Conformation, defects, and dynamics of a discotic liquid crystal and their influence on charge transport.
Future applications of discotic liquid crystals (DLCs) in electronic devices depend on a marked improvement of their conductivity properties. We present a study of 2,3,6,7,10,11-hexakishexyloxytriphenylene (HAT6) and show how local conformation, structural defects, and thermal motions on the picosecond time scale strongly affect the efficient charge transport in DLCs. A direct and successful comparison of classical molecular dynamics (MD) simulations with both neutron powder diffraction and quasielastic neutron scattering (QENS) give a full insight into the structural and dynamical properties of HAT6. The local conformation of HAT6 molecules is characterized by a mutual rotation (twist) angle of about 37° and typically a mutual aromatic-core distance of 3.4 Å instead of the average distance of 3.65 Å usually quoted. We show that a considerable number of structural traps is present in HAT6, which persist at the picosecond time scale. We find that the high disorder in the mutual positions of the aromatic cores is an important factor contributing to the limited conductivity of HAT6 compared to larger DLCs.


Glutathione-induced sodium currents in neocortex.
The present report demonstrates that glutathione (GSH), a tripeptide composed of glutamate, glycine and cysteine (gamma-L-glutamyl-L-cysteinyl-glycine) and best known as a free radical scavenger, elicits a large fast depolarizing potential when applied to cortical slices. This potential is maximally larger than that produced by either NMDA or AMPA. Like AMPA, the GSH current appears to be carried by sodium ions, but cannot be blocked by the glutamate receptor antagonists AP5 or DNQX. In addition, removal of external calcium or blockade of potassium currents by TEA does not diminish the GSH-induced potential. Together, these results suggest that GSH acts through its own receptor-mediated channels, independently of the known EAA receptors, and that its receptors may be a key, and previously unknown, component of cortical excitatory neurotransmission.


Love and duty: issue of concern for nurses when newly physically disabled persons are discharged into the care of families.
Richmond (1990, P.65) writes "spinal cord injury occurs not just to the individual but to the entire family. There exists during crisis the potential for growth for individual family members and the entire family system". This article is written from both personal experience and professional interest because little appears to be written in the nursing literature about the family adjustment following discharge from hospital of a person who has a permanent disability following damage to the spinal cord.


Effects of distance specialization on the backstroke swimming kinematics.
The purpose of the present study was to investigate different biomechanical variables of backstroke technique in swimmers specialized in different distance events, in order to investigate the capacity to modify the timing of the arm stroke when changing the swimming velocity from sub-maximal to maximal. Two 25-m backstroke trials respectively at 70% of maximum velocity (V70) and at 100% of maximum velocity (Vmax) were performed by 9 200-m distance swimmers and 9 50-m distance swimmers. Swimming velocity, stroke length, stroke rate, duration of different phases of the arm stroke and selected kinematic variables were assessed in both cases. In the 50-m distance swimmers, the duration of the propulsive phase at Vmax, expressed as a percentage of the duration of the total underwater arm stroke, increased significantly (p = 0.001) with increasing swimming velocity. Specifically, both the pull and push phases were fundamental in the increase of duration of the propulsive phase. When compared to 200-m specialists, 50-m distance swimmers seem to be more able to modify their arm stroke phases duration when increasing the swimming velocity in backstroke. Key pointsThe 50-m DS are able to find an optimal timing among the stroke phases increasing the duration of the propulsive phase.The 50-m DS, when increasing the swimming velocity, show a more efficient relationship between propulsive and non propulsive phases with respect to the 200-m DS.Both pull and push phases are key factors for increasing the duration of the propulsive phase for the 50-m DS.


The effect of substitution pattern of HPMC on polymer release from matrix tablets.
The purpose of this study was to gain further understanding of how the substituent heterogeneity of hydroxypropyl methylcellulose, HPMC, affects the polymer release from hydrophilic matrix tablets. The hypothesis was that the heterogeneous substituent pattern facilitated hydrophobic interactions that increased the viscosity and therefore affected the release rate to a major extent. Polymer tablets were prepared from three heterogeneously substituted HPMC batches of the same substituent (2208) and viscosity (100 cps) grade. To elucidate the hypothesis, fractions of both the dissolved polymer and the tablet residue were collected from the dissolution bath and further characterised. The extensive characterisation showed that, although the dissolved bath fraction and the tablet residue had a similar average degree of substitution, the residue was more heterogeneously substituted. It was further revealed that the heterogeneous substituent pattern of the tablet residue facilitated the formation of soluble gel-like components already at room temperature, which increased the viscosity. The viscosity increased by 150% at temperatures correlated to the dissolution bath, and it was thus concluded that the gel-like components grew in size with temperature. Finally, much lower release rates were obtained by tablets composed of the residue compared to tablets composed of the bath fraction, which clarified the hypothesis.


A network meta-analysis of association between cardiometabolic risk factors and COVID-19 outcome severity.
Cardiometabolic comorbidities have been associated with a higher risk of COVID-19 severity and mortality, but more investigations are needed to determine which comorbidity is more detrimental. Embase, Emcare, and MEDLINE were searched systematically for prospective and retrospective studies assessing the associations of cardiometabolic risk factors and COVID-19 outcomes of hospitalization, severity, and mortality among COVID-19-diagnosed patients. Literature search was performed from first publication to May 19, 2021. Study quality was assessed by the Newcastle-Ottawa Scale. From the literature search, 301 studies suggested that all included cardiometabolic risk factors were associated with a higher risk of COVID-19 hospitalization, severity, and mortality, except that overweight was associated with a decreased risk of mortality (relative risk [RR] 0.88; 95% CI, 0.80-0.98). Patients with diabetes (RR 1.46; 95% CI, 1.45-1.47) were most likely to be hospitalized; patients with heart failure had the highest risk for severe COVID-19 outcomes (RR 1.89; 95% CI, 1.71-2.09); while patients with stroke were most susceptible to overall mortality (RR 1.99; 95% CI, 1.90-2.08). In the network meta-analysis, cerebrovascular disease had the highest impact (RR 1.69; 95% CI, 1.65-1.73) on COVID-19 outcomes compared to other cardiometabolic risk factors. For different combinations of risk factors, cardiovascular disease and diabetes combined (RR 6.98; 95% CI, 5.28-9.22) was more detrimental than others. Considering the high prevalence of cardiometabolic comorbidities and risk of all severe outcomes, patients with cardiometabolic comorbidities should be prioritized in vaccination and treatment development of COVID-19.


Progressive deterioration of thalamic nuclei relates to cortical network decline in schizophrenia.
Thalamic abnormalities are considered part of the complex pathophysiology of schizophrenia, particularly the involvement of specific thalamic nuclei. The goals of this study were to: introduce a novel atlas-based parcellation scheme for defining various thalamic nuclei; compare their integrity in a schizophrenia sample against healthy individuals at baseline and follow-up time points, as well as rates of change over time; examine relationships between the nuclei and abnormalities in known connected cortical regions; and finally, to determine if schizophrenia-related thalamic nuclei changes relate to cognitive functioning and clinical symptoms. Subjects were from a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy individuals (n=20) were group-matched for age, gender, and recent-alcohol use. We used high-dimensional brain mapping to obtain thalamic morphology, and applied a novel atlas-based method for delineating anterior, mediodorsal, and pulvinar nuclei. Results from cross sectional GLMs revealed group differences in bilateral mediodorsal and anterior nuclei, while longitudinal models revealed significant group-by-time interactions for the mediodorsal and pulvinar nuclei. Cortical correlations were the strongest for the pulvinar in frontal, temporal and parietal regions, followed by the mediodorsal nucleus in frontal regions, but none in the anterior nucleus. Thalamic measures did not correlate with cognitive and clinical scores at any time point or longitudinally. Overall, findings revealed a pattern of persistent progressive abnormalities in thalamic nuclei that relate to advancing cortical decline in schizophrenia, but not with measures of behavior.


