The Effects of Six Weeks Pulmonary Rehabilitation on Functional and Psychological Outcomes in Long-COVID Patients: Preliminary Results from Serbian Single Center Study.

Background and Objectives: In this study, we aimed to evaluate the effects of six weeks of pulmonary rehabilitation on functional and psychological outcomes in long-COVID patients. Material and Methods: The prospective clinical study included 46 patients that were diagnosed with COVID-19. A respiratory rehabilitation program was implemented for six weeks. Further valuables were tested before the beginning of the rehabilitation program (admission) and six weeks after (discharge): SpO2, heart rate, respiratory rate, Visual Analogue Scale (VAS) score, Borg score, Sit-to-Stand (StS) test number of repetition, distance of 6-Minute Walking Test (6MWT), Patient Health Questionnaire (PHQ) 9 score and Generalized anxiety disorder (GAD) anxiety score. These parameters were tested before the rehabilitation program on admission and at discharge and after the rehabilitation program on admission and at discharge. The results were presented with standard descriptive and analytical methods. Differences between the continuous variables before and after physical rehabilitation intervention were tested using the Wilcoxon test. Graphical analysis is presented with a box plot. Results: On discharge, in comparison with admission, the values of SpO2 were significantly lower (p = 0.007) before the 6MWT, and VAS scores were significantly higher (p = 0.036), while after the 6MWT, VAS scores were significantly lower (p < 0.001) as were Borg scores (p = 0.016). On discharge, in comparison with admission, the respiratory rate was significantly higher (p = 0.005) before the StS test, and Borg scores were significantly lower (p = 0.001), while after the StS test, SpO2 levels were significantly higher (p = 0.036) and VAS scores were significantly lower (p < 0.001), as were Borg scores (p = 0.008). After discharge, the values of the StS test were significantly higher (p = 0.011), PHQ9 scores were significantly lower (p < 0.001) and GAD anxiety scores were significantly lower as well (p = 0.005), while the distances measured in meters on the 6MWT were significantly increased (p < 0.001). Conclusions: A structured rehabilitation program in our study was shown to have beneficial effects on physiological, psychological and functional improvements in patients with long-COVID, and therefore it is advisable for these patients.

Geraniol-Derived Monoterpenoid Glucosides from Rhodiola rosea: Resolving Structures by QM-HifSA Methodology.

Monoterpenoids are integral to the chemical composition of the widely used adaptogenic dietary supplement Rhodiola rosea. The present study expands the chemical space and stereochemical information about these taxon-specific constituents from the isolation and characterization of five geraniol-derived glucosides, 1-5. While 1 and 2 exhibited almost identical NMR spectra and shared the same 2D structure ascribed to the 4-hydroxygeraniolglucoside previously described as rosiridin, the NMR-based Mosher ester method revealed the enantiomeric nature of their aglycone moieties. This marks the first report of enantiomeric aglycones among geraniol derivatives. These findings also resolve the long-standing dispute regarding the absolute configuration of rosiridin and congeneric C-4 hydroxylated geraniols and may help explain incongruent bioactivity reports of R. rosea extract. Moreover, the three previously undescribed geranioloids 3-5 were fully characterized by extensive spectroscopic analysis. Quantum mechanics-driven 1H iterative functionalized spin analysis (QM-HifSA) was performed for all isolates and provides detailed NMR spin parameters, with adequate decimal place precision, which enable the distinction of such close congeners exhibiting near identical NMR spectra with high specificity. The outcomes also reinforce the importance of reporting chemical shifts and coupling constants with adequate decimal place precision as a means of achieving specificity and reproducibility in structural analysis.

Stroke vs. Preeclampsia: Dangerous Liaisons of Hypertension and Pregnancy.

