JOINTLESS Maintains Inflorescence Meristem Identity in Tomato.

JOINTLESS (J) was isolated in tomato (Solanum lycopersicum) from mutants lacking a flower pedicel abscission zone (AZ), and encodes a MADS-box protein of the SVP/AGL24 sub-family. The loss of J function also causes the return to leaf initiation in the inflorescences, indicating a pivotal role in inflorescence meristem identity. Here, we compared j mutants in different accessions that exhibit either an indeterminate shoot growth, producing regular sympodial segments, or a determinate shoot growth, due to the reduction of sympodial segments and causal mutation of the SELF PRUNING (SP) gene. We observed that the inflorescence phenotype of j mutants is stronger in indeterminate (SP) accessions such as Ailsa Craig (AC), than in determinate (sp) ones, such as Heinz (Hz). Moreover, RNA-seq analysis revealed that the return to vegetative fate in j mutants is accompanied by expression of SP, which supports conversion of the inflorescence meristem to sympodial shoot meristem in j inflorescences. Other markers of vegetative meristems such as APETALA2c, and branching genes such as BRANCHED 1 (BRC1a/b) were differentially expressed in the inflorescences of j(AC) mutants. We also found in the indeterminate AC accession that J represses homeotic genes of B- and C-classes, and that its overexpression causes an oversized leafy calyx phenotype and has a dominant negative effect on AZ formation. A model is therefore proposed where J, by repressing shoot fate and influencing reproductive organ formation, acts as a key determinant of inflorescence meristems.

Reflections on the Triptych of Meristems That Build Flowering Branches in Tomato.

Branching is an important component determining crop yield. In tomato, the sympodial pattern of shoot and inflorescence branching is initiated at floral transition and involves the precise regulation of three very close meristems: (i) the shoot apical meristem (SAM) that undergoes the first transition to flower meristem (FM) fate, (ii) the inflorescence sympodial meristem (SIM) that emerges on its flank and remains transiently indeterminate to continue flower initiation, and (iii) the shoot sympodial meristem (SYM), which is initiated at the axil of the youngest leaf primordium and takes over shoot growth before forming itself the next inflorescence. The proper fate of each type of meristems involves the spatiotemporal regulation of FM genes, since they all eventually terminate in a flower, but also the transient repression of other fates since conversions are observed in different mutants. In this paper, we summarize the current knowledge about the genetic determinants of meristem fate in tomato and share the reflections that led us to identify sepal and flower abscission zone initiation as a critical stage of FM development that affects the branching of the inflorescence.

LED color gradient as a new screening tool for rapid phenotyping of plant responses to light quality.

BACKGROUND: The increasing demand for local food production is fueling high interest in the development of controlled environment agriculture. In particular, LED technology brings energy-saving advantages together with the possibility of manipulating plant phenotypes through light quality control. However, optimizing light quality is required for each cultivated plant and specific purpose. FINDINGS: This article shows that the combination of LED gradient set-ups with imaging-based non-destructive plant phenotyping constitutes an interesting new screening tool with the potential to improve speed, logistics, and information output. To validate this concept, an experiment was performed to evaluate the effects of a complete range of red:blue ratios on 7 plant species: Arabidopsis thaliana, Brachypodium distachyon, Euphorbia peplus, Ocimum basilicum, Oryza sativa, Solanum lycopersicum, and Setaria viridis. Plants were exposed during 30 days to the light gradient and showed significant, but species-dependent, responses in terms of dimension, shape, and color. A time-series analysis of phenotypic descriptors highlighted growth changes but also transient responses of plant shapes to the red:blue ratio. CONCLUSION: This approach, which generated a large reusable dataset, can be adapted for addressing specific needs in crop production or fundamental questions in photobiology.

Hydration may reverse most symptoms of lower extremity intermittent claudication or rest pain.

