Peptidomimetics designed to bind to RAS effector domain are promising cancer therapeutic compounds.

Oncogenic RAS proteins are important for driving tumour formation, and for maintenance of the transformed phenotype, and thus their relevance as a cancer therapeutic target is undeniable. We focused here on obtaining peptidomimetics, which have good pharmacological properties, to block Ras-effector interaction. Computational analysis was used to identify hot spots of RAS relevant for these interactions and to screen a library of peptidomimetics. Nine compounds were synthesized and assayed for their activity as RAS inhibitors in cultured cells. Most of them induced a reduction in ERK and AKT activation by EGF, a marker of RAS activity. The most potent inhibitor disrupted Raf and PI3K interaction with oncogenic KRAS, corroborating its mechanism of action as an inhibitor of protein-protein interactions, and thus validating our computational methodology. Most interestingly, improvement of one of the compounds allowed us to obtain a peptidomimetic that decreased the survival of pancreatic cancer cell lines harbouring oncogenic KRAS.

The Gut Microbiota Metabolite Succinate Promotes Adipose Tissue Browning in Crohn's Disease.

BACKGROUND AND AIMS: Crohn's disease [CD] is associated with complex microbe-host interactions, involving changes in microbial communities, and gut barrier defects, leading to the translocation of microorganisms to surrounding adipose tissue [AT]. We evaluated the presence of beige AT depots in CD and questioned whether succinate and/or bacterial translocation promotes white-to-beige transition in adipocytes. METHODS: Visceral [VAT] and subcutaneous [SAT] AT biopsies, serum and plasma were obtained from patients with active [n = 21] or inactive [n = 12] CD, and from healthy controls [n = 15]. Adipose-derived stem cells [ASCs] and AT macrophages [ATMs] were isolated from VAT biopsies. RESULTS: Plasma succinate levels were significantly higher in patients with active CD than in controls and were intermediate in those with inactive disease. Plasma succinate correlated with the inflammatory marker high-sensitivity C-reactive protein. Expression of the succinate receptor SUCNR1 was higher in VAT, ASCs and ATMs from the active CD group than from the inactive or control groups. Succinate treatment of ASCs elevated the expression of several beige AT markers from controls and from patients with inactive disease, including uncoupling protein-1 [UCP1]. Notably, beige AT markers were prominent in ASCs from patients with active CD. Secretome profiling revealed that ASCs from patients with active disease secrete beige AT-related proteins, and co-culture assays showed that bacteria also trigger the white-to-beige switch of ASCs from patients with CD. Finally, AT depots from patients with CD exhibited a conversion from white to beige AT together with high UCP1 expression, which was corroborated by in situ thermal imaging analysis. CONCLUSIONS: Succinate and bacteria trigger white-to-beige AT transition in CD. Understanding the role of beige AT in CD might aid in the development of therapeutic or diagnostic interventions.

Effects of stem cells from inducible brown adipose tissue on diet-induced obesity in mice.

Adipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

AOA-2 Derivatives as Outer Membrane Protein A Inhibitors for Treatment of Gram-Negative Bacilli Infections.

Previously, we identified that a cyclic hexapeptide AOA-2 inhibited the interaction of Gram-negative bacilli (GNB) like Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli to host cells thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. In this work, we aimed to evaluate in vitro a library of AOA-2 derivatives in order to improve the effect of AOA-2 against GNB infections. Ten AOA-2 derivatives were synthetized for the in vitro assays. Their toxicities to human lung epithelial cells (A549 cells) for 24 h were evaluated by determining the A549 cells viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of these peptide derivatives and AOA-2 at 250, 125, 62.5, and 31.25 µg/mL on the attachment of A. baumannii ATCC 17978, P. aeruginosa PAO1 and E. coli ATCC 25922 strains to A549 cells was characterized by adherence and viability assays. None of the 10 derivatives showed toxicity to A549 cells. RW01 and RW06 have reduced more the adherence of ATCC 17978, PAO1 and ATCC 2599 strains to A549 cells when compared with the original compound AOA-2. Moreover, both peptides have increased slightly the viability of infected A549 cells by PAO1 and ATCC 25922 than those observed with AOA-2. Finally, RW01 and RW06 have potentiated the activity of colistin against ATCC 17978 strain in the same level with AOA-2. The optimization program of AOA-2 has generated two derivatives (RW01 and RW06) with best effect against interaction of GNB with host cells, specifically against P. aeruginosa and E. coli.