Stroke during pregnancy and preeclampsia are two distinct but interrelated medical conditions, sharing a common denominator-blood control failure. Along with cardiovascular diseases, diabetes, dyslipidemia, and hypercoagulability, hypertension is undoubtedly a major risk factor associated with stroke. Even though men have higher age-specific stroke rates, women are facing higher life-long stroke risk, primarily due to longer life expectancy. Sex hormones, especially estrogen and testosterone, seem to play a key link in the chain of blood pressure control differences between the genders. Women affected with stroke are more susceptible to experience some atypical stroke manifestations, which might eventually lead to delayed diagnosis establishment, and result in higher morbidity and mortality rates in the population of women. Preeclampsia is a part of hypertensive disorder of pregnancy spectrum, and it is common knowledge that women with a positive history of preeclampsia are at increased stroke risk during their lifetime. Preeclampsia and stroke display similar pathophysiological patterns, including hypertension, endothelial dysfunction, dyslipidemia, hypercoagulability, and cerebral vasomotor reactivity abnormalities. High-risk pregnancies carrying the burden of hypertensive disorder of pregnancy have up to a six-fold higher chance of suffering from stroke. Resemblance shared between placental and cerebral vascular changes, adaptations, and sophisticated auto-regulatory mechanisms are not merely coincidental, but they reflect distinctive and complex cardiovascular performances occurring in the maternal circulatory system during pregnancy. Placental and cerebral malperfusion appears to be in the midline of both of these conditions; placental malperfusion eventually leads to preeclampsia, and cerebral to stoke. Suboptimal performances of the cardiovascular system are proposed as a primary cause of uteroplacental malperfusion. Placental dysfunction is therefore designated as a secondary condition, initiated by the primary disturbances of the cardiovascular system, rather than an immunological disorder associated with abnormal trophoblast invasion. In most cases, with properly and timely applied measures of prevention, stroke is predictable, and preeclampsia is a controllable condition. Understanding the differences between preeclampsia and stroke in pregnancy is vital for healthcare providers to enhance their clinical decision-making strategies, improve patient care, and promote positive maternal and pregnancy outcomes. Management approaches for preeclampsia and stroke require a multidisciplinary approach involving obstetricians, neurologists, and other healthcare professionals.

Exploring the Connection between Migraines and Pregnancy: The Impact of Physical Activity on Symptom Management.

Migraine is a prevalent neurological disorder that significantly impacts the quality of life for affected individuals. The pathogenesis behind migraines is not yet fully understood, but hormonal changes, especially fluctuations in, estrogen and progesterone levels, have a significant role in the susceptibility of women to migraines. Pregnancy introduces a unique set of challenges for women who experience migraines, as they must navigate the complexities of managing their condition while safeguarding the health of both them and their unborn child. Pharmacological options for treating migraines during pregnancy are limited, and, therefore, there is a growing interest in exploring alternative approaches to migraine symptom relief and management. Physical activity during pregnancy provides a range of benefits, and it has gained attention as a potentially valuable tool for alleviating migraine symptoms in pregnant patients. This review explores the intricate relationship between migraines and pregnancy, emphasizing how physical activity and other alternative approaches may influence the frequency, severity, and overall experience of migraines during pregnancy. Through collaboration with healthcare providers and the adoption of personalized management strategies, women can strike a balance that supports both their own well-being and the healthy development of their unborn child. By examining existing research and emerging insights, we aim to provide a comprehensive understanding of the potential benefits and considerations of incorporating physical activity and other treatment options into migraine management strategies for pregnant women. Further research is needed to elucidate the specific mechanisms linking migraines, pregnancy, and physical activity, enabling the development of more targeted interventions and guidelines.

Morphometric Parameters and MRI Morphological Changes of the Knee and Patella in Physically Active Adolescents.

Background and Objectives: The immature skeleton in a pediatric population exposed to frequent physical activity might be extremely prone to injuries, with possible consequences later in adulthood. The main aim of this study is to present specific morphometric parameters and magnetic resonance imaging (MRI) morphological changes of the knee and patella in a physically active pediatric population. Additionally, we wanted to investigate the morphological risk factors for patellar instability. Materials and Methods: The study included the MRI findings of 193 physically active pediatric patients with knee pain. The participants underwent sports activities for 5 to 8 h per week. Two divisions were performed: by age and by patellar type. We evaluated three age groups: group 1 (age 11-14), group 2 (age 15-17), and group 3 (age 18-21 years). In addition, participants were divided by the patellar type (according to Wiberg) into three groups. The following morphometric parameters were calculated: lateral trochlear inclination (LTI), the tibial tubercle-trochlear groove distance (TT-TG), trochlear facet asymmetry (TFA), Insall-Salvati index, modified Insall-Salvati index, Caton-Deschamps index, articular overlap, morphology ratio and contact surface ratio. Results: We found a statistically significant association between patellar type groups in LTI (p < 0.001), TFA (p < 0.001), Insal-Salvati (p = 0.001) index, and Caton-Deschamps index (p = 0.018). According to age groups, we found statistical significance in the Caton-Deschamps index (p = 0.039). The most frequent knee injury parameter, according to Wiberg, in physically active pediatric patients was patella type 2 in boys and type 3 in girls. Conclusions: The MRI morphometric parameters observed in our study might be factors of prediction of knee injury in physically active children. In addition, it might be very useful in sports programs to improve the biomechanics of the knee in order to reduce the injury rate in sports-active children.

