Adolescents with Neuropsychiatric Disorders during the COVID-19 Pandemic: Focus on Emotional Well-Being and Parental Stress.

(1) Introduction: The aim of our research was to explore emotional/behavioral changes in adolescents with neuropsychiatric conditions during the COVID-19 pandemic, and parental stress levels through a standardized assessment, comparing the data collected before and during the first months of lockdown. Moreover, an additional goal was to detect a possible relationship between emotional/behavioural symptoms of adolescents and the stress levels of their parents. (2) Methods: We enrolled 178 Italian adolescents aged between 12-18 that were referred to the Child Neuropsychiatry Unit of the University Hospital of Salerno with different neuropsychiatric diagnoses. Two standardized questionnaires were provided to all parents for the assessment of parental stress (PSI-Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour Check List). The data collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice, were compared to those recorded during the pandemic. (3) Results: The statistical comparison of PSI and CBCL scores before/during the pandemic showed a statistically significant increase in all subscales in the total sample. The correlation analysis highlighted a significant positive relationship between Parental Stress and Internalizing/Externalizing symptoms of adolescent patients. Age and gender did not significantly affect CBCL and PSI scores, while the type of diagnosis could affect behavioral symptoms and parental stress. (4) Conclusions: our study suggests that the lockdown and the containment measures adopted during the COVID-19 pandemic could have aggravated the emotional/behavioral symptoms of adolescents with neuropsychiatric disorders and the stress of their parents. Further studies should be conducted in order to monitor the evolution of these aspects over time.

Postural Threat Influences the Coupling Between Anticipatory and Compensatory Postural Adjustments in Response to an External Perturbation.

Fear of falling increases conscious control of balance and postural threat warrants accurate anticipatory motor commands for keeping a safe body posture. This study examines the anticipatory (APAs) and compensatory (CPAs) postural adjustments generated in response to an external perturbation while individuals are positioned at two different altitudes (2 cm and 80 cm) from the floor level. The main result indicates that due to the perceived emotional threat, different agonist and antagonist muscles synergies (R and C-Indexes) are manifested, particularly during the anticipatory phase. The results suggest that the CNS sends central commands for anticipating postural adjustments by adopting primarily a muscle reciprocal activation instead of a muscle co-activation strategy. Interestingly, the APAs strategies were modified under different postural threats by controlling the agonist-antagonist muscles at different joints of lower extremity. For CPAs the reciprocal activation was less applied compared to muscles co-activation to unsure larger margin for compensatory adjustments as needed and re-establish the postural stability. The results indicate that when facing to a postural threat, the CNS modulates the anticipatory and compensatory phases of postural adjustments to minimize the risk of falling.

Metabolic effect of bodyweight whole-body vibration in a 20-min exercise session: A crossover study using verified vibration stimulus.

The ability of whole body vibration (WBV) to increase energy expenditure (EE) has been investigated to some extent in the past using short-term single exercises or sets of single exercises. However, the current practice in WBV training for fitness is based on the execution of multiple exercises during a WBV training session for a period of at least 20 min; nevertheless, very limited and inconsistent data are available on EE during long term WBV training session. This crossover study was designed to demonstrate, in an adequately powered sample of participants, the ability of WBV to increase the metabolic cost of exercise vs. no vibration over the time span of a typical WBV session for fitness (20 min). Twenty-two physically active young males exercised on a vibration platform (three identical sets of six different exercises) using an accelerometer-verified vibration stimulus in both the WBV and no vibration condition. Oxygen consumption was measured with indirect calorimetry and expressed as area under the curve (O2(AUC)). Results showed that, in the overall 20-min training session, WBV increased both the O2(AUC) and the estimated EE vs. no vibration by about 22% and 20%, respectively (P<0.001 for both, partial eta squared [η2] ≥0.35) as well as the metabolic equivalent of task (+5.5%, P = 0.043; η2 = 0.02) and the rate of perceived exertion (+13%, P<0.001; ŋ2 = 0.16). Results demonstrated that vibration is able to significantly increase the metabolic cost of exercise in a 20-min WBV training session.