BACKGROUND: Medical treatment of severe intermittent claudication or critical limb-threatening ischemia causing rest pain frequently achieves only partial relief or is not effective at all. METHODS: Patients with severe intermittent claudication or rest pain of the lower extremities who did not improve after control of risk factors, supervised exercises, and cilostazol medication were included in this study. All patients were treated with hydration. They were asked to drink 2500 mL of fluids (water, soup, milk) during a 24-hour period and to ingest 0.6 g/kg of albumin a day, as egg white or albumin powder. Total salt administered daily was 3.5 g. Symptoms, skin temperature, ankle-brachial index, albumin concentration in serum, and time and distance to claudication were recorded before treatment, at 6 weeks, and at 6 months. Electrolytes were measured monthly. No additional treatment was used during the study. Walking was encouraged but not supervised. The trial has continued indefinitely. For statistical analysis, SPSS software (IBM Corp, Armonk, NY) was used. The Ethical Committee approved the protocol, and an informed consent was signed by all patients. RESULTS: There were 132 patients (94 male, 38 female) included in the study. Median age was 72.5 years (range, 67-77 years); all had severe claudication of a mean of 100 meters or rest pain. Symptoms had been present for >5 months in all patients; 22 (16.8%) had rest pain. Proper hydration, determined as drinking at least 2000 mL of water during 24 hours for a period of 6 months, was achieved in 131 compliant patients. Only one patient failed to drink 2000 mL of water or more. Ankle-brachial index in 131 compliant patients improved from 0.6 to 0.75 (P < .0001) after 6 months. Skin temperature of the feet increased from 29.4°C to 31.7°C (P = .009). Distance to claudication using the treadmill improved from 100 meters to 535 meters (P < .0001) at 6 weeks and remained stable at 6 month in 65.83% of the patients; in 34.17% of them, distance to claudication increased further by 200 (100-500) meters and time to claudication improved from 1.3 to 6.3 minutes (P < .0001) at 6 weeks, but the same group of patients (34.17%) that increased the distance to claudication further prolonged the time to claudication by 2.49 (1.24-6.23) minutes. All 131 compliant patients improved their status related to lower extremity ischemia; the noncompliant patient did not have any variation of symptoms, skin temperature, ankle-brachial index, or time and distance to claudication. All patients survived the initial 6 months of treatment; afterward, three patients abandoned the treatment and four died of unrelated causes. After the 6-month control, 49% of the patients continued to improve the time and distance to claudication as well as the ankle-brachial index. The rest of the patients conserved the initial improvement. Five patients who had significantly improved the time and distance to claudication were asked to decrease water intake for 3 days. No changes in time and distance to claudication were detected. Hydration was reinitiated. CONCLUSIONS: This study suggests that proper hydration by drinking ≥2000 mL of water daily and albumin complement orally to reach 4 g/dL in serum could be included in the armamentarium of physicians treating patients with disabling claudication or rest pain caused by peripheral artery disease. Further comparative studies to assess the benefit of hydration and increasing the serum oncotic pressure are warranted.

Impact of Lymphocyte and Neutrophil Counts on Mortality Risk in Severe Community-Acquired Pneumonia with or without Septic Shock.

BACKGROUND: Community-acquired pneumonia (CAP) is a frequent cause of death worldwide. As recently described, CAP shows different biological endotypes. Improving characterization of these endotypes is needed to optimize individualized treatment of this disease. The potential value of the leukogram to assist prognosis in severe CAP has not been previously addressed. METHODS: A cohort of 710 patients with CAP admitted to the intensive care units (ICUs) at Hospital of Mataró and Parc Taulí Hospital of Sabadell was retrospectively analyzed. Patients were split in those with septic shock (n = 304) and those with no septic shock (n = 406). A single blood sample was drawn from all the patients at the time of admission to the emergency room. ICU mortality was the main outcome. RESULTS: Multivariate analysis demonstrated that lymphopenia <675 cells/mm3 or <501 cells/mm3 translated into 2.32- and 3.76-fold risk of mortality in patients with or without septic shock, respectively. In turn, neutrophil counts were associated with prognosis just in the group of patients with septic shock, where neutrophils <8850 cells/mm3 translated into 3.6-fold risk of mortality. CONCLUSION: lymphopenia is a preserved risk factor for mortality across the different clinical presentations of severe CAP (sCAP), while failing to expand circulating neutrophils counts beyond the upper limit of normality represents an incremental immunological failure observed just in those patients with the most severe form of CAP, septic shock.