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options.

Strokes within pediatric populations are considered to be the 10th leading cause of death in the United States of America, with over half of such events occurring in children younger than one year of life. The multifactorial etiopathology that has an influence on stroke development and occurrence signify the importance of the timely recognition of both modifiable and non-modifiable factors for adequate diagnostic and treatment approaches. The early recognition of a stroke and stroke risk in children has the potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after the onset of a stroke, improving the outcomes and quality of life for affected children and their families. The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of single-gene disorders. In this review, the most significant single gene disorders associated with pediatric stroke are presented, along with specific therapeutic options whenever they exist. Besides monogenic disorders that may present with stroke as a first symptom, genetic polymorphisms may contribute to the risk of pediatric and perinatal stroke. The most frequently studied genetic risk factors are several common polymorphisms in genes associated with thrombophilia; these genes code for proteins that are part of the coagulation cascade, fibrolysis, homocystein metabolism, lipid metabolism, or platelets. Single polymorphism frequencies may not be sufficient to completely explain the stroke causality and an analysis of several genotype combinations is a more promising approach. The recent steps forward in our understanding of the disorders underlying strokes has given us a next generation of therapeutics and therapeutic targets by which to improve stroke survival, protect or rebuild neuronal connections in the brain, and enhance neural function. Advances in DNA sequencing and the development of new tools to correct human gene mutations have brought genetic analysis and gene therapy into the focus of investigations for new therapeutic options for stroke patients.

Knowledge and barriers to early detection of breast cancer among female primary care patients in Serbia.

OBJECTIVES: Breast cancer is the leading cause of cancer mortality among women in Serbia and accounts for 22.8% of total cancer mortality in 2018. This study assessed the knowledge and barriers to early detection of breast cancer in women. METHODS: In March 2019, at the Primary Healthcare Centre Kikinda, Serbia, a 22-item questionnaire was distributed to a series of patients (N = 403, response rate 91.8%) to assess the odds ratio (OR) and 95% confidence interval (CI) between variables explaining knowledge of breast cancer symptoms and risk factors and barriers to screening, and four types of early detection of breast cancer. RESULTS: The majority of patients (85.4%) know that a lump in a breast is a common symptom of breast cancer and that a family history of breast cancer is a risk factor (80.1%); 63.8% of respondents aged ≥ 30 years self-examined their breasts in the past month, 39.1% of patients aged ≥ 40 years had clinical, while 34.4% had ultrasound breast examination in the past year, and 51.1% of patients aged ≥ 50 years had mammography once in the past two years. Patients aged ≥ 40 years retired and those with a positive family history were 84% and 63% less likely not to undergo a clinical breast examination in the past year. Participants over 40 years of age who reported a lack of funds were 2.46 times more likely to miss a clinical breast examination than those who did not have that barrier. Among participants aged 50-69 years, the likelihood of not receiving the mammography increases by 2.82 with an increase in wealth status and it was 65% lower for those who lack information about the available treatment. CONCLUSION: Women under the age of 50 rarely practice breast cancer screening. Study findings can be used to improve breast cancer screening at the primary level.

Postacute Rehabilitation Impact on Functional Recovery Outcome and Quality of Life in Stroke Survivors: Six Month Follow-Up.

