. Objectives: The aim of the present study was to develop and validate a simple and quick olfactory test to evaluate odor identification and threshold in a Spanish pediatric population. METHODS: The Pediatric Barcelona Olfactory Test-6 (pBOT-6) consisted of a set of 6 odorants for a forced choice identification test and a 6-dilution phenyl ethyl alcohol geometric series for the threshold test. The pBOT-6 was compared with the Universal Sniff test (a validated international pediatric smell test) in 131 healthy Spanish volunteers aged 6-17 years. A Bland-Altman plot was used to determine the agreement between the 2 tests. Reliability was analyzed in 15 volunteers using the intraclass correlation coefficient. Normative data were obtained, and 8 children diagnosed with subjective loss of smell were tested for validation. RESULTS: The Bland-Altman analysis demonstrated a minimal bias of -1.71% with upper and lower limits of agreement of -31.1% and 27.6%, respectively. The intraclass correlation coefficient was 0.83 (95%CI, 0.6-0.96) for the identification test and 0.73 (95%CI, 0.36-0.9) for the threshold test, with excellent and good consistency between measurements over time. Mean pBOT-6 scores were significantly higher in healthy volunteers than in patients with loss of smell. Discrimination between normosmia and loss of smell was achieved with a sensitivity of 96.9% and a specificity of 100%. CONCLUSIONS: pBOT-6 offers an effective and fast method that is useful in clinical routine to distinguish, with high sensitivity and specificity, between pediatric patients with normosmia and those with loss of smell.

Retroperitoneal soft-tissue sarcomas: Radiotherapy experience from a tertiary cancer center and review of current evidence.

BACKGROUND: Surgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy. PATIENTS AND METHODS: We retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months (2-114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, p = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2. CONCLUSIONS: Complementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.

MicroRNA (miR)-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution. OBJECTIVES: We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours. METHODS: Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC. RESULTS: miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. CONCLUSIONS: miR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC.

[Video-assisted sigmoidectomy as an option for Sigmoid volvulus management in the pediatric population]. / Sigmoidectomía videoasistida como opción de manejo del vólvulo del sigmoides en la población pediátrica.

INTRODUCTION: The aim of the present study was to evaluate clinical presentation and management of sigmoid volvulus in children. Sigmoid volvulus is one of the three leading causes of acute obstruction of the colon and is between 50 and 90% of all large bowel volvulus. In the pediatric population only 3 to 5% of bowel obstructions are caused by volvulus and there are less than 100 cases reported in the literature. The presence of a redundant sigmoid with a narrow mesentery (dolicosigmoide) is a prerequisite for the volvulus formation. The etiology in the pediatric population is considered secondary to the presence of a broad meso with a narrow base associated with abnormal fixation colon. Other factors include history of anorectal malformation, Prune Belly syndrome, intestinal malrotation and Hirschsprung disease. Initial management followed by endoscopic minimally invasive sigmoidectomy has proven safe and effective. MATERIALS AND METHODS: This paper presents the experience of 4 patients between 9 and 14 managed in our department in 2013, with a diagnosis of volvulus of the sigmoid, which were initially taken to a first surgical endoscopic decompression of volvulus and a second half were carried sigmoid which took place in a video-assisted. In this series, no intraoperative complications were documented and monitoring more than six months only one patient has required new interventions, in a special case because the patient has associated myopathy; inflammatory leiomioscitis, which predisposes to episodes of intestinal obstruction. CONCLUSION: We believe that endoscopic detorsion followed by an early video-assisted sigmoid is the ideal technique for the management of these patients.

