Diabetic foot ulcer (DFU) is a debilitating and severe manifestation ofuncontrolled and prolonged diabetes that presents as ulceration, usually locatedon the plantar aspect of the foot. Approximately 15% of individual...Diabetic foot ulcer (DFU) is a debilitating and severe manifestation ofuncontrolled and prolonged diabetes that presents as ulceration, usually locatedon the plantar aspect of the foot. Approximately 15% of individuals with diabeteswill eventually develop DFU, and 14%-24% of them will require amputation ofthe ulcerated foot due to bone infection or other ulcer-related complications. Thepathologic mechanisms underlying DFU are comprise a triad: Neuropathy,vascular insufficiency, and secondary infection due to trauma of the foot.Standard local and invasive care along with novel approaches like stem celltherapy pave the way to reduce morbidity, decrease amputations, and preventmortality from DFU. In this manuscript, we review the current literature withfocus on the pathophysiology, preventive options, and definitive management ofDFU.展开更多
Firmness is one of the most important fruit quality traits in strawberries.The postharvest shelf life of this soft fruit is highly limited by the loss of firmness,where cell wall disassembly plays an important role.Pr...Firmness is one of the most important fruit quality traits in strawberries.The postharvest shelf life of this soft fruit is highly limited by the loss of firmness,where cell wall disassembly plays an important role.Previous studies demonstrated that the polygalacturonase FaPG1 has a key role in remodelling pectins during strawberry softening.In this study,FaPG1 knockout strawberry plants have been generated using the CRISPR/Cas9 system delivered via Agrobacterium tumefaciens.Ten independent lines,cv.“Chandler”,were obtained,and all of them were successfully edited as determined by PCR amplification and T7 endonuclease assay.The targeted mutagenesis insertion and deletion rates were analyzed using targeted deep sequencing.The percentage of edited sequences varied from 47%up to almost 100%,being higher than 95%for seven of the selected lines.Phenotypic analyses showed that 7 out of the eight lines analyzed produced fruits significantly firmer than the control,ranging from 33 to 70%increase in firmness.There was a positive relationship between the degree of FaPG1 editing and the rise in fruit firmness.Minor changes were observed in other fruit quality traits,such as colour,soluble solids,titratable acidity or anthocyanin content.Edited fruits showed a reduced softening rate during postharvest,displayed a reduced transpirational water loss,and were less damaged by Botrytis cinerea inoculation.The analysis of four potential off-target sites revealed no mutation events.In conclusion,editing the FaPG1 gene using the CRISPR/Cas9 system is an efficient method for improving strawberry fruit firmness and shelf life.展开更多
Recently,the Andean subparamo in Colombia has experienced severe wildfires,but little is known about the functional composition of recovering or not after a wildfire.Therefore,we examined the functional community comp...Recently,the Andean subparamo in Colombia has experienced severe wildfires,but little is known about the functional composition of recovering or not after a wildfire.Therefore,we examined the functional community composition subparamo affected byfire in 2016.We documented how functional traits changed 31 months after the disturbance and compared them with an unburned site.We sampled from one to two years after the fire every four months,then registered all recruits in 1655m plots.New individuals were classified into strategy functional groups based on the traits of persistence and dispersal.The first group was stem type and regeneration mechanism(seedling and resprout),and the second was fruit type and dispersal mode.We investigated the degree to which functional diversity changes plant communities over time(woody and non-woody),and we compared it with an unburned site.The most relevant results showed that resprouts and seed regenerated increased post-fire time and significant differences between sampling periods.The anemochory is the most relevant dispersal mode that indicates the community capacity to colonize the new gaps opened by the fire rapidly.We discuss how wildfire appears to be a triggering factor for persistence and dispersal strategy groups in subparamo burned given their characteristics of tolerance to stress.For this reason,a greater functional divergence between the ecosystems studied post-fire recovery has been related to higher levels of biodiversity at the landscape scale due to the high degree of endemism and significant differences in species composition between paramos.展开更多
