Physicochemical stability of bortezomib solutions for subcutaneous administration.

For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.

Modelling Polyphenol Extraction through Ultrasound-Assisted Extraction by Machine Learning in Olea europaea Leaves.

The study of the phenolic compounds present in olive leaves (Olea europaea) is of great interest due to their health benefits. In this research, different machine learning algorithms such as RF, SVM, and ANN, with temperature, time, and volume as input variables, were developed to model the extract yield and the total phenolic content (TPC) from experimental data reported in the literature. In terms of extract yield, the neural network-based ANNZ-L model presents the lowest root mean square error (RMSE) value in the validation phase (9.44 mg/g DL), which corresponds with a mean absolute percentage error (MAPE) of 3.7%. On the other hand, the best model to determine the TPC value was the neural network-based model ANNR, with an RMSE of 0.89 mg GAE/g DL in the validation phase (MAPE of 2.9%). Both models obtain, for the test phase, MAPE values of 4.9 and 3.5%, respectively. This affirms that ANN models would be good modelling tools to determine the extract yield and TPC value of the ultrasound-assisted extraction (UAE) process of olive leaves under different temperatures, times, and solvents.

Review: Evaluating existing policies to address overweight and obesity in the Anglophone Caribbean: A narrative review of Barbados, Grenada, St. Lucia, and Trinidad & Tobago.

Overweight and obesity continues to be a burden to the health and well-being of Caribbean residents. The rise of childhood obesity and non-communicable diseases within the Caribbean is a major public health challenge for policymakers, educators and health professionals. These alarming rates of obesity also pose a threat to the sustainability of existing health systems particularly in small island developing states like the Caribbean. Therefore, it is crucial to evaluate existing policies and create policy solutions to address these problems and reduce the potential impact later on. This systematic review explored existing policies among countries within the Anglophone Caribbean to identify trends within the region. The literature search focused on the following themes: (i) national policies (ii) school nutrition policies and programs (iii) physical activity among youth, and (iv) food import bill and food security. An analysis was conducted on literature from national, regional and international institutions including but not limited to the World Health Organization, Ministries of Health and the Healthy Caribbean Coalition. Countries throughout the region has acknowledged the challenges with overweight and obesity in the region. Collectively decisions have been made to address food insecurity and promote healthy lifestyle behaviours through policy changes. There's still a need for Caribbean countries to work together to create effective policy solutions in collaboration with community service organizations and other stakeholders. As small island developing states grappling with the same issues, pooling resources to create effective regional policies can help to address this public health crisis.

Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency.

Lamb-Shaffer Syndrome (LSS; OMIM #616803; ORPHA #313892; ORPHA #313884) is an infrequent genetic disorder that affects multiple aspects of human development especially those related to the development of the nervous system. LSS is caused by variants in the SOX5 gene. At the molecular level, SOX5 gene encodes for a transcription factor containing a High Mobility Group (HMG) DNA-Binding domain with relevant functions in brain development in different vertebrate species. Clinical features of Lamb-Shaffer syndrome may include intellectual disability, delayed speech and language development, attention deficits, hyperactivity, autism spectrum disorder, visual problems and seizures. Additionally, patients with the syndrome may present distinct facial dimorphism such as a wide mouth with full lips, small chin, broad nasal bridge, and deep-set eyes. Other physical features that have been reported in some patients include short stature, scoliosis, and joint hypermobility. Here, we report the clinical and molecular characterization of a Spanish LSS cohort of new 20 patients and review all the patients published so far which amount for 111 patients. The most frequent features included developmental delay, intellectual disability, visual problems, poor speech development and facial dysmorphic features. Strikingly, pain insensitivity and hypermetropia seems to be more frequent than previously reported, based on the frequency seen in the Spanish cohort. Eighty-three variants have been reported so far, single nucleotide variants (SNV) and copy number variants represent 47% and 53%, respectively, from the total of variants reported. Similarly to previous reports, the majority of the SNVs variants of the novel patients reported herein fall in the HMG domain of the protein. However, new variants, affecting other functional domains, were also detected. In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to SOX5 haploinsufficiency.

Functional Traits in Bees: the Role of Body Size and Hairs in the Pollination of a Passiflora Crop.