INTRODUCCION: El objetivo del estudio es evaluar la presentación y el manejo del vólvulo del Colon Sigmoides (VS) en pacientes pediátricos. El (VS) es una de las tres principales causas de obstrucción aguda del colon y constituye entre el 50 y 90% de todos los vólvulos del intestino grueso. En la población pediátrica, solo del 3 al 5% de las obstrucciones intestinales son causadas por vólvulo, y son menos de 100 los casos publicados en la literatura médica. La etiología en la población pediátrica se considera secundaria a la presencia de un meso amplio con una base estrecha asociado a una fijación anormal del colon. Otros factores incluyen historia de malformación anorectal, síndrome de Prune Belly, malrotacion intestinal y enfermedad de Hirschsprung. El manejo inicial por vía endoscópica, seguido de la sigmoidectomía mínimamente invasiva, han demostrado ser seguros y efectivos. MATERIAL Y METODOS: El presente trabajo recoge la experiencia de 4 pacientes entre los 9 y 14 años manejados en nuestro servicio, en el año 2013, con diagnóstico de vólvulo del sigmoides, los cuales inicialmente fueron llevados a un primer tiempo quirúrgico para descompresión endoscópica del vólvulo y en un segundo tiempo fueron llevados a sigmoidectomía, la cual se llevó a cabo de forma videoasistida. En esta serie no se documentaron complicaciones intraoperatorias y, en el seguimiento a más de 6 meses, solo uno de los pacientes ha requerido nuevas intervenciones, en un caso especial, dado que el paciente presenta asociada una miopatía (leiomioscitis inflamatoria), la cual lo predispone a episodios de obstrucción intestinal. CONCLUSION: Consideramos que la devolvulación endoscópica seguida de una pronta sigmoidectomía videoasistida es la técnica ideal para el manejo de estos pacientes.

Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by an expanded CAG/polyglutamine repeat in the coding region of the huntingtin (htt) gene. Although HD is classically considered a motor disorder, there is now considerable evidence that early cognitive deficits appear in patients before the onset of motor disturbances. Here we demonstrate early impairment of long-term spatial and recognition memory in heterozygous HD knock-in mutant mice (Hdh(Q7/Q111)), a genetically accurate HD mouse model. Cognitive deficits are associated with reduced hippocampal expression of CREB-binding protein (CBP) and diminished levels of histone H3 acetylation. In agreement with reduced CBP, the expression of CREB/CBP target genes related to memory, such c-fos, Arc and Nr4a2, was significantly reduced in the hippocampus of Hdh(Q7/Q111) mice compared with wild-type mice. Finally, and consistent with a role of CBP in cognitive impairment in Hdh(Q7/Q111) mice, administration of the histone deacetylase inhibitor trichostatin A rescues recognition memory deficits and transcription of selective CREB/CBP target genes in Hdh(Q7/Q111) mice. These findings demonstrate an important role for CBP in cognitive dysfunction in HD and suggest the use of histone deacetylase inhibitors as a novel therapeutic strategy for the treatment of memory deficits in this disease.

Subungual squamous cell carcinoma and exostosis in third toe--case report and literature review.

BACKGROUND: Squamous cell carcinoma (SCC) in the ungual apparatus is a rare neoplasia. Although it is the most prevalent malignant tumour in this region, its diagnosis is often delayed because it is likened to benign or infectious processes. OBJECTIVES: Present a case of SCC with subungual location in a toe, and carry out a review of the literature in relation to the most important aspects of subungual SCC in toes. METHODS: We describe the case of a white woman aged 72, with SCC located in the pulp and in the distal area of the nail bed of the third toe, associated with subungual exostosis. The literature on SCC in the subungual area of toes, in all its forms under clinical or histopathological presentation, is reviewed by means of a search involving Medline, PubMed, and Google Academic, from January 1994 to December 2011. RESULTS: Only 36 cases of subungual SCC in toes were reported in the 18 years that were reviewed. The average age of cases reviewed was 58.92, and the male-to-female ratio was 2:1. The most affected toe is the hallux, in 69.4% of cases. In 50% of cases, aetiology is unknown or indeterminate; in 22.3% of cases, aetiology is metastatic; and in 19.5% of cases, it is associated with human papillomavirus (HPV). In 58.2% of cases, partial or total resection of the distal phalanx was carried out, of the entire toe, or of the osseous ray of the foot. CONCLUSIONS: Chronic tissue irritation caused by microtrauma associated with subungual exostosis is the most probable aetiology of the case presented.

Arbuscular mycorrhizal symbiosis alleviates detrimental effects of saline reclaimed water in lettuce plants.

