Towards Chemoenzymatic Syntheses of Both Enantiomers of Phosphoemeriamine.

An enzyme-promoted addition of nitromethane to the appropriate phosphorylated imine (aza-Henry reaction) intended to be used in the synthesis of the title phosphoemeriamine, a phospha-analog of emeriamine (aminocarnitine), failed due to the tautomerization of the imine to the corresponding enamine. Nevertheless, both enantiomers of phosphoemeriamine were synthesized in high yield and enantiomeric purity using another chemoenzymatic approach, starting with a crucial step involving a CAL-B-mediated acetylation of the appropriate racemic precursor-diethyl 2-amino-3-dimethylaminopropylphosphonate-under kinetic resolution conditions. The enzymatic reaction was very efficient and provided each enantiomeric product in acceptable yield and with enantiomeric excess of 91 and 92%. The following appropriate chemical transformations led to the desired enantiomers of phosphoemeriamine in the form of phosphoemeriamine sesquichloride with enantiomeric excess up to 90%.

Prospective association of occupational and leisure-time physical activity with orthostatic blood pressure changes in older adults.

Orthostatic hypotension (OH) is common in older people. We examined the influence of self-reported occupational-related physical activity (PA) and leisure-time physical exercise (PE) on orthostatic response in a sample of older people over a 2 year period. Supine and orthostatic systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were assessed in response to Active Stand (AS) test in 205 older subjects (> 60 years old) at baseline and 2-year follow-up. OH was found in 24 subjects (11.71%) at baseline and 20 subjects (9.76%) after 2 years, with a significant degree of variability in the occurrence of OH after 2 years. Twenty-two subjects who had OH at baseline were free of it after 2 years, two subjects had persistent OH at baseline and after 2 years. After 2 years, adults with occupational PA showed no significant decrease of blood pressure in response to AS test, while lack of undertaking an occupation-related PA was significantly related with a greater decrease in sBP and mBP in response to AS testing in the 1st min. Occupation-related PA and leisure-time-related PE were related to an increase in the response of BP on AS in change between baseline and after 2 years. High between-subjects variance in OH over 2 years was noted. Occupations that involved continuous physical activity and leisure-time physical exercise in middle age were both protective for BP decline on orthostatic stress test within 2 years.

Influence of Ethanol on Porous Anodic Alumina Growth in Etidronic Acid Solutions at Various Temperatures.

Etidronic acid, used in aluminum anodization, has a great potential for the fabrication of porous anodic alumina (PAA) with large cell sizes (>540 nm). PAAs are particularly suited to applications in optics and photonics where large-scale periodicity corresponding to visible or infrared light is needed. Additionally, such PAAs should be characterized by long-range pore ordering. However, to obtain regular pore arrangement in an etidronic electrolyte, the anodization should be performed at high electric fields using relatively high temperatures, which makes the process challenging in terms of its stability. To stabilize the process, the electrolyte can be modified with ethanol. In this work, the impact of ethanol on pore geometry and a level of pore ordering is systematically analyzed. It is shown that the additive tends to reduce pore ordering. Moreover, by changing the anodizing temperature and the amount of ethanol, it is possible to tune the porosity of the PAA template. At 20 °C, porosity drops from 14% in PAA grown in a pure water-based electrolyte to ca. 8% in PAA fabricated in the 1:3 v/v EtOH:H2O electrolyte. The larger PAA thickness obtained for the same charge density strongly suggests that PAA formation efficiency increases in the 1:3 v/v EtOH:H2O mixture.

Adipokines Level and Cognitive Function-Disturbance in Homeostasis in Older People with Poorly Managed Hypertension: A Pilot Study.

AIM: To explore the network relationship between cognitive function, depressive symptom intensity, body composition, proxies of cognitive reserve, trophic factor, adipokines and myokines, physical performance and blood pressure in a group of older people with poorly managed hypertension (PMHTN) compared to a normotensive (NTN) group. MATERIALS AND METHODS: History of hypertension and blood pressure level were examined in older participants. Thirty-one subjects diagnosed with PMHTN (history of hypertension diagnosis and values of sBP or dBP over 140/90 mmHg) and eighteen NTN (lack of history of hypertension and sBP and dBP lower than 140/90 mmHg) participated. Participants completed physical and cognitive function assessments: including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and its two subtests Delayed Recall (DR) and Verbal Fluency (VF) and Trail Making Test Part B (TMT B). Factors associated with cognitive functioning: age, years of education, cognitive and travel activity were assessed using a questionnaire. Visceral fat was determined by bioimpedance testing and gait velocity and agility assessed using an Up and Go test. To summarize the strength and direction (negative or positive) of a relationship between two variables, Spearman's rank correlation coefficient was used. Then, network graphs were created to illustrate the relationship between variables. Node strength (number of edges per node), neighbourhood connectivity (the average connectivity of all the neighbours of a node), stress (the number of shortest paths passing through each node) were compared in network from PMHTN group to network from NTN group. RESULTS: Neighbourhood connectivity and stress were significantly higher in of the PMHTN network compared to NTN (6.03 ± 1.5 vs. 4.23 ± 2.5, p = 0.005 and 118.21 ± 137.6 vs. 56.87 ± 101.5, p = 0.02, accordingly). CONCLUSION: In older subjects with poorly managed hypertension, dyshomeostasis was observed, compared to normotensive subjects.

