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Here, the authors show structural, biochemical, and functional insights into the discovery of epichaperome‐ directed chemical probes for use in central nervous system diseases. Probes emerging from this work have translated to human clinical studies in Alzheimer’s disease and cancer.

Post‐translational modifications such as protein N‐glycosylation, significantly influence cellular processes. Dysregulated N‐glycosylation, exemplified in Grp94, a member of the Hsp90 family, leads to structural changes and the formation of epichaperomes, contributing to pathologies. Targeting N‐glycosylation‐induced conformations offers opportunities for developing selective chemical tools and drugs for these pathologic forms of chaperones. We here demonstrate how a specific Grp94 conformation induced by N‐glycosylation, identified previously via molecular dynamics simulations, rationalizes the distinct behavior of similar ligands. Integrating dynamic ligand unbinding information with SAR development, we differentiate ligands productively engaging the pathologic Grp94 conformers from those that are not. Additionally, analyzing binding site stereoelectronic properties and QSAR models using cytotoxicity data unveils relationships between chemical, conformational properties, and biological activities. These findings facilitate the design of ligands targeting specific Grp94 conformations induced by abnormal glycosylation, selectively disrupting pathogenic protein networks while sparing normal mechanisms. [ABSTRACT FROM AUTHOR]

Patients with type-2 diabetes mellitus (T2DM) have normal or increased bone mineral density (BMD) but despite that, they are characterized by an increased hip and vertebral fracture risk that involves the alteration of bone quality and not the reduction in bone mass. BMD is utilized for the diagnosis and evaluation of osteoporosis, but BMD itself cannot provide an accurate diagnosis of the individuals at increased risk of fracture and, therefore, studies have focused on identifying other risk factors that are partially or fully independent of BMD. The fracture risk score tool-FRAX® models provide information about a 10-year probability of osteoporotic fractures, but do not include risk factors specific to illness such as diabetes duration, diabetes drug therapy, glycemic control, or the presence of micro-vascular complications. Multiple markers have been investigated to provide information on the risk of fractures in patients with T2DM such as: advanced glycation end products (AGEs), insulin-like growth factor-I (IGF-I), osteocalcin (OC), adiponectin, and sclerostin, but epidemiological studies did not provide homogeneous information regarding the link between these markers and bone fragility in T2DM subjects. Markers that increase the accuracy of fracture risk estimation in patients with T2DM need to be identified and employed in current medical practice.

The purpose of this study concerning the role of electrotherapy and of physical therapy in the recovery of cervical arthrosis is to maintain a high quality family, social and professional activity, by eliminating the pain and the muscle contractures. The hypothesis that was the starting point of this paper was that: if we associate electrotherapy techniques and cervical spine alignment techniques to the recovery programme, the pain and the paresthesias will diminish until they fade away for good. The study was conducted on a number of 24 subjects with the diagnosis of cervical arthrosis, over a period of 6 months. The subjects in the experimental group were 12 and they benefited from electrotherapy and physical therapy, while those in the control group had only medication. The methods, procedures and the techniques used in the recovery for the subjects included in the experimental group were: TENS currents, ultrasounds, tractions on an axis, facilitation techniques and the adjustment of the cervical spine. The results materialized in: the disappearance of pain, of paresthesias and of muscle contractions obtain in a relatively short period of time, allows us to notice the benefit of associating electrotherapy and physical therapy to the recovery of cervical arthroses. The conclusions underline the importance of the position adopted during all the activities that require head flexion in order to prevent the rectitude of the cervical spine and implicitly the pain, the paresthesias and the contractures.

Amongst different methods of quality analysis of the table tennis player's game, the basic idea of this study was to detect those indicators (data) for collection of which only the final result in particular competitions in a larger number of events, of one game, or certain sets in one table tennis game would be sufficient. The basic aim of the research is to establish to what extent the indexes and variables derived directly from the results of individual table tennis games could predict indexes which are described by the final result for an individual in a larger number of individual table tennis games. The research involves an analysis of an intentional sample of 956 table tennis players competing in various leagues during 2007. Results show that correlations between individual variables of the table tennis competitors' efficiency are statistically significant. The correlations between indexes of the competitor’s efficiency are also statistically significant. In particular, we found positive (and significant) correlations between all the direct and indirect indicators of players' efficacy (medium strongly to strongly correlated). The correlation between individual variables and indexes of the table tennis competitor’s efficiency, with the total efficacy index, are statistically significant. It can be concluded that all the indexes and variables can describe specific aspects of the performance in table tennis, predicting total efficacy of the players.