Departure from Network Equilibrium (DNE): an efficient and scalable measure of instantaneous network dynamics, with an application to magnetoencephalography.
The assessment of the dynamic status of a network is currently unavailable. It is important to know how far a network is away from its equilibrium (as an indicator of instability) at a moment, and over periods of time. Here, we introduce the Departure from Network Equilibrium (DNE), a new measure of instantaneous network dynamics. DNE is simple, fast to compute, and scalable with network size. We present the results of its application on white noise networks (as a basis) and on networks derived from magnetoencephalographic recordings from the human brain.


[Transverse myelitis syndrom as a result of neuromyelitis optica spectrum disorders, systemic lupus erythematosus and myasthenia gravis combination].
Neuromyelitis optica spectrum disorders (NMOSD) - autoimmune condition characterized by an inflammatory lesions mainly of the spinal cord with the development of longitudinally extensive transverse myelitis (LETM) and/or involvement of the optic nerve with the development of usually bilateral optical neuritis (ON). In recent years, there has been increased awareness that NMOSD can be combined with other autoimmune diseases, including myasthenia gravis (MG), systemic lupus erythematosus (SLE) et al. The simultaneous presence of several autoimmune diseases in one patient can adversely affect the course of each of the diseases, causing the so-called mutual burden or «overlap syndrome». In this article, we describe our own clinical observation of a 51-year-old woman of European origin who developed acute relapsing TM seropositive for AQP4-IgG, by 23 years after the diagnosis of generalized MG seropositive for antibodies to acetylcholine receptors (AChR-Ab) and the occurrence of SLE, criterially confirmed, several months after the initial TM attack. During the fourth TM attack, partial positive dynamics was achieved only against the background of the combined use of intravenous methylprednisolone (pulse therapy), high-volume plasma exchange, rituximab and cyclophosphamide. The NMOSD is a rare disease leading to severe disability. In patients with MG, when symptoms of damage to the central nervous system appear, an analysis should be performed for AQP4-IgG and possibly for antibodies to myelin glycoprotein of oligodendrocytes (MOG-Ab), as well as markers characteristic of systemic connective tissue diseases (SCTD). In patients with STDD, when symptoms of involvement nervous systemappear, testing for AQP4-IgG (and, if necessary, for MOG-Ab) should be performed to exclude NMOSD, as well as AChR-Ab (and, if necessary, antibodies against muscle specific kinase (MuSK-Ab)) to exclude MG.


Multiple column synthesis of a library of T-cell stimulating Tn-antigenic glycopeptide analogues for the molecular characterization of T-cell-glycan specificity.
A series of peptides and glycopeptides derived by amino acid and glycosyl amino acid scans through the self peptide from CBA/J mouse haemoglobin Hb (67-76). VITAFNEGLK, was synthesized by multiple column peptide synthesis (MCPS). Investigation of glycopeptide binding to the mouse major histocompatibility class II molecule Ek showed that glycans in position 72 did not interfere with the binding to Ek. Immunization experiments revealed that glycopeptides with the glycan in position 72 were immunogenic. Therefore a series of N-linked and O-linked glycopeptides with the glycan attached in the position 72 either to serine, threonine or asparagine was synthesized by MCPS. The glycan structure was furthermore varied with respect to monosaccharide component, size of oligosaccharide, anomer configuration and stereochemistry of essential hydroxyl groups in order to investigate the specificity of the interaction with the T-cell receptor. Easy synthesis of ready to use Ser and Thr building blocks corresponding to mucin core 1, the Tn-antigen and its beta-anomer were developed using trichloroacetimidates as glycosyl donors and reduction with in situ acetylation of the azide containing glycosylation products. Synthesis of an alpha-linked GlcNAc-Thr building block was achieved by glycosylation of Fmoc-Thr-OPip with 2-azido-2-deoxy-3,4,6-tri-O-acetyl-D-glycopyranosyl trichloroacetimidate as a glycosyl donor. Other building blocks were obtained by previously described procedures.


The combined effects of reverberation and nonstationary noise on sentence intelligibility.
Listening conditions in everyday life typically include a combination of reverberation and nonstationary background noise. It is well known that sentence intelligibility is adversely affected by these factors. To assess their combined effects, an approach is introduced which combines two methods of predicting speech intelligibility, the extended speech intelligibility index (ESII) and the speech transmission index. First, the effects of reverberation on nonstationary noise (i.e., reduction of masker modulations) and on speech modulations are evaluated separately. Subsequently, the ESII is applied to predict the speech reception threshold (SRT) in the masker with reduced modulations. To validate this approach, SRTs were measured for ten normal-hearing listeners, in various combinations of nonstationary noise and artificially created reverberation. After taking the characteristics of the speech corpus into account, results show that the approach accurately predicts SRTs in nonstationary noise and reverberation for normal-hearing listeners. Furthermore, it is shown that, when reverberation is present, the benefit from masker fluctuations may be substantially reduced.


Comparison of two multiple blood sampling regimens using an indwelling vascular access device for investigations of the hen's ovulatory cycle and calcium metabolism.
The objectives of the present study were to compare the effects of two regimens of serial blood sampling on the concentrations of hormones and ions during the ovulatory cycle of the domestic hen, and to examine the effectiveness of an indwelling vascular access device for repeated collection of blood samples. Single Comb White Leghorn hens were bled every 2 h over a period of 24 to 26 h, either from one oviposition to the next oviposition (OVIP-OVIP), or from 10 h prior to ovulation until the same time 24 h later (AFTN-AFTN). Whole blood was analyzed for ionized calcium concentration. Plasma was analyzed for total calcium, inorganic phosphorus, 1,25-dihydroxycholecalciferol, estradiol-17beta, and progesterone concentrations. The OVIP-OVIP regimen, using oviposition as a reference point, provided more accurate measurements of ionized calcium, inorganic phosphorus, and estradiol-17beta than did the AFTN-AFTN regimen. Either bleeding regimen was suitable for observing the patterns of 1,25-dihydroxycholecalciferol and progesterone concentrations. The decrease in bound calcium concentration observed with both regimens appeared to be an artifact of repeated blood sampling. The chance of a bird laying an egg following her second oviposition was lower following the OVIP-OVIP regimen than the AFTN-AFTN regimen. The vascular access device was a helpful tool in procuring multiple blood samples for measurement of ions and hormones during the ovulatory cycle of the domestic fowl.


Coping With Food Insecurity Using the Sociotype Ecological Framework.
Ensuring Food Security (FS) for all citizens is a fundamental human right and policy for all countries. Dealing with Food Insecurity (FINS) is a challenge causing stress at many levels-national, household, and individual. The conceptual framework of the Sociotype has been developed as a summary ecological construct to organize the multiple, dynamic, reciprocal inputs from the environment that interact with the genotype to determine the expression of phenotypic behaviors such as coping with stress. The Sociotype ecological framework has three domains-Individual (intra-personal), Relationships (inter-personal, family and community), and Context (environment, national)-and their interactions determine an individual's resilience across the life trajectory from birth to old age. We have applied the principles of the Sociotype to classify both the stresses of, and the coping strategies to, FINS. The stresses of FINS may occur at any place along the FS pathway-Availability, Accessibility, Utilization, and Stability. The elicited coping responses may take place in one or more of the three Sociotype domains. The two processes are inter-related linearly with re-iterative feedback loops such that stress leads to coping responses that may or may not be adequate, thereby requiring modifications in the coping strategies until FS is regained. Resilience is considered to represent long-term coping strategies. The Sociotype framework is both a determinant of, and constant input to, building and strengthening resilience. However, the people with the most problems with FINS are rarely included in these discussions. They are the marginalized members of society: unemployed, homeless, displaced persons, special needs, elderly, single parents, mentally frail, and more. Applying the Sociotype ecological framework for coping with FINS stresses can allow better strategic planning for FS at national, household and individual levels and understanding the interactions between them to reach out to and help these sectors of the population.