Introduction and Objectives: Since its advent in 2019, Corona Virus Disease 19 (Covid-19) has changed everyday life in many unprecedented ways. With the availability of Covid-19 vaccines, clinical practice has stepped...Introduction and Objectives: Since its advent in 2019, Corona Virus Disease 19 (Covid-19) has changed everyday life in many unprecedented ways. With the availability of Covid-19 vaccines, clinical practice has stepped gradually towards its everyday routine. The clinician, however, needs to address such concerns as “Can Covid-19 present with urinary tract symptoms predominantly?”, “Can the urinary tract develop long-term Covid-19 symptoms?”, “Can Covid-19 vaccines/drug therapy cause male infertility?” Methods: This mini-review of the current literature has been carried out by searching the Pubmed database. Results and Conclusions: Our literature review suggests that there is insufficient evidence to conclude a significant impact on the urinary tract from Covid-19 infection. There is supporting evidence that mRNA anti-SARS-CoV-2 vaccines are safe for male gonads. Research to further support these conclusions is required.展开更多
Strawberry(Fragaria×ananassa)fruits are an excellent source of L-ascorbic acid(AsA),a powerful antioxidant for plants and humans.Identifying the genetic components underlying AsA accumulation is crucial for enhan...Strawberry(Fragaria×ananassa)fruits are an excellent source of L-ascorbic acid(AsA),a powerful antioxidant for plants and humans.Identifying the genetic components underlying AsA accumulation is crucial for enhancing strawberry nutritional quality.Here,we unravel the genetic architecture of AsA accumulation using an F1 population derived from parental lines‘Candonga’and‘Senga Sengana’,adapted to distinct Southern and Northern European areas.To account for environmental effects,the F1 and parental lines were grown and phenotyped in five locations across Europe(France,Germany,Italy,Poland and Spain).Fruit AsA content displayed normal distribution typical of quantitative traits and ranged five-fold,with significant differences among genotypes and environments.AsA content in each country and the average in all of them was used in combination with 6,974 markers for quantitative trait locus(QTL)analysis.Environmentally stable QTLs for AsA content were detected in linkage group(LG)3A,LG 5A,LG 5B,LG 6B and LG 7C.Candidate genes were identified within stable QTL intervals and expression analysis in lines with contrasting AsA content suggested that GDP-L-Galactose Phosphorylase FaGGP(3A),and the chloroplast-located AsA transporter gene FaPHT4;4(7C)might be the underlying genetic factors for QTLs on LG 3A and 7C,respectively.We show that recessive alleles of FaGGP(3A)inherited from both parental lines increase fruit AsA content.Furthermore,expression of FaGGP(3A)was two-fold higher in lines with high AsA.Markers here identified represent a useful resource for efficient selection of new strawberry cultivars with increased AsA content.展开更多
Grapevine is one of the most economically important crops worldwide.However,the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres,li...Grapevine is one of the most economically important crops worldwide.However,the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres,limiting the accessibility of the repetitive sequences,the centromeric and telomeric regions,and the study of inheritance of important agronomic traits in these regions.Here,we assembled a telomere-to-telomere(T2T)gap-free reference genome for the cultivar PN40024 using PacBio HiFi long reads.The T2T reference genome(PN_T2T)is 69 Mb longer with 9018 more genes identified than the 12X.v0 version.We annotated 67%repetitive sequences,19 centromeres and 36 telomeres,and incorporated gene annotations of previous versions into the PN_T2T assembly.We detected a total of 377 gene clusters,which showed associations with complex traits,such as aroma and disease resistance.Even though PN40024 derives from nine generations of selfing,we still found nine genomic hotspots of heterozygous sites associated with biological processes,such as the oxidation–reduction process and protein phosphorylation.The fully annotated complete reference genome therefore constitutes an important resource for grapevine genetic studies and breeding programs.展开更多
Diabetes is the most important risk factors for chronic kidney disease(CKD). The risk of CKD attributable to diabetes continues to rise worldwide. Diabetic patients with CKD need complicated treatment for their metabo...Diabetes is the most important risk factors for chronic kidney disease(CKD). The risk of CKD attributable to diabetes continues to rise worldwide. Diabetic patients with CKD need complicated treatment for their metabolic disorders as well as for related comorbidities. They have to treat, often intensively, hypertension, dyslipidaemia, bone disease, anaemia, and frequently established cardiovascular disease. The treatment of hypoglycaemia in diabetic persons with CKD must tie their individual goals of glycaemia(usually less tight glycaemic control) and knowledge on the pharmacokinetics and pharmacodynamics of drugs available to a person with kidney disease. The problem is complicated from the fact that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. This results in fear of use by lack of evidence. Metformin is globally accepted as the first choice in practically all therapeutic algorithms for diabetic subjects. The advantages of metformin are low risk of hypoglycaemia, modest weight loss, effectiveness and low cost. Data of UKPDS indicate that treatment based on metformin results in less total as well cardiovascular mortality. Metformin