Među različitim metodama analize kvaliteta igre stonotenisera, osnovna ideja ovog istraživanja bila je utvrditi one indikatore (podatke) za čije je prikupljanje dovoljan samo konačni rezultat u određenim takmičenjima u većem broju događaja: stonoteniskih mečeva ili setova. Glavni cilj istraživanja je utvrđivanje u kojem obimu indeksi i varijable izvedene direktno iz rezultata pojedinačnih susreta mogu predvidjeti indekse koji su izvedeni iz konačnog rezultata pojedinca u većem broju pojedinačnih mečeva. Istraživanje uključuje analizu namjernog uzorka od 956 stonotenisera, koji su se takmičili na različitim ligaškim nivoima tokom 2007. Rezultati pokazuju da su korelacije između pojedinačnih varijabli koje su pokazatelji stonoteniserove uspješnosti statistički značajne. Korelacije između indeksa stonoteniserove uspješnosti su takođe statistički značajne. Takođe, pronašli smo pozitivne (i statistički značajne) korelacije između svih direktnih i indirektnih pokazatelja stonoteniserove uspješnosti (osrednje visoke do visoke povezanosti). Povezanost između pojedinačnih varijabli i indeksa stonoteniserove efikasnosti, s indeksom ukupne uspješnosti, statistički su značajne. Može se zaključiti da svi indeksi i varijable tumače specifične aspekte stonoteniserove uspješnosti, prognozirajući ukupnu uspješnost stonotenisera.

Diseases are a manifestation of how thousands of proteins interact. In several diseases, such as cancer and Alzheimer's disease, proteome-wide disturbances in protein-protein interactions are caused by alterations to chaperome scaffolds termed epichaperomes. Epichaperome-directed chemical probes may be useful for detecting and reversing defective chaperomes. Here we provide structural, biochemical, and functional insights into the discovery of epichaperome probes, with a focus on their use in central nervous system diseases. We demonstrate on-target activity and kinetic selectivity of a radiolabeled epichaperome probe in both cells and mice, together with a proof-of-principle in human patients in an exploratory single group assignment diagnostic study (ClinicalTrials.gov Identifier: NCT03371420). The clinical study is designed to determine the pharmacokinetic parameters and the incidence of adverse events in patients receiving a single microdose of the radiolabeled probe administered by intravenous injection. In sum, we introduce a discovery platform for brain-directed chemical probes that specifically modulate epichaperomes and provide proof-of-principle applications in their use in the detection, quantification, and modulation of the target in complex biological systems. Here, the authors show structural, biochemical, and functional insights into the discovery of epichaperome‐ directed chemical probes for use in central nervous system diseases. Probes emerging from this work have translated to human clinical studies in Alzheimer's disease and cancer. [ABSTRACT FROM AUTHOR]

Granuloma annulare (GA) is a benign chronic inflammatory dermatosis, self-limited, slightly pruritic or asymptomatic in the majority of the cases, with specific clinically and histologically features, that occurs in all age groups, but it is rare in infancy. GA is associated to five clinical variants: localized, generalized, perforating, subcutaneous and arcuate dermal erythema. The etiology of GA is usually unknown, but in 60-75% of the cases it is associated with metabolic disorders (diabetes mellitus, dyslipidemia), thyroid disorders, neoplasms, infections or drug induced. We present a psoriasis case treated with anti TNFa agents, Adalimumab, that after three and a half years of treatment developed GA. [ABSTRACT FROM AUTHOR]

Patients with type-2 diabetes mellitus (T2DM) have normal or increased bone mineral density (BMD) but despite that, they are characterized by an increased hip and vertebral fracture risk that involves the alteration of bone quality and not the reduction in bone mass. BMD is utilized for the diagnosis and evaluation of osteoporosis, but BMD itself cannot provide an accurate diagnosis of the individuals at increased risk of fracture and, therefore, studies have focused on identifying other risk factors that are partially or fully independent of BMD. The fracture risk score tool-FRAX® models provide information about a 10-year probability of osteoporotic fractures, but do not include risk factors specific to illness such as diabetes duration, diabetes drug therapy, glycemic control, or the presence of micro-vascular complications. Multiple markers have been investigated to provide information on the risk of fractures in patients with T2DM such as: advanced glycation end products (AGEs), insulin-like growth factor-I (IGF-I), osteocalcin (OC), adiponectin, and sclerostin, but epidemiological studies did not provide homogeneous information regarding the link between these markers and bone fragility in T2DM subjects. Markers that increase the accuracy of fracture risk estimation in patients with T2DM need to be identified and employed in current medical practice. [ABSTRACT FROM AUTHOR]