The matrix metalloproteinase inhibitor IPR-179 has antiseizure and antiepileptogenic effects.

Matrix metalloproteinases (MMPs) are synthesized by neurons and glia and released into the extracellular space, where they act as modulators of neuroplasticity and neuroinflammatory agents. Development of epilepsy (epileptogenesis) is associated with increased expression of MMPs, and therefore, they may represent potential therapeutic drug targets. Using quantitative PCR (qPCR) and immunohistochemistry, we studied the expression of MMPs and their endogenous inhibitors tissue inhibitors of metalloproteinases (TIMPs) in patients with status epilepticus (SE) or temporal lobe epilepsy (TLE) and in a rat TLE model. Furthermore, we tested the MMP2/9 inhibitor IPR-179 in the rapid-kindling rat model and in the intrahippocampal kainic acid mouse model. In both human and experimental epilepsy, MMP and TIMP expression were persistently dysregulated in the hippocampus compared with in controls. IPR-179 treatment reduced seizure severity in the rapid-kindling model and reduced the number of spontaneous seizures in the kainic acid model (during and up to 7 weeks after delivery) without side effects while improving cognitive behavior. Moreover, our data suggest that IPR-179 prevented an MMP2/9-dependent switch-off normally restraining network excitability during the activity period. Since increased MMP expression is a prominent hallmark of the human epileptogenic brain and the MMP inhibitor IPR-179 exhibits antiseizure and antiepileptogenic effects in rodent epilepsy models and attenuates seizure-induced cognitive decline, it deserves further investigation in clinical trials.

Design and synthesis of selective and blood-brain barrier-permeable hydroxamate-based gelatinase inhibitors.

Matrix metalloproteinases (MMPs), a family of zinc-containing endopeptidases involved in the degradation of the extracellular matrix, make a major contribution to the progression of a vast number of diseases, such cancer or epilepsy. Although several MMP inhibitors (MMPi) have been developed to date for the treatment of cancer, they have all failed in clinical trials due to lack of efficacy and, most importantly, the presence of severe side effects. The latter can be explained by their lack of selectivity of these inhibitors. In this regard, MMPs' family members have a high structural homology, which challenge the development of selective inhibitors for a specific MMP. Here, we have used in silico calculations and in vitro data to design MMPi that selectively target gelatinases (MMP-2 and MMP-9) and have the capacity to cross the blood-brain barrier. Following this approach, we obtained compound 40 that shows high proteolytic stability and low cytotoxicity. This compound may be of particular interest for the treatment of central nervous diseases such epilepsy or Alzheimer's disease, where gelatinase activity is increased. Our data show the specificity of compound 40 for recombinant MMP-9 and MMP-2 and endogenous MMP-9 from rat hippocampal cell cultures, and reveals its permeability across the blood-brain barrier in vivo.

Reliability of a Method to Measure Neck Surface Electromyography, Kinematics, and Pain Occurrence in Participants With Neck Pain.

OBJECTIVE: To investigate the reliability of a novel method to measure neck surface electromyography (SEMG), kinematics, and pain during active movements in participants with neck pain. METHODS: This test-retest study evaluated 23 participants with chronic neck pain. Each was measured twice within a single session. Three-dimensional kinematics and SEMG were recorded in 10° increments during forward and side flexion, extension, and rotation of the neck. Neck position during pain occurrence was also measured. RESULTS: Intraclass correlation coefficients were >0.80 for 96% and 100% of SEMG and kinematic data, respectively. The percentage of standard error of the measurement (SEM) values were <25% for 91% of all SEMG measures; most were <15%, and some were <10%. For ranges of motion in the primary plane, percentage of SEM values were all <6% (SEM 1°-3°). Intraclass correlation coefficients for neck position during pain occurrence were all >0.60, except for right rotation (0.48) (SEM values 2°-8°). Pain occurred approximately 59% to 75% into the total range of motion and persisted to its end. CONCLUSIONS: This methodology showed good reliability. It may be suitable for neck pain subclassification to evaluate the effects of treatment on pain, kinematics, and muscle activity during functional neck movements. The point of pain occurrence suggests increasing mechanical load on tissues may be one of the causative factors for movement-associated neck pain.

Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides.

Peptides are experiencing a new era in medical research, finding applications ranging from therapeutics to vaccines. In spite of the promising properties of peptide pharmaceuticals, their development continues to be hindered by three weaknesses intrinsic to their structure, namely protease sensitivity, clearance through the kidneys, and immune system activation. Here we report on two retro-D-peptides (H2N-hrpyiah-CONH2 and H2N-pwvpswmpprht-CONH2), which are protease-resistant and retain the original BBB shuttle activity of the parent peptide but are much less immunogenic than the parent peptide. Hence, we envisage that retro-D-peptides, which display a similar topological arrangement as their parent peptides, will expand drug design and help to overcome factors that lead to the failure of peptide pharmaceuticals in pre- and clinical trials. Furthermore, we reveal requirements to avoid or elicit specific humoral responses to therapeutic peptides, which might have a strong impact in both vaccine design and peptide therapeutic agents.

Prevalence and factors associated with a higher risk of neck and back pain among permanent wheelchair users: a cross-sectional study.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To determine the prevalence of, and factors associated with, spinal pain among wheelchair users. SETTING: Four Spanish hospitals specialized in providing care for wheelchair users. METHODS: Persons who had used a wheelchair for a median (IRQ) of 10 (5;19) years, 27% of them due to reasons other than spinal cord injury, were recruited consecutively (n = 750). Data on 43 demographic, psychosocial, ergonomic, and clinical variables were collected, and analyzed. Main outcome measures were: point prevalence of neck (NP), thoracic (TP), low back pain (LBP), and pain at any spinal level (PASL); and factors associated with them. RESULTS: Point prevalence was 56% for NP, 54% for TP, 45% for LBP, and 76% for PSAL. PASL was associated with a lower quality of life (OR (95% CI) 0.91 (0.86; 0.97)). Multivariable regression models showed that the main factors associated with significant pain (≥1.5 VAS points) were: (a) For NP: cervical spinal injury and wheelchair seat cushion thickness, (b) For TP: thoracic spinal injury and sagittal index, (c) For LBP: thoracic or lumbar spinal injury, with some sensitivity remaining, (d) For PASL: being female, living alone, and using a non-power wheelchair. Discrimination (AUC) of these models ranged between 0.638 and 0.818. p-values in the Hosmer-Lemeshow test ranged between 0.420 and 0.701. CONCLUSIONS: Prevalence of spinal pain among wheelchair users is high. It is associated with a lower quality of life. Future studies should assess whether using a power wheelchair affects PASL, and if the thickness of seat cushion affects NP. SPONSORSHIP: Spanish Back Pain Research Network.

Toward a Novel Drug To Target the EGF-EGFR Interaction: Design of Metabolically Stable Bicyclic Peptides.

In cancer, proliferation of malignant cells is driven by overactivation of growth-signalling mechanisms, such as the epidermal growth factor receptor (EGFR) pathway. Despite its therapeutic relevance, the EGF-EGFR interaction has remained elusive to inhibition by synthetic molecules, mostly as a result of its large size and lack of binding pockets and cavities. Designed peptides, featuring cyclic motifs and other structural constraints, have the potential to modulate such challenging protein-protein interactions (PPIs). Herein, we present the structure-based design of a series of bicyclic constrained peptides that mimic an interface domain of EGFR and inhibit the EGF-EGFR interaction by targeting the smaller partner (i.e., EGF). This design process was guided by the integrated use of in silico methods and biophysical techniques, such as NMR spectroscopy and surface acoustic wave. The best analogues were able to reduce selectively the viability of EGFR+ human cancer cells. In addition to their efficacy, these bicyclic peptides are endowed with exceptional stability and metabolic resistance-two features that make them suitable candidates for in vivo applications.