Isotherm, kinetic, thermodynamics and reusability data on the adsorption of antidepressant onto silver nanoparticle-loaded biowaste.
There has been an increase in the use of antidepressant drugs owing to significant economic challenges across the globe. Consequently, the increase in production of such drugs has impacted pharmaceutical pollution of industrial wastewaters discharged into the environment. Hence, there is a need to develop efficient adsorbents for antidepressant wastewater treatment. The impregnation of silver nanoparticles on biowaste was found to be highly effective in the treatment of oil-polluted water but has not been utilized in the adsorption of drugs. Herein, the dataset associated with the adsorption of antidepressants onto Ananas Comosus Peel (AP) and Silver nanoparticle-loaded Ananas Comosus peel (AgAP) was reported. Batch adsorption methodology was used to study the effect of antidepressant concentration (10-50 mg/L), sonication time (10-120 min), temperature (300-320 K) and adsorbent dosage (0.10-0.18 g). The concentration of antidepressant (Nortriptyline) in solution before and after adsorption was determined by the UV-Spectrophotometer at a maximum wavelength of 239 nm. The isotherm dataset was obtained from the Langmuir, Freundlich, Temkin and Dubinin-Raduskevich models, while kinetic data was evaluated by the pseudo-first order-pseudo-second-order, film diffusion and intraparticle diffusion rate equations. The data on the thermodynamics and adsorbent reusability were also provided. The dataset showed an adsorption capacity of 3.27 mg/g and 4.74 mg/g for AP and AgAP, respectively. The dataset is important to material and environmental scientists and revealed the efficiency of AP and AgAP in the treatment of antidepressant wastewater.


The effect of a Life Care Specialist on pain management and opioid-related outcomes among patients with orthopedic trauma: study protocol for a randomized controlled trial.
Orthopedic trauma patients face complex pain management needs and are frequently prescribed opioids, leaving them at-risk for prolonged opioid use. To date, post-trauma pain management research has placed little emphasis on individualized risk assessments for misuse and systematically implementing non-pharmacologic pain management strategies. Therefore, a community-academic partnership was formed to design a novel position in the healthcare field (Life Care Specialist (LCS)), who will educate patients on the risks of opioids, tapering usage, safe disposal practices, and harm reduction strategies. In addition, the LCS teaches patients behavior-based strategies for pain management, utilizing well-described techniques for coping and resilience. This study aims to determine the effects of LCS intervention on opioid utilization, pain control, and patient satisfaction in the aftermath of orthopedic trauma. In total, 200 orthopedic trauma patients will be randomized to receive an intervention (LCS) or a standard-of-care control at an urban level 1 trauma center. All patients will be assessed with comprehensive social determinants of health and substance use surveys immediately after surgery (baseline). Follow-up assessments will be performed at 2, 6, and 12 weeks postoperatively, and will include pain medication utilization (morphine milligram equivalents), pain scores, and other substance use. In addition, overall patient wellness will be evaluated with objective actigraphy measures and patient-reported outcomes. Finally, a survey of patient understanding of risks of opioid use and misuse will be collected, to assess the influence of LCS opioid education. There is limited data on the role of individualized, multimodal, non-pharmacologic, behavioral-based pain management intervention in opioid-related risk-mitigation in high-risk populations, including the orthopedic trauma patients. The findings from this randomized controlled trial will provide scientific and clinical evidence on the efficacy and feasibility of the LCS intervention. Moreover, the final aim will provide early evidence into which patients benefit most from LCS intervention. ClinicalTrials.gov NCT04154384 . Registered on 11/6/2019 (last updated on 6/10/2021).


Effects of anti-caries antibodies on Lactobacillus GG in its fermentation and storage periods.
To investigate how antibodies influence the fermentation of Lactobacillus GG and how Lactobacillus GG influences the biological properties of antibodies during the fermentation and storage periods. Anti-caries immune colostrum powder (IP) and control colostrum powder (CP), skimmed milk powder (SP) at concentrations of 1%, 2.5%, 5% and 10% (w/v) were added to MRS and 50 mM Hepes buffer system was used in the milk, the growth curves of Lactobacillus GG including viable cells, lactic acid concentratrion and pH, and also the titer of specific antibodies were determined during the fermentation and storage periods. In MRS, SP could improve the growth of Lactobacillus GG in all periods of fermentation, especially at the concentrations of 5% and 10%. CP at the concentrations of 1% and 2.5% had a good initial velocity at the beginning and CP (1%, 2.5%, 5%, 10%) in all the groups could reach a high viable cell concentration at the end of fermentation, which suggested that there were some growth factors for Lactobacillus GG in CP overcoming the inhibition of unspecific antibodies. IP at 1%, 2.5%, 5% and 10% could inhibit the growth of Lactobacillus GG in all the fermentation periods, the critical concentration point was between 2.5%-5%, and there was a competition between growth factors and the inhibition of specific antibodies. In pasteurized milk, the influence of Hepes could help the fermentation start quickly and reach the log phase earlier than in the control group; however, when combined with 5% IP, the growth of Lactobacillus GG was strongly inhibited during all the fermentation periods. The fermentation of Lactobacillus GG had no significant effect on the titer change of anti-caries antibodies during the fermentation and storage periods. SP and CP is beneficial to the growth of Lactobacillus GG in MRS, whereas there is a competition between growth factors and the inhibition of specific antibodies to the growth of Lactobacillus GG, the critical concentration of IP is 2.5%-5%. Hepes could influence the titer of antibodies through buffering Ph, thus influence the fermentation of Lactobacillus GG. The fermentation of Lactobacillus GG with IP or CP could be used for the development of functionally fermented immune milk in the future.


α-Alkylation of Nitriles with Primary Alcohols by a Well-Defined Molecular Cobalt Catalyst.
The α-alkylation of nitriles with primary alcohols to selectively synthesize nitriles by a well-defined molecular homogeneous cobalt catalyst is presented. Thirty-two examples with up to 95% yield are reported. Remarkably, this transformation is environmentally friendly and atom economical with water as the only byproduct.


Sodium thiopental and mean arterial pressure during cardiopulmonary bypass.
Sodium thiopental is known to have a number of cardiovascular effects, but injection into the cardiopulmonary bypass reservoir has not been studied. The effect of sodium thiopental on mean arterial blood pressure during cardiopulmonary bypass was assessed in 150 patients undergoing elective coronary artery bypass grafting. Sodium thiopental 3 mg · kg(-1) was administered via the cardiopulmonary bypass reservoir. Mean arterial pressure was recorded just before drug administration and at 15-sec intervals up to 120 sec afterwards. Compared to the baseline value, mean arterial pressure was significantly higher at 30, 45, 60, and 75 sec after drug administration, and it was significantly lower at 90, 105, and 120 sec. Sodium thiopental, in addition to its effects on myocardial tissue, acts initially as a potent vasopressor, and shortly after, as a potent vasodilator.


Cesarean deliveries and other risks for persistent pulmonary hypertension of the newborn.
To evaluate risks for persistent pulmonary hypertension in the newborn, confirmed by echocardiography, associated with cesarean deliveries and other factors. Cohort of all deliveries >36 weeks within a period of 23 months. A nested case-control study was performed in a subset of the cohort, involving newborns admitted into neonatal intensive care unit with diagnosis of persistent pulmonary hypertension matched with normal controls, with application of questionnaires to mothers to identify risks. Logistic regression was used to calculate odds ratios. From 9452 newborns, 8388 (88.7%) were delivered by cesarean and 1064 (11.3%) by vaginal delivery. Questionnaires were applied to 173 mothers. Infants from cesareans had a fivefold increased risk of persistent pulmonary hypertension of the newborn: 42 (0.5%) versus 1 case (0.09%) in the vaginal group (OR 5.32, p=0.027). No interactions were found between smoking, parity, arterial hypertension and labor before cesarean section and persistent pulmonary hypertension of the newborn. First minute Apgar score <7 and maternal diabetes were related to increased risk. Reducing cesarean deliveries could prevent many cases of serious persistent pulmonary hypertension of the newborn.