Background and Objectives: This study aimed to examine the impact of postacute rehabilitation duration on the outcome of the functional recovery and patients' quality of life after the stroke. Materials and Methods: One hundred patients (52 females, 48 males, mean age: 66.5 ± 7.3; range 53 to 79 years) who experienced a stroke (50 with ischemic stroke (IS) and 50 with intracranial hemorrhage (ICH)) took part in the study. Patients (treated with postacute rehabilitation measures for six months) were examined after one, three, and six months of postacute rehabilitation. Functional independence was measured using the functional independence measure (FIM) test, while the EQ-5D-3L questionnaire was used to assess the quality of life. Results: Patients with ICH had a slightly lower FIM score (FIM motor = 29.8 ± 11.8; FIM cognitive = 14.4 ± 4.6) on admission compared to patients with IS (FIM motor = 41.8 ± 18.8; FIM cognitive = 18.7 ± 6.3), but, after six months of postacute rehabilitation, patients with ICH reached an approximate level of functional independence (FIM motor = 53.8 ± 14.4; FIM cognitive = 25.8 ± 4.7), as did patients with IS (FIM motor = 67.6 ± 16.4; FIM cognitive = 29.2 ± 4.0). The motor and cognitive FIM, as well as quality of life, was statistically significantly increased at all four measurement points (p < 0.001). Furthermore, there is a statistically significant connection between functional independence and quality of life at all tested times. Conclusion: Patients achieved the highest degree of functional independence after six months. Furthermore, our findings point out that inpatient rehabilitation as well as outpatient rehabilitation are effective in functionality and quality of life improvement after a stroke; thus, both should be emphasized and regularly implemented.

Reliability, Validity and Temporal Stability of the Serbian Version of the Boston Carpal Tunnel Questionnaire.

Background and Objectives: The aim of this study was to validate the Serbian version of the Boston Carpal Tunnel Questionnaire (BCTQ) and to evaluate temporal stability for the purpose of its implementation in the evaluation of Serbian patients with carpal tunnel syndrome (CTS). Materials and Methods: For the validation of the Serbian version of the BCTQ (BCTQSR), we tested 69 individuals with diagnosed CTS that were referred for a conservative treatment at the Institute for Rehabilitation. Neurophysiological tests were used for the electrophysiological grading (EG) of CTS severity in the study sample. The final version of the BCTQSR was given to the tested participants from the study on two occasions: test and retest, with a five-day period between the two measurements. Results: The mean value for the symptom severity subscale (SSS) of the BCTQSR was 3.01 ± 0.94; for the functional status subscale (FSS) of the BCTQSR it was 2.85 ± 1.00. Cronbach's α for the SSS was 0.91 and 0.93 for the FSS. The intraclass correlation coefficients (ICCs) concerning the test−retest were significant (p < 0.001) and were 0.949 for the SSS and 0.959 for the FSS. Those with a higher EG grade had higher values of the SSS and FSS but without a statistical significance (p = 0.103 and p = 0.053, respectively). The intercorrelation of the BCTQSR subscales (SSS and FSS) on the test was significant (p < 0.001) with a correlation coefficient equal to 0.777. Conclusion: The Serbian version of the BCTQ (BCTQSR) was successfully culturally adopted. The BCTQSR was a valid and reliable instrument for the measurement of symptom severity and functional status in adults with CTS. Therefore, it can be used in clinical practice for patients with CTS.

Impact of the COVID-19 Pandemic on the Outcomes of Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma: A Single Center Experience from a Developing Country.

Background and Objectives: Treatment of cancer patients during the COVID-19 pandemic has been a challenge worldwide. In accordance with the current recommendations for hepatocellular carcinoma (HCC) management during the COVID-19 pandemic, loco-regional therapy such as transarterial chemoembolization (TACE) was proposed with the purpose of achieving local tumor control and improving overall survival. The aim of this prospective cohort study was to evaluate the outcomes of TACE treatment in patients with HCC during the COVID-19 pandemic in comparison with the outcomes of patients treated in the pre-pandemic period. Materials and Methods: Between September 2018 and December 2021, 154 patients were managed by serial TACE procedures for different liver tumors. Ninety-seven patients met the study criteria and were divided into two groups: the study group n = 49 (patients treated from May 2020 to December 2021); the control group n = 48 (patients treated from September 2018 to May 2020). Results: The mean waiting time for TACE was significantly longer in the study group compared to the control group (p < 0.001). No significant difference in survival between the groups is noted (log-rank test p = 0.823). In multivariate analysis, the MELD score (HR 1.329, 95% CI 1.140−1.548, p < 0.001) remained a significant predictor of mortality. Conclusions: COVID-19 pandemic did not affect the final outcome of TACE treatment.