ITCBio, a Clinical and Translational Research Platform.

An informatics platform has been designed, deployed and validated around the ITCBio initiative to provide support to clinical and translational research in Andalusia. To this end, an infrastructure has been developed which, in a scalable manner, incorporates functionalities aimed to facilitate the consistent definition of information models, the data reusability from electronic health records, as well as the analysis and processing of information. All this with the purpose of providing support to the different clinical and translational research processes associated with clinical trials and research projects. This initiative is based on the creation of a suite of applications that, through using standards, incorporates open-software tools intended to support these research processes. It is currently in widespread and growing use in university hospitals in which the platform is deployed.

Expression and function of TLR4- induced B1R bradykinin receptor on cardiac fibroblasts.

Cardiac fibroblasts (CF) are key cells for maintaining extracellular matrix (ECM) protein homeostasis in the heart, and for cardiac repair through CF-to-cardiac myofibroblast (CMF) differentiation. Additionally, CF play an important role in the inflammatory process after cardiac injury, and they express Toll like receptor 4 (TLR4), B1 and B2 bradykinin receptors (B1R and B2R) which are important in the inflammatory response. B1R and B2R are induced by proinflammatory cytokines and their activation by bradykinin (BK: B2R agonist) or des-arg-kallidin (DAKD: B1R agonist), induces NO and PGI2 production which is key for reducing collagen I levels. However, whether TLR4 activation regulates bradykinin receptor expression remains unknown. CF were isolated from human, neonatal rat and adult mouse heart. B1R mRNA expression was evaluated by qRT-PCR, whereas B1R, collagen, COX-2 and iNOS protein levels were evaluated by Western Blot. NO and PGI2 were evaluated by commercial kits. We report here that in CF, TLR4 activation increased B1R mRNA and protein levels, as well as COX-2 and iNOS levels. B1R mRNA levels were also induced by interleukin-1α via its cognate receptor IL-1R1. In LPS-pretreated CF the DAKD treatment induced higher responses with respect to those observed in non LPS-pretreated CF, increasing PGI2 secretion and NO production; and reducing collagen I protein levels in CF. In conclusion, no significant response to DAKD was observed (due to very low expression of B1R in CF) - but pre-activation of TLR4 in CF, conditions that significantly enhanced B1R expression, led to an additional response of DAKD.

Reversal of Lower-Extremity Intermittent Claudication and Rest Pain by Hydration.

BACKGROUND: Medical treatment of disabling intermittent claudication or critical limb-threatening ischemia causing rest pain often fails or has partial response. METHODS: In this pilot study, 36 patients (12 females) affected by disabling intermittent claudication or rest pain of the lower extremities were exposed to a daily 3-L water intake for up to 6 weeks. Cutaneous foot temperature, ankle/brachial index, time and distance of claudication, and pain intensity were recorded before and at the completion of the hydration period. RESULTS: Patients with a mean ± SE age of 71 ± 2 years (range, 40-86) had disabling claudication (less than 100 meters) for more than 5 months while 11% reported pain at rest. A 6-week water intake of more than 2,500 mL/24 hr was achieved in 35 of the 36 patients enrolled in the study. Increased water intake was associated with significant improvements in median ankle/brachial index (from 0.60 to 0.76; P < 0.0001) and skin temperature (first dorsal right toe, from 29.95°C to 30.0°C, P < 0.001). Time and distance to report claudication of supervised treadmill exercise improved from 1.25 to 6.25 min (P < 0.0001) and from 100 meters to 535 meters (P < 0.0001), respectively. CONCLUSIONS: This study suggests that hydration attained by daily water consumption of more than 2.5 L has a robust impact on reducing the symptoms of disabling claudication and rest pain caused by peripheral vascular disease.