Lower Extremity Overuse Conditions Affecting Figure Skaters During Daily Training.

BACKGROUND: Most ice figure skaters train and compete with ongoing issues in the lower extremities, which are often overlooked by the skaters and considered injuries only when they prevent the athletes from skating. Although not severe, these conditions impair the quality of daily training and compromise the skaters' state of mind and performances. PURPOSE: (1) To determine the point prevalence of the ongoing lower extremity overuse conditions in a population of ice figure skaters of all ages and levels and (2) to identify the risk factors contributing to the development of the most common ongoing conditions. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 95 skaters of all ages and skating levels were evaluated in a single examination in the middle of the competitive season. Data collection consisted of a questionnaire, clinical examination, and measurement of the skaters' characteristics and the equipment used. RESULTS: Retrocalcaneal bursitis was the most common problem, affecting at least 1 foot in 34% of the skaters evaluated, followed by posterior heel skin calluses and superficial calcaneal bursitis, which affected 29% and 28% of skaters, respectively. The prevalence of the majority of these conditions was 10% to 32% higher in elite skaters than in nonelite skaters. Higher boot-foot length difference was associated with greater risk of superficial calcaneal bursitis in the landing foot of elite skaters, while higher body weight and greater in-skate ankle flexibility were associated with the development of retrocalcaneal bursitis in nonelite skaters. Only 30 skaters (32%) wore the appropriate boot size, while 57 skaters (51%) could not dorsiflex their ankles properly while wearing skates. CONCLUSION: The heel represents a major area of concern for the high prevalence of calcaneal bursitis and calluses in proximity of the Achilles tendon, suggesting that improvements on the boot heel cup design should take priority. The association of bursitis with higher in-skate ankle flexibility suggests that these conditions may be the results of a process developing when the ankle is bending within the boot. Also, since wearing oversized boots is a major risk factor for the development of subcutaneous bursitis and skin abrasions, boot retailers should be better educated to sell the appropriate boot size to the skaters.

FFA4/GPR120 agonists: a survey of the recent patent literature.

FFA4/GPR120, a member of the rhodopsin family of G-protein-coupled receptors (GPCRs), is becoming an important target for therapeutic intervention in several areas of disease, including metabolic diseases, inflammation and cancer. In the last few years several patents on original chemotypes have been generated by different companies. In this review an analysis of the patents in the FFA4 agonism field is presented, with an emphasis on the documents published between 2013 and mid-2015. A discussion of the biological methods used in the patents is included. The general interest in this area is growing fast as half of the existing patents on FFA4 agonists have been issued after 2013. There is, however, a need of further diversifying new chemical classes away form the current substrate-like, carboxylic acid-containing agonists.

Robust automatic measurement of 3D scanned models for the human body fat estimation.

In this paper, we present an automatic tool for estimating geometrical parameters from 3-D human scans independent on pose and robustly against the topological noise. It is based on an automatic segmentation of body parts exploiting curve skeleton processing and ad hoc heuristics able to remove problems due to different acquisition poses and body types. The software is able to locate body trunk and limbs, detect their directions, and compute parameters like volumes, areas, girths, and lengths. Experimental results demonstrate that measurements provided by our system on 3-D body scans of normal and overweight subjects acquired in different poses are highly correlated with the body fat estimates obtained on the same subjects with dual-energy X-rays absorptiometry (DXA) scanning. In particular, maximal lengths and girths, not requiring precise localization of anatomical landmarks, demonstrate a good correlation (up to 96%) with the body fat and trunk fat. Regression models based on our automatic measurements can be used to predict body fat values reasonably well.

Effect of low-intensity, low-frequency ultrasound treatment on anthropometry, subcutaneous adipose tissue, and body composition of young normal weight females.