Pollination is a vitally important function in nature and becomes an ecosystem service because it influences the food and nutritional security for people. However, the contribution of different functional traits of insects for pollen transport of plants is still poorly known. We explore the relationship between pollinator insect functional traits and the transport of pollen of sweet granadilla (Passiflora ligularis Juss) in eight crops. We sampled flower-visiting insects of this crop and recorded 10 functional traits (five by direct measurements and five from the literature) that were related to the amount of pollen carried by each insect. Bees (Apidae) were not only the most abundant insects but also the ones that loaded the highest amounts of pollen. Within these, the most abundant species was the exotic common honeybee (Apis mellifera (Linnaeus)) making up almost half of the specimens collected; however, this bee carried less pollen grains than other native bees. Bombus hortulanus (Smith) was one of the large-bodied native bees that carried more sweet granadilla pollen, despite not being an abundant species in the community. Body size was the most important trait determining the transport of sweet granadilla pollen, while the traits related to body hairs were not significant for the body's pollen load. None of the functional traits evaluated was influenced by taxonomy at species-level. Our results suggest that large body sizes in bees are the most important traits in granadilla pollen transport, regardless of other changes in composition and structure of pollinating insect assemblages in the crop.

Response of sleep slow oscillations to acoustic stimulation is evidenced by distinctive synchronization processes.

Closed-loop acoustic stimulation (CLAS) during sleep has shown to boost slow wave (SW) amplitude and spindle power. Moreover, sleep SW have been classified based on different processes of neuronal synchronization. Thus, different types of SW events may have distinct functional roles and be differentially affected by external stimuli. However, the SW synchronization processes affected by CLAS are not well understood. Here, we studied the effect of CLAS on the dissociation of SW events based on two features of neuronal synchronization in the electroencephalogram (topological spread and wave slope). We evaluated and classified individual SW events of 14 healthy subjects during a CLAS stimulated (STM) and a control night (CNT). Three main categories of SW events were found denoting (C1) steep slope SW with global spread, (C2) flat-slope waves with localized spread and homeostatic decline, and (C3) multipeaked flat-slope events with global spread. Comparing between conditions, we found a consistent increase of event proportion and trough amplitudes for C1 events during the time of stimulation. Furthermore, we found similar increases in post-stimulus spectral power in θ, ß, and σ frequencies for CNT vs STIM condition independently of sleep stage or SW categories. However, topological analysis showed differentiated spatial dynamics in N2 and N3 for SW categories and the co-occurrence with spindle events. Our findings support the existence of multiple types of SW with differential response to external stimuli and possible distinct neuronal mechanisms.

Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma.

A challenge when targeting T-cell lymphoma with chimeric antigen receptor (CAR) T-cell therapy is that target antigens are often shared between T cells and tumor cells, resulting in fratricide between CAR T cells and on-target cytotoxicity on normal T cells. CC chemokine receptor 4 (CCR4) is highly expressed in many mature T-cell malignancies, such as adult T-cell leukemia/lymphoma (ATLL) and cutaneous T-cell lymphoma (CTCL), and has a unique expression profile in normal T cells. CCR4 is predominantly expressed by type-2 and type-17 helper T cells (Th2 and Th17) and regulatory T cells (Treg), but it is rarely expressed by other T helper (Th) subsets and CD8+ cells. Although fratricide in CAR T cells is generally thought to be detrimental to anticancer functions, in this study, we demonstrated that anti-CCR4 CAR T cells specifically depleted Th2 and Tregs, while sparing CD8+ and Th1 T cells. Moreover, fratricide increased the percentage of CAR+ T cells in the final product. CCR4-CAR T cells were characterized by high transduction efficiency, robust T-cell expansion, and rapid fratricidal depletion of CCR4-positive T cells during CAR transduction and expansion. Furthermore, mogamulizumab-based CCR4-CAR T cells induced superior antitumor efficacy and long-term remission in mice engrafted with human T-cell lymphoma cells. In summary, CCR4-depleted anti-CCR4 CAR T cells are enriched in Th1 and CD8+ T cells and exhibit high antitumor efficacy against CCR4-expressing T-cell malignancies.

Divergent regulation of auxin responsive genes in root-knot and cyst nematodes feeding sites formed in Arabidopsis.