Natural and induced loss of function mutations in SlMBP21 MADS-box gene led to jointless-2 phenotype in tomato.

Abscission is the mechanism by which plants disconnect unfertilized flowers, ripe fruits, senescent or diseased organs from the plant. In tomato, pedicel abscission is an important agronomic factor that controls yield and post-harvest fruit quality. Two non-allelic mutations, jointless (j) and jointless-2 (j-2), controlling pedicel abscission zone formation have been documented but only j-2 has been extensively used in breeding. J was shown to encode a MADS-box protein. Using a combination of physical mapping and gene expression analysis we identified a positional candidate, Solyc12g038510, associated with j-2 phenotype. Targeted knockout of Solyc12g038510, using CRISPR/Cas9 system, validated our hypothesis. Solyc12g038510 encodes the MADS-box protein SlMBP21. Molecular analysis of j-2 natural variation revealed two independent loss-of-function mutants. The first results of an insertion of a Rider retrotransposable element. The second results of a stop codon mutation that leads to a truncated protein form. To bring new insights into the role of J and J-2 in abscission zone formation, we phenotyped the single and the double mutants and the engineered alleles. We showed that J is epistatic to J-2 and that the branched inflorescences and the leafy sepals observed in accessions harboring j-2 alleles are likely the consequences of linkage drags.

Lipopolysaccharide Activates Toll-Like Receptor 4 and Prevents Cardiac Fibroblast-to-Myofibroblast Differentiation.

Bacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-ß1 (TGF-ß1), increasing alpha-smooth muscle actin (α-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-ß1 signaling was described; however, it has not been studied whether in CF and CMF the expression of α-SMA induced by TGF-ß1 is antagonized by LPS and the mechanism involved. In adult rat CF and CMF, α-SMA, ERK1/2, Akt, NF-κß, Smad3, and Smad7 protein levels were determined by western blot, TGF-ß isoforms by ELISA, and α-SMA stress fibers by immunocytochemistry. CF and CMF secrete the three TGF-ß isoforms, and the secretion levels of TGF-ß2 was affected by LPS treatment. In CF, LPS treatment decreased the protein levels of α-SMA, and this effect was prevented by TAK-242 (TLR4 inhibitor) and LY294002 (Akt inhibitor), but not by BAY 11-7082 (NF-κß inhibitor) and PD98059 (ERK1/2 inhibitor). TGF-ß1 increased α-SMA protein levels in CF, and LPS prevented partially this effect. In addition, in CMF α-SMA protein levels were decreased by LPS treatment, which was abolished by TAK-242. Finally, in CF LPS decreased the p-Smad3 phosphorylation and increased the Smad7 protein levels. LPS treatment prevents the CF-to-CMF differentiation and reverses the CMF phenotype induced by TGF-ß1, through decreasing p-Smad3 and increasing Smad7 protein levels.

Rigid urea and self-healing thiourea ethanolamine monolayers.

A series of long-tail alkyl ethanolamine analogs containing amide-, urea-, and thiourea moieties was synthesized and the behavior of the corresponding monolayers was assessed on the Langmuir-Pockels trough combined with grazing incidence X-ray diffraction experiments and complemented by computer simulations. All compounds form stable monolayers at the soft air/water interface. The phase behavior is dominated by strong intermolecular headgroup hydrogen bond networks. While the amide analog forms well-defined monolayer structures, the stronger hydrogen bonds in the urea analogs lead to the formation of small three-dimensional crystallites already during spreading due to concentration fluctuations. The hydrogen bonds in the thiourea case form a two-dimensional network, which ruptures temporarily during compression and is recovered in a self-healing process, while in the urea clusters the hydrogen bonds form a more planar framework with gliding planes keeping the structure intact during compression. Because the thiourea analogs are able to self-heal after rupture, such compounds could have interesting properties as tight, ordered, and self-healing monolayers.

