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Objective To formatively evaluate the Make Movement Your Mission (MMYM) digital health initiative to promote physical activity (PA) levels and help avert the negative consequences of sedentary behaviours in older adults during the SARS-CoV2 pandemic. Methods Mixed-method study to explore activity levels, changes in physical function and Activities of Daily Living (ADLs), quality-of-life, social engagement, technology use, and accessibility. Survey data were analysed descriptively. Qualitative interviews were analysed using framework analysis. Results Forty-one respondents completed the survey (Mean age 68.4 (8.9) years; 34 Female), 68% aged ≥ 65 years. Average attendance was 14.3 sessions per week (3.5 h). 73% had been with MMYM for >1 year, 90% reported they were engaging in more movement on a typical day, and 75% reported improvement in ability to perform moderate PA. Since starting MMYM, participation in activities targeting strength, balance and flexibility increased (by 48%, 73% and 75%, respectively). 83% met strength and 90% balance PA guidelines for health (≥ 2x per week). Between 18% and 53% of respondents reported improvements in ADLs, 53% reported better quality-of-life, and 28% increased use of the internet. Eight participants were interviewed (Mean age 70.7 (6.7) years; 7 Female). Activity levels were promoted by having direct support from the instructor through Facebook messages pre and post live sessions, having group expectation about quality and level of engagement, having a sense of control and encouragement from others, MMYMs regularity, choice around level of engagement and accessibility. Noticing short-term outcomes in balance and posture helped boost confidence and continued participation. Conclusion Clinical trials need to robustly assess its effectiveness and acceptability.

Background: The study aimed to analyze the 5-year survival of adult patients with glial tumors and to define characteristics that are associated with the disease outcomes in Kazakhstan., Methods: Medical records of patients that were surgically treated at the National Center for Neurosurgery during the 5-year period from 2016 to 2020 were collected retrospectively. Patients with a histologically confirmed diagnosis of diffuse astrocytic or oligodendroglial tumor type were included and their survival was assessed with life tables, Kaplan-Meier plot, and Cox regression using STATA 16 statistical software., Results: Almost half of the patients had glioblastoma. The 5-year survival rate of the whole sample was 45.93%. Among Grade 4 patients, 15.6% survived the 5-year mark. Differences in survival between grades 1-3 were not significant. Grade 1 patients demonstrated worse survival rates compared to Grade 2 patients (69% vs. 74%). Worse survival rates were observed among patients of Russian ethnicity and in rural residents., Conclusions: The study described the unusual patterns in survival rates of glial tumor patients in Kazakhstan, pointing to the need for reassessment of diagnostic accuracy and resulting treatment of glial patients in Kazakhstan, and the need to introduce molecular and genetic parameters in tumor type classification. Moreover, the observed difference in survival of different ethnic groups and residents of rural and urban areas should be further investigated and addressed by healthcare professionals.

Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.

Background: Rupture of intracranial aneurysms (RIA) leads to subarachnoid hemorrhage (SAH) with severe consequences. Although risks for RIA are established, the results vary between ethnic groups and were never studied in Kazakhstan. This study aimed to establish the risk factors of RIA in the Kazakh population.  METHODS: Retrospective analysis of 762 patients with single IAs, who attended the neurosurgical center from 2008 until 2018, was conducted. Demographic characteristics, such as age, sex, smoking status, and hypertension were considered. Descriptive and bivariate analyses were performed. A multivariable logistic regression model was built to identify factors correlated with RIA., Results: The mean age of participants was 48.49 ± 0.44 years old. The majority (68.37%) of IAs have ruptured. Of the ruptured aneurysms, 43.76% were < 6 mm, and 38.39% were located on the anterior cerebral and anterior communicating arteries (ACA). Logistic regression model indicates younger age group (16-40 years), smoking, having stage 3 hypertension, smaller IA size and its location on ACA increase the odds of rupture., Conclusions: This study has revealed that younger, smoking patients with stage 3 arterial hypertension are at higher risk for RIA. Small aneurysms (< 6 mm) and location on ACA had increased odds of rupture, while larger aneurysms on internal carotid arteries had lower odds., (© 2022. The Author(s).)