Cysts (CNs) and root-knot nematodes (RKNs) induce specialized feeding cells, syncytia, and giant cells (GCs), respectively, within plant roots. The plant tissues around the GCs usually by respond forming a root swelling called a gall that contains the GCs. The ontogenesis of feeding cells is different. GC formation is a process of new organogenesis from vascular cells, which are still not well characterized, that differentiate into GCs. In contrast, syncytia formation involves the fusion of adjacent cells that have already differentiated. Nonetheless, both feeding sites show an auxin maximum pertinent to feeding site formation. However, data on the molecular divergences and similarities between the formation of both feeding sites regarding auxin-responsive genes are still scarce. We studied genes from the auxin transduction pathways that are crucial during gall and lateral root (LR) development in the CN interaction by using promoter-reporter (GUS/LUC)transgenic lines, as well as loss of function lines of Arabidopsis. The promoters pGATA23 and several deletions of pmiR390a were active in syncytia, as were in galls, but pAHP6 or putative up-stream regulators as ARF5/7/19 were not active in syncytia. Additionally, none of these genes seemed to play a key role during cyst nematode establishment in Arabidopsis, as the infection rates in loss of function lines did not show significant differences compared to control Col-0 plants. Furthermore, the presence of only canonical AuxRe elements in their proximal promoter regions is highly correlated with their activation in galls/GCs (AHP6, LBD16), but those promoters active in syncytia (miR390, GATA23) carry AuxRe overlapping core cis-elements for other transcription factor families (i.e., bHLH, bZIP). Strikingly, in silico transcriptomic analysis showed very few genes upregulated by auxins common to those induced in GCs and syncytia, despite the high number of upregulated IAA responsive genes in syncytia and galls. The complex regulation of auxin transduction pathways, where different members of the auxin response factor (ARF) family may interact with other factors, and the differences in auxin sensitivity, as indicated by the lower induction of the DR5 sensor in syncytia than galls, among other factors, may explain the divergent regulation of auxin responsive genes in the two types of nematode feeding sites.

Anthropometric characteristics of young elite sailors based on performance level.

Background: /Objectives: The aim of the present study was to analyse possible differences in anthropometric characteristics of elite sailors based on categories and performance level. Methods: ː A total of 42 young (aged 12-18 years) elite sailors (men = 31; women = 11) of the Monohull (n = 21) and Windsurfing (n = 21) categories composed the study sample. Testing was per-formed in one session the day before the start of an official and international competition. Body composition was measured using an octopolar and multi-frequency electrical bioimpedance analyser, and height was recorded using a telescopic measuring instrument. Cross-sectional study. The total sample was divided into two groups based on their performance level (ranking), 50th percentile (P1), and 100th percentile (P2). Results: ː P1 presented a lower BMI, total body fat mass, and body fat mass in the trunk, arms, and legs (p < 0.05). Similarly, P1 reported a higher total body muscle mass and body muscle mass on the trunk, arms, and legs compared to the less level performance group (p < 0.05). In addition, P2 sailors were taller and heavier (p < 0.05). Regarding categories, the Windsurf sailors presented statistically significantly lower arm fat mass than the Monohull (p < 0.05). The Windsurf sailors showed differences between the two performance-level groups (p < 0.05). Additionally, comparing the high-level performance group in both categories, higher arm muscle mass on the Windsurfing sailors was detected (p < 0.05). Conclusions: ː These findings could help to differentiate the anthropometric variables that determine sport performance in young elite sailors and could be used to differentiate the anthropometric variables in each category.

Overview of the use of biochar from main cereals to stimulate plant growth.

The total global food demand is expected to increase up to 50% between 2010 and 2050; hence, there is a clear need to increase plant productivity with little or no damage to the environment. In this respect, biochar is a carbon-rich material derived from the pyrolysis of organic matter at high temperatures with a limited oxygen supply, with different physicochemical characteristics that depend on the feedstock and pyrolysis conditions. When used as a soil amendment, it has shown many positive environmental effects such as carbon sequestration, reduction of greenhouse gas emissions, and soil improvement. Biochar application has also shown huge benefits when applied to agri-systems, among them, the improvement of plant growth either in optimal conditions or under abiotic or biotic stress. Several mechanisms, such as enhancing the soil microbial diversity and thus increasing soil nutrient-cycling functions, improving soil physicochemical properties, stimulating the microbial colonization, or increasing soil P, K, or N content, have been described to exert these positive effects on plant growth, either alone or in combination with other resources. In addition, it can also improve the plant antioxidant defenses, an evident advantage for plant growth under stress conditions. Although agricultural residues are generated from a wide variety of crops, cereals account for more than half of the world's harvested area. Yet, in this review, we will focus on biochar obtained from residues of the most common and relevant cereal crops in terms of global production (rice, wheat, maize, and barley) and in their use as recycled residues to stimulate plant growth. The harvesting and processing of these crops generate a vast number and variety of residues that could be locally recycled into valuable products such as biochar, reducing the waste management problem and accomplishing the circular economy premise. However, very scarce literature focused on the use of biochar from a crop to improve its own growth is available. Herein, we present an overview of the literature focused on this topic, compiling most of the studies and discussing the urgent need to deepen into the molecular mechanisms and pathways involved in the beneficial effects of biochar on plant productivity.