The present study evaluated the effects of inoculation with arbuscular mycorrhizal fungi (AMF; Glomus iranicum var. tenuihypharum sp. nova) on the physiological performance and production of lettuce plants grown under greenhouse conditions and supplied with reclaimed water (RW; urban-treated wastewater with high electrical conductivity; 4.19 dS m(-1)). Four treatments, fresh water, fresh water plus AMF inoculation, RW and RW plus AMF inoculation, were applied and their effects, over time, analyzed. Root mycorrhizal colonization, plant biomass, leaf-ion content, stomatal conductance and net photosynthesis were assessed. Overall, our results highlight the significance of the AMF in alleviation of salt stress and their beneficial effects on plant growth and productivity. Inoculated plants increased the ability to acquire N, Ca, and K from both non-saline and saline media. Moreover, mycorrhization significantly reduced Na plant uptake. Under RW conditions, inoculated plants also showed a better performance of physiological parameters such as net photosynthesis, stomatal conductance and water-use efficiency than non-mycorrhizal plants. Additionally, the high concentration of nutrients already dissolved in reclaimed water suggested that adjustments in the calculation of the fertigation should be conducted by farmers. Finally, this experiment has proved that mycorrhization could be a suitable way to induce salt stress resistance in iceberg lettuce crops as plants supplied with reclaimed water satisfied minimum legal commercial size thresholds. Moreover, the maximum values of Escherichia coli in the reclaimed water were close to but never exceeded the international thresholds established (Spanish Royal Decree 1620/2007; Italian Decree, 2003) and hence lettuces were apt for sale.

Unravelling the thermodynamic properties of soil ecosystems in mature beech forests.

Thermodynamics is a vast area of knowledge with a debatable role in explaining the evolution of ecosystems. In the case of soil ecosystems, this role is still unclear due to difficulties in determining the thermodynamic functions that are involved in the survival and evolution of soils as living systems. The existing knowledge is largely based on theoretical approaches and has never been applied to soils using thermodynamic functions that have been experimentally determined. In this study, we present a method for the complete experimental thermodynamic characterization of soil organic matter. This method quantifies all the thermodynamic functions for combustion and formation reactions which are involved in the thermodynamic principles governing the evolution of the universe. We applied them to track the progress of soil organic matter with soil depth in mature beech forests. Our results show that soil organic matter evolves to a higher degree of reduction as it is mineralized, yielding products with lower carbon but higher energy content than the original organic matter used as reference. These products have higher entropy than the original one, demonstrating how the soil ecosystem evolves with depth, in accordance with the second law of thermodynamics. The results were sensitive to soil organic matter transformation in forests under different management, indicating potential applicability in elucidating the energy strategies for evolution and survival of soil systems as well as in settling their evolutionary states.

Epidemiology of musculoskeletal tumors in a reference unit. / Epidemiología de los tumores musculoesqueléticos en una unidad de referencia.

OBJECTIVE: The objective of this study was to perform an epidemiological analysis of patients presented to the Musculoskeletal Tumors Committee of a reference hospital. MATERIAL AND METHOD: A retrospective analysis of patients with sarcomas treated in a reference Sarcoma Unit between 2009 and 2022 was carried out. RESULTS: A total of 1978 patients were analyzed, of which 1477 (74.67%) were diagnosed as sarcomas. They were divided into 446 (30.20%) bone tumors and 1.031 (69.80%) soft tissue tumors. The most common benign bone tumor was enchondroma (27.23%), giant cell tumor (59.21%) was the most common tumor of intermediate malignancy and the malignant one was osteosarcoma (24.78%). The most frequently observed benign soft tissue tumor was lipoma (50.74%), the atypical lipomatous tumor (53.25%) was the most frequent tumor of intermediate malignancy and the malignant one was sarcoma of uncertain differentiation (38.10%). CONCLUSION: Our study represents the first work on the epidemiology of sarcomas and other musculoskeletal tumors in our country, being very useful to adapt the resources destined for their diagnosis and treatment.

[Translated article] Mechanical resistance of polylactic acid bone matrices developed by 3D printing for the reconstruction of bone defects.