Purpose: Classic track-and-field studies demonstrated that elite endurance athletes exhibit a slow muscle typology, whereas elite sprint athletes have a predominant fast muscle typology. In elite cycling, conclusive data on muscle typology are scarce, which may be due to the invasive nature of muscle biopsies. The noninvasive estimation of muscle typology through the measurement of muscle carnosine enabled to explore the muscle typology of 80 world-class cyclists of different disciplines., Methods: The muscle carnosine content of 80 cyclists (4 bicycle motor cross racing [BMX], 33 track, 8 cyclo-cross, 24 road, and 11 mountain bike) was measured in the soleus and gastrocnemius by proton magnetic resonance spectroscopy and expressed as a z-score relative to a reference population. Track cyclists were divided into track sprint and endurance cyclists based on their Union Cycliste Internationale (UCI) ranking. Moreover, road cyclists were further characterized based on the percentage of UCI points earned during either single and multistage races., Results: BMX cyclists (carnosine aggregate z-score of 1.33) are characterized by a faster muscle typology than track, cyclo-cross, road, and mountain bike cyclists (carnosine aggregate z-score of -0.08, -0.76, -0.96, and -1.02, respectively; P < 0.05). Track cyclists also possess a faster muscle typology compared with mountain bikers (P = 0.033) and road cyclists (P = 0.005). Moreover, track sprinters show a significant faster muscle typology (carnosine aggregate z-score of 0.87) compared with track endurance cyclists (carnosine aggregate z-score of -0.44) (P < 0.001). In road cyclists, the higher the carnosine aggregate z-score, the higher the percentage of UCI points gained during single-stage races (r = 0.517, P = 0.010)., Conclusions: Prominent differences in the noninvasively determined muscle typology exist between elite cyclists of various disciplines, which opens opportunities for application in talent orientation and transfer., (Copyright © 2020 by the American College of Sports Medicine.)

Introduction: In Kazakhstan, a post-Soviet country in Central Asia, salt intake is estimated as high, potentially contributing to the morbidity and mortality from cardiovascular diseases. The aim of this study was to explore salt intake in residents of the capital of Kazakhstan, Nur-Sultan., Methods: An online cross-sectional survey of knowledge, attitudes, and behaviors on salt intake among young adult residents of the capital city of Kazakhstan was conducted ( n = 237). Bivariate and multivariate linear regression analyses were performed., Results: Although 95% (n=225) reported knowledge on the adverse health effects of high salt intake, older respondents were more aware of its association with high blood pressure (p = 0.007), heart disease (p = 0.037), and heart attack (p = 0.002). Only one-third (n=79) correctly identified the recommended level of daily salt intake. Females reported more awareness of Kazakhstani people consuming salt more than recommended (p = 0.0027) and that processed products constituted the major source of salt in diet (p = 0.007). General dietary concern (p < 0.001), high self-assessmen of salt intake (p < 0.001), and older age (p = 0.012) were found to be adjusted predictors of salt-reducing behavior., Conclusions: Lack of reported knowledge on salt-health relationship is of concern, especially among young males. A greater dietary concern and individual awareness of the excessive salt consumption is likely to assist in reducing salt intake. Further studies are required to validate the findings of this pilot study on a bigger population level in order to provide a basis for future salt related interventions and policy changes in Kazakhstan., (Copyright © 2020 Mina Aubakirova, Marat Sultanov, Aidarkhan Izimov, Yesbolat Sakko, Torekhan Bex, Anuar Mussagazin, Raushan Alibekova.)

