Metaphedrone (3-Methylmethcathinone): Pharmacological, Clinical, and Toxicological Profile.

Introduction: Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older generations of these compounds, new formulations appeared on the drug market. One of them is metaphedrone (3-methylmethcathinone, 3-MMC), a structural isomer of 4-methylmethcathinone and a psychostimulant drug. Metaphedrone became popular in a large number of countries in a short period of time. The aim: The collection, analysis, and review of relevant research on the subject of metaphedrone in order to present information about the pharmacological, clinical, and toxicological profile of this compound. An assessment of the significance and role of metaphedrone in consumption patterns of novel psychoactive substances among recreational drug users. Methodology: By using search engines like Google Scholar and PubMed, the relevant literature on metaphedrone was looked for and analyzed. The search was not limited to a specific period of time. All information regarding the compound of interest was analyzed and presented. Key results and discussion: All novel psychoactive substances are abused due to their pronounced stimulatory, hallucinogenic, dissociative, and euphoric and/or relaxing characteristics. Users of 3-methylmethcathinone usually opt for this substance for recreational purposes and/or sexual stimulation. Metaphedrone has the potential to cause a psychological dependence to the users. It was determined in relevant studies that most users are from 17 to 50 years of age. Older users usually administer metaphedrone intravenously, while younger ones usually choose snorting and oral ingestion of the drug. In Serbia, metaphedrone is a legally controlled substance. The pharmacodynamic properties make metaphedrone similar to classical recreational drugs. The method of administration, mainly repeated administration in a single session, could be explained using the pharmacokinetic profile of the drug. The most reported symptoms of intoxication were those of a sympathomimetic nature, such as tachycardia, chest pain, hypertension, diaphoresis, and agitation. Most intoxications and fatal outcomes occurred to users who combined several psychoactive substances. The correlation between measured blood concentrations of the drug and outcomes of intoxication was not found. The mechanisms of metaphedrone's toxicity are not fully understood. Conclusions: There is an increasing trend of abuse of metaphedrone among recreational drugs users. Future studies should focus on pharmacological and toxicological effects of metaphedrone on animals and humans.

Invasive Diagnostic Procedures from Bronchoscopy to Surgical Biopsy-Optimization of Non-Small Cell Lung Cancer Samples for Molecular Testing.

Background and Objectives: Treatment of advanced lung cancer (LC) has become increasingly personalized over the past decade due to an improved understanding of tumor molecular biology and antitumor immunity. The main task of a pulmonologist oncologist is to establish a tumor diagnosis and, ideally, to confirm the stage of the disease with the least invasive technique possible. Materials and Methods: The paper will summarize published reviews and original papers, as well as published clinical studies and case reports, which studied the role and compared the methods of invasive pulmonology diagnostics to obtain adequate tumor tissue samples for molecular analysis, thereby determining the most effective molecular treatments. Results: Bronchoscopy is often recommended as the initial diagnostic procedure for LC. If the tumor is endoscopically visible, the biopsy sample is susceptible to molecular testing, the same as tumor tissue samples obtained from surgical resection and mediastinoscopy. The use of new sampling methods, such as cryobiopsy for peripheral tumor lesions or cytoblock obtained by ultrasound-guided transbronchial needle aspiration (TBNA), enables obtaining adequate small biopsies and cytological samples for molecular testing, which have until recently been considered unsuitable for this type of analysis. During LC patients' treatment, resistance occurs due to changes in the mutational tumor status or pathohistological tumor type. Therefore, the repeated taking of liquid biopsies for molecular analysis or rebiopsy of tumor tissue for new pathohistological and molecular profiling has recently been mandated. Conclusions: In thoracic oncology, preference should be given to the least invasive diagnostic procedure providing a sample for histology rather than for cytology. However, there is increasing evidence that, when properly processed, cytology samples can be sufficient for both the cancer diagnosis and molecular analyses. A good knowledge of diagnostic procedures is essential for LC diagnosing and treatment in the personalized therapy era.