The DNA methylation landscape of the root-knot nematode-induced pseudo-organ, the gall, in Arabidopsis, is dynamic, contrasting over time, and critically important for successful parasitism.

Root-knot nematodes (RKNs) induce giant cells (GCs) within galls which are characterized by large-scale gene repression at early stages. However, the epigenetic mechanism(s) underlying gene silencing is (are) still poorly characterized. DNA methylation in Arabidopsis galls induced by Meloidogyne javanica was studied at crucial infection stages (3 d post-infection (dpi) and 14 dpi) using enzymatic, cytological, and sequencing approaches. DNA methyltransferase mutants (met1, cmt2, cmt3, cmt2/3, drm1/2, ddc) and a DNA demethylase mutant (ros1), were analyzed for RKN resistance/tolerance, and galls were characterized by confocal microscopy and RNA-seq. Early galls were hypermethylated, and the GCs were found to be the major contributors to this hypermethylation, consistent with the very high degree of gene repression they exhibit. By contrast, medium/late galls showed no global increase in DNA methylation compared to uninfected roots, but exhibited large-scale redistribution of differentially methylated regions (DMRs). In line with these findings, it was also shown that DNA methylation and demethylation mutants showed impaired nematode reproduction and gall/GC-development. Moreover, siRNAs that were exclusively present in early galls accumulated at hypermethylated DMRs, overlapping mostly with retrotransposons in the CHG/CG contexts that might be involved in their repression, contributing to their stability/genome integrity. Promoter/gene methylation correlated with differentially expressed genes encoding proteins with basic cell functions. Both mechanisms are consistent with reprogramming host tissues for gall/GC formation. In conclusion, RNA-directed DNA methylation (RdDM; DRM2/1) pathways, maintenance methyltransferases (MET1/CMT3) and demethylation (ROS1) appear to be prominent mechanisms driving a dynamic regulation of the epigenetic landscape during RKN infection.

Brief incubation of corneal grafts in activated platelet rich plasma enhances corneal endothelial cell survival and regeneration.

Corneal transplantation is the most frequent organ transplantation worldwide. Unfortunately, corneal graft failure is common and endothelial decompensation is considered the major cause. Corneal endothelial cells (CECs) lack the capacity to reproduce, and perioperative and postoperative endothelial cell loss remains a significant challenge associated with corneal graft viability. Therefore, strategies to preserve CEC density are critical to extend graft survival. Activated platelet rich plasma (aPRP), a product extracted from autologous blood, has both antioxidant and regenerative properties. aPRP eye drops have shown effectiveness in the treatment of corneal pathologies such as ulcers, dry eye, and burns. Our purpose is to determine the protective and regenerative effect of aPRP on corneal grafts by evaluating aPRP's effect on the survival and proliferation of human CECs. Human corneal grafts were incubated in aPRP for 15 min to assess the activation of the CEC pAkt survival pathway as measured by ELISA. Evaluation of the protective effect of aPRP was made using an apoptotic model, which simulated oxidative stress conditions. Expression of apoptotic markers was measured using ELISA and endothelial cell viability was determined by optical microscopy. The CEC proliferation rate was measured in vitro with Ki-67 staining. Corneal graft gross structure was evaluated by Hematoxylin & Eosin and Masson trichrome staining. Our results indicate that a short incubation of human corneal grafts in aPRP protects CECs from apoptosis by upregulating the pAkt survival pathway and promoting CEC proliferation. Additionally, aPRP incubation does not induce histological changes in the grafts. A brief pre-treatment of human corneal grafts in aPRP may be beneficial for transplant longevity, as it protects CECs from apoptosis by upregulating intracellular survival pathways and promoting proliferation. In addition, this approach appears to be safe and has the potential to improve surgical outcomes following corneal transplantation.

Simulation of the electrical stimulation of the rat brain using sleep frequencies: A finite element modeling approach.