INTRODUCTION: Bone defects are one of the main limitations in orthopaedic surgery and traumatology. For this reason, multiple bone replacement systems have been developed, either by prosthetic implant or by substitution with osteoforming substances, whose limitations are their survival and lack of structurality, respectively. The objective of this work is the generation of a new material for the creation of biologically active structures that have sufficient tensile strength to maintain the structure during remodelling. MATERIAL AND METHODS: A new filament based on the fusion of natural polylactide acid (PLA) powder was designed for the generation of pieces by means of fused deposition modelling (FDM) on which to carry out tensile mechanical tests of osteosynthesis material. A total of 13 groups with different cortical thickness, filling and layer height were carried out, with 10 tensile tests in each group, defining the tensile breaking limit for each group. The regression lines for each group and their mechanical resistance to traction on the filament used were determined. RESULTS: The filament ratio per contact surface unit with the osteosynthesis used was the main determinant of the mechanical resistance to traction, either at the expense of the increase in cortical thickness or by the increase in the percentage of cancellous bone filling. Layer height had a minor effect on tensile strength. The regression value was high for cortical thickness and cancellous filling, being elements with a predictable biomechanical behaviour. CONCLUSIONS: The new methodology allows the creation of personalised neutral and implantable PLA bone matrices for the reconstruction of large bone defects by means of 3D printing by FDM with a mechanical resistance to traction greater than that of current biological support structures.

Mechanical resistance of polylactic acid bone matrices developed by 3D printing for the reconstruction of bone defects. / Resistencia mecánica de matrices óseas de ácido poliláctico desarrolladas por impresión 3D para la reconstrucción de defectos óseos.

INTRODUCTION: Bone defects are one of the main limitations in orthopedic surgery and traumatology. For this reason, multiple bone replacement systems have been developed, either by prosthetic implant or by substitution with osteoforming substances, whose limitations are their survival and lack of structurality, respectively. The objective of this work is the generation of a new material for the creation of biologically active structures that have sufficient tensile strength to maintain the structure during remodeling. MATERIAL AND METHODS: A new filament based on the fusion of natural polylactide acid (PLA) powder was designed for the generation of pieces by means of fused deposition modeling (FDM) on which to carry out tensile mechanical tests of osteosynthesis material. A total of 13 groups with different cortical thickness, filling and layer height were carried out, with 10 tensile tests in each group, defining the tensile breaking limit for each group. The regression lines for each group and their mechanical resistance to traction on the filament used were determined. RESULTS: The filament ratio per contact surface unit with the osteosynthesis used was the main determinant of the mechanical resistance to traction, either at the expense of the increase in cortical thickness or by the increase in the percentage of cancellous bone filling. Layer height had a minor effect on tensile strength. The regression value was high for cortical thickness and cancellous filling, being elements with a predictable biomechanical behavior. CONCLUSIONS: The new methodology allows the creation of personalized neutral and implantable PLA bone matrices for the reconstruction of large bone defects by means of 3D printing by FDM with a mechanical resistance to traction greater than that of current biological support structures.

Bio-processing of agro-byproducts to animal feed.

Agricultural and food-industry residues constitute a major proportion (almost 30%) of worldwide agricultural production. These wastes mainly comprise lignocellulosic materials, fruit and vegetable wastes, sugar-industry wastes as well as animal and fisheries refuse and byproducts. Agro-residues are rich in many bioactive and nutraceutical compounds, such as polyphenolics, carotenoids and dietary fiber among others. Agro residues are a major valuable biomass and present potential solutions to problems of animal nutrition and the worldwide supply of protein and calories, if appropriate technologies can be used for their valorization by nutrient enrichment. Technologies available for protein enrichment of these wastes include solid substrate fermentation, ensiling, and high solid or slurry processes. Technologies to be developed for the reprocessing of these wastes need to take account of the peculiarities of individual wastes and the environment in which they are generated, reprocessed, and used. In particular, such technologies need to deliver products that are safe, not just for animal feed use, but also from the perspective of human feeding. This review focuses on the major current applications of solid-state fermentation in relation to the feed sector.

Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature.

BACKGROUND: Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes. CDPX2 results from mutations in EBP (emopamil binding protein), and presents with increased levels of sterol precursors 8(9)-cholesterol and 8-dehydrocholesterol. OBJECTIVES: To expand the understanding of CDPX2, clinically, biochemically and genetically. METHODS: We present one of the largest series reported to date, including 13 female patients belonging to nine Spanish families. Patients were studied biochemically using gas chromatography-mass spectrometry, genetically using polymerase chain reaction and in their methylation status using the HUMARA assay. RESULTS: In our cases, there was a clear relationship between abnormal sterol profile and the EBP gene mutation. We describe three novel mutations in the EBP gene. EBP mutations were inherited in three out of nine families and were sporadic in the remaining cases. CONCLUSIONS: No clear genotype-phenotype correlation was found. Patients' biochemical profiles did not reveal a relationship between sterol profiles and severity of disease. A skewed X-chromosome inactivation may explain the clinical phenotype in CDPX2 in some familial cases.