This study investigated tennis players' speed before, during and after the split-step, deceleration before and acceleration after the split-step in four different stroke groups in three age categories. Seven male professional, eleven male and ten female junior tennis players were recorded with video cameras at official tournaments. Using the SAGIT system, we gathered data on 8,545 split-steps. Tennis players performed a split-step in 82.9% of cases. A tennis player's speed, deceleration and acceleration were measured 0.2 s before and after the split-step. Differences between categories and stroke groups for each of the five variables were analyzed with a two-way ANOVA. The differences between the groups of players were generally much higher in the speed before, during and after the split-step than in the deceleration before and acceleration after the split-step. Most of these differences were observed between the various stroke groups. These results suggest that players use three types of movement while performing a split-step. In the first type, which is typical of serving and returning, the speed before, during and after the split-step is lower (0.55 to 1.2 m/s). The second type of movement is characteristic of baseline strokes where tennis players achieve higher speed than in the first type (0.7 to 1.66 m/s). The third type occurs in strokes where a tennis player is moving or already at the net (0.78 to 1.9 m/s). Movement in tennis is an area that requires constant development in terms of designing and upgrading movement patterns, increasing speed and practice in specific game situations. [ABSTRACT FROM AUTHOR]

Emerging from the game of man and his wish, but also the need, for Agon, sport has orbited from politics towards the economy and vice versa and has been left devoid of game but at the same time it has grown into something more than a game. Its attributes, such as health, socialization, and education, and the attributes promoted through and for them - sporting chivalry, sporting ideals, and the motto that the most important thing is to take part - have all become old-fashioned to an extent and substituted by new ones. Money and political utilitarianism as the new attributes of sport in some of its segments are based on the slogan of the mighty and the haughty - the end justifies the means. Therefore, one readily "justifies" the emergence of the following characteristics in sport and sport training: violence, stimulants, extreme physical effort, individualization, alienation, and propaganda, especially if they serve to realize the set goals. The goal is always to win, which is in the function of politics and/or economy. Through different examples of the (ab)use of sport, starting from the Olympic Games all the way to the continental championships and local competitions, this paper points out to great exploitation of sport for political and economic purposes. This shows that sport, with all its new attributes, has again made current Juvenal's (not merely) cynical message - panem et circenses. Therefore, it is necessary even in the 21st century for us to ask ourselves where our civilization is heading and, of course, to turn ourselves towards man and his personality. [ABSTRACT FROM AUTHOR]

In table tennis a great number of shots are performed at high speed developing high levels of explosive strength of lower extremities. The aim of this study was to determine the explosive and elastic-explosive strength of the lower limbs in Spanish young top-level table tennis players. A total of 165 players (95 boys and 70 girls) aged 7-17 years were randomly selected to participate in the study. Differences in the vertical jumps battery by category, gender and playing styles were observed. The girls obtained best results in the vertical jump in under 13 and cadet category and boys in the under 11 and junior category respectively. This information could have a great useful and interesting as talent detection, training planning method and as physical performance system control in table tennis. The explosive strength is one of very important physical capacities in this sport. [ABSTRACT FROM AUTHOR]

Chromosomal aberrations can be generally classified in two main categories: structural abnormalities (such as translocations, deletions or duplications) and numerical changes or aneuploidy. Aneuploidies are considered the most frequent chromosomal defects occurring in humans and the leading cause of miscarriage and congenital birth defects. Here we present the case of an 8-year old girl with remarkable prenatal history, low birth weight and length associated with increased height in early childhood and developmental delay. On chromosomal analysis a rare form of aneuploidy involving the sex chromosomes has been found in all cells: 48, XXXX. Tetrasomy X (48,XXXX) is a sex chromosome aneuploidy condition in which females have two extra X chromosomes compared to the 46,XX karyotype in typical females. There is significant phenotypical variability for tetrasomy X syndrome and many cases escape detection therefore the prevalence for tetrasomy X is unknown. This disorder is commonly associated with delayed speech, learning difficulties, developmental delay and facial dysmorphism, reminiscent of Down syndrome. Genetic counseling is recommended. Although no cure exists specifically for this condition, the treatment of the symptoms can be efficient. Individuals should undergo medical and psychological evaluations. [ABSTRACT FROM AUTHOR]