Orthosis noncompliance after the Ponseti method for the treatment of idiopathic clubfeet: a relevant problem that needs reevaluation.

INTRODUCTION: Idiopathic talipes equinovarus is the most common congenital defect characterized by the presence of a congenital dysplasia of all musculoskeletal tissues distal to the knee. For many years, the treatment has been based on extensive surgery after manipulation and cast trial. Owing to poor surgical results, Ponseti developed a new treatment protocol consisting of manipulation with cast and an Achilles tenotomy. The new technique requires 4 years of orthotic management to guarantee good results. The most recent studies have emphasized how difficult it is to comply with the orthotic posttreatment protocol. Poor compliance has been attributed to parent's low educational and low income level. The purpose of the study is to evaluate if poor compliance is due to the complexity of the orthotic use or if it is related to family education, cultural, or income factors. METHOD: Fifty-three patients with 73 idiopathic talipes equinovarus feet were treated with the Ponseti technique and followed for 48 months after completing the cast treatment. There was a male predominance (72%). The mean age at presentation was 1 month (range: 1 wk to 7 mo). Twenty patients (38%) had bilateral involvement, 17 patients (32%) had right side affected, and 16 patients (30%) had the left side involved. The mean time of manipulation and casting treatment was 6 weeks (range: 4 to 10 wk). Thirty-eight patients (72%) required Achilles tenotomy as stipulated by the protocol. Recurrence was considered if there was a deterioration of the Dimeglio severity score requiring remanipulation and casting. RESULTS: Twenty-four out of 73 feet treated by our service showed the evidence of recurrence (33%). Sex, age at presentation, cast treatment duration, unilateral or bilateral, severity score, the necessity of Achilles tenotomy, family educational, or income level did not reveal any significant correlation with the recurrence risk. Noncompliance with the orthotic use showed a significant correlation with the recurrence rate. The noncompliance rate did not show any correlation with the patient demographic data or parent's education level, insurance, or cultural factors as proposed previously. CONCLUSION: The use of the brace is extremely relevant with the Ponseti technique outcome (recurrence) in the treatment of idiopathic talipes equinovarus. Noncompliance is not related to family education, cultural, or income level. The Ponseti postcasting orthotic protocol needs to be reevaluated to a less demanding option to improve outcome and brace compliance.

Remodeling of the proximal femur after varus osteotomy.

The purpose of this study was to measure the remodeling of the proximal femur after varus osteotomy and to determine the factors that may affect the degree of angular correction. In addition, we wanted to determine the degree of remodeling over time. One hundred nine varus proximal osteotomies were performed on 66 children with hip dysplasia. Neck-shaft angles were measured on preoperative, immediate postoperative, and follow-up radiographs. Remodeling of the proximal femur occurred after varus osteotomy as long as the physes of the proximal femur continued growing. Patients' remodeling varied widely; however, gender, ambulatory status, and original diagnosis had little effect on the magnitude of remodeling. Results from this study reinforce the need to follow patients with periodic hip radiographs until growth is complete.

Cerebral protection during carotid stenting using flow reversal.