A realistic rat brain model was used to simulate current density and electric field distributions under frequencies characteristic of sleeping states (0.8, 5, and 12 Hz). Two anode-electrode setups were simulated: plate vs. screws-anode, both with a cephalic cathode. Our simulations showed that these frequencies have limited impact on electric field and current density; however, the highest frequency evidenced higher values for both variables. The type of electrode setup had a greater effect on current distribution and induced fields. In that sense, the screws setup resulted in higher values of the modeled variables. The numeric results obtained are within the range of available data for rodent models using the finite elements method. These modeled effects should be analyzed regarding anatomical consequences (depth of penetration of the currents) and purpose of the experiment (i.e., entrainment of brain oscillations) in the context of sleep research.

Putting interactions on the map.

A method called functional connectivity mapping helps model some of the complex interactions between multiple ecosystem services.

Targeting IRE1 endoribonuclease activity alleviates cardiovascular lesions in a murine model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of noncongenital heart disease in children. Studies in mice and humans propound the NLRP3/IL-1ß pathway as the principal driver of KD pathophysiology. Endoplasmic reticulum (ER) stress can activate the NLRP3 inflammasome, but the potential implication of ER stress in KD pathophysiology has not been investigated to our knowledge. We used human patient data and the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to characterize the impact of ER stress on the development of cardiovascular lesions. KD patient transcriptomics and single-cell RNA sequencing of the abdominal aorta from LCWE-injected mice revealed changes in the expression of ER stress genes. Alleviating ER stress genetically, by conditional deletion of inositol-requiring enzyme 1 (IRE1) in myeloid cells, or pharmacologically, by inhibition of IRE1 endoribonuclease (RNase) activity, led to significant reduction of LCWE-induced cardiovascular lesion formation as well as reduced caspase-1 activity and IL-1ß secretion. These results demonstrate the causal relationship of ER stress to KD pathogenesis and highlight IRE1 RNase activity as a potential new therapeutic target.

The Acute Effects of Normobaric Hypoxia on Strength, Muscular Endurance and Cognitive Function: Influence of Dose and Sex.

The aim of this study was to examine the acute effects of different levels of hypoxia on maximal strength, muscular endurance, and cognitive function in males and females. In total, 13 males (mean ± SD: age, 23.6 ± 2.8 years; height, 176.6 ± 3.9 cm; body mass, 76.6 ± 2.1 kg) and 13 females (mean ± SD: age, 22.8 ± 1.4 years; height, 166.4 ± 1.9 cm; body mass, 61.6 ± 3.4 kg) volunteered for a randomized, double-blind, crossover study. Participants completed a one repetition strength and muscular endurance test (60% of one repetition maximum to failure) for squat and bench press following four conditions; (i) normoxia (900 m altitude; FiO2: 21%); (ii) low dose hypoxia (2000 m altitude; FiO2: 16%); (iii) moderate dose hypoxia (3000 m altitude; FiO2: 14%); and (iv) high dose hypoxia (4000 m altitude; FiO2: 12%). Heart rate, blood lactate, rating of perceived exertion, and cognitive function was also determined during each condition. The one repetition maximum squat (p = 0.33) and bench press (p = 0.68) did not differ between conditions or sexes. Furthermore, squat endurance did not differ between conditions (p = 0.34). There was a significant decrease in bench press endurance following moderate (p = 0.02; p = 0.04) and high (p = 0.01; p = 0.01) doses of hypoxia in both males and females compared to normoxia and low dose hypoxia, respectively. Cognitive function, ratings of perceived exertion, and lactate were also significantly different in high and moderate dose hypoxia conditions compared to normoxia (p < 0.05). Heart rate was not different between the conditions (p = 0.30). In conclusion, high and moderate doses of acute normobaric hypoxia decrease upper body muscular endurance and cognitive performance regardless of sex; however, lower body muscular endurance and maximal strength are not altered.

Role of Caspase-1 as a Biomarker of Ocular Surface Damage.