Expression of VAV1 in the tumour microenvironment of glioblastoma multiforme.

Even though much progress has been made towards understanding the molecular nature of glioma, the survival rates of patients affected by this tumour have not changed significantly over recent years. Better knowledge of this malignancy is still needed in order to predict its outcome and improve patient treatment. VAV1 is an GDP/GTP exchange factor for Rho/Rac proteins with oncogenic potential that is involved in the regulation of cytoskeletal dynamics and cell migration. Here we report its overexpression in 59 patients diagnosed with high-grade glioma, and the associated upregulation of a number of genes coding for proteins also involved in cell invasion- and migration-related processes. Unexpectedly, immunohistochemical experiments revealed that VAV1 is not expressed in glioma cells. Instead, VAV1 is found in non-tumoural astrocyte-like cells that are located either peritumouraly or perivascularly. We propose that the expression of VAV1 is linked to synergistic signalling cross-talk between cancer and infiltrating cells. Interestingly, we show that the pattern of expression of VAV1 could have a role in the neoplastic process in glioblastoma tumours.

Lignin analysis using microwave digestion.

Lignin quantification in apple pomace residues was carried out using a microwave oven to replace traditional refluxing during the mild acidolysis step to augment the selectivity of this step towards cleavage of lignin-carbohydrate bonds and to reduce the time needed to quantify lignin. The pressure, temperature and time were optimized by response surface methodology and the results were compared to the Klason lignin methodology. Temperature and pressure had a significant positive effect (p < 0.05) on the determination of lignin. However, the time was also significant (p < 0.05) on lignin quantification. The optimal conditions of digestion were: 30 bar, 170 °C for 15 min. The digestion using microwave (lignin content = 33 % w/w) was more accurate (p < 0.05) than the the traditional refluxing (lignin content = 27 % w/w).

Low-dose radiation therapy for hand osteoarthritis: shaking hands again?

BACKGROUND: Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. MATERIALS AND METHODS: Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5-1 Gy on every other day up to a total dose of 3-6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. RESULTS: With a median follow-up of 10.5 months (range 7.55-12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p < 0.001). Sixty-three patients needed a second course of treatment at a median time interval of 12 weeks (range 9-14). The mean VAS score before treatment was 8 (range 3-10). After treatment, it was 5 (range 1-10). After 3, 6 and 12 months, the mean VAS scores were 4 (range 0-9), 3 (range 0-9) and 3.5 (range 0-9), respectively. Seventy patients reported functionality improvements after LDRT according to the von Pannewitz score. No acute or late complications were observed. CONCLUSION: LDRT appears to be safe and useful for HOA and is associated with good rates of pain relief and functionality improvements. However, further studies are necessary to confirm these promising results.

Significant increase of CD57+ cells in pulmonary lymphoid follicles of COPD patients.

Although the presence of pulmonary lymphoid follicles (LFs) has been associated with the progression of chronic obstructive pulmonary disease (COPD), there is no information regarding the pattern of vascularisation, expression of addressins or inflammatory cell densities within these structures in COPD. Histological and immunohistochemical techniques were used to assess the prevalence, structure, localisation, vascularisation and cell proliferation/apoptosis of LFs, as well as the follicular density of B- and T-lymphocytes, macrophages, dendritic cells and CD57(+) cells, in lung tissue of nine nonsmokers, 18 smokers without COPD, 16 smokers with moderate COPD and 16 patients with very severe COPD. The density of CD57(+) cells within LFs of COPD patients was significantly increased compared to that of nonsmokers and smokers without COPD (p<0.05). Moreover, the percentage of LF profiles with cell apoptosis was also significantly higher in COPD patients (p = 0.03). By contrast, no significant differences among groups were observed in the follicular densities of other inflammatory cells, nor in the distribution of blood and lymphatic vessels within LFs. Since CD57(+) cells are important effectors of cytotoxicity and immune regulation, an increase in their follicular density supports the hypothesis of local immune dysfunction in COPD.