BACKGROUND: Carotid angioplasty and stenting can be used in stroke prevention in high-risk patients. As embolic complications can occur during carotid angioplasty and stenting, a device was developed to protect from cerebral embolization. METHODS: Between September 1999 and May 2002, carotid angioplasty and stenting was performed in 100 patients (84 men; mean age, 69.2 years) with symptomatic (26%) or asymptomatic (74%) severe carotid artery stenosis. Wallstents were used in all cases with selective pre-dilatation. Cerebral protection devices (Parodi Anti-Emboli System [PAES], ArteriA, San Francisco, Calif) were used in all patients. All patients were evaluated by a neurologist, both before and after the procedure. According to the criteria set forth by the large trials, the occurrence of minor, major or fatal stroke and myocardial infarction (end points) within 30 days and follow-up were determined as end points. Data were collected prospectively. RESULTS: The overall perioperative stroke and death rate was 3% (1 noncorresponding minor stroke, 1 hemorrhagic stroke, and 1 cardiac event). Four patients developed postoperative transient neurologic events (three related to hemodynamic instability and the fourth due to postoperative embolization). The overall technical success rate for carotid angioplasty (protection device placed in position percutaneously) was 99%. CONCLUSION: The efficacy and safety of carotid angioplasty and stenting with PAES are confirmed. This innovative protection device may prevent the debris released by angioplasty from entering the cerebral circulation. Further investigation is warranted.

Técnica quirúrgica “calcáneo-stop” en el tratamiento del pie plano valgo flexible severo sintomático / Surgical technique calcaneum stop in the therapy of symptomatic severe flexible pie valgus

Se realizó un estudio prospectivo de intervención a 27 pacientes afectados de pie plano valgo flexible doloroso, quienes fueron intervenidos quirúrgicamente en el Hospital Pediátrico Provincial Universitario “José Luís Miranda” de Santa Clara, Villa Clara, con la utilización de la técnica “calcáneo-stop”, en el período comprendido entre enero de 1997 y diciembre de 1998, con el propósito fundamental de evaluar los resultados de los diferentes aspectos que conforman esta afección, alivio de dolor y tiempo de reincorporación a la marcha y a las actividades habituales. Se concluyó que un elevado número de pacientes (88,9 por ciento) obtuvo buenos resultados, lo que se evidenció en el alivio del dolor, corrección de las deformidades y rápido inicio de la marcha, así como reintegración a las actividades habituales. Se recomienda tener presente el empleo de esta técnica quirúrgica, por las múltiples ventajas que ofrece y el mínimo de complicaciones que a ella se asocian; debe valorarse adecuadamente la existencia del dolor y la detección de la laxitud anormal, lo que pudiera influir negativamente(AU)

Mano zamba congénita / Congenital manus valga

La mano zamba congénita es una de las afecciones ortopédicas de más difícil tratamiento. Procederemos a presentar el caso de un paciente portador de esta entidad por agenesia del radio, que fue tratado con el minifijador externo modelo RALCA. Se obtienen resultados satisfactorios, y se muestran las bondades de este sistema de fijación externa.

Enfermedad luxante de la cadera. Reultados de su tratamiento / Congenital dislocation of hip. Its treatment results

En este trabajo se realiza una revisión de 31 pacientes con enfermedad luxante de la cadera, atendidos y tratados en el Servicio de Ortopedia y Traumatología del Hospital Pediátrico Provincial Docente "José Luis Miranda" de Santa Clara, en el periodo comprendido entre enero de 1989 y junio de 1991. Se realiza un Análisis de variables importantes como edad, sexo, elementos clínicos que propiciaron el diagnóstico, clasificación, tratamiento empleado y periodo de sanidad. Se hace especial énfasis en las ventajas que reportaron el arnés de Pavlik y la órtesis de Ponseti, así como los efectos favorables que nos brindaron su colocación precoz. Se muestran los resultados finales obtenidos al tratar esta patología que continúa siendo un problema difícil que debe enfrentar el cirujano ortopédico. Se recomienda nuestro esquema de tratamiento por considerar que favorece la curación y porque acorta el periodo de rehabilitación.

Mano zamba congénita / Congenital kneed hand

La mano zamba congénita es una de las afecciones ortopédica de más difícil tratamiento. Procederemos a presentar el caso de un paciente portador de esta entidad por agenesia del radio, que fue tratado con el minifijador externo modelo RALCA. Se obtiene satisfactorios y se demuestran las bondades de este sistema de fijación externa(AU)