Relationship of long-term macronutrients intake on anabolic-catabolic hormones in female elite volleyball players.

INTRODUCTION: Specific macronutrient distribution and training can alter acute and chronic hormone behavior and, subsequently, sport performance. OBJECTIVE: The main aim was to examine relationships between dietary intake and anabolic/catabolic hormone response in elite female volleyball players during a 29-week season. METHODS: Twenty-two elite female volleyballers (26.4 ± 5.6 years; 178 ± 9 cm; 67.1 ± 7.5 kg) had dietary intake (seven-day dietary recall and food frequency questionnaire), blood concentration of anabolic/catabolic hormones concentration, physical performance, and body composition assessed at four time points: a) T1: baseline/pre-testing; b) T2: eleven weeks after T1; c) T3: ten weeks after T2; and d) T4: eight weeks after T3. Hormones evaluated were: total testosterone (TT), free testosterone (FT) adrenocorticotropic hormone (ACTH), and cortisol (C), along with hormone ratios. RESULTS: Positive correlations were observed between carbohydrate/protein ratio with ΔFT (r = 0.955; p < 0.001), ΔTT/C ratio (r = 0.638; p = 0.047), and ΔFT/C ratio (r = 0.909; p < 0.001). Significant and negative correlations were found between protein intake with ΔTT (r = -0.670; p = 0.034), and FT (r = -0.743; p < 0.001), carbohydrate intake and ΔACTH (r = -0.658; p = 0.006). No relationships were observed regarding Δcortisol. On the other hand, there was no change (p > 0.05) in body mass or body mass index at any time point, and the sum of six skinfolds improved (p < 0.05) from T1 (86.5 ± 6.9 mm) to T4 (75.2 ± 5.6 mm) as did muscle mass (T1: 28.9 ± 0.7 kg vsT4: 30.1 ± 0.8 kg). Vertical jump, spike-jump and speed improved (p < 0.05) from T1 to T4. CONCLUSIONS: A high carbohydrate/protein ratio was associated with positive changes in anabolism, while high protein and low carbohydrates (CHO) were associated with an attenuated anabolic response.

Relationship of long-term macronutrients intake on anabolic-catabolic hormones in female elite volleyball players / Relación de la ingesta a largo plazo de macronutrientes en las hormonas anabólicas catabólicas de jugadoras de voleibol elite

Introduction: Specific macronutrient distribution and training can alter acute and chronic hormone behavior and, subsequently, sport performance. Objective: The main aim was to examine relationships between dietary intake and anabolic catabolic hormone response in elite female volleyball players during a 29-week season. Methods: Twenty-two elite female volleyballers (26.4 ± 5.6 years; 178 ± 9 cm; 67.1 ± 7.5 kg) had dietary intake (seven-day dietary recall and food frequency questionnaire), blood concentration of anabolic/catabolic hormones concentration, physical performance, and body composition assessed at four time points: a) T1: baseline/pre-testing; b) T2: eleven weeks after T1; c) T3: ten weeks after T2; and d) T4: eight weeks after T3. Hormones evaluated were: total testosterone (TT), free testosterone (FT) adrenocorticotropic hormone (ACTH), and cortisol (C), along with hormone ratios. Results: Positive correlations were observed between carbohydrate/protein ratio with ΔFT (r = 0.955; p < 0.001), ΔTT/C ratio (r = 0.638; p = 0.047), and ΔFT/C ratio (r = 0.909; p < 0.001). Significant and negative correlations were found between protein intake with ΔTT (r = -0.670; p = 0.034), and FT (r = -0.743; p < 0.001), carbohydrate intake and ΔACTH (r = -0.658; p = 0.006). No relationships were observed regarding Δcortisol. On the other hand, there was no change (p > 0.05) in body mass or body mass index at any time point, and the sum of six skinfolds improved (p < 0.05) from T1 (86.5 ± 6.9 mm) to T4 (75.2 ± 5.6 mm) as did muscle mass (T1: 28.9 ± 0.7 kg vs T4: 30.1 ± 0.8 kg). Vertical jump, spike-jump and speed improved (p < 0.05) from T1 to T4. Conclusions: A high carbohydrate/protein ratio was associated with positive changes in anabolism, while high protein and low carbohydrates (CHO) were associated with an attenuated anabolic response (AU)