remains the drug of choice for patients with diabetes and CKD provided that their estimate Glomerular Filtration Rate(eGFR) remains above 30 mL/min per square meter. For diabetic patients with eGFR between 30-60 mL/min per square meter more frequent monitoring of renal function and dose reduction of metformin is needed. The use of sulfonylureas, glinides and insulin carry a higher risk of hypoglycemia in these patients and must be very careful. Lower doses and slower titration of the dose is needed. Is better to avoid sulfonylureas with active hepatic metabolites, which are renally excreted. Very useful drugs for this group of patients emerge dipeptidyl peptidase 4 inhibitors. These drugs do not cause hypoglycemia and most of them(linagliptin is an exception) require dose reduction in various stages of renal disease.展开更多
The number of revision total hip arthroplasties is expected to rise as the indications for arthroplasty will expand due to the aging population. The prevalence of extensive proximal femoral bone loss is expected to in...The number of revision total hip arthroplasties is expected to rise as the indications for arthroplasty will expand due to the aging population. The prevalence of extensive proximal femoral bone loss is expected to increase subsequently. The etiology of bone loss from the proximal femur after total hip arthroplasty is multifactorial. Stress shielding, massive osteolysis, extensive loosening and history of multiple surgeries consist the most common etiologies. Reconstruction of extensive bone loss of the proximal femur during a revision hip arthroplasty is a major challenge for even the most experienced orthopaedic surgeon. The amount of femoral bone loss and the bone quality of the remaining metaphyseal and diaphyseal bone dictate the selection of appropriate reconstructive option. These include the use of impaction allografting, distal press-fit fixation, allograft-prosthesis composites and tumor megaprostheses. This review article is a concise review of the current literature and provides an algorithmic approachfor reconstruction of different types of proximal femoral bone defects.展开更多
Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmit...Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients(BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilatorinduced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.展开更多
文摘Diabetic foot ulcer (DFU) is a debilitating and severe manifestation ofuncontrolled and prolonged diabetes that presents as ulceration, usually locatedon the plantar aspect of the foot. Approximately 15% of individuals with diabeteswill eventually develop DFU, and 14%-24% of them will require amputation ofthe ulcerated foot due to bone infection or other ulcer-related complications. Thepathologic mechanisms underlying DFU are comprise a triad: Neuropathy,vascular insufficiency, and secondary infection due to trauma of the foot.Standard local and invasive care along with novel approaches like stem celltherapy pave the way to reduce morbidity, decrease amputations, and preventmortality from DFU. In this manuscript, we review the current literature withfocus on the pathophysiology, preventive options, and definitive management ofDFU.
基金supported by the Ministerio de Ciencia,Innovación y Universidades and FEDER EU funds(grant numbers AGL2017-86531-C2-1R and PID2020-118468RB-C21)the University of Malaga(grant number B1-2020_09)+1 种基金CS-R was awarded a PhD Fellowship from the Ministerio de Ciencia,Innovación y Universidades(PRE2018-085509)PhD Program Advanced Biotechnology,University of Málaga.
文摘Firmness is one of the most important fruit quality traits in strawberries.The postharvest shelf life of this soft fruit is highly limited by the loss of firmness,where cell wall disassembly plays an important role.Previous studies demonstrated that the polygalacturonase FaPG1 has a key role in remodelling pectins during strawberry softening.In this study,FaPG1 knockout strawberry plants have been generated using the CRISPR/Cas9 system delivered via Agrobacterium tumefaciens.Ten independent lines,cv.“Chandler”,were obtained,and all of them were successfully edited as determined by PCR amplification and T7 endonuclease assay.The targeted mutagenesis insertion and deletion rates were analyzed using targeted deep sequencing.The percentage of edited sequences varied from 47%up to almost 100%,being higher than 95%for seven of the selected lines.Phenotypic analyses showed that 7 out of the eight lines analyzed produced fruits significantly firmer than the control,ranging from 33 to 70%increase in firmness.There was a positive relationship between the degree of FaPG1 editing and the rise in fruit firmness.Minor changes were observed in other fruit quality traits,such as colour,soluble solids,titratable acidity or anthocyanin content.Edited fruits showed a reduced softening rate during postharvest,displayed a reduced transpirational water loss,and were less damaged by Botrytis cinerea inoculation.The analysis of four potential off-target sites revealed no mutation events.In conclusion,editing the FaPG1 gene using the CRISPR/Cas9 system is an efficient method for improving strawberry fruit firmness and shelf life.