Copyright of Gymnasium: Scientific Journal of Education, Sports & Health is the property of Alma Mater and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of SportLogia is the property of University Banja Luka, Faculty of Physical Education & Sports and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of SportLogia is the property of University Banja Luka, Faculty of Physical Education & Sports and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: to analyze the types of chromosomal abnormalities in patients suspected of genetic disease and to estimate the frequency of chromosome aberrations detected in selected children and the comparison of the obtained results with other similar studies. Material and methods: chromosome analysis was performed on 592 patients of pediatric age, selected in the Clinical Genetics Department of IOMC ,,Prof. Dr. Alfred Rusescu" during an interval of 4 years, 2007-2010, using as selection criteria the following features: pre/postnatal growth retardation, facial dysmorphism, multiple congenital anomalies, mental retardation. Results: various types of chromosomal aberrations had been identified; out of the 321 cases diagnosed with some chromosomal anomalies, 285 cases (88.79%) had numerical anomalies, trisomy 21 representing the most common genetic abnormality, followed by Patau and Edwards syndromes, and 36 cases (11,21%) had structural chromosomal anomalies. Conclusions: cytogenetic analysis is useful for investigation of children with genetic diseases of unknown cause in order to confirm the clinical diagnosis and provide genetic counseling. [ABSTRACT FROM AUTHOR]

Background: Tetrasomy 18p is a very rare chromosomal disorder and is the result of a spontaneous mutation early in embryonic development in most of the cases. This condition is characterised by the presence of a supernumerary 18p isochromosome (i(18p)) in all or some cells of the affected individual. It has a prevalence of 1/180000 live births and affects both genders equally. Materials and methods: In this paper we report a de novo tetrasomy 18p in a 3 months old female dys morphic child. The clinical features were distinctive with a particular facies, strabismus, microcephaly, growth delay, neonatal hypertonia and talipes varus. An additional small metacentric marker chromosome has been identified after standard cytogenetic analysis, without recognized parental origin of the supplementary genetic material. The child's parents were also tested and their karyotype results were normal. The characterization of the marker chromosome was performed in our genetics laboratory using conventional cytogenetic methods and Fluorescence in Situ Hybridization (FISH) analysis. Also, our patient was compared with other published cases with the same diagnosis. Conclusion: Cytogenetic investigation is an essential step towards the accurate diagnosis of individuals with clinical suspicion of a genetic anomaly. Also, this type of investigation could offer critical information to the practitioner for prognosis of patient and the correct appreciation of the recurrence risk of a certain genetic condition. With current advances in preventive and interventional procedures, patients with rare chromosomal disorders can live longer. Therefore, proper medical and behavioural management of each case is important for the enhancement of the quality of life for the patients and their families. [ABSTRACT FROM AUTHOR]

The aim of this investigation were to determine the level of physical activity practice and to define the presence of cardiovascular risk factors associated with body composition and caloric intake in college students. A total of 81 college students (38 and 41 females and males, respectively) were submitted to a complete evaluation that consisted of an analysis of food-intake behavior, measures of several body composition variables (height, weight, body mass index, fat and muscle mass, waist and hip circumferences, waist-hip ratio, and sum of 6 skinfolds), blood pressure assessment, and physical activity level calculation. The results show sex differences in blood pressure and body composition variables; although an optimal food-intake patterns, a high level of physical activity practice and the absence of cardiovascular risk factors seem to generate healthy profiles in this population. [ABSTRACT FROM AUTHOR]

Copyright of Kinesiologia Slovenica is the property of Faculty of Sport and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Kinesiologia Slovenica is the property of Faculty of Sport and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. Materials and methods: In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). Discussion: All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. Conclusion: The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the validity and reliability of a graded exercise test on a specific kayak ergometer (Dansprint®) in which certain physiological and technical parameters that can to define kayaking performance were assessed. Fourteen male top-level kayak paddlers (all members of Spanish Kayaking National Team) participated in this investigation. All subjects carried out two ergometric tests (Ergo1 and Ergo2) and one flat water test (FWT) in random order. At anaerobic threshold (AnT) intensity, the results showed acceptable levels of reliability (comparison between data of Ergo1 and Ergo2 tests) in the assessment of velocity (r=0.784; p=0.004), stroke frequency (r=0.976; p<0.001), heart rate (r=0.964; p<0.001), and blood lactic acid concentration (r=0.899; p<0.001). Validity coefficients showed a strong relationships between Ergo2 and FWT tests in all physiological and technical parameters with the exception of velocity (r=0.498; p=0.121). It can be concluded that specific ergometry can be used to evaluate and to prescribe training AnT intensities of top-level kayakers attending to parameters such us heart rate, whole blood lactic acid concentration, and stroke frequency. Nevertheless, the training prescription through specific ergometry must be taken cautiously when velocity is the parameter of reference. [ABSTRACT FROM AUTHOR]