Coffee Consumption and Blood Pressure: Results of the Second Wave of the Cognition of Older People, Education, Recreational Activities, Nutrition, Comorbidities, and Functional Capacity Studies (COPERNICUS).

This study examined the relationship between the frequency of coffee consumption and blood pressure over a two year follow up of a cohort of elderly people. Healthy, older people (N = 205) were examined at baseline and at two years. Participants completed physical and behavioural assessments, which included body composition, current pharmacological treatment, and frequency of coffee consumption grouped into three categories: "never to a few times per month", "once a week to a few times per week", and "every day". Blood pressure (systolic (sBP), diastolic (dBP), mean (mBP), and pulse pressure (PP)) was measured at baseline and after two years. After adjusting for body composition, smoking status, age, sex, heart rate, and number of antihypertensive agents taken, participants who drank coffee everyday had a significant increase in sBP, with a mean of 8.63 (1.27; 15.77) and an mBP, with a mean of 5.55 mmHg (0.52; 10.37) after two years (t = 2.37, p = 0.02 and t = 2.17, p = 0.03, respectively) compared to participants who never or very rarely (up to a few times per month) drank coffee. DBP and PP were not affected by coffee consumption frequency in a statistically significant manner.

Enzymatic Approach to the Synthesis of Enantiomerically Pure Hydroxy Derivatives of 1,3,5-Triaza-7-phosphaadamantane.

A series of enantiomerically pure derivatives of 6-(1-hydroxyalkyl)-1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane 5 were successfully synthesized for the first time. A series of hydrolytic enzymes was applied in a stereoselective acetylation performed under kinetic resolution conditions. Although the secondary alcohols: α-aryl-hydroxymethyl-PTA (phosphines) 5b-d', PTA-oxides 8b-d', and PTA-sulfides 9b-d' were found to be totally unreactive in the presence of all the enzymes and various conditions applied, the primary alcohols, i.e., the hydroxymethyl derivatives PTA oxide 8a and PTA sulfide 9a, were successfully resolved into enantiomers with moderate to good enantioselectivity (up to 95%). The absolute configurations of the products were determined by an X-ray analysis and chemical correlation.

Cognitive Function Changes in Older People. Results of Second Wave of Cognition of Older People, Education, Recreational Activities, NutritIon, Comorbidities, fUnctional Capacity Studies (COPERNICUS).

BACKGROUND: Cognitive reserve explains why subjects with more years of education, professional achievement, or participation in recreational activities show less cognitive decline with aging. We hypothesize that levels of recreational travel, education, occupation, systemic health, physical performance, and current cognitive activity levels affect the trajectory of cognitive function in older, healthy people in Poland. MATERIALS AND METHODS: Healthy, older people (N = 205) were examined and followed-up at 2 years. Participants completed physical and cognitive function assessments: including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and its two subtests Delayed Recall (DR) and Verbal Fluency (VF), and Trail Making Test Part B (TMT B). Factors associated with cognitive functioning were also examined. RESULTS: The MMSE result significantly decreased over 2 years. No significant decrease in other cognitive tests was noted. However, the trajectory of cognitive tests results varied between individual participants. Percentage of variance of change was explained by the following predictors: 21 in MMSE, 24 in MoCA, 8 in DR, 25 in VF, and 24 in TMT B. Age and the presence of varicose veins were significantly linked to negative changes in MMSE and MoCA scores, while working in a professional occupational status associated with a higher score. The subgroup with varicose veins did worse on the Delayed Recall subtest of MoCA. CONCLUSION: Cognitive reserve could be extended by proxies of reserve that are related to systemic health and travel activity. The latter is a combination of social, physical, and cognitive activity and potentially might serve as an intervention to improve cognitive function in older people. However, due to the limitations of this study, results should be interpreted with caution and needs to be replicated in the further studies.