BACKGROUND: Low-intensity, low-frequency ultrasound is increasingly being used for noninvasive, external body contouring as an alternative to liposuction or laser treatments. OBJECTIVES: To evaluate the effect of chronic localized treatment with a novel ultrasound device on subcutaneous adipose tissue thickness and fat mass in young, normal weight women. METHODS: Twenty-eight females (mean age = 25.5 ± 0.66 [SE] year, mean BMI = 22.1 ± 0.37 kg/m2) underwent a 10-week bilateral treatment with the device in the gluteus-buttock-thigh area (Lipolysis program: ultrasound frequency = 150 kHz; power = 1.65 W/cm2), 48 min per session, two sessions a week. Subcutaneous adipose tissue thickness and fat mass were evaluated before and after treatment with ultrasound and dual-energy X-ray absorptiometry, respectively. RESULTS: Treatment was well tolerated by all participants. At the end of treatment, statistically significant reduction of subcutaneous adipose tissue thickness was found bilaterally at the gluteus and thigh site (-2.03 ÷ -2.79%). Trunk and lower limb fat mass were reduced as well (-3.48 ÷ -3.97%). CONCLUSIONS: A 10-week, low-intensity, low-frequency localized external ultrasound treatment is effective in reducing adipose tissue in females.

Ca(2+) release-activated Ca(2+) channel inhibitors.

Ca(2+) release-activated Ca(2+) (CRAC) channels are becoming important targets for therapeutic intervention in several areas of disease, including immunology, allergy and cancer. In parallel to the progression towards reliable methods for measuring CRAC currents and their inhibition, patents have been generated by several companies. In this Patent Review, an analysis of the patents in the CRAC channel inhibition filed is presented. A discussion of the biological methods used in the patents is included. The general interest in this area is growing fast with almost 80% of the patents issued after 2010.

Erratum: A novel small-angle neutron scattering detector geometry. Corrigendum.

Errors in the paper by Kanaki, Jackson, Hall-Wilton, Piscitelli, Kirstein & Andersen [J. Appl. Cryst. (2013), 46, 1031-1037] are corrected.[This corrects the article DOI: 10.1107/S0021889813011862.].

A novel small-angle neutron scattering detector geometry.

A novel 2π detector geometry for small-angle neutron scattering (SANS) applications is presented and its theoretical performance evaluated. Such a novel geometry is ideally suited for a SANS instrument at the European Spallation Source (ESS). Motivated by the low availability and high price of 3He, the new concept utilizes gaseous detectors with 10B as the neutron converter. The shape of the detector is inspired by an optimization process based on the properties of the conversion material. Advantages over the detector geometry traditionally used on SANS instruments are discussed. The angular and time resolutions of the proposed detector concept are shown to satisfy the requirements of the particular SANS instrument.

Ten-week whole-body vibration training improves body composition and muscle strength in obese women.

This work explored the short-term effect of whole body vibration (WBV) training on anthropometry, body composition and muscular strength in obese women. Fifty obese women (age = 46.8 ± 7.81[SD]y; BMI = 35.1 ± 3.55 kg/m(2)) were assigned to a ten-week WBV training period, two times a week (in each session, 14 min vibration training, 5 min rest; vibration amplitude 2.0-5.0mm, frequency 40-60 Hz), with (n = 18) or without (n = 17) radiofrequency, or to a non-exercise control group (n = 15). Subjects were instructed not to change their habitual lifestyle. Before and after the ten-week experimental period, anthropometric measurements, dual-energy X-ray absorptiometry (DXA), and the leg press, leg curl and leg extension strength tests were carried out. All changes in the two groups of WBV training, with or without radiofrequency, were similar and these groups were combined in a single WBV intervention group. As compared to controls, subjects submitted to WBV training had significantly lower BMI, total body and trunk fat, sum of skinfolds and body circumferences. On the other hand, lower limb strength tests were increased in the WBV group. These preliminary results suggest that WBV training may improve body composition and muscular strength in obese women and may be a useful adjuvant to lifestyle prescriptions.

Toward highly potent cancer agents by modulating the C-2 group of the arylthioindole class of tubulin polymerization inhibitors.