基金Thanks to the Scientific Sub-direction of the Bogota BotanicalGarden in Colombia,which funded this research[Investment project No.1121,2016]In addition to ANID PhD fellowship,Chile[No.21190817,2019]Vicerrectoría de Investigacion,Desarrolloy Creacion Artística(VIDCA)grant from the Universidad Austral deChile[No.TD-2021-01,2021]awarded to KOZ.
文摘Recently,the Andean subparamo in Colombia has experienced severe wildfires,but little is known about the functional composition of recovering or not after a wildfire.Therefore,we examined the functional community composition subparamo affected byfire in 2016.We documented how functional traits changed 31 months after the disturbance and compared them with an unburned site.We sampled from one to two years after the fire every four months,then registered all recruits in 1655m plots.New individuals were classified into strategy functional groups based on the traits of persistence and dispersal.The first group was stem type and regeneration mechanism(seedling and resprout),and the second was fruit type and dispersal mode.We investigated the degree to which functional diversity changes plant communities over time(woody and non-woody),and we compared it with an unburned site.The most relevant results showed that resprouts and seed regenerated increased post-fire time and significant differences between sampling periods.The anemochory is the most relevant dispersal mode that indicates the community capacity to colonize the new gaps opened by the fire rapidly.We discuss how wildfire appears to be a triggering factor for persistence and dispersal strategy groups in subparamo burned given their characteristics of tolerance to stress.For this reason,a greater functional divergence between the ecosystems studied post-fire recovery has been related to higher levels of biodiversity at the landscape scale due to the high degree of endemism and significant differences in species composition between paramos.
文摘Introduction and Objectives: Since its advent in 2019, Corona Virus Disease 19 (Covid-19) has changed everyday life in many unprecedented ways. With the availability of Covid-19 vaccines, clinical practice has stepped gradually towards its everyday routine. The clinician, however, needs to address such concerns as “Can Covid-19 present with urinary tract symptoms predominantly?”, “Can the urinary tract develop long-term Covid-19 symptoms?”, “Can Covid-19 vaccines/drug therapy cause male infertility?” Methods: This mini-review of the current literature has been carried out by searching the Pubmed database. Results and Conclusions: Our literature review suggests that there is insufficient evidence to conclude a significant impact on the urinary tract from Covid-19 infection. There is supporting evidence that mRNA anti-SARS-CoV-2 vaccines are safe for male gonads. Research to further support these conclusions is required.
基金supported by the European Union’s Horizon 2020 research and innovation program(GoodBerrygrant agreement number 679303)Agencia Estatal de Investigación(PID2019-111496RR-I00/AEI/10.13039/501100011033)and PR.AVA.AVA2019.034(IFAPA,FEDER funds)。
文摘Strawberry(Fragaria×ananassa)fruits are an excellent source of L-ascorbic acid(AsA),a powerful antioxidant for plants and humans.Identifying the genetic components underlying AsA accumulation is crucial for enhancing strawberry nutritional quality.Here,we unravel the genetic architecture of AsA accumulation using an F1 population derived from parental lines‘Candonga’and‘Senga Sengana’,adapted to distinct Southern and Northern European areas.To account for environmental effects,the F1 and parental lines were grown and phenotyped in five locations across Europe(France,Germany,Italy,Poland and Spain).Fruit AsA content displayed normal distribution typical of quantitative traits and ranged five-fold,with significant differences among genotypes and environments.AsA content in each country and the average in all of them was used in combination with 6,974 markers for quantitative trait locus(QTL)analysis.Environmentally stable QTLs for AsA content were detected in linkage group(LG)3A,LG 5A,LG 5B,LG 6B and LG 7C.Candidate genes were identified within stable QTL intervals and expression analysis in lines with contrasting AsA content suggested that GDP-L-Galactose Phosphorylase FaGGP(3A),and the chloroplast-located AsA transporter gene FaPHT4;4(7C)might be the underlying genetic factors for QTLs on LG 3A and 7C,respectively.We show that recessive alleles of FaGGP(3A)inherited from both parental lines increase fruit AsA content.Furthermore,expression of FaGGP(3A)was two-fold higher in lines with high AsA.Markers here identified represent a useful resource for efficient selection of new strawberry cultivars with increased AsA content.
