Major determinants of primary non function from kidney donation after Maastricht II circulatory death: A single center experience.

PURPOSE: Organ shortage greatly limits treatment of patients with end-stage chronic kidney. Maastricht type 2 donation after circulatory death (DCD) has been shown to have similar results in long term outcomes in kidney transplantation, when compared with brain dead donation. Our main goal was to assess Maastricht type 2 DCD and evaluate factors that impact on early graft function. METHODS: A retrospective study was conducted in an ECMO Referral Centre. All patients who received a kidney transplant from Maastricht type 2 DCD were included in study. Early graft function and short term outcomes were assessed. RESULTS: From October 2017 to December 2022, 47 renal grafts were collected from 24 uDCD donors. Median warm ischemia time was 106 min (94-115), cannulation time was 10 min (8; 20) and duration of extracorporeal reperfusion (ANOR) was 180 min (126-214). Regarding early graft function, 25% had immediate graft function, 63.6% had delayed graft function and 11.4% had primary non-function (PNF). There was a correlation between cannulation time (p = 0.006) and ANOR with PNF (p = 0.016). CONCLUSIONS: Cannulation time and ANOR were the main factors that correlated with PNF. Better understanding of underlying mechanisms should be sought in future studies to reduce the incidence of PNF.

Anticoagulation Management in V-V ECMO Patients: A Multidisciplinary Pragmatic Protocol.

(1) Background: Extracorporeal membrane oxygenation (ECMO) is a complex procedure affecting both the risk of thrombosis and bleeding. High-quality data to personalize anticoagulation management in ECMO are lacking, resulting in a high variability in practice among centers. For this reason, we review coagulation methods and monitoring and share a pragmatic proposal of coagulation management, as performed in our high-volume ECMO Referral Centre; (2) Methods: We revised the anticoagulation options and monitoring methods available for coagulation management in ECMO through PubMed search based on words including "anticoagulation," "coagulation assays," "ECMO," "ELSO," and "ISTH"; (3) Results: Actual revision of the literature was described as our routine practice regarding ECMO anticoagulation and monitoring; (4) Conclusions: No coagulation test is exclusively predictive of bleeding or thrombotic risk in patients undergoing ECMO support. An approach that allows for a tailored regimen of anticoagulation (regardless of agent used) and monitoring is mandatory. To accomplish this, we propose that the titration of anticoagulation therapies should include multiple laboratory tests, including anti-Xa, aPTT, ACT, viscoelastic tests, AT levels, platelet count, fibrinogen, and FXIII levels. Anticoagulation regimens should be tailored to a specific patient and personalized based on this complex array of essays.

Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness.

Ageing, a sedentary lifestyle, and obesity are associated with increased oxidative stress, while regular exercise is associated with an increased antioxidant capacity in trained skeletal muscles. Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO2max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO2max, age and adiposity differences. Multiple regression analysis indicates that the VO2max in mL.kg LLM-1.min-1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO2max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO2max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO2max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.

Thermal resting pattern and acute skin temperature response to exercise in older adults: Role of cardiorespiratory fitness.

BACKGROUND: Infrared thermography is a growing area of interest in sports science due to the potential of skin temperature (Tsk) measurements to provide valuable information from rest to exercise. However, limited research exists on Tsk in older adults and the impact of factors such as sex and cardiorespiratory fitness (CRF) on Tsk. This study aims to investigate Tsk at rest and after acute exercise in older adults and assess whether sex or CRF influences Tsk. METHODS: Ninety-two participants (41 women, 68.48 ± 3.01 years) were examined with a thermographic camera in a conditioned room (23.02 ± 3.01 °C) at rest and after a graded protocol. The Tsk of 25 regions of interest (ROIs) were extracted and analysed. RESULTS: Men had higher overall Tsk at rest in 76% of ROIs, showing significant differences (p < 0.010) in six specific ROIs, independent of CRF. Both sexes had similar Tsk responses after graded exercise, with increases in distal parts (1.06 ± 0.50 °C), decreases in proximal parts (-0.62 ± 0.42 °C), and stable central Tsk (0.23 ± 0.59 °C). Increases in lower limb Tsk were significantly associated with CRF in men and women (ß = 0.438, p = 0.001, and ß = 0.535, p < 0.001, respectively), explaining 17% and 27% of the variance, respectively. CONCLUSIONS: This study demonstrates a sex-specific effect on resting Tsk in older adults, suggesting that sex-specific Tsk patterns should be considered when analysing Tsk in this population. Additionally, the association between increases in lower limb Tsk and CRF suggests that Tsk could be a promising predictor of CRF in older adults.