Validation and Cultural Adaptation of the Serbian Version of the Pediatric Outcome Data Collection Instrument (PODCI) in Children with Obstetrical Brachial Plexus Lesion.

Background and objectives: Pediatric Outcome Data Collection Instrument (PODCI) is among the most described scales developed to evaluate the physical status of children and adolescents with various musculoskeletal disorders. We aimed to translate PODCI from English to Serbian, culturally adopt items and domains, evaluate the temporal stability, internal consistency and the test−retest reliability of PODCISR in children with obstetrical brachial plexus lesion (OBPL), and finally, to test the construct validity of PODCISR against muscular manual test (MMT) Materials and Methods: The study included 48 eligible participants aged between 2 and 10 years with OBPL. The MMT was used to test the construct validity. Results: There were no significant differences (p > 0.05) between test and retest for all PODCISR domains. Correlations for all tested domains with MMT were statistically significant except for biceps muscle and domains II and IV. Cronbach's alpha value of the Global Functioning Scale was good and equaled 0.838 for test and 0.832 for retest session. Cronbach's α was more than 0.600 for all PODCISR domains except for Domain II and for Domain IV. The observed Test−Retest ICC for all PODCISR domains scores ranged from 0.899 to 0.996. Conclusion: The Serbian version of PODCI (PODCISR) was successfully translated and transculturally adopted. It has satisfactory temporal stability, construct validity and test−retest reliability as well as relevant internal consistency.

Anxiety and Comorbidities Differences in Adults with Chronic Pulmonary Diseases: Serbian Single Center Experience.

Background and objectives: The purpose of this study is to investigate the differences in the degree of the anxiety and comorbidity levels in patients with different chronic pulmonary diseases such as chronic obstructive bronchitis (COPD) without emphysema phenotype, pulmonary emphysema, bronchial asthma and lung cancer. Materials and Methods: The prospective clinical study included 272 patients that were diagnosed and treated of pulmonary pathology. COPD (without emphysema phenotype) (Group-1), pulmonary emphysema (Group-2), bronchial asthma (Group-3) and lung cancer (Group-4) were assessed. For the evaluation of the anxiety degree, we used Hamilton Anxiety Rating Scale (HAM-A). Results: The degree of cardiovascular symptoms was significantly higher in Group-1 versus Group-2 (p < 0.001), Group-3 (p = 0.001) and Group-4 (p = 0.013), and significantly higher in Group-4 versus Group-2 (p = 0.046). The degree of respiratory symptoms was significantly higher in Group-1 versus Group-2 (p < 0.001), Group-3 (p < 0.001) and Group-4 (p = 0.002), and significantly higher in Group-4 versus Group-2 (p = 0.013) and versus Group-3 (p = 0.023). For gastrointestinal symptoms, the degree of one was significantly higher in Group-1 versus Group-2 (p < 0.001), Group-3 (p < 0.001) and Group-4 (p = 0.017). Somatic subscale values were significantly higher in Group-1 versus Group-2 (p < 0.001), Group-3 (p < 0.001) and Group-4 (p = 0.015), and significantly higher in Group-4 versus Group-2 (p = 0.024). Total HAM-A score was significantly higher in Group-1 versus Group-2 (p = 0.002) and Group-3 (p = 0.007). Conclusions: Patients with COPD (without emphysema phenotype) followed by the lung cancer are at elevated risk of being more mentally challenged in terms of increased anxiety. Furthermore, patients with exacerbation of evaluated pulmonary pathologies have various levels of comorbidities degrees.

Tandem of Countercurrent Separation and qHNMR Enables Gravimetric Analyses: Absolute Quantitation of the Rhodiola rosea Metabolome.