Human fast-twitch muscle fibers generate high power in a short amount of time but are easily fatigued, whereas slow-twitch fibers are more fatigue resistant. The transfer of this knowledge to coaching is hampered by the invasive nature of the current evaluation of muscle typology by biopsies. Therefore, a noninvasive method was developed to estimate muscle typology through proton magnetic resonance spectroscopy in the gastrocnemius. The aim of this study was to investigate whether male subjects with an a priori-determined fast typology (FT) are characterized by a more pronounced Wingate exercise-induced fatigue and delayed recovery compared with subjects with a slow typology (ST). Ten subjects with an estimated higher percentage of fast-twitch fibers and 10 subjects with an estimated higher percentage of slow-twitch fibers underwent the test protocol, consisting of three 30-s all-out Wingate tests. Recovery of knee extension torque was evaluated by maximal voluntary contraction combined with electrical stimulation up to 5 h after the Wingate tests. Although both groups delivered the same mean power across all Wingates, the power drop was higher in the FT group (-61%) compared with the ST group (-41%). The torque at maximal voluntary contraction had fully recovered in the ST group after 20 min, whereas the FT group had not yet recovered 5 h into recovery. This noninvasive estimation of muscle typology can predict the extent of fatigue and time to recover following repeated all-out exercise and may have applications as a tool to individualize training and recovery cycles. NEW & NOTEWORTHY A one-fits-all training regime is present in most sports, though the same training implies different stimuli in athletes with a distinct muscle typology. Individualization of training based on this muscle typology might be important to optimize performance and to lower the risk for accumulated fatigue and potentially injury. When conducting research, one should keep in mind that the muscle typology of participants influences the severity of fatigue and might therefore impact the results.

Carnosine (beta-alanyl-L-histidine) and its methylated analogue anserine are present in relevant concentrations in the omnivore human diet. Several studies reported promising therapeutic potential for carnosine in various rodent models of oxidative stress and inflammation-related chronic diseases. Nevertheless, the poor serum stability of carnosine in humans makes the translation of rodent models hard. Even though anserine and carnosine have similar biochemical properties, anserine has better serum stability. Despite this interesting profile, the research on anserine is scarce. The aim of this study was to explore the bioavailability and stability of synthesized anserine by (1) performing in vitro stability experiments in human plasma and molecular modelling studies and by (2) evaluating the plasma and urinary pharmacokinetic profile in healthy volunteers following different doses of anserine (4-10-20 mg/kg body weight). A bio-analytical method for measuring anserine levels was developed and validated using liquid chromatography-electrospray mass spectrometry. Both plasma (C MAX : 0.54-1.10-3.12 µM) and urinary (C MAX : 0.09-0.41-0.72 mg/mg creatinine) anserine increased dose-dependently following ingestion of 4-10-20 anserine mg/kg BW, respectively. The inter-individual variation in plasma anserine was mainly explained by the activity (R 2  = 0.75) and content (R 2  = 0.77) of the enzyme serum carnosinase-1. Compared to carnosine, a lower interaction energy of anserine with carnosinase-1 was suggested by molecular modelling studies. Conversely, the two dipeptides seems to have similar interaction with the PEPT1 transporter. It can be concluded that nutritionally relevant doses of synthesized anserine are well-absorbed and that its degradation by serum carnosinase-1 is less pronounced compared to carnosine. This makes anserine a good candidate as a more stable carnosine-analogue to attenuate chronic diseases in humans.

Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily β-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (P<0·001) and gastrocnemius (P=0·001) muscle. To conclude, the body creatine pool declined over a 3-month vegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