DNA strand scission and cross-linking by diaziridinylbenzoquinone (diaziquone) in human cells and relation to cell killing.
The effects of 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (diaziquone; AZQ) on various cell types were studied in relation to two chemical reactivities that this drug would be expected to have intracellularly. AZQ can undergo a reduction-oxidation cycle of the quinone function; this could generate free radicals which could produce DNA damage, especially DNA strand scission. The second reactivity, based on the two aziridine groups, could produce alkylation reactions that could produce DNA cross-links. DNA strand breakage and cross-linking were measured by alkaline elution and were compared with cell killing assayed by colony survival. Among the cell strains studied (human IMR-90, VA-13, and HT-29 and mouse L1210), marked differences were found in the magnitudes of DNA strand breakage and interstrand cross-linking produced by AZQ. Most striking, IMR-90 cells exhibited substantial strand breakage and little or no interstrand cross-linking, whereas the reverse was true for HT-29 cells. Cell killing correlated well with interstrand cross-linking but did not correlate with strand scission in these cell lines. It is concluded that AZQ produces DNA strand breaks and interstrand cross-links by different mechanisms which vary independently among different cell lines.


Functional results after resective procedures involving the supplementary motor area.
In this article, the authors report their experience with surgically induced supplementary motor area (SMA) deficiency syndrome in a prospective clinical trial of 28 patients who underwent surgery for tumorous (19 patients) or nontumorous (nine patients) lesions. The dominant side was affected in 17 patients and the nondominant side in 11 patients. The primary presenting symptoms included seizure activity (23 patients), hemiparesis (four patients), and aphasia (one patient). Functional topographic mapping, achieved by phase reversal of somatosensory evoked potentials, allowed precise localization of the central sulcus in 25 of the 28 patients. Motor evoked potential (MEP) monitoring, which was performed successfully in 13 of 15 cases during the resective procedure, showed no significant changes in the potentials in any patient. Immediately after surgery, 25 (89%) of the 28 patients displayed additional neurological deficits (aphasia and/or hemiparesis) that depended on the extent of the SMA resection. In 12 patients the SMA was resected completely: nine of these patients demonstrated a complete and three an incomplete deficit. In 16 patients the SMA resection was incomplete: 13 of these patients displayed an incomplete deficit, whereas three had no deficit. Neurological disorders resolved completely within 3 to 42 days (mean 11 days), except for a minimal disturbance of fine motor and/or speech function in complex tasks or at high speed. Electromagnetically elicited MEPs, examined postoperatively in five patients, were initially absent but recovered with improvement of motor function. In conclusion, although the SMA is known to control important functions such as initiation of motor activity or speech, our findings show that unilateral SMA removal can be accomplished without resulting in significant permanent deficits. Functional topographic mapping and monitoring facilitate the exact delineation of the adequate resection plane along the precentral sulcus, and postoperative magnetic resonance imaging allows precise correlation of clinical and anatomical data.


The Choice of Renal Replacement Therapy (CORETH) project: dialysis patients' psychosocial characteristics and treatment satisfaction.
Until today, research has underestimated the role of psychosocial conditions as contributing factors to dialysis modality choice. The novelty within the Choice of Renal Replacement Therapy (CORETH) project (German Clinical Trials Register #DRKS00006350) is its focus on the multivariate associations between these aspects and their consecutive significance regarding treatment satisfaction (TS) in peritoneal dialysis (PD) versus haemodialysis (HD) patients. In this article, we present the baseline results of a multicentre study, which is supported by a grant from the German Ministry for Education and Research. Six to 24 months after initiation of dialysis, 780 patients from 55 dialysis centres all over Germany were surveyed. The questionnaire addressed psychosocial, physical, socio-demographic and shared decision-making (SDM) aspects. Furthermore, cognitive functioning was tested. After indexing the measures, two propensity score-matched groups (n = 482) were compared in a first step, after having chosen PD or HD. In a second step, a moderated multiple regression (n = 445) was conducted to initially investigate the multivariate impact of patient characteristics on TS. In comparison with HD patients, PD patients were more satisfied with their treatment (P < 0.001), had a more autonomy-seeking personality (P = 0.04), had better cognitive functioning (P = 0.001), indicated more satisfying SDM (P < 0.001) and had a larger living space (P < 0.001). All patients were more satisfied when they had a good psychological state and received SDM. Especially in HD patients, TS was higher when the patient had a less autonomous personality, lower cognitive functioning, more social support, a poorer physical state and poorer socio-demographic conditions (R2 = 0.26). Psychosocial characteristics play a major role in TS in dialysis patients. Within a multivariate approach, these factors are even more important than physical or environment-related factors. In practice, focusing on SDM and screening patient characteristics at an early stage can foster patients' TS. Changes will be examined in a 1-year follow-up.


Endoscopic Carpal Tunnel Release: Techniques, Controversies, and Comparison to Open Techniques.
Endoscopic carpal tunnel release (ECTR) continues to rise in popularity as a treatment option for carpal tunnel syndrome. Numerous variations in technique and instrumentation currently exist, broadly classified into two-portal and single-portal techniques with antegrade and retrograde designs. ECTR is equally effective as open carpal tunnel release for alleviating symptoms of carpal tunnel syndrome with no differences in long-term outcomes. ECTR has an increased risk of transient nerve injury, whereas open carpal tunnel release has an increased risk of wound and scar complications. ECTR has higher direct costs but is associated with earlier return to work. ECTR is a safe and effective approach to carpal tunnel release in the hands of experienced surgeons.


Exopolysaccharide of Enterococcus faecium L15 promotes the osteogenic differentiation of human dental pulp stem cells via p38 MAPK pathway.
Bone has important functions in the body. Several researchers have reported that the polysaccharides and lipopolysaccharide derived from microbes can promote osteogenic differentiation of stem cells. Enterococcus faecium, a lactic acid bacterium (LAB), produces several bioactive metabolites and has been widely applied in the food and nutraceutical industries. The exopolysaccharide (EPS) from LAB has also been extensively examined for its postbiotic effects and for its in vivo and in vitro functionalities. However, studies on promoting bone differentiation using polysaccharides from LAB are lacking. Therefore, the purpose of this study was to investigate the effect of E. faecium L15 extract and EPS on osteogenic differentiation of human dental pulp stem cells (hDPSCs) and to identify the underlying mechanisms. hDPSCs were obtained from dental pulp tissue, and L15 extract and EPS were isolated from L15. Gene and protein expression of the osteogenic differentiation markers were analyzed with qPCR and western blotting and the possible signaling pathways were also investigated using western blotting. Osteogenic differentiation potential was examined by alkaline phosphatase (ALP) staining and alizarin red s (ARS) staining. In addition, osteogenic differentiation potential of L15 EPS was explored in ex vivo culture of neonate murine calvaria. The calcium deposition and ALP activity were enhanced by addition of L15 extract or EPS. The expression levels of RUNX2, ALP, and COL1A1 mRNA and the protein expression levels of RUNX2, ALP, and BMP4 were increased in hDPSCs treated with the L15 extract or EPS. The L15 EPS treatment enhanced phosphorylation of the p38 mitogen-activated protein kinase (MAPK). The L15 EPS-induced increases in RUNX2, ALP, and BMP4 expression were suppressed by the p38 MAPK inhibitor SB203580. The promoting effect of L15 EPS on osteogenic differentiation was not only seen in hDPSCs, but also in osteoblast precursors. ALP activity and the expression of RUNX2, ALP, and COL1A1 increased in the L15 EPS-treated osteoblast precursors. In addition, L15 EPS increased bone thickness of neonate murine calvaria in ex vivo culture. The stimulatory effect of L15 extract and EPS on osteogenic differentiation occurred through the p38 MAPK pathway, and L15 EPS enhanced new bone formation in neonate murine calvaria. These data suggest that L15 EPS has therapeutic potential applicable to bone regeneration.