基金This work was supported by the National Natural Science Fund for Excellent Young Scientists Fund Program(Overseas)to Y.Z.,the National Key Research and Development Program of China(grant 2019YFA0906200)the Agricultural Science and Technology Innovation Program(CAAS-ZDRW202101)+1 种基金the Shenzhen Science and Technology Program(grant KQTD2016113010482651)the BMBF-funded de.
文摘Grapevine is one of the most economically important crops worldwide.However,the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres,limiting the accessibility of the repetitive sequences,the centromeric and telomeric regions,and the study of inheritance of important agronomic traits in these regions.Here,we assembled a telomere-to-telomere(T2T)gap-free reference genome for the cultivar PN40024 using PacBio HiFi long reads.The T2T reference genome(PN_T2T)is 69 Mb longer with 9018 more genes identified than the 12X.v0 version.We annotated 67%repetitive sequences,19 centromeres and 36 telomeres,and incorporated gene annotations of previous versions into the PN_T2T assembly.We detected a total of 377 gene clusters,which showed associations with complex traits,such as aroma and disease resistance.Even though PN40024 derives from nine generations of selfing,we still found nine genomic hotspots of heterozygous sites associated with biological processes,such as the oxidation–reduction process and protein phosphorylation.The fully annotated complete reference genome therefore constitutes an important resource for grapevine genetic studies and breeding programs.
文摘Diabetes is the most important risk factors for chronic kidney disease(CKD). The risk of CKD attributable to diabetes continues to rise worldwide. Diabetic patients with CKD need complicated treatment for their metabolic disorders as well as for related comorbidities. They have to treat, often intensively, hypertension, dyslipidaemia, bone disease, anaemia, and frequently established cardiovascular disease. The treatment of hypoglycaemia in diabetic persons with CKD must tie their individual goals of glycaemia(usually less tight glycaemic control) and knowledge on the pharmacokinetics and pharmacodynamics of drugs available to a person with kidney disease. The problem is complicated from the fact that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. This results in fear of use by lack of evidence. Metformin is globally accepted as the first choice in practically all therapeutic algorithms for diabetic subjects. The advantages of metformin are low risk of hypoglycaemia, modest weight loss, effectiveness and low cost. Data of UKPDS indicate that treatment based on metformin results in less total as well cardiovascular mortality. Metformin remains the drug of choice for patients with diabetes and CKD provided that their estimate Glomerular Filtration Rate(eGFR) remains above 30 mL/min per square meter. For diabetic patients with eGFR between 30-60 mL/min per square meter more frequent monitoring of renal function and dose reduction of metformin is needed. The use of sulfonylureas, glinides and insulin carry a higher risk of hypoglycemia in these patients and must be very careful. Lower doses and slower titration of the dose is needed. Is better to avoid sulfonylureas with active hepatic metabolites, which are renally excreted. Very useful drugs for this group of patients emerge dipeptidyl peptidase 4 inhibitors. These drugs do not cause hypoglycemia and most of them(linagliptin is an exception) require dose reduction in various stages of renal disease.
文摘The number of revision total hip arthroplasties is expected to rise as the indications for arthroplasty will expand due to the aging population. The prevalence of extensive proximal femoral bone loss is expected to increase subsequently. The etiology of bone loss from the proximal femur after total hip arthroplasty is multifactorial. Stress shielding, massive osteolysis, extensive loosening and history of multiple surgeries consist the most common etiologies. Reconstruction of extensive bone loss of the proximal femur during a revision hip arthroplasty is a major challenge for even the most experienced orthopaedic surgeon. The amount of femoral bone loss and the bone quality of the remaining metaphyseal and diaphyseal bone dictate the selection of appropriate reconstructive option. These include the use of impaction allografting, distal press-fit fixation, allograft-prosthesis composites and tumor megaprostheses. This review article is a concise review of the current literature and provides an algorithmic approachfor reconstruction of different types of proximal femoral bone defects.
文摘Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients(BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilatorinduced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.