Interaction between Subjective Memory Decline and Depression Symptom Intensity in Older People. Results of the Second Wave of Cognition of Older People, Education, Recreational Activities, Nutrition, Comorbidities, and Functional Capacity Studies (COPERNICUS).

BACKGROUND: Prevalence of subjective memory impairment (SMC), with or without objective memory impairment, and the mediating role of depression symptom intensity was examined in older people. METHODS: n = 205 subjects (60 years old and older) were examined and followed up at two years. Cognitive function was examined using the Montreal Cognitive Assessment (MoCA) Delayed Recall (DR) subtest. Geriatric Depression Scale (GDS) was used as a screening tool for depression. Statistical analysis was performed using linear mixed models. RESULTS: A total of 144 subjects (70.24%) had SMC. MoCA Delayed Recall scores were not significantly changed in relation to time and SMC. Dynamics of SMC significantly influenced changes in GDS score (p = 0.008). CONCLUSIONS: SMC and objective memory impairment do not fully overlap each other. Subjects without SMC for longer than two years noted less intensity of depression symptoms in comparison to subgroup with SMC. However, occurrence of SMC in subjects who were previously free of SMC, was not related to increase in depression symptom intensity.

Cutaneous T-cell lymphoma in erythrodermic cases may be suspected on the basis of scalp examination with dermoscopy.

Erythrodermic variants of cutaneous T-cell lymphoma (CTLC) are one of the case of erythroderma. The aim of the study was to assess the value of scalp dermoscopy in differentiation between erythrodermic CTCL, psoriasis, and atopic dermatitis. A total of 76 patients were included into the study (16 patients with erythrodermic CTCL, 20 patients with psoriatic erythroderma, 20 with erythrodermic atopic dermatitis, and 20 healthy volunteers). The most common trichoscopic features of erythrodermic CTCL were: numerous pili torti, numerous broken hairs, white thick interfollicular bands, and patchy hyperpigmentation of the background. They were observed in 81% (13/16), 75% (12/16), 56% (9/16), and 37.5% (6/16) of patients with CTCL, respectively (p < 0.001). Other specific features of erythrodermic CTCL were 8-shaped hairs (19%; 3/16) and visible anagen bulbs (12.5%; 2/16) (p < 0.05 and p = 0.052, respectively). The most common vascular pattern of erythrodermic CTCL was perifollicular arrangement of glomerular (50%; 8/16; p < 0.001) or linear vessels (31%; 5/16; p < 0.05). Follicular spicules-like scaling was pathognomonic for erythrodermic CTCL (12%, 2/16) although its presence did not reach statistical significance (p = 0.052). In conclusion, the characteristic trichoscopic findings of erythrodermic CTCL are numerous pili torti, eight-shaped hairs, thick white interfollicular bands, color heterogeneity of the background and perifollicular arrangement of vessels.

Fluoroaryl analogs of sulforaphane - A group of compounds of anticancer and antimicrobial activity.

A series of new sulforaphane analogs bearing various (poly)fluoroaryl substituents bonded to the sulfinyl sulfur atom in place of the original methyl group and having different number of methylene groups in the central alkyl chain were synthesized and fully characterized. The new compounds were tested in vitro for their anticancer, antibacterial, antifungal and antiviral properties. Some of them demonstrated a much higher anticancer activity against selected lines of cancer: skin (MALME-3M), colon (HT-29) and breast (MCF7 and MDA-MB-231) cells than that exhibited by native sulforaphane (SFN). Related lines of untransformed (normal) cells, taken from the same organs as the cancer ones, i.e. MALME3, CRL-1790 and MCF10, respectively, were checked, which allowed for the determination of the selectivity indexes (SI). In certain cases, the latter exceeded 3.2. Concerning the antibacterial activity, gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) were susceptible to some newly synthesized SFN analogs, while the selected probiotic strains were from 10 to 100 fold more resistant to them, which gives a possibility of protection of symbiont strains during a potential therapy with such compounds. The antifungal activity of the new compounds possessing the fluorophenyl substituent was found to be higher than the activity of the parent SFN. In turn, most of the new compounds showed generally no anti-HIV activity. The influence of the particular structural differences in the new molecules, analogs of SFN, on their biological activity is discussed.

The Polish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Polish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 154 JIA patients (10.4% systemic, 50.0% oligoarticular, 24.7% RF-negative polyarthritis, 14.9% other categories) and 91 healthy children, were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Polish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Chiral Organosulfur Ligands/Catalysts with a Stereogenic Sulfur Atom: Applications in Asymmetric Synthesis.