COVID-19-associated Coagulopathy Characterization using Rotational Thromboelastometry in a Prospective, Observational Cohort Study: The HemoCoV Study.

INTRODUCTION: COVID-19-associated coagulopathy includes systemic and endothelial inflammation with coagulation dysregulation related to immunothrombosis. The aim of this study was to characterize this complication of SARS-CoV-2 infection in patients with moderate to severe COVID-19. METHODS: An open-label, prospective observational study conducted in patients with COVID-19 moderate to severe acute respiratory failure admitted to an intensive care unit (ICU). Coagulation testing, including thromboelastometry, biochemical analysis and clinical variables, were collected at prespecified time points during the 30 days of ICU stay. RESULTS: The study included 145 patients, 73.8% male, with a median age of 68 years (interquartile range - IQR 55 - 74). The most prevalent comorbidities were arterial hypertension (63.4%), obesity (44.1%) and diabetes (22.1%). Simplified acute physiology score II (SAPS II) was on average 43.5 (11 - 105) and sequential organ failure assessment (SOFA) at admission was 7.5 (0 - 14). During ICU stay, 66.9% of patients underwent invasive mechanical ventilation and 18.4% extracorporeal membrane oxygenation support; thrombotic and hemorrhagic events occurred in 22.1% and 15.1% of the patients respectively; anticoagulation with heparin was present in 99.2% of patients since early ICU stay. Death occurred in 35% of patients. Longitudinal studies revealed changes in almost all coagulation tests during the ICU stay. SOFA score, lymphocyte counts, some biochemical, inflammatory and coagulation parameters, including hypercoagulability and hypofibrinolysis seen in thromboelastometry, differed significantly (p < 0.05), between ICU admission and discharge. Hypercoagulability and hypofibrinolysis persisted throughout ICU hospitalization, showing higher incidence and severity in non-survivors. CONCLUSION: COVID-19-associated coagulopathy is characterized by hypercoagulability and hypofibrinolysis from ICU admission, and persisted throughout the clinical course in severe COVID-19. These changes were more pronounced in patients with higher disease burden and in non-survivors.

Sustained secretion of human growth hormone from TheraCyte devices encapsulated with PiggyBac-engineered retinal pigment epithelium cells.

Growth hormone (GH) deficiency is characterized by impaired growth and development, and is currently treated by repeated administration of recombinant human GH (hGH). Encapsulated cell therapy (ECT) may offer a less demanding treatment-strategy for long-term production and release of GH into circulation. We used PiggyBac-based (PB) transposon delivery for engineering retinal pigment epithelial cells (ARPE-19), and tested a series of viral and non-viral promoters as well as codon-optimization to enhance transgene expression. Engineered cells were loaded into TheraCyte macrocapsules and secretion was followed in vitro and in vivo. The cytomegalovirus (CMV) promoter supports strong and persistent transgene expression, and we achieved clonal cell lines secreting over 6 µg hGH/106 cells/day. Codon-optimization of the hGH gene did not improve secretion. ARPE-19 cells endured encapsulation in TheraCyte devices, and resulted in steady hormone release for at least 60 days in vitro. A short-term pilot experiment in immunodeficient SCID mice demonstrated low systemic levels of hGH from a single 40 µL capsule implanted subcutaneously. No significant increase in weight increase or systemic hGH was detected after 23 days in the GH-deficient lit/SCID mouse model using 4.5 µL capsules loaded with the highest secreting clone of ARPE-19 cells. Our results demonstrate that PB-mediated engineering of ARPE-19 is an efficient way to generate hormone secreting cell lines compatible with macroencapsulation, and our CMV-driven expression cassette allows for identification of clones with high level and long-term secretory activity without addition of insulator elements. Our results pave the way for further in vivo studies of encapsulated cell therapy.

Changes in Muscle Deoxygenation During Squat Exercise After 6-Week Resistance Training With Different Percentages of Velocity Loss.