The role of osteoarthritis severity, BMI and age on clinical efficacy of bone marrow aspirate concentrate in the treatment of knee osteoarthritis.

Aim: The aim of this study was to assess whether BMI, severity of knee osteoarthritis, age and gender have any influence on the final clinical results of bone marrow aspirate concentrate injection. Method: A total of 111 study participants with painful knee osteoarthritis and different characteristics concerning before mentioned factors underwent bone marrow aspirate concentrate (BMAC) therapy and were followed up for 1 year. Result: Significant pain and functional improvement were observed in all participant groups. Participants' age and BMI did not influence the clinical outcome, but there was an influence of OA severity, especially among older patients. Conclusion: This study shows that BMAC therapy is effective. Younger patients with milder OA changes could be better candidates for long-lasting and more efficient BMAC therapy. Clinical Trial Registration: NCT03825133 (ClinicalTrials.gov).

How does the increase of body mass and ageing affect sprinter's results in a 100 m run? / ¿Cómo afecta el aumento de la masa corporal y el envejecimiento a los resultados del velocista en una carrera de 100 m?

SUMMARY: The career of a sprinter is analyzed with U. Bolt achievements as an example. The effects of the increase of body mass and ageing are discussed within the framework of the polynomial models for the velocity, muscular isometric force and age. The analysis presented demonstrates the influence of the BM factor in analyzed racing. The nonlinear increase of the BM for 9 kg in the period 2009 - 2017 in was one of the reasons of Bolt's unsuccessful attempt to repeat or confirm the time 9.58 s. Another limiting factor was the fact that due to the age, Bolt was not able to increase isometric muscular force which, after the year of maximal efficiency (2009) decreased.

RESUMEN: La carrera de un velocista se analiza con los logros de U. Bolt como ejemplo. Los efectos del aumento de la masa corporal y el envejecimiento se discuten en el marco de los modelos polinomiales de velocidad, fuerza isométrica muscular y edad. El análisis presentado demuestra la influencia del factor MC en el análisis en las carreras. El aumento no lineal de la MC para 9 kg en el período 2009 - 2017 fue una de las razones del intento fallido de Bolt de repetir o confirmar el tiempo 9,58 s. Otro factor limitante fue el hecho de que debido a la edad, Bolt no fue capaz de aumentar la fuerza muscular isométrica que disminuyó luego del año de máxima eficiencia (2009).

Evaluation of The Final Time and Velocity of a 100 m Run Under the Realistic Conditions.

The aim of the research was to provide an analytical expression for the final time and velocity at the 100 m run, taking into account realistic conditions of the run, more precisely the effect of the wind and resistance of the medium (air). Combining the polynomial model for the distance vs time with the solution of the algebraic cubic equation, such an analytical expression was derived. The expression allowed to evaluate the dependence of the final time of the race on the wind velocity. This enabled the quantification of the time effect of the mentioned influences on the final time and velocity. It is possible to calculate the dependence of the sprinter's velocity on expired running time for various wind velocities (from 0 up to ± 10 m/s) as well as determine the maximal running velocity vmax and corresponding time moment tmax. The results obtained were verified using split time data for six top sprinters: C. Lewis, M. Green, U. Bolt and F. Griffith-Joyner, E. Ashford and H. Drechsler. The results confirmed that it was possible to quantify the time effect of the influence of the wind velocity and resistance of the medium on the final time of the 100 m run. Although the applicability of the approach was tested using the data concerning top sprinters, the mathematical expressions involved are simple enough to be used by any coach to estimate the results of a sprinter under various weather conditions.

A Model for Determining the Effect of the Wind Velocity on 100 m Sprinting Performance.