Introducción: la distribución específica de macronutrientes y el entrenamiento pueden alterar el comportamiento agudo y crónico de las hormonas y, posteriormente, el rendimiento deportivo. Objetivo: el objetivo principal del estudio fue examinar la relación entre la ingesta dietética y la respuesta anabólica/catabólica hormonal de jugadoras de élite de voleibol durante una temporada de 29 semanas. Métodos: se evaluó en 22 jugadoras de élite (26,4 ± 5,6 años, 178 ± 9 cm, 67,1 ± 7,5 kg) la ingesta dietética (mediante un registro de siete días y un cuestionario de frecuencia de consumo de alimentos), la concentración de hormona anabólica/catabólica en sangre, el rendimiento físico y la composición corporal en cuatro puntos durante la temporada: a) T1: pre-pretemporada; b) T2: once semanas después de T1; c) T3: diez semanas después de T2; y d) T4: ocho semanas después de T3. Las hormonas evaluadas fueron: testosterona total (TT), testosterona libre (FT), hormona adrenocorticotropa (ACTH) y cortisol (C); se calcularon distintos ratios hormonales. Resultados: se observaron correlaciones positivas entre la ratio carbohidratos/proteínas con ΔFT (r = 0,955; p < 0,001), ΔTT/C (r = 0,638; p = 0,047) y ΔFT/C (r = 0,909; p < 0,001). Se encontraron correlaciones significativas y negativas entre la ingesta proteica con ΔTT (r = -0,670; p = 0,034) y FT (r = -0,743; p < 0,001), la ingesta de carbohidratos y ΔACTH (r = -0,658; p = 0,006). No se observó ningún tipo de correlación con el Δcortisol. Por otro lado, no hubo cambios (p > 0,05) en la masa corporal ni en el índice de masa corporal en ningún momento, mientras que el sumatorio de seis pliegues mejoró (p < 0,05) de T1 (86,5 ± 6,9 mm) a T4 (75,2 ± 5,6 mm), así como la masa muscular (T1: 28,9 ± 0,7 kg frente a T4: 30,1 ± 0,8 kg). El salto vertical, el salto de remate y la velocidad mejoraron (p < 0,05) de T1 a T4. Conclusión: en conclusión, una alta ratio de carbohidratos/proteínas se asoció con cambios positivos en el anabolismo, mientras que una ingesta alta de proteína y baja de CHO se asoció con una respuesta anabólica atenuada (AU)

Los ejercicios respiratorios postoperatorios reducen el riesgo de complicaciones pulmonares en pacientes sometidos a lobectomía / Postoperative Respiratory Exercises Reduce the Risk of Developing Pulmonary Complications in Patients Undergoing Lobectomy