Asymmetric synthesis, in which chiral organocatalysts or metal complexes with chiral ligands are used, has become the most valuable methodology for the preparation of enantiomerically pure organic compounds. Among such catalysts/ligands, a growing number constitute various organosulfur compounds. This Review provides comprehensive and critical information on the plethora of sulfur-based chiral ligands and organocatalysts used in asymmetric synthesis, which have been published within the last 15 years. However, it is confined to the presentation of only those chiral catalysts/ligands that possess a stereogenic sulfur atom and includes sulfoxides, sulfinamides, N-sulfinyl ureas, sulfoximines, and some related S-chiral derivatives.

The diagnostic value of trichoscopy in systemic sclerosis.

BACKGROUND/OBJECTIVES: Systemic sclerosis is a connective tissue disease, which is characterized by fibrosis of the skin and internal organs, presence of specific antibodies and vascular involvement. Capillaroscopy is a useful method for the diagnosis and follow-up of patients with systemic sclerosis. Trichoscopy is a rapid, non-invasive technique, which has become a standard procedure in differential diagnosis of scalp and hair diseases. The aim of this study was to assess whether trichoscopy may be applied in imaging microvessels in patients with systemic sclerosis. METHODS: The study included 17 patients with systemic sclerosis, and 31 healthy patients. In every patient 10 trichoscopy images were taken with Fotofinder II. RESULTS: In patients with systemic sclerosis trichoscopy of the frontal scalp area revealed polymorphic microvessels in 64,7% of patients, spider vessels (76,4%), capillary loops (52,9%), arborising vessels (41,1%) and avascular areas (35,2%). In healthy individuals these features were observed in polymorphic microvessels 6,4% of patients, spider vessels 6,4%, capillary loops 100%, arborising vessels 16,1%, avascular areas 9,6%, respectively. CONCLUSIONS: In conclusion, the presence of polymorphic vessels in frontal area in trichoscopy is characteristic for systemic sclerosis.

Organofluorine Isoselenocyanate Analogues of Sulforaphane: Synthesis and Anticancer Activity.

A series of previously unknown sulforaphane analogues with organofluorine substituents bonded to the sulfinyl sulfur atom, an isoselenocyanate moiety in place of the isothiocyanate group, the central sulfur atom in various oxidation states, and different numbers of methylene groups in the central alkyl chain were synthesized and fully characterized. All new compounds were tested for their biological properties in vitro and demonstrated much higher anticancer activity against two breast cancer cell lines than that shown by native sulforaphane; at the same time, the compounds were less toxic for normal cells. The influence of the particular structural changes in the molecules on the cytotoxicity is discussed.

Qualitative evaluation of diets of students at the University of the Third Age at Koszalin University of Technology.

BACKGROUND: Nutrition plays an important role in the elderly stage of life. A proper proportion of the individual nutritional ingredients in a diet may positively impact the ageing body. This positive influence consists in slowing down the undesired and unfavourable physiological alterations leading inevitably to the general weakness of the body. OBJECTIVE: The aim of the paper was to perform a qualitative analysis with the Starzynska scoring system for diets, the daily food rations (DFR), among students of the University of the Third Age at the Koszalin University of Technology (Poland). MATERIAL AND METHODS: The studied materials consisted of the 7-day current records made by 79 students (16 males and 63 females) of the University of the Third Age at the Koszalin University of Technology and the measurements of body weight, height and waistline. The records were qualitatively evaluated with Starzynska's test. RESULTS: It was found that approximately half of the students were overweight or obese. The majority consumed the recommended number of meals. About 44% of the students consumed animal protein with all meals. Milk and cheese were ingested daily with at least two meals by approximately 11% of the students. Fruit and vegetables are eaten on a daily basis by about 60% of the students. Almost 40% ate wholegrain bread, groats, and dried legumes. The statistical analysis of the means for the points of individual indicators did not reveal any statistically significant difference between women and men (p>0.05). CONCLUSIONS: Approximately ¾ of the evaluated diets were inaccurately formulated and required radical modification. The low frequency of animal protein, milk and cheese, wholegrain bread, groats and dried legume consumption may result in deficiencies in certain nutrients. Nutritional education is recommended, focusing on the correct way to formulate meals. The recorded level of overweight and obesity in the students indicates a need for a quantitative assessment of consumption considering, among others, the energy input in their diets.

Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression.

OBJECTIVES: Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained. MATERIAL AND METHODS: The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases - 37 girls (74%) and 13 boys (26%), aged 1.5-17.5 years - during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children - 28 girls (56%) and 22 boys (44%) aged 2-17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0-1-6 months schedule. The antibody concentration of ≥ 10 mIU/ml in patients is regarded as protective. RESULTS: No protective antibody concentrations were found in 25 cases (50%) in the group of diseased children and only in 2 children in the control group (4%). CONCLUSIONS: The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B.