The whole body vibrations (WBV) it is nowadays one of the most widely used methods for improving the explosive strength. In this study, 12 subjects participating in recreational physical activity were allocated to a 5 sets of 60 s training, using a frequency of 30 Hz, an amplitude of 2.5 mm. and a isometric position (110 °bending knees) on a Galileo Fitness ® (Novotech, Germany) platform. The results showed an increase in SJ (+1.76 ± 4.05 cm) and CMJ (+1.10 ± 3.20 cm) in the post-test conducted just after the vibration. The values of the post-test performed 30 minutes after the squat jump remained above the ones of pre-test but just below the ones of the immediate post-test (+0.42 ± 4.43 cm). By contrast the values in the counter movement jump drop below the pre-test ones (-0.12 ± 2.45 cm). Based on these data it seems that when the frequency is not high it is necessary to use a greater amplitude in order to achieve the desired effects. The effect achieved after the vibration is transient, not remaining after 30 minutes. [ABSTRACT FROM AUTHOR]

The aim of this investigation were to determine the level of physical activity practice and to define the presence of cardiovascular risk factors associated with body composition and caloric intake in college students. A total of 81 college students (38 and 41 females and males, respectively) were submitted to a complete evaluation that consisted of an analysis of food-intake behavior, measures of several body composition variables (height, weight, body mass index, fat and muscle mass, waist and hip circumferences, waist-hip ratio, and sum of 6 skinfolds), blood pressure assessment, and physical activity level calculation. The results show sex differences in blood pressure and body composition variables; although an optimal food-intake patterns, a high level of physical activity practice and the absence of cardiovascular risk factors seem to generate healthy profiles in this population. [ABSTRACT FROM AUTHOR]

Abstract: In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1. [Copyright &y& Elsevier]

Copyright of Sportekspert is the property of Association of Professors & Experts in Physical Education & Sport, Canton Sarajevo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Haematological and biochemical parameters have not yet been analysed in professional padel players. The aim of this study was to determine the basal values of these parameters and to observe the effect of a simulated competition on them, including gender-related differences. A total of 14 male professional players (age: 28.2 ± 7.9 years), and 16 female professional players (age: 29.7 ± 3.7 years) participated in this study. Players were allowed to hydrate ad libitum during the matches. Haematological and biochemical values were obtained before and after a simulated competitive padel match. The men's group showed higher baseline values in red blood cells, haematocrit, haemoglobin, urea, creatinine, uric acid, albumin, glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH) and creatine kinase (CK) (p < 0.01) than the women's group. Attending to match effect, significant differences were obtained in urea, creatinine, CK and glucose (p < 0.05). Finally, the group x match interaction revealed significant differences in serum concentrations of sodium and chloride (p < 0.05). In conclusion, high-level padel matches provoke several changes in biochemical parameters related to muscle damage and protein catabolism. Recovery and fluid intake strategies could be added regarding gender. The results obtained could be due to the differences in the intensity and volume of the simulated competition. [ABSTRACT FROM AUTHOR]

Abstract: Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease that affects 10,000 patients each year. Current treatments are sub-optimal, and the disease is fatal if not treated. Herein, we report our continuing efforts to repurpose the human phosphodiesterase 4 (hPDE4) inhibitor piclamilast to target trypanosomal phosphodiesterase TbrPDEB1. We prepared a range of substituted heterocyclic replacements for the 4-amino-3,5-dichloro-pyridine headgroup of piclamilast, and found that these compounds exhibited weak inhibitory activity of TbrPDEB1. [Copyright &y& Elsevier]

Mixed gonadal dysgenesis and ovotesticular disorders of sex development, are rare conditions that occur sporadically, with unknown prevalence. Clinical manifestation of this diseases is sexual ambiguity. The authors present a pediatric case with sexual ambiguity and karyotype 45, X/46, XY, the child of a HIV-positive mother receiving multiple antiretroviral treatments for a period of 16 years. [ABSTRACT FROM AUTHOR]