ABSTRACT: Costilla, M, Casals, C, Marín-Galindo, A, Sánchez-Sixto, A, Muñoz-López, A, Sañudo, B, Corral-Pérez, J, and Ponce-González, JG. Changes in muscle deoxygenation during squat exercise after 6-week resistance training with different percentages of velocity loss. J Strength Cond Res 37(8): 1573-1580, 2023-The present study compared, for the first time, the effects of 6 weeks of 20% (20VL) vs. 40% (40VL) velocity loss (VL) resistance training (RT) programs on muscle oxygen dynamics during the squat exercise. Twenty-three young men (21.4 ± 2.4 years) were randomly allocated into the 20VL group ( n = 8), 40VL group ( n = 7), or control group (CG; n = 8). The RT program consisted of 3 sets of Smith machine back squat exercise at 20VL or 40VL with a 3-minute rest between sets, twice per week for 6 weeks. Tissue oxygenation index (TOI) was measured using near-infrared spectroscopy in the vastus medialis and vastus lateralis during a squat test (8-repetition 1 m·s -1 load test), and the maximum (maxTOI) and minimum (minTOI) TOIs were measured during a 3-min recovery period. After the 6-week RT program, TOI increased significantly at the beginning of the test in both muscles (during the first 4 repetitions in the vastus lateralis and 5 repetitions in the vastus medialis) in the 20VL group ( p < 0.05), with nonsignificant changes in the 40VL group and CG. The maxTOI was significantly increased in the vastus medialis (+3.76%) and vastus lateralis (+3.97%) after the training only in the 20VL group ( p < 0.05). The minTOI in the vastus medialis reached during the test remained unchanged postintervention for both training groups, with the CG showing significantly higher values compared with the 20VL group (+14.1%; p < 0.05). In conclusion, depending on the VL reached during a squat RT program, different changes in muscle oxygen dynamics can be expected. Training at 20% of VL improves metabolic efficiency and the reoxygenation peak after the set.

Drug repositioning: diacerein as a new therapeutic approach in a mice model of sciatic nerve injury.

BACKGROUND: Peripheral nerve injuries negatively impact the quality of life of patients, with no effective treatment available that accelerates sensorimotor recovery and promotes functional improvement and pain relief. The aim of this study was to evaluate the effects of diacerein (DIA) in an experimental mice model of sciatic nerve crush. METHOD: In this study, male Swiss mice were used, randomly separated into six groups as follows: FO (false-operated + vehicle); FO + DIA (false-operated + diacerein 30 mg/kg); SNI (sciatic nerve injury + vehicle); SNI + DIA in doses of 3, 10 and 30 mg/kg (sciatic nerve injury + treatment with diacerein in doses of 3-30 mg/kg). DIA or vehicle was administered 24 h after the surgical procedure, intragastrically, twice a day. The lesion of the right sciatic nerve was generated by crush. RESULTS: We found that the treatment of animals with DIA accelerated sensorimotor recovery of the animal. In addition, animals in the sciatic nerve injury + vehicle (SNI) group showed hopelessness, anhedonia, and lack of well-being, which were significantly inhibited by DIA treatment. The SNI group showed a reduction in the diameters of nerve fibers, axons, and myelin sheaths, while DIA treatment recovered all these parameters. In addition, the treatment of animals with DIA prevented an increase the levels of interleukin (IL)-1ß and a reduction in the levels of the brain-derived growth factor (BDNF). CONCLUSIONS: Treatment with DIA reduces hypersensitivity and depression like behaviors in animals. Furthermore, DIA promotes functional recovery and regulates IL-1ß and BDNF concentrations.

Feasibility and performance of a combined extracorporeal assisted cardiac resuscitation and an organ donation program after uncontrolled cardiocirculatory death (Maastricht II).

INTRODUCTION: Approximately 500.000 people in Europe sustain cardiac arrest (CA) every year, being myocardial infarction the main etiology. Interest has been raised in a new approach to refractory cardiac arrest (rCA) using extra-corporeal oxygenation (ECMO). In settings where it can be rapidly implemented, ECMO assisted resuscitation (ECPR) may be considered. Additionally, donation after circulatory death, which seeks to obtain solid organs donation from patients suffering rCA, has increased its role effectively increasing the pool of donors. Combined programs with integration of ECPR and uncontrolled donation after circulatory determination of death (uDCDD) are worldwide limited and experience integrating these two techniques is lacking. METHODS: We report a 24 months experience of ECPR and uDCDD kidney transplantation based on a management protocol in a university teaching hospital in the urban area of Lisbon. RESULTS: Over a period of 24 months, 58 patients were admitted to our ICU with rCA, 6 (10%) in the ECPR program and 52 (90%) in the uDCDD. Seventy-eight percent of patients were male, with an average age of 49 year-old. CA was witnessed in 83% of cases and initial rhythm was ventricular fibrillation in 20 cases (35%). 13 (25%) patients were effective organ donors. Refusal for effective donation was mainly due to prior comorbidities. DISCUSSION: The development of an integrated program for ECPR and uDCDD is feasible and requires a well-established and efficient activation program. In an era of significant organ shortage, it provides a viable option for increasing the organ donation pool, with promising results.