[Principles, indications and results of radiotherapy of spinal tumors].
In primary and secondary tumors of the spinal column, radiotherapy is used to effect a cure, but mainly the goal is palliative. In the latter case, the course is either accelerated over less than 2 weeks (e.g., 1 dose of 10 Gy, 5 X 4 Gy, 10 X 3 Gy) or extended over 3 or more weeks (e.g., 40-50 Gy over 4-5 weeks). For teletherapy, megavolt radiotherapeutical devices are mainly used. In addition, supplementary brachytherapy is available with iodine-125 or iridium-192 seeds.


Treatment of hypertension in dialysis patients.
Hypertension is common in hemodialyzed patients and constitutes an important cardiovascular risk factor. Fluid retention, inappropriate stimulation of the renin-angiotensin system, sympathetic overactivity and changes of vessel wall structure have been shown to be important factors in its pathogenesis. It has been claimed that hemofiltration permits a better control of hypertension in the interdialytic interval, although the evidence is not perfectly convincing; blood pressure tends to be lower with continuous ambulatory peritoneal dialysis. While fluid withdrawal and - within certain limits - adjustment of dialysate sodium concentration constitutes a primary line of therapy, antihypertensive medication is necessary in approximately 20% of patients. Specific problems with dialysis patients are cumulation of drugs (some cardioselective beta-blockers, alpha-methyldopa, captopril), altered dose-response relationship (diuretics) and particularly interaction with cardiovascular stability during fluid withdrawal.


[Lopinavir/ritonavir monotherapy for the treatment of HIV-1 infection: the emergence of resistance].
Treatment with lopinavir/ritonavir (LPV/r) monotherapy has been shown to be an effective alternative, especially in the maintenance of patients previously treated with combination therapy and prolonged virological suppression. LPV/r monotherapy is associated with a greater number of low-level viremia episodes than combination therapy, without resistance mutations being detected in the majority of patients. The incidence of the development of major resistance mutations in the OK pilot and OK04 studies was very low: 0.51 per 100 patients-year, and was mainly related to mutations in positions 46, 54 and 82, which have not compromised other therapeutic options. The contribution of low-level resistance mutations to loss of virological control seems small, and no different from that observed in combination therapy. However, this phenomenon should be studied in larger, long-term trials.


The Macroeconomic Consequences Of Firearm-Related Fatalities In OECD Countries, 2018-30: A Value-Of-Lost-Output Analysis.
We modeled gross domestic product (GDP) losses attributable to firearm-related fatalities in each of thirty-six Organization for Economic Cooperation and Development (OECD) countries using the value-of-lost-output approach from 2018 to 2030. There are three categories of firearm-related fatalities: physical violence, self-harm, and unintentional injury. We project that the thirty-six OECD countries will lose $239.0 billion in cumulative GDP from 2018 to 2030 from firearm-related fatalities. Most of these losses ($152.5 billion) will occur as a result of fatalities in the US. In 2030 alone, the OECD countries will collectively lose $30.4 billion (0.04 percent) of their estimated annual GDP from firearm-related fatalities. The highest relative losses will occur in Mexico and the US; the lowest will occur in Japan. Firearm-related fatalities are expected to disproportionately affect the US and Mexican economies. Across the OECD, 48.5 percent of economic losses will be attributable to physical violence, 47.0 percent to self-harm, and 4.6 percent to unintentional injury. These findings provide a more complete picture of the toll of firearm-related fatalities, a global public health crisis that, without intervention, will continue to impose significant economic losses across OECD countries.


Social media and ADHD: implications for clinical assessment and treatment.
The interaction between social media use and mental health is complicated. The mental health information shared on these platforms is frequently of poor quality but has the potential to exert powerful influence on users. Social media trend peaks in some mental disorders have led to increases in illness behaviour through social contagion. There has been a marked upsurge in online interest in attention deficit hyperactivity disorder (ADHD) over the last number of years, which has been particularly noticeable since the onset of the COVID-19 pandemic. The exponential increase in online ADHD interest has the potential to contribute to overloading mental health services with referrals. Mental health professionals and organisations need to consider strategies to ensure that quality health information is disseminated to younger audiences.


Use of health insurance in county-funded clinics: issues for health care reform.
This article determines to what extent people with and without health care insurance use public health care facilities and various health care services. A descriptive study analyzed the characteristics of 6,298 patients from four county-funded primary health care clinics. The patients were overwhelmingly poor regardless of insurance status. High cost-sharing requirements, coupled with larger families and low wages, may be causing some people with insurance to use public clinics. Implications for social work policy and practice are discussed.


Deamidation and cross-linking of gliadin peptides by transglutaminases and the relation to celiac disease.
Activation of small intestinal gluten-reactive CD4+ T cells is a critical event in celiac disease. Such cells predominantly recognise gluten peptides in which specific glutamines are deamidated. Deamidation may be catalysed by intestinal tissue transglutaminase (TG2), a protein which is also the main autoantigen in celiac disease. Our aim was to study how the two main catalytic activities of transglutaminase--deamidation and transamidation (cross-linking) of an immunodominant gliadin epitope--are influenced by the presence of acceptor amines in the intestinal mucosa, and thereby contribute to further elucidation of the pathogenetic mechanisms in celiac disease. We prepared monoclonal antibodies, reacting specifically with the non-deamidated epitope QPFPQPQLPYPQPQ-amide and/or the deamidated epitope QPFPQPELPYPQPQ-amide. A solid phase immunoassay combined with gel filtration chromatography was used to analyse deamidation and cross-linking of these peptides to proteins. Our results show that QPFPQPQLPYPQPQ-amide was deamidated when incubated with purified TG2, with fresh mucosal sheets and with mucosal homogenates. Of other transglutaminases tested, only Streptoverticillium transglutaminase was able to generate the deamidated epitope. A fraction of the non-deamidated epitope was cross-linked to proteins, including TG2. The results suggest that intestinal TG2 is responsible for generation of the active deamidated epitope. As the epitope often occurs in a repeat structure, the result may be cross-linking of a deamidated, i.e., activated cell epitope. Alternatively, the deamidation may occur by reversal of the cross-linking reaction. The results provide a basis for the suggestion that binding of a peptide to a protein, in connection to its modification to a T cell epitope, might be a general explanation for the role of TG2 in celiac disease and a possible mechanism for the generation of autoantigens.


Pregnancy after safe IVF with hepatitis C virus RNA-positive sperm.
In France, assisted reproductive technology (ART) for hepatitis C virus (HCV)-infected patients is now subject to strict control after the publication of recent guidelines. Infertile serodiscordant couples (HCV-viraemic men and their seronegative female partners) require special care to carried out in designated 'viral risk' laboratories. Twelve sequential semen samples taken from an HCV chronically infected patient were analysed within 22 months. HCV RNA was detected in all the seminal plasma sampled before antiviral treatment with relatively high viral loads, and in two of the corresponding fractions of motile sperm obtained after a gradient selection, suggesting that a contamination risk by HCV through ART cannot be excluded. When the selection of sperm on a discontinuous gradient was followed by an additional swim-up step, HCV RNA was never detected in the motile sperm suspension that was frozen in highly secure straws. IVF was performed using cryopreserved sperm that tested negative for HCV RNA, resulting in a pregnancy. One month after embryo transfer, testing for HCV RNA and antibodies in the woman gave negative results.