PURPOSE: To examine the potential of caspase-1 as a biomarker for ocular surface damage. DESIGN: Cross-sectional study. METHODS: A total of 113 tear samples (64 subjects) were analyzed. Sixty-one samples were from individuals with dry eye disease (DED), defined as Ocular Surface Disease Index (OSDI) ≥13 and/or corneal staining (CS) ≥3; 32 were from individuals who used glaucoma medication, irrespective of DED metrics; and 20 were from controls (CS <3 and OSDI <13). All individuals completed a medical history form and underwent an ocular surface assessment. Protein levels of caspase-1 were determined by enzyme-linked immunosorbent assay off Schirmer's strips. The primary analysis compared caspase-1 levels in individuals with signs of ocular surface damage (CS ≥3) in both case groups and controls. Secondary correlational analyses were conducted to examine relationships between caspase-1 levels and ocular signs and symptoms. Finally, area under the curve (AUC) analyses were performed to examine relationships between inflammatory markers and CS. RESULTS: The mean age of the population was 58±18 years; 70% were female. Tear samples from individuals with ocular surface damage presented higher caspase-1 levels than the control group. Caspase-1 levels showed a moderate positive correlation with CS (Spearman r = 0.31; P = .001) and eye redness (Spearman r = 0.39; P = .004), and a negative correlation with Schirmer's (Spearman r = -0.46; P < .001) and tear break-up time (Spearman r = -0.33; P = .0006). Caspase-1 showed higher sensitivity and AUC for detecting ocular surface damage than InflammaDry, and its expression was not affected by anti-inflammatory agents. CONCLUSION: Caspase-1 levels were higher in the tears of individuals with ocular surface damage, suggesting its potential to be used as a biomarker and/or therapeutic target.

Effects of ß-Hydroxy ß-Methylbutyric Supplementation in Combination with Conservative Non-Invasive Treatments in Athletes with Patellar Tendinopathy: A Pilot Study.

The aim of the present study was to analyze the effect of conservative non-invasive treatments based on eccentric training, stretching and extracorporeal shock wave therapy (ESWT) supplemented with ß-Hydroxy ß-methylbutyric (HMB) or placebo (PLAC) on body composition, pain and muscular function (jump ability, muscular power and muscular strength) in athletes with patellar tendinopathy (PT). In a double-blind randomized trial, 8 athletes (4 males and 4 females) performed a physical rehabilitation for 4 weeks. They were randomly divided into two experimental groups (two males and two females in each one) that ingested HMB (HMBG) or PLAC (PLACG). In pre- and post-intervention were assessed body composition, pain, countermovement jump (CMJ), back-squat (BS) for analyzing peak power (W) (PPPP), load (kg) associated to PPPP (PPKG) and mean velocity (m/s) (PPMV) in addition to a 5-RM leg extension tests. An interaction intervention·supplementation (p = 0.049; È 2p = 0.774) was observed in the height reached in the CMJ as an intervention effect in PPPP detected for the HMBG (p = 0.049). In addition, an enhancement in PPKG (p = 0.028; È 2p = 0.842) was detected in the intervention, but not in PPMV, as an increase in the intervention in the 5-RM test (p = 0.001; È 2p = 0.981) was observed. No changes were noted on body composition or pain (p > 0.05). The combination of eccentric training with stretching and ESWT increased concentric muscular power and strength after 4 weeks without changes in body lean mass or pain. In addition, HMB supplementation could enhance the power muscular performance in athletes with PT, optimizing the intervention adaptions.

Effects of Mitomycin-C and 5-Fluorouracil on Ocular Adnexal Sebaceous Carcinoma Cells.

PURPOSE: To investigate the effects of mitomycin-C (MMC) and 5-fluorouracil (5-FU) on the viability, proliferation, and migratory capacity of cultured ocular adnexal sebaceous carcinoma (SC) cells. DESIGN: Laboratory investigation. METHODS: Human SC cell lines (Bascom Palmer 50 and 52 [BP50 and BP52]) and human limbal stem cells (LSCs) were treated with various concentrations of MMC and 5-FU. Cytotoxicity was assessed with the tetrazolium MTT colorimetric viability assay on normal corneal vs tumor cells. Growth curves and scratch assays were performed to characterize the effects of these chemotherapeutic agents on SC proliferation and migration, respectively. RESULTS: MMC decreased BP52 cell viability in a dose-dependent manner with a half-maximal effective dose (EC50) of 11.8 µM after 72 hours. SC viability decreased >50% at 80 mM 5-FU after 72 hours. MMC reduced LSC viability in a dose-dependent manner with an EC50 value of 3.24 µM, and 5-FU decreased LSC viability >50% at 160 µM. MMC decreased SC cell proliferation and migration in a dose-dependent manner. 5-FU displayed antiproliferative effects but did not affect cell migration at concentrations below 1000 µM. CONCLUSIONS: Our in vitro data corroborate clinical observations that MMC is efficacious for treating ocular adnexal SC, albeit at the expense of LSC viability. Our findings also demonstrate that topical 5-FU exhibits antiproliferative effects that supersede its cancer-killing and antimigratory effects on cultured SC cells.