This paper introduces an equation for determining instantaneous and final velocity of a sprinter in a 100 m run completed with a wind resistance ranging from 0.1 to 4.5 m/s. The validity of the equation was verified using the data of three world class sprinters: Carl Lewis, Maurice Green, and Usain Bolt. For the given constant wind velocity with the values + 0.9 and + 1.1 m/s, the wind contribution to the change of sprinter velocity was the same for the maximum as well as for the final velocity. This study assessed how the effect of the wind velocity influenced the change of sprinting velocity. The analysis led to the conclusion that the official limit of safely neglecting the wind influence could be chosen as 1 m/s instead of 2 m/s, if the velocity were presented using three, instead of two decimal digits. This implies that wind velocity should be rounded off to two decimal places instead of the present practice of one decimal place. In particular, the results indicated that the influence of wind on the change of sprinting velocity in the range of up to 2 m/s and was of order of magnitude of 10-3 m/s. This proves that the IAAF Competition Rules correctly neglect the influence of the wind with regard to such velocities. However, for the wind velocity over 2 m/s, the wind influence is of order 10-2 m/s and cannot be neglected.

Model for assessment of the velocity and force at the start of sprint race.

A mathematical model was developed for the assessment of the starting velocity and initial velocity and force of a 100-m sprint, based on a non-homogeneous differential equation with the air resistance proportional to the velocity, and the initial conditions for [Formula: see text], [Formula: see text]The use of this model requires the measurement of reaction time and segmental velocities over the course of the race. The model was validated by comparison with the data obtained from 100-m sprints of men: Carl Lewis (1988), Maurice Green (2001) and Usain Bolt (2009), and women: Florence Griffith-Joyner, Evelyn Ashford and Drechsler Heike (1988) showing a high level of agreement. Combined with the previous work of the authors, the present model allows for the assessment of important physical abilities, such as the exertion of a high starting force, development of high starting velocity and, later on, maximisation of the peak running velocity. These data could be of importance for practitioners to identify possible weaknesses and refine training methods for sprinters and other athletes whose performance depend on rapid movement initiations.

Pharmacokinetics and toxicity predictors of new s-triazines, herbicide candidates, in correlation with chromatogrpahic retention constants.

Herbicides, which are ubiquitously present in soil and food, have been proven to cause human health hazard effects, hence development of new herbicide-active compounds is recommended. In this paper, nine 2,4-bis(cycloalkyl)-6-chloro-s-triazines were considered as herbicide candidates and their pharmacokinetics and toxicity were reviewed on the basis of in silico descriptors. Both, pharmacokinetic and toxicity predictors were presented as functions of their lipophilicity, quantified with retention constants that were obtained by liquid chromatography. None of the candidates investigated has functional groups for genotoxicity hazards and endocrine disruptions; they have acceptable toxicity and favorable pharmacokinetic properties based on computer-aided analyses. Two candidates have been selected as lead compounds for further research.

Surgical treatment of shoulder rotator cuff injuries.

INTRODUCTION: The rotator cuff is the most important functional structure of the shoulder. The aim of this study was to determine which factors contribute to a rotator cuff injury and to evaluate the results of the surgical treatment at the Department of Orthopedic Surgery and Traumatology in Novi Sad since December 2009 until May 2012. MATERIAL AND METHODS: The study sample consisted of 20 patients who had been operated for a shoulder rotator cuff injury. Their mean age was 56.8 +/- 9.1. RESULTS: According to the Constant Shoulder Score, 75% of the patients had excellent and good results. A statistically significant difference (p < 0.05) was found between Constant Shoulder Score of the operated should and the opposite shoulder as well as between the range of external and internal rotation and abduction. After the surgical treatment, 95% of the patients have no limitations in the activities of daily living and they are satisfied with the results of treatment. CONCLUSION: Surgical treatment of a shoulder rotator cuff injury is reliable, time-tested and provides good clinical results especially in patients who were operated within the first three weeks after the injury.

Model for the determination of instantaneous values of the velocity, instantaneous, and average acceleration for 100-m sprinters.