Does a Diet Rich in the Bacterium Rhodopirellula rubra Improve Daphnia magna Performance?

BACKGROUND: In the wild various organisms contribute to daphnids diet. This study, intendeds to evaluate the potential of the concentration of Rhodopirellula rubra as a single or supplementary food source for Daphnia magna. METHODS: Feeding assays were performed according to standard guidelines for chronic assays (21 days), and life-history parameters and several biomarkers (protein content, oxidative stress, energetic reserves and pigments) were measured. Five food regimens were conducted with 20 individual replicates (A - R. subcapitata; 0.2 - suspension of R. rubra at 0.2 arbitrary units (AU); 0.4 - suspension of R. rubra at 0.4 AU; 0.2+A - suspension of R. rubra at 0.2+alga; 0.2+A-suspension of R. rubra at 0.4 AU + alga). Additionally, the effects of three diets (A, 0.2, and 0.2+A) on the longevity of D. magna were assessed. RESULTS: The five diets showed a different C, N, and carotenoids composition, with an increase in the mixed diets. The results confirmed that the mixed diets improved D. magna life-history parameters. A decrease in glycogen, and the increase of haemoglobin, protein, and gluthione-S-transferase (GST) were observed. Furthermore, D. magna fed with bacterial single diets, presented worsen life history parameters and a decrease in the protein content. An induction of oxidative stress response (increased catalase and GST), and a significant decrease in lipid peroxidation and an accumulation of glycogen and carotenoids were observed. Overall, an increase in the amount of R. rubra provided to D. magna, from 0.2 AU to 0.4 AU, negatively impacted daphnid performance. No significant effects on Daphnia longevity (a 110-day assay) were observed among the three diets tested. However, a significant survival percentage and fertility (cumulative offspring is more than twice) was observed when D. magna was fed with the mixed diet. CONCLUSIONS: Results demonstrated that different diets provided a nutritional diversified food to the daphnids that induced differences in D. magna performance. The mixed diets proved to be beneficial (with increase in offspring) on D. magna performance, independently of the bacterial concentration tested. When in single diet, bacterial concentration is not nutritionally sufficient to raise D. magna even when in increased concentration.

Preclinical Pharmacokinetic and Pharmacodynamic Investigation of 5'-Methoxynobiletin from Ageratum conyzoides: In vivo and In silico Approaches.

PURPOSE: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown. Considering the anti-inflammatory potential of the 5'-MeONB, this study aimed to investigate the pre-clinical PK behavior of 5'-MeONB, as well as its time course antinociceptive activity. METHODS: 5'-MeONB plasma concentrations were determined in Wistar rats after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) administration, and in Swiss mice after oral administration (100 mg/kg). Plasma samples were deproteinization and 5'-MeONB quantified by a validated UPLC-MS method. Additionally, the antinociceptive activity of 5'-MeONB was evaluated after 15, 30, 60, 180 and 360 min following oral administration on the acute nocifensive behavior of mice induced by formalin. RESULTS: 5'-MeONB rats and mice plasma concentration-time profiles were best one-compartment model. After i.v. administration to rats, a short half-life, a high clearance and moderate volume of distribution at steady state were observed. Similar results were obtained after oral administration. The oral bioavailability ranged from 8 to 11%. Additionally, 5'-MeONB exhibited antinociceptive activity in both formalin phases, especially in the inflammatory phase of the model, inhibiting 68% and 91% of neurogenic and inflammatory responses, respectively, after 30 min of oral administration. CONCLUSIONS: The results described here provide novel insights on 5'-MeONB pharmacokinetics and pharmacodynamic effect, serving as support for future studies to confirm this compound as anti-nociceptive and anti-inflammatory effective agent.

Antioxidants Markers of Professional Soccer Players During the Season and their Relationship with Competitive Performance.