Development and characterization of novel EST-SSR markers and their application for genetic diversity analysis of Jerusalem artichoke (Helianthus tuberosus L.).
Jerusalem artichoke (Helianthus tuberosus L.) is a perennial tuberous plant and a traditional inulin-rich crop in Thailand. It has become the most important source of inulin and has great potential for use in chemical and food industries. In this study, expressed sequence tag (EST)-based simple sequence repeat (SSR) markers were developed from 40,362 Jerusalem artichoke ESTs retrieved from the NCBI database. Among 23,691 non-redundant identified ESTs, 1949 SSR motifs harboring 2 to 6 nucleotides with varied repeat motifs were discovered from 1676 assembled sequences. Seventy-nine primer pairs were generated from EST sequences harboring SSR motifs. Our results show that 43 primers are polymorphic for the six studied populations, while the remaining 36 were either monomorphic or failed to amplify. These 43 SSR loci exhibited a high level of genetic diversity among populations, with allele numbers varying from 2 to 7, with an average of 3.95 alleles per loci. Heterozygosity ranged from 0.096 to 0.774, with an average of 0.536; polymorphic index content ranged from 0.096 to 0.854, with an average of 0.568. Principal component analysis and neighbor-joining analysis revealed that the six populations could be divided into six clusters. Our results indicate that these newly characterized EST-SSR markers may be useful in the exploration of genetic diversity and range expansion of the Jerusalem artichoke, and in cross-species application for the genus Helianthus.


RhoA protein is generally distributed in the nuclei of cancer cells.
The aim of this study was to elucidate the localization of RhoA in human cancer tissues and cancer cell lines. Immunohistochemistry and immunofluorescence microscopy were used to determine the localization of RhoA in cancer tissues and cell lines, respectively. Western blotting was used to determine the quantity of RhoA in cell nucleus, cytosol and membrane. Immunofluorescence microscopy revealed that in all cell lines examined in this experiment (including SGC-7901, Hela, A549 and SW480), RhoA was localized not only on the membrane, in the cytosol, but also in the nucleus. Within the nucleus its precise localization was in the nucleolus. In the transformed gastric epithelial cell line GES, RhoA was also found to be localized on the membrane, in the cytosol and the nucleus, but the nuclear location was less than that of cancer cell lines. Immunohistochemistry microscopy revealed that in cancer tissues the nuclear RhoA was obviously more than that of para-cancer tissue; in the cancer tissues undergoing inflammation and necrosis, nuclear RhoA was even higher. RhoA is generally distributed in the nucleus of cells and the distribution increases when the cells undergo tumorigenesis, suggesting a new role for RhoA.


Oral health component of child health services research.
The June 11 JAMA article outlines a rationale for developing a focus on child health services research and offers several strategies for facilitating the process. Developing a child health research agenda is essential to advancing dental care and professional education and, thus, is relevant to educators as well as researchers and policy makers. Oral health considerations are not likely to have high visibility or priority within that agenda unless dental health services researchers and dental schools become involved. An obvious question that is bound to be raised is "does it make sense to attempt to direct some portion of the already scarce resources available for dental health services research to children's issues?" Many individuals in leadership positions will probably think not; however, with an appropriate strategy, a small number of organized individuals and institutions can make a significant difference. Given the nature of dental diseases and the historical values of the profession, what better place to start?


Arabidopsis SAG protein containing the MDN1 domain participates in seed germination and seedling development by negatively regulating ABI3 and ABI5.
Three proteins containing a midasin homologue 1 (MDN1) domain from the yeast Solanum chacoense and Arabidopsis thaliana have important functions in yeast survival, seed development, and female gametogenesis. In this study, a novel protein containing the MDN1 domain from Arabidopsis negatively regulated abscisic acid (ABA) signalling during seed germination. Seeds of a T-DNA insertion line of this gene exhibited increased sensitivity to ABA during seed germination and seedling development (named sag). By contrast, seeds with overexpressed AtSAG (OX2) were less sensitive to ABA. The seeds of the sag mutant showed similar sensitivity to high concentrations of mannitol and NaCl during these stages. AtSAG was also highly expressed in germinating seeds. However, ABA-induced AtSAG expression remained almost unchanged. ABA-responsive marker genes, including ABI3, ABI5, Em1, Em6, RD29A, and RAB18, were upregulated in sag mutants but were downregulated in OX2. Genetic analyses indicated that the function of AtSAG in ABA signalling depended on ABI3 and ABI5. The expression of some target genes of ABI3 and ABI5, such as seed storage protein and oleosin genes, was induced higher by ABA in sag mutants than in wild-type germinated seeds, even higher than in abi5 mutants. This finding indicated that other regulators similar to ABI3 or ABI5 played a role during these stages. Taken together, these results indicate that AtSAG is an important negative regulator of ABA signalling during seed germination and seedling development.


Functional role of Na+/H+ exchanger in Ca2+ influx mediated via human endothelin type A receptor stably expressed in Chinese hamster ovary cells.
This study examines the functional role of Na+/H+ exchanger (NHE) in Ca2+ influx mediated by human endothelin type A receptor (ET(A)R) expressed in Chinese hamster ovary (CHO) cells. Endothelin-1 (ET-1) increased extracellular acidification rate (ECAR), which was abolished by 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an NHE inhibitor. EIPA and KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, inhibited ET-1-induced sustained increases in intracellular Ca2+ concentration ([Ca2+]i), and EIPA had no effect on [Ca2+]i after KB-R7943 treatment. ET-1-elicited sustained [Ca2+]i increase was suppressed by reducing extracellular Na+ concentration. These results suggest that possible coupling of NHE with NCX via Na+ transport is involved in ET(A)R-mediated sustained [Ca2+]i increase.


Antisaccadic training to improve impulsivity in binge eating disorder.
Patients with binge eating disorder (BED) show generally increased impulsivity and especially increased food-related impulsivity. Both are closely linked to the core pathology of BED, which relates to regular binge eating episodes with experienced loss of control. The antisaccade task is an established paradigm assessing response inhibition as a pivotal component of impulsivity. It requires participants to execute antisaccades; that is, they are supposed to look in the opposite direction of a stimulus that automatically catches attention by appearing in the peripheral visual field. High rates of prosaccades to the peripheral stimuli are considered indicators of increased impulsivity. Presenting food pictures as peripheral stimuli, this task can be used to investigate food-related impulsivity. We propose modifications of this task in order to design it as an antisaccadic training in which BED patients practise the suppression of food-related responses, which should result in enhanced control over their eating behaviour.


Self-referenced characterization of optical frequency combs and arbitrary waveforms using a simple, linear, zero-delay implementation of spectral shearing interferometry.
We discuss a simple, linear, zero-delay implementation of spectral shearing interferometry for amplitude and phase characterization of optical frequency comb sources and arbitrary waveforms. We demonstrate this technique by characterizing two different high repetition rate (approximately 10 GHz) frequency comb sources, generated respectively by strong external and intracavity phase modulation of a continuous-wave laser. This technique is easy to implement, requiring only an intensity modulator and an optical spectrum analyzer (OSA), and is demonstrated to work at average power levels down to 100 nW (10 aJ/pulse at 10 GHz). By exploiting the long coherence lengths of these frequency combs and the self-referenced nature of the measurement, we also demonstrate a simple single-ended measurement of dispersion and dispersion slope in long lengths of fiber (>25 km).


Free Ulnar Forearm Flap: Design, Elevation, and Utility in Microvascular Nasal Lining Reconstruction.
Reconstruction of the nasal lining has traditionally been performed using the folded radial forearm free flap, given its reliable blood supply, pliability, and familiarity to surgeons with respect to its harvest. More recently, the free ulnar forearm flap has been proposed as an alternative reconstructive option for the nasal lining, with safe and reliable outcomes, and improved donor-site morbidity compared with its radial counterpart. In this article, the authors provide educational video footage with accompanying text description of the senior author's (E.D.R) approach to design and elevation of the free ulnar forearm flap for the purpose of reconstructing a composite nasal defect. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, V.


[Epithelioid hemangiosarcoma of the thyroid gland].
Authors present a case of epithelioid haemangiosarcoma of the thyroid gland in a 54-year-old female with a history of eufunctional nodular goitre. The patient was treated by total thyroidectomy with extirpation of cervical lymph nodes and by subsequent chemotherapy. The tumour behaved highly aggressively with early generalization and unusual way of metastatic spread into the wall of the stomach and duodenum. The patient died 3 months after the surgery due to therapeutically unmanageable bleeding into the GIT. The clinico-pathological aspects of the case are discussed.