New arylthioindole derivatives having different cyclic substituents at position 2 of the indole were synthesized as anticancer agents. Several compounds inhibited tubulin polymerization at submicromolar concentration and inhibited cell growth at low nanomolar concentrations. Compounds 18 and 57 were superior to the previously synthesized 5. Compound 18 was exceptionally potent as an inhibitor of cell growth: it showed IC50 = 1.0 nM in MCF-7 cells, and it was uniformly active in the whole panel of cancer cells and superior to colchicine and combretastatin A-4. Compounds 18, 20, 55, and 57 were notably more potent than vinorelbine, vinblastine, and paclitaxel in the NCI/ADR-RES and Messa/Dx5 cell lines, which overexpress P-glycoprotein. Compounds 18 and 57 showed initial vascular disrupting effects in a tumor model of liver rhabdomyosarcomas at 15 mg/kg intravenous dosage. Derivative 18 showed water solubility and higher metabolic stability than 5 in human liver microsomes.

New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors.

New indolylarylsulfone (IAS) derivatives bearing nitrogen containing substituents at the indole-2-carboxamide inhibited the HIV-1 WT in MT-4 cells at low nanomolar concentrations. In particular, compound 9 was uniformly effective against the mutant Y181C, Y188L, and K103N HIV-1 strains; it was highly active against the multidrug resistant mutant IRLL98 HIV-1 strain bearing the K101Q, Y181C, and G190A mutations conferring resistance to NVP, DLV, and EFV and several HIV-1 clades A in PBMC.

Aminothienopyridazine inhibitors of tau aggregation: evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties.

Previous studies demonstrated that members of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors exhibit a promising combination of in vitro activity as well as favorable pharmacokinetic properties (i.e., brain-penetration and oral bioavailability). Here we report the synthesis and evaluation of several new analogues. These studies indicate that the thienopyridazine core is essential for inhibition of tau fibrillization in vitro, while the choice of the appropriate scaffold decoration is critical to impart desirable ADME-PK properties. Among the active, brain-penetrant ATPZ inhibitors evaluated, 5-amino-N-cyclopropyl-3-(4-fluorophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide (43) was selected to undergo maximum tolerated dose and one-month tolerability testing in mice. The latter studies revealed that this compound is well-tolerated with no notable side-effects at an oral dose of 50mg/kg/day.

Indole-2-carboxamides as allosteric modulators of the cannabinoid CB1 receptor.

We synthesized new N-phenylethyl-1H-indole-2-carboxamides as the first SAR study of allosteric modulators of the CB(1) receptor. The presence of the carboxamide functionality was required in order to obtain a stimulatory effect. The maximum stimulatory activity on CB(1) was exerted by carboxamides 13 (EC(50) = 50 nM) and 21 (EC(50) = 90 nM) bearing a dimethylamino or piperidinyl group, respectively, at position 4 of the phenethyl moiety and a chlorine atom at position 5 of the indole.

Venting-while-heating microwave-assisted synthesis of 3-arylthioindoles.

We report the first example of venting-while-heating microwave-assisted synthesis of a small library of 3-arylthioindoles. Compounds were prepared in excellent isolated yields (90-98%) within 4 min in a closed vessel by treating indoles with disulfides in the presence of sodium hydride in anhydrous N,N-dimethylformamide. The method was not affected by electron-donating and -withdrawing substituents both on 3-arylthio moiety and at 2- and 5-positions of the indole nucleus.

Effects of whole-body vibration with or without localized radiofrequency on anthropometry, body composition, and motor performance in young nonobese women.