The aim of this study was to assess antioxidant markers before and after a mid-season of professional soccer players from the 3rd Spanish Division, and to correlate antioxidant markers with competitive performance. Sixty-five male players (age = 25.3 ± 4.2 yr, body mass = 73.2 ± 6.7 kg, body height = 177.8 ± 5.7 cm) from three soccer clubs from Cádiz (Spain) participated in the study. Body composition, maximal aerobic capacity (VO2max), and baseline antioxidant blood markers (Total Antioxidant Status (TAS) and Reduced glutathione/Oxidized glutathione ratio) were assessed in the first week of the championship season (pre-test) and after 18 weeks in the mid-season (post-test). Soccer performance was registered according to the official classification ranking at both the mid-season and at the end of the season; ranking positions for Team A were 2nd and 1st, for Team B were 5th and 5th, while for Team C were 12th and 14th, respectively. Regression analyses showed that TAS and VO2max were able to independently predict (p < 0.05) performance in our participants. Moreover, antioxidant levels showed significant main effects on performance (p < 0.001); where a higher antioxidant capacity was observed in the best performance soccer team, both before and after the mid-season. Notwithstanding, the competitive period compromised the antioxidant status since TAS levels significantly decreased after the 18-week training program and competition compared with baseline values in all soccer teams (p < 0.001). These results suggest the need of monitoring antioxidants in soccer players to prevent excessive oxidative stress and cellular damage which could compromise success in competition, by adjusting the training loads, diet or ergogenic aids, if needed.

When Paranoia Comes with the Treatment: Psychosis Associated with Tacrolimus Use.

Tacrolimus is an immunosuppressive drug frequently used in solid organ transplant recipients. This drug has well-documented neuropsychiatric side effects in the literature, although emergence of psychotic symptoms is rare, being only described in a very few case reports. We present a case of a renal transplant recipient with no prior psychiatric history, who developed a severe psychosis secondary to supratherapeutic tacrolimus' blood concentrations. This case highlights the importance of clinical awareness to rare but severe neuropsychiatric effects due to tacrolimus use.

Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.

Maximal fat oxidation capacity is associated with cardiometabolic risk factors in healthy young adults.

It is unknown whether resting fat oxidation (RFO), maximal fat oxidation (MFO) and FatMax (intensity at which MFO is reached) are related to cardiometabolic risk (CMR). Thus the aim of this study was to examine the association of RFO, MFO and FatMax with CMR. 81 healthy adults (n = 31 women; 22.72 ± 4.40 years) participated in this cross-sectional study. Glucose and triglycerides were analysed in plasma. Body composition, anthropometry, physical activity, blood pressure (BP) and heart rate measurements were taken. RFO and MFO were determined through indirect calorimetry. Maximal oxygen uptake (VO2max) test was performed until exhaustion after MFO test. The CMR cluster was created from individual CMR factors: waist circumference, body fat percentage, systolic BP, diastolic BP, blood glucose and plasma triglycerides. Groups of high and low MFO and VO2max were created. RFO was not associated with CMR (p < 0.05). FatMax, MFO and VO2max were associated with individual CMR factors as waist circumference (R2 = 0.144; R2 = 0.241; R2 = 0.285; p = 0.001; respectively) and plasma triglycerides (R2 = 0.111; p = 0.004 and R2 = 0.130; p = 0.002 and R2 = 0.093; p = 0.008; respectively) and clustered CMR factors (R2 = 0.105; p = 0.008 and R2 = 0.162; p = 0.001 and R2 = 0.239; p = 0.001; respectively). VO2max was also associated with body fat percentage (R2 = 0.105; p = 0.003) and diastolic BP (R2 = 0.083; p = 0.01), even adjusting for sex or age (p < 0.05). Groups with high level of MFO or VO2max obtained lower CMR (p = 0.001), even adjusting for sex or age (p < 0.01). FatMax, MFO and, especially, VO2max are associated with CMR, regardless of age and sex. However, RFO is not associated with CMR.

Optimization of Mouse Growth Hormone Plasmid DNA Electrotransfer into Tibialis Cranialis Muscle of "Little" Mice.