Objetivo: Evaluar los efectos de un programa intensivo de fisioterapia postoperatoria basado en ejercicios respiratorios dirigido a pacientes lobectomizados mediante toracotomía abierta. Diseño : Estudio cuasiexperimental. Emplazamiento: Hospital universitario terciario. Participantes: Doscientos ocho (208) pacientes lobectomizados mediante toracotomía abierta. Intervención: Los pacientes del grupo control (n=102) recibieron atención médica/de enfermería estándar y los pacientes del grupo experimental (n=106), además de la atención clínica estándar, se sometieron a un programa de fisioterapia diaria basada en ejercicios respiratorios hasta el momento del alta hospitalaria. Variables de resultado: Las variables de resultado estudiadas incluyeron la frecuencia de complicaciones pulmonares postoperatorias (CPP) más susceptibles de tratamiento fisioterapéutico (neumonía, atelectasias e insuficiencia respiratoria) y la duración de la estancia hospitalaria (DEH). Resultados: Las características preoperatorias y quirúrgicas de ambos grupos fueron comparables. La incidencia de CPP registrada fue de un 20,6% en el grupo control y un 6,6% en el grupo experimental (p = 0,003). La mediana y el RIC de la DEH fue de 14 y 7días, respectivamente (estimador M de Huber 14,21) en el grupo control y de 12 y 6días (estimador M de Huber 12,81) en el grupo experimental. El modelo de regresión logística creado identificó al programa de fisioterapia evaluado (p = 0,017; EXP (B) [IC 95% 0,081-0,780]) y al porcentaje del FEV1 (p = 0,042; EXP (B) [IC 95% 0,941-0,999]) como factores protectores frente al desarrollo de CPP en los pacientes intervenidos de lobectomía. Conclusiones: La implementación de un programa intensivo de fisioterapia postoperatoria basado en ejercicios respiratorios reduce el riesgo de desarrollar CPP y la DEH en pacientes lobectomizados

Objective: To evaluate the effects of an intensive postoperative physiotherapy program focused on respiratory exercises in patients undergoing lobectomy by open thoracotomy. Design: Quasi-experimental study. Setting: Tertiary referral academic hospital. Participants: 208 patients undergoing lobectomy by open thoracotomy. Interventions: Control group patients (n = 102) received standard medical/nursing care, and experimental group patients (n=106) added to the standard clinical pathway a daily physiotherapy program focused on respiratory exercises until discharge. Outcomes: Analyzed outcomes were the frequency of postoperative pulmonary complications (PPCs) more amenable to physiotherapy (pneumonia, atelectasis and respiratory insufficiency) and length of hospital stay (LOS). Results: Both groups were comparable regarding preoperative and surgical characteristics. Incidence of PPCs was 20.6% in control and 6.6% in experimental group (P = .003). Median (IQR) LOS in control group was 14 (7) days (Huber M estimator 14.21) and 12 (6) days (Huber M estimator 12.81) in experimental. Logistic regression model identified the evaluated physiotherapy program (P = .017; EXP [B] 95% CI 0.081-0.780) and % FEV1 (P = .042; EXP [B] 95% CI 0.941-0.999) as protective factors for the development of PPCs in patients undergoing lobectomy. Conclusions: Implementing a postoperative intensive physiotherapy program focused on respiratory exercises reduces the risk of PPCs and resultant LOS on patients undergoing lobectomy

Postoperative Respiratory Exercises Reduce the Risk of Developing Pulmonary Complications in Patients Undergoing Lobectomy. / Los ejercicios respiratorios postoperatorios reducen el riesgo de complicaciones pulmonares en pacientes sometidos a lobectomía.

OBJECTIVE: To evaluate the effects of an intensive postoperative physiotherapy program focused on respiratory exercises in patients undergoing lobectomy by open thoracotomy. DESIGN: Quasi-experimental study. SETTING: Tertiary referral academic hospital. PARTICIPANTS: 208 patients undergoing lobectomy by open thoracotomy. INTERVENTIONS: Control group patients (n=102) received standard medical/nursing care, and experimental group patients (n=106) added to the standard clinical pathway a daily physiotherapy program focused on respiratory exercises until discharge. OUTCOMES: Analyzed outcomes were the frequency of postoperative pulmonary complications (PPCs) more amenable to physiotherapy (pneumonia, atelectasis and respiratory insufficiency) and length of hospital stay (LOS). RESULTS: Both groups were comparable regarding preoperative and surgical characteristics. Incidence of PPCs was 20.6% in control and 6.6% in experimental group (P=.003). Median (IQR) LOS in control group was 14 (7) days (Huber M estimator 14.21) and 12 (6) days (Huber M estimator 12.81) in experimental. Logistic regression model identified the evaluated physiotherapy program (P=.017; EXP [B] 95% CI 0.081-0.780) and % FEV1 (P=.042; EXP [B] 95% CI 0.941-0.999) as protective factors for the development of PPCs in patients undergoing lobectomy. CONCLUSIONS: Implementing a postoperative intensive physiotherapy program focused on respiratory exercises reduces the risk of PPCs and resultant LOS on patients undergoing lobectomy.