Pain associated with the musculoskeletal system in children from Warsaw schools.

OBJECTIVE: To assess the prevalence of pain in the musculoskeletal system and possible reasons for these complaints among early age children from Warsaw schools. MATERIAL AND METHODS: The study was conducted in 34 randomly selected primary schools in Warsaw in 2011. 2748 survey-questionnaires were given to parents or legal guardians by children. Of these, 1509 surveys were subject to a final analysis. The survey included 66 questions regarding, among other things, pain in the musculoskeletal system in children. Additionally, there were questions about possibly occurring diseases, any postural defects, significant obesity, as well as effects of these complaints on the child's physical activity. Survey data regarded 6-7-year-old children. RESULTS: In the group of 1509 respondents, 242 children (16%) complained about pain in the musculoskeletal system. Pain was located most frequently in the knee joints, and more rarely in the spine and joints in the upper extremities. In the group of children who complained about pain, moderate physical activity was statistically significantly limited. According to parents, physicians did not diagnose any medical conditions in 106 children. Joint disease was diagnosed in 33 children. Postural defects were diagnosed in 589 children. In 123 children complaining about pain at least one postural defect was diagnosed. Such defects were diagnosed statistically significantly more rarely (p = 0.011) in 1234 children who did not complain about pain (460 children). Platypodia or other foot deformation was observed in 25% of these children, spinal curvature in 12%, abnormal knee joint position in 11% and uneven hip position in 2% children. Of note, 17% of all children were significantly overweight. In overweight children the prevalence of pain, especially in the knee joints and feet, was significantly higher. CONCLUSIONS: This study aims to underline the problem of musculoskeletal pain in early-age children which limits their physical activity. Also the authors draw attention to the issue of postural defects in a large group of school children. This issue undoubtedly requires more attention and a plan how to create more effective methods of prevention.

Juvenile idiopathic arthritis complicated by amyloidosis with secondary nephrotic syndrome - effective treatment with tocilizumab.

A case report of a boy with juvenile idiopathic arthritis since the age of 2 years, generalized onset, complicated by nephrotic syndrome due to secondary type A amyloidosis is presented. In the patient the disease had an especially severe course, complicated by frequent infections, making routine treatment difficult. Amyloidosis was diagnosed in the 5(th) year of the disease based on a rectal biopsy. Since the disease onset the boy has been taking prednisolone and sequentially cyclosporine A, methotrexate, chlorambucil, etanercept, and cyclophosphamide. Clinical and laboratory remission was observed after treatment with tocilizumab. After 42 months of treatment with tocilizumab the boy's condition is good. There is no pain or joint edema, and no signs of nephrotic syndrome.

Temporomandibular joint dysfunction and disorders in the development of the mandible in patients with juvenile idiopathic arthritis - preliminary study.

BACKGROUND: The temporomandibular joint (TMJ) may be affected unilaterally or bilaterally in the course of juvenile idiopathic arthritis (JIA). Permanent complications involve joint damage or stiffness and disorders in the development of the mandible, such as micrognathia, posterior rotation of the mandible, crowding and protrusion of the front teeth and malocclusion. OBJECTIVES: The aim of the study was the clinical and radiological assessment of TMJ dysfunctions and disorders in the development of the mandible in patients suffering from JIA, depending on the duration of the disease. MATERIAL AND METHODS: The research involved 46 patients with JIA, recognized according to the criteria established by the International League of Associations for Rheumatology (ILAR). Among the patients, 20 suffered from polyarticular JIA and 26 from pauciarticular JIA. The clinical assessment included determination of the facial profile according to Ricketts, intraoral assessment according to Angle's classification and canine class. There were 15 patients (9 with polyarticular and 6 with pauciarticular JIA) qualified for radiological examination. The location of the mandible was determined with the use of a lateral cephalometric image on the basis of a compilation of various analyses. RESULTS: Out of the 46 patients, 15 individuals (32.6%) displayed clinical features of TMJ dysfunction (pain, clicking, crepitus). Of these, 6 patients (40.0%) reported disorders in mandibular development typical of JIA in the form of retrognathia and posterior rotation of the mandible. According to the grading system developed by Rohlin and Petersson, articular surface damage was considerably higher in the patients with a longer history of the disease (p < 0.01) and positively correlated with the deficit in mandible growth (r = 0.66, p < 0.008). CONCLUSIONS: Early detection of temporomandibular joint damage, even in the case of juvenile idiopathic arthritis with a low level of inflammation, may prevent permanent and significant facial deformities when combined with orthodontic treatment of disorders in the development of the mandible.