[Hypophysitis autoimmune. Case series and literature review].
Autoimmune hypophysitis is a rare condition that must be considered in the differential diagnosis of any pituitary tumor. We present a series of nine patients with clinical and radiologic diagnosis of autoimmune hypophysitis that were admitted to the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) in Mexico City between 2000-2012. Clinical, biochemical, imaging features (on MRI), treatment, and follow-up are described, and a review on this disease is presented.


A visible-light-responsive molecularly imprinted polyurethane for specific detection of dibenzothiophene in gasoline.
Dibenzothiophene and its derivatives in gasoline and diesel would release sulfur oxides during combustion, and this is harmful to human health and the environment. This paper reports a method based on a visible-light-responsive molecularly imprinted polyurethane (VMIPU) to monitor trace dibenzothiophene in gasoline. The VMIPU was prepared by a polyaddition reaction using N,N-bis-(2-hydroxyethyl)-4-phenylazoaniline as the functional monomer, dibenzothiophene as the template molecule, diphenylmethane diisocyanate as the crosslinker and castor oil as the chain extender. The VMIPU showed good visible-light-response and specific adsorption for dibenzothiophene. The trans → cis photoisomerization rate constant of azobenzene chromophores in the VMIPU shows a linear relationship with the dibenzothiophene concentration in the range of 0-20 μmol L-1. This was used to estimate trace dibenzothiophene in spiked gasoline with recoveries of 95.7-101.0% and relative standard deviations of 7.0-12.7%.


Hypoglycemic effects of Rhodiola crenulata (HK. f. et. Thoms) H. Ohba in vitro and in vivo and its ingredient identification by UPLC-triple-TOF/MS.
Rhodiola crenulata (HK. f. et. Thoms) H. Ohba (RC), mainly distributed in the highly cold region of China, has long been used as a medicine/healthy food for eliminating fatigue and increasing blood circulation. This study aimed to evaluate the inhibitory effects of the RCRS extract on α-amylase and α-glucosidase (sucrase and maltase) in vitro and in vivo, and tentatively analyze and identify its chemical ingredients using UPLC-Triple-TOF/MS. The Rhodiola crenulata RCRS extract had strong inhibitory activities against α-amylase, sucrase and maltase with an IC50 of 0.031 mg mL-1, 0.142 mg mL-1 and 0.214 mg mL-1, respectively. Furthermore, the RCRS extract could significantly decrease the postprandial blood glucose (PBG) level of normal mice in a starch tolerance test, and reduce the PBG levels of diabetic mice in a starch/maltose/sucrose tolerance test. UHPLC-Triple-TOF-MS/MS analysis indicated that hydroxybenzoic acids, hydroxycinnamic acids, alcohol glycosides, flavonols and their derivatives were the main active ingredients in the RCRS extract. The results demonstrate that the RCRS extract of Rhodiola crenulata could be employed as a healthy food or medicine for controlling postprandial blood glucose levels.


Anti-viral drugs in continuous ambulatory peritoneal dialysis (CAPD).
The prevalence of HIV-positive subjects in dialysis (hemodialysis and peritoneal dialysis) population varies from 0.13 to 0.36% in italian and french studies, respectively. Most drugs used in HIV therapy are primarily excreted by the kidney. In patients with renal insufficiency, careful dosage adjustment is mandatory to optimize drug exposure and reduce the risk for adverse events. We review the impact of peritoneal dialysis on the pharmacokinetics of antiviral drugs, and discuss on the dosage recommendations needed to achieve efficacy and avoid toxicity in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD).


Calcium requirement and inhibitor spectrum for intracellular HIV type 1 gp160 processing in cultured HeLa cells and CD4+ lymphocytes: similarity to those of viral envelope glycoprotein maturase.
We recently purified the calcium-independent processing protease named viral envelope glycoprotein maturase (VEM), that converts human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor gp160 to gp120 and gp41, from the human CD4+ T cell line, Molt-4 clone 8 [Kido, H., Kamoshita, K., Fukutomi, A., and Katunuma, N. (1993) J. Biol. Chem. 268, 13406-13413]. In this report, we deal with the inhibitor specificity and calcium requirement for intracellular gp160 processing in cultured HeLa cells and human CD4+ lymphocytes. Processing of gp160 in these cells infected with recombinant vaccinia virus encoding the gp160 gene was not affected by intracellular calcium depletion induced by the calcium ionophore A23187 and EGTA or by intracellular calcium administration. Processing of gp160 by the purified VEM in vitro was not inhibited by EDTA, EGTA, or the metallo-protease inhibitor phosphoramidon, but was specifically inhibited by a substrate analog, decanoyl-RVKR-chloromethylketone, and the trypsin-type protease inhibitors aprotinin, HI-30, and diisopropyl fluorophosphate (DFP). It was also inhibited by E-64 and thiol reagents. But intracellular gp160 processing was inhibited only by permeable, low molecular mass inhibitors of VEM, such as DFP, E-64, and thiol reagents. Syncytium formation induced by cell surface gp120 was also inhibited by permeable inhibitors of VEM. Taken together, our results indicate that calcium ions may not be essential for intracellular gp160 processing and so HIV-1 gp160 induced by recombinant vaccinia virus may be processed mainly by a protease(s) that does not require calcium ions, such as VEM in these cells.


Specific Cognitive Changes due to Hippocalcin Alterations? A Novel Familial Homozygous Hippocalcin Variant Associated with Inherited Dystonia and Altered Cognition.
Recent research suggested an hippocalcin (HPCA)-related form of DYT2-like autosomal recessive dystonia. Two reports highlight a broad spectrum of the clinical phenotype. Here, we describe a novel HPCA gene variant in a pediatric patient and two affected relatives. Whole exome sequencing was applied after a thorough clinical and neurological examination of the index patient and her family members. Results of neuropsychological testing were analyzed. Whole exome sequencing revealed a novel homozygous missense variant in the HPCA gene [c.182C>T p.(Ala61Val)] in our pediatric patient and the two affected family members. Clinically, the cases presented with dystonia, dysarthria, and jerky movements. We observed a particular cognitive profile with executive dysfunctions in our patient, which corresponds to the cognitive deficits that have been observed in the patients previously described. We present a novel genetic variant of the HPCA gene associated with autosomal recessive dystonia in a child with childhood-onset dystonia supporting its clinical features. Furthermore, we propose specific HPCA-related cognitive changes in homozygous carriers, underlining the importance of undertaking a systematic assessment of cognition in HPCA-related dystonia.


NLRP3 Inflammasome Expression in Gingival Crevicular Fluid of Patients with Periodontitis and Chronic Hepatitis C.
The study is aimed at assessing the impact that periodontal disease and chronic hepatitis C could have on gingival crevicular fluid levels of the NLRP3 inflammasome, caspase-1 (CASP-1), and interleukin-18 (IL-18) and at evaluating whether the increased local inflammatory reaction with clinical periodontal consequences is correlated to their upregulation. Patients were divided into four groups, according to their periodontal status and previously diagnosed hepatitis C, as follows: (i) CHC group, chronic hepatitis C patients; (ii) P group, periodontal disease patients, systemically healthy; (iii) CHC + P group, patients suffering from both conditions; and (iv) H group, systemically and periodontally healthy controls. Gingival crevicular samples were collected for quantitative analysis of the NLRP3 inflammasome, CASP-1, and IL-18. CHC + P patients expressed the worse periodontal status and the highest NLRP3, CASP-1, and IL-18 levels, the difference being statistically significant (p < 0.05). The P group patients also expressed significantly more elevated NLRP3, CASP-1, and IL-18 levels, as compared to nonperiodontal patients (CHC and H groups). Chronic hepatitis C and periodontal disease could have a significant influence on the upregulation of NLRP3 inflammasome and its components, possibly contributing to an increased local inflammatory reaction and clinical periodontal consequences.