Purpose: Beta-alanine (BA) supplementation has been shown to augment muscle carnosine concentration, thereby promoting high-intensity (HI) exercise performance. Trained muscles of athletes have a higher increase in carnosine concentration after BA supplementation compared to untrained muscles, but it remains to be determined whether this is due to an accumulation of acute exercise effects or to chronic adaptations from prior training. The aim of the present study was to investigate whether high-volume (HV) and/or HI exercise can improve BA-induced carnosine loading in untrained subjects., Methods: All participants (n = 28) were supplemented with 6.4 g/day of BA for 23 days. The subjects were allocated to a control group, HV, or HI training group. During the BA supplementation period, the training groups performed nine exercise sessions, consisting of either 75-90 min continuous cycling at 35-45% Wmax (HV) or 3 to 5 repeats of 30 s cycling at 165% Wmax with 4 min recovery (HI). Carnosine content was measured in soleus and gastrocnemius medialis by proton magnetic resonance spectroscopy., Results: There was no difference in absolute increase in carnosine content between the groups in soleus and gastrocnemius muscle. For the average muscle carnosine content, a higher absolute increase was found in HV (+2.95 mM; P = 0.046) and HI (+3.26 mM; P = 0.028) group compared to the control group (+1.91 mM). However, there was no additional difference between the HV and HI training group., Conclusion: HV and HI exercise training showed no significant difference on BA-induced muscle carnosine loading in soleus and gastrocnemius muscle. It can be suggested that there can be a small cumulative effect of exercise on BA supplementation efficiency, although differences did not reach significance on individual muscle level.

Introduction: Chronic β-alanine (BA) supplementation is an increasingly popular nutritional strategy, because it can elevate muscle carnosine content and thereby enhance high-intensity exercise performance. The current study investigated 1) whether sex and body mass are determinants of BA-induced muscle carnosine loading and 2) the optimal maintenance dose for ensuring constantly elevated muscle carnosine stores., Methods: During the loading phase, 34 participants (men and women) were supplemented with 3.2 g (4 × 800 mg) BA per day for 46 d (slightly different loading strategies were applied concerning the effect of meal timing and supplementation form). Thereafter, 19 participants (men and women) continued taking free-powder BA for six more weeks (maintenance phase). The participants were matched and redivided into three groups receiving 0.4, 0.8, and 1.2 g·d(-1) BA, respectively. Muscle carnosine content was measured in the soleus and gastrocnemius muscles using proton magnetic resonance spectroscopy., Results: Body mass and sex had only minimal effect on the absolute increase in muscle carnosine. Given the lower baseline values in women, the relative increase for women was higher, indicating that women required less BA for the same relative increase. In addition, a significant negative correlation was observed between body mass and the relative increase in muscle carnosine (r = -0.45, P = 0.007). A maintenance dose of ∼1.2 g·d(-1) BA was the most effective in keeping muscle carnosine content elevated at the postsupplementation level., Conclusions: Sex and body mass did not markedly affect the absolute increase during muscle carnosine loading, although they are determinants for the relative increase. In addition, we established for the first time an effective maintenance dose of ∼1.2 g·d(-1) BA to keep muscle carnosine content elevated at 30%-50% above baseline for a prolonged period.

Muscle carnosine loading through chronic oral beta-alanine supplementation has been shown to be effective for short-duration, high-intensity exercise. This randomized, placebo-controlled study explored whether the ergogenic effect of beta-alanine supplementation is also present for longer duration exercise. Subjects (27 well-trained cyclists/triathletes) were supplemented with either beta-alanine or placebo (6.4 g/day) for 6 weeks. Time to completion and physiological variables for a 1-hr cycling time-trial were compared between preand postsupplementation. Muscle carnosine concentration was also assessed via proton magnetic resonance spectroscopy before and after supplementation. Following beta-alanine supplementation, muscle carnosine concentration was increased by 143 ± 151% (mean ± SD; p < .001) in the gastrocnemius and 161 ± 56% (p < .001) in the soleus. Postsupplementation time trial performance was significantly slower in the placebo group (60.6 ± 4.4-63.0 ± 5.4 min; p < .01) and trended toward a slower performance following beta-alanine supplementation (59.8 ± 2.8-61.7 ± 3.0 min; p = .069). We found an increase in lactate/proton concentration ratio following beta-alanine supplementation during the time-trial (209.0 ± 44.0 (beta-alanine) vs. 161.9 ± 54.4 (placebo); p < .05), indicating that a similar lactate concentration was accompanied by a lower degree of systemic acidosis, even though this acidosis was quite moderate (pH ranging from 7.30 to 7.40). In conclusion, chronic beta-alanine supplementation in well-trained cyclists had a very pronounced effect on muscle carnosine concentration and a moderate attenuating effect on the acidosis associated with lactate accumulation, yet without affecting 1-h time-trial performance under laboratory conditions.