Off-line combination of countercurrent separation (CCS) and quantitative 1H NMR (qHNMR) methodologies enabled the systematic dissection and gravimetric quantification of a chemically complex Rhodiola rosea crude extract (RCE). The loss-free nature and high selectivity of CCS achieved the quantitative discrimination of fatty acids (FAs), sugars, and proanthocyanidins (PACs) from ten other metabolite classes: phenylpropanoids, phenylethanoids, acyclic monoterpenoid glycosides, pinene derived glycosides, benzyl alcohol glycosides, cyanogenic glycosides, flavonoids, gallic acids, methylparabens, and cuminol glycosides. The ability of CCS to remove ("knockout") PACs completely resolved challenges with baselines that plague NMR and UHPLC analyses and produce inaccurate integral and AUC quantitation, respectively. NMR analysis of the non-PAC fractions enabled unambiguous identification of metabolites and their characteristic resonances for subsequent multitarget absolute quantification by qHNMR using a single, nonidentical internal calibrant (IC). An orthogonal LC-MS/MS method validated the gravimetric nature of the CCS-qHNMR analytical tandem. Underlying this LC-based cross-validation, comprehensive phytochemical isolation and characterization established 19 single-compound reference standards that represented all ten metabolite classes. Finally, quantum mechanical 1H iterative Full Spin Analysis (HiFSA) of each standard provided a blueprint for future structural dereplication, identification, and quantification of Rhodiola marker constituents. The combination of two gravimetric analytical methods, loss-free CCS and IC-qHNMR, realizes the first chemical standardization of a botanical material that comprehensively captures a metabolome and permits absolute quantification.

Living with a giant, flowering parasite: metabolic differences between Tetrastigma loheri Gagnep. (Vitaceae) shoots uninfected and infected with Rafflesia (Rafflesiaceae) and potential applications for propagation.

MAIN CONCLUSION: Metabolites in Rafflesia-infected and non-infected Tetrastigma were compared which may have applications in Rafflesia propagation. Benzylisoquinoline alkaloids, here reported for the first time in Vitaceae, were abundant in non-infected shoots and may be a form of defense. In Rafflesia-infected shoots, oxylipins, which mediate immune response, were elevated. Endemic to the forests of Southeast Asia, Rafflesia (Rafflesiaceae) is a genus of holoparasitic plants producing the largest flowers in the world, yet completely dependent on its host, the tropical grape vine, Tetrastigma. Rafflesia species are threatened with extinction, making them an iconic symbol of plant conservation. Thus far, propagation has proved challenging, greatly decreasing efficacy of conservation efforts. This study compared the metabolites in the shoots of Rafflesia-infected and non-infected Tetrastigma loheri to examine how Rafflesia infection affects host metabolomics and elucidate the Rafflesia infection process. Results from LC-MS-based untargeted metabolomics analysis showed benzylisoquinoline alkaloids were naturally more abundant in non-infected shoots and are here reported for the first time in the genus Tetrastigma, and in the grape family, Vitaceae. These metabolites have been implicated in plant defense mechanisms and may prevent a Rafflesia infection. In Rafflesia-infected shoots, oxygenated fatty acids, or oxylipins, and a flavonoid, previously shown involved in plant immune response, were significantly elevated. This study provides a preliminary assessment of metabolites that differ between Rafflesia-infected and non-infected Tetrastigma hosts and may have applications in Rafflesia propagation to meet conservation goals.

Silica Gel-mediated Oxidation of Prenyl Motifs Generates Natural Product-Like Artifacts.

Prenyl moieties are commonly encountered in the natural products of terpenoid and mixed biosynthetic origin. The reactivity of unsaturated prenyl motifs is less recognized and shown here to affect the acyclic Rhodiola rosea monoterpene glycoside, kenposide A (8: ), which oxidizes readily on silica gel when exposed to air. The major degradation product mediated under these conditions was a new aldehyde, 9: . Exhibiting a shortened carbon skeleton formed through the breakdown of the terminal isopropenyl group, 9: is prone to acetalization in protic solvents. Further investigation of minor degradation products of both 8: and 8-prenylapigenin (8-PA, 12: ), a flavonoid with an ortho-prenyl substituent, revealed that the aldehyde formation was likely realized through epoxidation and subsequent cleavage at the prenyl olefinic bond. Employment of 1H NMR full spin analysis (HiFSA) achieved the assignment of all chemical shifts and coupling constants of the investigated terpenoids and facilitated the structural validation of the degradation product, 9: . This study indicates that prenylated compounds are generally susceptible to oxidative degradation, particularly in the presence of catalytic mediators, but also under physiological conditions. Such oxidative artifact/metabolite formation leads to a series of compounds with prenyl-derived (cyclic) partial structures that are analogous to species formed during Phase I metabolism in vivo. Phytochemical and pharmacological studies should take precautions or at least consider the impact of (unavoidable) exposure of prenyl-containing compounds to catalytic and/or oxidative conditions.

Genetic and Epigenomic Modifiers of Diabetic Neuropathy.