OBJECTIVES: The study investigated the effect of whole-body vibration (WBV) alone and in association with localized radiofrequency on fat deposits in young nonobese subjects. METHODS: Forty-four (44) healthy, nonobese women aged 25.3±5.26 years, body-mass index (BMI) 21.7±2.47 kg/m(2) were randomly assigned to an 8-week trial of WBV (2 sessions per week) or WBV plus localized radiofrequency (WBV+RF) in the abdominal, buttock, and thigh region. Anthropometry, body composition (dual-energy x-ray absorptiometry, DXA), and motor performance were assessed before and after the trial. Data were analyzed by one-way analysis of variance (ANOVA) or ANOVA for repeated measures (group×time). RESULTS: Valid data were obtained for 36 women (WBV, n=18; WBV+RF, n=18). Body mass and BMI did not change after trial. Body circumferences were unchanged or slightly reduced, with no difference between groups. Skinfold thickness was significantly reduced at several sites in the whole study population (n=36), reduction being higher at the thigh site in the WBV+RF group. According to DXA analysis, total body lean mass increased (p=0.009) and total body fat mass decreased (p=0.036) in the whole study population after trial with no significant difference between the WBV and WBV+RF group in spite of larger absolute changes in the latter. Standing long jump improved after trial with no change in flamingo balance test. CONCLUSIONS: An 8-week WBV training is effective in inducing positive body composition changes as well as increased muscle strength in women; it could be recommended as an alternative/complementary tool in physical activity or fitness programs as it is well tolerated. The current data give limited support to the association of localized RF treatment and WBV training as synergistic in inducing body fat mass loss; such a beneficial effect should be further investigated in subject with larger subcutaneous fat deposits (i.e., overweight or obese).

Design and synthesis of 2-heterocyclyl-3-arylthio-1H-indoles as potent tubulin polymerization and cell growth inhibitors with improved metabolic stability.

New arylthioindoles (ATIs) were obtained by replacing the 2-alkoxycarbonyl group with a bioisosteric 5-membered heterocycle nucleus. The new ATIs 5, 8, and 10 inhibited tubulin polymerization, reduced cell growth of a panel of human transformed cell lines, and showed higher metabolic stability than the reference ester 3. These compounds induced mitotic arrest and apoptosis at a similar level as combretastatin A-4 and vinblastine and triggered caspase-3 expression in a significant fraction of cells in both p53-proficient and p53-defective cell lines. Importantly, ATIs 5, 8, and 10 were more effective than vinorelbine, vinblastine, and paclitaxel as growth inhibitors of the P-glycoprotein-overexpressing cell line NCI/ADR-RES. Compound 5 was shown to have medium metabolic stability in both human and mouse liver microsomes, in contrast to the rapidly degraded reference ester 3, and a pharmacokinetic profile in the mouse characterized by a low systemic clearance and excellent oral bioavailability.

Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates.

BACKGROUND: Novel indolylarylsulfones (IASs), designed through rational structure-based molecular modelling and docking approaches, have been recently characterized as effective inhibitors of the wild-type and drug-resistant mutant HIV-1 reverse transcriptase (RT). METHODS: Here, we studied the interaction of selected halo- and nitro-substituted IAS derivatives, with the RT enzyme carrying the single resistance mutations K103N and Y181I through steady-state kinetic experiments. RESULTS: The studied compounds exhibited high selectivity to the mutant RT in complex with its substrates, behaving as uncompetitive inhibitors. The presence of the K103N mutation, and to a lesser extent the Y181I, stabilized the drug interactions with the viral RT, when both its substrates were bound. CONCLUSIONS: The characterization of these mutation-specific effects on inhibitor binding might be relevant to the design of more effective new generation non-nucleoside reverse transcriptase inhibitors, with better resilience towards drug resistant mutants.

1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: an effective scaffold for the design of either CB1 or CB2 receptor ligands.

New 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as cannabinoid (CB) receptor ligands. Compound 11 (CB(1)K(i) = 2.3 nM, CB(1) SI = 163.6) showed CB(1) receptor affinity and selectivity superior to Rimonabant and AM251. Acute administration of 2mg/kg 11 reduced sucrose, but not regular food, intake in rats. On the other hand, compound 23 (CB(2)K(i) = 0.51 nM, CB(2) SI = 30.0) showed significant affinity and selectivity for the CB(2) receptor. The results presented here show that the 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide may serve as an effective scaffold for the design of either CB(1) or CB(2) receptor ligands.