Temporal patterns of running velocity is of profound interest for coaches and researchers involved in sprint racing. In this study, we applied a nonhomogeneous differential equation for the motion with resistance force proportional to the velocity for the determination of the instantaneous velocity and instantaneous and average acceleration in the sprinter discipline at 100 m. Results obtained for the instantaneous velocity in this study using the presented model indicate good agreement with values measured directly, which is a good verification of the proposed procedure. To perform a comprehensive analysis of the applicability of the results obtained, the harmonic canon of running for the 100-m sprint discipline was formed. Using the data obtained by the measurement of split times for segments of 100-m run of the sprinters K. Lewis (1988), M. Green (2001), and U. Bolt (2009), the method described yielded results that enable comparative analysis of the kinematical parameters for each sprinter. Further treatment allowed the derivation of the ideal harmonic velocity canon of running, which can be helpful to any coach in evaluating the results achieved at particular distances in this and other disciplines. The method described can be applied for the analysis of any race.

[Comparative analysis of the position of the graft in the femur after anterior cruciate ligament reconstruction done through the front inner portal and through the shin bone].

Anterior cruciate ligament (ACL) is the most common surgically treated knee ligament. If we take into account the fact that incidence of ACL injuries is growing, it is clearly that the interest of orthopedic surgeons for this pathology is also growing. Increasing number of this operations leads to increasing of complications, which requires its analysis. One of the most common failure of ACL reconstruction is a bad position of the graft in the femoral condyle. This study aimed to analyze the positioning of the graft in to the femur by two generally accepted techniques--transtibial technique and technique through the antero-medial portal. The analysis included postoperative radiographs in 60 patients, of whom 30 were operated by transtibial technique and 30 by technique through anteromedial portal. Radiographic analysis involved the measurement of the AP digital imaging, the tunnel projection X ray measurements and measurements of the computed tomography (CT), which was here a control method. The accuracy of measurement was set at 0.5 degrees or 1 min. All radiographs were made in the same way according to the literature. The results showed that the neoligaments were placed lower in the femoral condyle by technique through anteromedial portal than by transtibial technique, and the difference was statistically significant (on tunnel X ray by anteromedial portal screws were average placed at 50.0 degrees and 10:20 am, and by transtibial technique at 37.5 degrees or 10:45 am). Based on the results, it was concluded that the neoligaments were positioned closer to its anatomical position by technique through anteromedial portal.

Isometric force development of some muscle groups in athletes.

In a large sample of both male and female athletes, subdivided by age and sex, a development curve of isometric muscule force (F) was analyzed for hand flexors, upper-body flexors and extensors, and knee extensors (PDS). A sample of 1,857 male and 1,009 female athletes, aged 8-30 years, subdivided by their age and sex, was used to measure the mean values of isometric muscle force of certain muscle groups by way of 5 topologically defined tests. Based on the results, isometric muscle force (F) development curves are shown and analyzed for the right-hand and left-hand (PLS) flexors, upper-body flexors (PTR), upper-body extensors (OTR), and knee extensors (ONO). The application of certain statistical programs gave rise to equations of the relationship between isometric force and age. The maximum mean value of PLS was chosen as the reference value or "the gold standard," with which PTR, OTR, and ONO were subsequently compared. The relationships were 1:1:1:2.8:5.9 (for male athletes), and 1:1:1.3:3.2:5.2 (for female athletes). The newly derived relationship was recognized as "the canon." The results may have practical application in athletes' fitness and conditioning. Every topologically defined muscle force has its own patterns and rules that should be closely followed in the training process, because any generalization may lead to false conclusions.

Hybrid hamstring graft tibial fixation in anterior cruciate ligament reconstruction.

Tibial fixation of the anterior cruciate ligament hamstring tendon graft is commonly considered more problematic than femoral fixation. When interference screws are used for tibial hamstring tendon graft fixation, graft sometimes looses its tension, so a hybrid fixation (more than one method of fixation) must be applied. Biomechanical studies show that an implementation of interference screws combined with different indirect distal hamstring tendon fixation techniques can withstand much higher tearing forces when compared with one type of fixation. We made a technique of hybrid tibial fixation of the hamstring graft using round interference screws and an additional bi-cortical 4.5-mm diameter screw with a modified head that allows control over the initial tension of the graft.