Basketball Performance Is Related to Maturity and Relative Age in Elite Adolescent Players.

During a national championship, the anthropometric, physiological, and maturation characteristics of 13- to 14-year-old players of elite basketball teams and their association with sport performance were analyzed. Body parameters (weight, height, skinfold thicknesses, and lengths) were measured and physiological capacities assessed by sprint (20 m) and jump tests (i.e., countermovement jump with arm swing). Chronological age (CA) and maturity offset (years from age at peak height velocity; YAPHV) were calculated, and then predicted age at peak height velocity, as the difference between CA and YAPHV. Game performance was assessed with point averages and the performance index rating (PIR). The birth-date distribution of players was biased, those born early in the selection year outnumbering those born later. Anthropometric analysis indicated that players who performed better had longer body lengths. Physiological testing showed that semi-finalists had better sprint performance than quarter-finalists and those players with greater jump capacity scored more points. Early maturation and advanced maturity status were also associated with better PIR and scored points per game. Multiple blockwise regression analysis showed that, among the factors analyzed, YAPHV was the best predictor of basketball performance. In conclusion, around puberty, physical and physiological parameters associated with maturity and CA are important in determining the success of elite basketball players. Consequently, boys who are born in the second half of the year and/or late maturing tend to be marginalized or totally excluded, and not given the chance to play under equal conditions; their careers may then be held back by the relative disadvantage associated with inexperience.

Peptides Targeting EGF Block the EGF-EGFR Interaction.

Epidermal growth factor receptor (EGFR) is a key target in chemotherapy. Some drugs acting on the receptor are currently in use; however, drug resistance, which causes tumour relapse, calls for the discovery of alternative inhibitors. Using docking and receptor hotspot mimicry, we have designed novel peptides directed at EGF, the main growth factor ligand of EGFR. An array of biophysical techniques was used to characterise the structure and interaction of these ligands with the target protein. Both design methods identified peptides able to bind EGF, and the capacity of these peptides to inhibit the interaction between EGF and EGFR was demonstrated in two in vitro systems. Based on targeting the smaller companion of a protein-protein interaction, the new approach described herein can be envisaged as a parallel drug design strategy, and our compounds represent the first in a new class of binders that could serve as complementary compounds in potential multidrug cancer therapy.

Patients with neck pain are less likely to improve if they experience poor sleep quality: a prospective study in routine practice.

OBJECTIVE: To assess whether sleep quality (SQ) at baseline is associated with improvement in pain and disability at 3 months. MATERIALS AND METHODS: Four hundred twenty-two subacute and chronic patients with neck pain (NP) were recruited in 32 physiotherapy, primary care, and specialized centers. NP, referred pain, disability, catastrophizing, depression, and SQ were assessed through validated questionnaires, upon recruitment and 3 months later. Correlations between baseline scores were calculated through the Spearman coefficient. Improvements in NP, disability, and SQ were defined as a reduction of ≥30% of baseline score. Six estimative logistic regression models were developed to assess the association between baseline SQ and improvement of NP, baseline SQ and improvement of disability, baseline NP and improvement of SQ, baseline disability and improvement of SQ, the evolutions of NP and SQ, and the evolutions of disability and SQ. RESULTS: Most patients were subacute and mildly impaired. Regression models showed that better SQ at baseline was associated with improvement of NP (odds ratio=0.91 [95% confidence interval, 0.83-0.99]), but not disability (1.04 [0.95-1.13]); the improvement of SQ was associated with more severe NP at baseline (1.26 [1.07-1.49)], but not with baseline disability (0.99 [0.97-1.02]); and that improvement in SQ was associated with improvements in NP (3.48 [1.68-7.20]), and disability (5.02 [2.39-10.11]). DISCUSSION: NP is less likely to improve in patients with poorer SQ, irrespective of age, sex, catastrophizing, depression, or treatments prescribed for NP. Future studies should confirm these results with more severely impaired patients.