Introduction: Beta-alanine (BA) is a popular ergogenic supplement because it can induce muscle carnosine loading. We hypothesize that, by analogy with creatine supplementation, 1) an inverse relationship between urinary excretion and muscle loading is present, and 2) the latter is stimulated by carbohydrate- and protein-induced insulin action., Methods: In study A, the effect of a 5-wk slow-release BA (SRBA) supplementation (4.8 g · d(-1)) on whole body BA retention was determined in seven men. We further determined whether the coingestion of carbohydrates and proteins with SRBA would improve retention. In study B (34 subjects), we explored the effect of meal timing on muscle carnosine loading (3.2 g · d(-1) during 6-7 wk). One group received pure BA (PBA) in between the meals; the other received PBA at the start of the meals, to explore the effect of meal-induced insulin release. Further, we compared with a third group receiving SRBA at the start of the meals., Results and Conclusion: Orally ingested SRBA has a very high whole body retention (97%-98%) that is not declining throughout the 5-wk supplementation period, nor is it influenced by the coingestion of macronutrients. Thus, a very small portion (1%-2%) is lost through urinary excretion, and equally only a small portion is incorporated into muscle carnosine (≈ 3%), indicating that most ingested BA is metabolized (possibly through oxidation). Second, in soleus muscles, the efficiency of carnosine loading is significantly higher when PBA is coingested with a meal (+64%) compared with in between the meals (+41%), suggesting that insulin stimulates muscle carnosine loading. Finally, the chronic supplementation of SRBA versus PBA seems equally effective.

Objectives: Within the laboratory protocols, used for the study of BCR-ABL resistance mutations in chronic myeloid leukemia patients treated with Imatinib, direct sequencing remains the reference method. Since the incidence of patients with a mutation-related loss of response is not very high, it is very useful in the routine laboratory to perform a fast pre-screening method., Design and Methods: With this in mind, we have designed a new technique, based on a single Real-Time FRET-based PCR, followed by a study of melting peaks. This new tool, developed in a LightCycler 2.0, combines four different fluorescence channels for the simultaneous detection, in a single close tube, of critical mutations within the ABL kinase domain., Results: Assay evaluation performed on 33 samples, previously genotyped by sequentiation, resulted in full concordance of results., Conclusions: This new methodology detects in a few steps the presence of critical mutations associated to Imatinib resistance., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Trabectedin, a naturally occurring substance isolated from the Caribbean marine invertebrate Ecteinascidia turbinata, is the active compound of the antitumor drug Yondelis®. The mechanism of action of Trabectedin has been attributed to interactions with the minor groove of the DNA double helix, thereby affecting transcription of different genes involved in DNA repair and thus facilitating lethal DNA strand breaks. Nevertheless, the existence of other clinically important molecular mechanisms has not yet been fully explored. In this paper we demonstrate how Yondelis®, apart from activating the caspase-8-dependent cascade of apoptosis, sensitizes cancer cells to Fas-mediated cell death at achievable concentrations similar to those found in the plasma of patients. In addition we show that the facilitated apoptosis activated through the Fas death receptor, is associated with a significant increase of membrane Fas/FasL, as well as the modulation of accessory proteins regulating this route, such as FLIP (L) or Akt. Thus, our results propose that the sensitization of the death receptor pathway is an essential mechanism amplifying the cytotoxic properties of Yondelis® that could explain the hepatotoxicity observed in patients treated with this drug. Finally, we also show how the use of dexamethasone as a prophylactic agent that protects against hepatotoxicity induced by Yondelis® may also inhibit some of the cytotoxic properties described in this work. The study of this important mechanism of action should set up the basis for reassessing clinical therapy with Yondelis® in order to improve antitumor treatment outcome., (Copyright © 2011 Elsevier B.V. All rights reserved.)