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients' quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of "metabolic memory" in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.

Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly.

Gestational Diabetes and Risk Assessment of Adverse Perinatal Outcomes and Newborns Early Motoric Development.

Background and Objectives: The aim of this study was to analyze the presence of gestational diabetes mellitus (GDM) on maternal and fetal perinatal parameters, as well to evaluate the influence of GDM on neonatal early motoric development. Materials and Methods: In this prospective study, we evaluated 203 eligible participants that were admitted to obstetrics department for a labor. GDM was assessed by evaluation of maternal parameters, fetal parameters, as well its impact on infants early motoric development (Alberta Infant Motor Scale-AIMS). Results: Presence of GDM was significantly positively associated with: pre-pregnancy weight, obesity degree, weight at delivery, gestational weight gain (GWG), body mass index (BMI) at delivery, GWG and increased pre-pregnancy BMI, glucose levels in mother's venous blood after the delivery, positive family history for cardiovascular disease, pregnancy-related hypertension, congenital thrombophilia, drug use in pregnancy, large for gestational age (LGA), mode of delivery (Cesarean section and instrumental delivery). Likewise, GDM association was detected for tested ultrasound parameters (biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femoral length (FL)), length at birth, birth weight, newborn's head circumference, newborn's chest circumference, AIMS supination and pronation at three months, AIMS supination, pronation, sitting and standing at six months. Only Amniotic Fluid Index and AIMS supination at three months of infant's age remained significantly associated in multivariate regression model. Conclusions: The presence of significant positive association of numerous tested parameters in our study on perinatal outcomes and early motoric development, points to the necessity of establishing appropriate clinical decision-making strategies for all pregnant woman at risk and emphasize the importance of providing adequate glycaemia control options and further regular follow ups during the pregnancy.

Development of the Melanoma Concerns Questionnaire (MCQ-28); refinement of the EORTC QLQ-MEL38 module.

OBJECTIVE: Few patient-reported outcome measures (PROMs) have been developed that adequately measure the patient-experience following diagnosis and treatment of melanoma. Building on previous research, which developed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Module (QLQ-MEL38), the aim of this study was to further test the hypothesised domain structure and psychometric properties of the phase 3 module, in a new larger sample of melanoma patients. METHODS: Melanoma patients (n = 270) were recruited from four countries (Australia, England, Serbia, and Spain). Patients completed the EORTC core questionnaire (QLQ-C30), the QLQ-MEL38, and a sociodemographic survey. Using this new larger dataset, comparisons were made with the hypothesised domain structure of the EORTC phase 3 module using principal component analysis. Items which formed subscales in a revised domain structure were then tested for goodness of fit (GoF) to the Rasch model. RESULTS: The original hypothesised and final domain structures were similar but not identical. Twenty-four items (83%) loaded onto the same distinct subscales previously generated by phase 3, and item-by-item comparison of the two pattern matrices indicated an extremely close match. Ten items were removed from the QLQ-MEL38 phase 3 module, and rescoring of some items was required. Four subscales, together with five individual items, comprised the final instrument. CONCLUSION: The newly developed measure (named the Melanoma Concerns Questionnaire; MCQ-28) was found to tap into several important psychosocial domains of concern to melanoma patients, particularly those being managed in "usual" clinic settings.

Quantum Mechanics-Based Structure Analysis of Cyclic Monoterpene Glycosides from Rhodiola rosea.

NMR- and MS-guided metabolomic mining for new phytoconstituents from a widely used dietary supplement, Rhodiola rosea, yielded two new (+)-myrtenol glycosides, 1 and 2, and two new cuminol glycosides, 3 and 4, along with three known analogues, 5-7. The structures of the new compounds were determined by extensive spectroscopic data analysis. Quantum mechanics-driven 1H iterative full spin analysis (QM-HiFSA) decoded the spatial arrangement of the methyl groups in 1 and 2, as well as other features not recognizable by conventional methods, including higher order spin-coupling effects. Expanding applied HiFSA methodology to monoterpene glycosides advances the toolbox for stereochemical assignments, facilitates their structural dereplication, and provides a more definitive reference point for future phytochemical and biological studies of R. rosea as a resilience botanical. Application of a new NMR data analysis software package, CT, for QM-based iteration of NMR spectra is also discussed.