Previous non-viral gene therapy was directed towards two animal models of dwarfism: Immunodeficient (lit/scid) and immunocompetent (lit/lit) dwarf mice. The former, based on hGH DNA administration into muscle, performed better, while the latter, a homologous model based on mGH DNA, was less efficient, though recommended as useful for pre-clinical assays. We have now improved the growth parameters aiming at a complete recovery of the lit/lit phenotype. Electrotransfer was based on three pulses of 375 V/cm of 25 ms each, after mGH-DNA administration into two sites of each non-exposed tibialis cranialis muscle. A 36-day bioassay, performed using 60-day old lit/lit mice, provided the highest GH circulatory levels we have ever obtained for GH non-viral gene therapy: 14.7 ± 3.7 ng mGH/mL. These levels, at the end of the experiment, were 8.5 ± 2.3 ng/mL, i.e., significantly higher than those of the positive control (4.5 ± 1.5 ng/mL). The catch-up growth reached 40.9% for body weight, 38.2% for body length and 82.6%-76.9% for femur length. The catch-up in terms of the mIGF-1 levels remained low, increasing from the previous value of 5.9% to the actual 8.5%. Although a complete phenotypic recovery was not obtained, it should be possible starting with much younger animals and/or increasing the number of injection sites.

Austrian Syndrome: a report of an exceptionally rare and deadly syndrome / Síndrome de Austrian: descrição de uma entidade excepcionalmente rara e mortal

ABSTRACT: Austrian Syndrome is the rare combination of a triad of endocarditis, meningitis, and pneumonia in the context of pneumococcal infection. Due to the involvement of several anatomical sites, the Austrian syndrome has a high mortality. Importantly, endocarditis is usually not considered during pneumococcal infection. We present a case of Austrian syndrome in a previously healthy 67-year-old woman. She featured with mental state alteration, respiratory failure, and shock, and was diagnosed with ceftriaxone-sensitive pneumococcal bacteremia, meningitis, and pneumonia. A transesophageal echocardiogram revealed vegetation of the mitral valve. Despite an improvement in her medical condition, she remained in a coma and died due to neurological complications. Even though the major cause of mortality in Austrian syndrome is cardiac involvement, meningitis is also linked with high morbidity and eventually death. We emphasize the relevance of an early diagnosis of the triad in order to decrease the very high mortality associated with this syndrome

RESUMO: A síndrome de Austrian é uma entidade extremamente rara, pautada por meningite, endocardite e pneumonia secundárias a doença pneumocócica invasiva. Devido à expressão multissistêmica, a mortalidade associada é elevada. Particularmente, a manifestação como endocardite é muitas vezes clinicamente insuspeita, carecendo de elevado índice de suspeita. Apresenta-se um caso de síndrome de Austrian numa doente do sexo feminino, 67 anos, previamente saudável. Clinicamente, apresentava coma, insuficiência respiratória e choque, tendo sido diagnosticada pneumonia e meningite, e com bacteremia a Streptococcus pneumoniae. Ecocardiograma transesofágico evidenciou uma vegetação na válvula mitral. Apesar da regressão do quadro respiratório, persistiu um quadro de coma, acabando a doente por morrer. Apesar da principal causa de morte descrita na síndrome de Austrian estar relacionada com complicações de endocardite, apresenta-se um caso único de apresentação e morte por meningite. Com poucos casos descritos mundialmente, sublinha-se a necessidade de um diagnóstico precoce desta tríade, motivo pelo qual relatamos o caso descrito

Impact of Active Recovery and Whole-Body Electromyostimulation on Blood-Flow and Blood Lactate Removal in Healthy People.

This study aimed to determine whether an active recovery with added whole-body electromyostimulation (WB-EMS) can increase blood flow and lead to blood lactate removal after intense exercise. Thirty-five healthy individuals (23.1 ± 4.6 years) were randomly assigned to: (a) an experimental group using active recovery together with the WB-EMS (n = 18) or (b) a control group using the same active recovery protocol with the suit with no-stimulation (CON, n = 17). Participants performed a maximal graded exercise test followed by an active recovery protocol (walking at 40% of their maximum aerobic velocity). During the recovery, participants in WB-EMS and CON received continuous stimulation at 7 Hz or no stimulation, respectively. Heart rate, blood lactate concentrations, pain/discomfort, and hemodynamic measurements were recorded before and after the test, and repeated immediately after and at min 30 and 60. The between-group analysis showed a substantially greater Peak blood velocity (-0.27 [-0.68; 0.14]) in WB-EMS compared to CON. The pain/discomfort levels were also lower in WB-EMS compared with CON (0.66 [-0.12; 1.45]). Non-significant differences in participants' blood lactate were observed in WB-EMS compared with CON both immediately; at 30and 60 min. Our findings suggest that increased local blood flow induced by WB-EMS may have contributed to greater lactate removal from active muscles and blood lactate clearance. WB-EMS may be an effective means of increasing muscle blood flow after a maximal graded exercise test and could result in improved recovery.