Inhibition of human leukemia cells growth by juglone is mediated via autophagy induction, endogenous ROS production, and inhibition of cell migration and invasion.
The purpose of the study was to examine the anticancer properties of a natural chemical entity - juglone molecule - against human HL-60 promyelocytic leukemia cells along with assessing the effects on normal human monocytes. Juglone molecule was examined for its role in autophagy induction, endogenous ROS production, and inhibition of cell migration and invasion. Cell viability was evaluated by MTT assay and clonogenic assay was performed to analyse colony formation. Autophagy studies were carried out by transmission electron microscopy (TEM) and western blotting analysis. Mitochondrial morphology was observed through MitoTracker Red CMXRos, and mitochondrial ROS production was assessed through confocal microscopy. The cell invasion and migration was assessed via transwell chambers with and without Matrigel. MTT assay revealed significant, selective (less cytotoxicity towards normal cells) and dose-dependent inhibition of HL-60 leukemia cells and clonogenic assay showed impressive decrease in the number of colonies on increased doses of the molecule. TEM analysis showed formation of autophagosomes and induction of cellular damage. Western blotting assay indicated a significant increase in LC3-I and LC3-II and a slight increase in Beclin-I. Confocal microscopy revealed tremendous increase in ROS concentrations in a dose-dependent manner. Transwell chamber assay revealed significant, dose- dependent inhibition of cell migration and invasion. Juglone induced anticancer effects on promyelocytic HL-60 leukemia cells mediated via autophagy induction, endogenous ROS production, and inhibition of cell migration and invasion, thus indicating that juglone may be a potential lead molecule against HL-60 promyelocytic leukemia cells.


[Extracting municipal solid waste dumps based on high resolution images].
The dramatically increasing informal MSW dumps are endangering the urban environment. Remote sensing (RS) technologies are more efficient to monitor and manage municipal solid wastes (MSW) than traditional survey-based methods. In high spatial resolution remotely sensed images, these irregularly distributed dumps have complex compositions and strong heterogeneities, thus it is still hard to extract them automatically no matter the pixel-or object-based image analysis method is used. Therefore, based on the analysis of MSW characteristics, the present study develops a multiresolution strategy to extract MSW dumps by combining image features at both high resolution and resampled low heterogeneity images, while the high resolution images can provide detailed information and the low resolution images can suppress the strong heterogeneities of informal MSW dumps. Taking the QuickBird image covering part of Beijing as an example, this multi-resolution strategy produced a high accuracy (75%), indicating that this multi-resolution strategy is quite effective for extracting the open-air informal MSW dumps.


Significant increase in the prevalence of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus, particularly the USA300 variant ΨUSA300, in the Japanese community.
USA300 is an MRSA clone producing PVL, a toxin associated with SSTIs. ΨUSA300 is a USA300 variant recently identified in Japan by Takadama et al. (15). Here, we found that the prevalence rate of PVL-positive MRSA in S. aureus was elevated in the Japanese community, and ΨUSA300 accounted for most of them. ΨUSA300 strains have been isolated from several areas in Japan and were associated with deep-seated SSTIs. This study highlighted the emerging threat posed by ΨUSA300 in Japan.


Neoglycorandomization and chemoenzymatic glycorandomization: two complementary tools for natural product diversification.
In an effort to explore the contribution of the sugar constituents of pharmaceutically relevant glycosylated natural products, chemists have developed glycosylation methods that are amenable to the generation of libraries of analogues with a broad array of glycosidic attachments. Recently, two complementary glycorandomization strategies have been described, namely, neoglycorandomization, a chemical approach based on a one-step sugar ligation reaction that does not require any prior sugar protection or activation, and chemoenzymatic glycorandomization, a biocatalytic approach that relies on the substrate promiscuity of enzymes to activate and attach sugars to natural products. Since both methods require reducing sugars, this review first highlights recent advances in monosaccharide generation and then follows with an overview of recent progress in the development of neoglycorandomization and chemoenzymatic glycorandomization.


In vitro integration of human immunodeficiency virus type 1 cDNA into targets containing protein-induced bends.
Integration of human immunodeficiency virus type 1 cDNA into a target DNA can be strongly influenced by the conformation of the target. For example, integration in vitro is sometimes favored in target DNAs containing sequence-directed bends or DNA distortions caused by bound proteins. We have analyzed the effect of DNA bending by studying integration into two well-characterized protein-DNA complexes: Escherichia coli integration host factor (IHF) protein bound to a phage IHF site, and the DNA binding domain of human lymphoid enhancer factor (LEF) bound to a LEF site. Both of these proteins have previously been reported to bend DNA by approximately 140 degrees. Binding of IHF greatly increases the efficiency of in vitro integration at hotspots within the IHF site. We analyzed a series of mutants in which the IHF site was modified at the most prominent hotspot. We found that each variant still displayed enhanced integration upon IHF binding. Evidently the local sequence is not critical for formation of an IHF hotspot. LEF binding did not create preferred sites for integration. The different effects of IHF and LEF binding can be rationalized in terms of the different proposed conformations of the two protein-DNA complexes.


[Pathophysiological role of cytokines in heart failure].
Plasma and myocardial levels of proinflammatory cytokines such as tumor necrosis factor(TNF)-alpha, interleukin 1beta, and interleukin 6 are elevated in patients with heart failure. Not only viral infection but also cardiac overload, ischemia, and neuro-humoral factors stimulate systemic and myocardial production of these cytokines. Administration of proinflammatory cytokines directly depresses myocardial contractility in vitro and in vivo. In addition, TNF and interleukin induce myocardial apoptosis and promote cardiac hypertrophy and fibrosis, suggesting that these cytokines are involved in the progression of cardiac remodeling. Vasoactive peptides such as endothelin and adrenomedullin also have cytokine-like functions in the heart, acting as autocrine and paracrine factors. Thus, proinflammatory cytokines and these peptides play important roles in the pathogenesis and pathophysiology of heart failure.


Basic features of phasic activation for reaching in vertical planes.
The purpose of this study was to fully characterize the timing and intensity of the phasic portion of the electromyographic (EMG) waveform for reaching movements in vertical planes. Electromyographic activity was simultaneously recorded from nine superficial elbow and/or shoulder muscles while human subjects made rapid arm movements. Hand paths comprised 20 directions in a sagittal plane and 20 directions in a frontal plane. In order to focus on the more phasic aspects of muscle activation, estimates of postural EMG activity were subtracted from the EMG traces recorded during rapid reaches. These postural estimates were obtained from activity recorded during very slow reaches to the same targets. After subtraction of this postural activity, agonist or antagonist burst patterns were often observed in the phasic EMG traces. For nearly all muscles and all subjects, the relation between phasic EMG intensity and movement direction was a function with multiple peaks. For all muscles, the timing of phasic EMG bursts varied as a function of movement direction: the data from each muscle exhibited a gradual temporal shift of activity over a certain range of directions. This gradual temporal shift has no obvious correspondence to the mechanical requirements of the task and might represent a neuromuscular control strategy in which burst timing contributes to the specification of movement direction.


A 9-gene prognostic signature for kidney renal clear cell carcinoma overall survival based on co-expression and regression analyses.
This research attempted to screen potential signatures associated with KIRC progression and overall survival by weighted gene co-expression network analysis (WGCNA) and Cox regression. The KIRC-associated mRNA expression and clinical data were accessed from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened by differential analysis. A co-expression network was constructed by "WGCNA". Based on WGCNA module, GO and KEGG analyses were performed. Protein-protein interaction (PPI) network was constructed. Prognostic signatures were screened by Lasso-Cox regression. Prognostic model was evaluated by Receiver Operating Characteristic (ROC) and Kaplan-Meier (K-M) curves. Multivariate Cox and nomogram were introduced to examine whether risk score could be an independent marker. qRT-PCR was introduced to determine expression of 9 hub genes in KIRC clinical tumor tissues and adjacent tissues, respectively. Genes in the green module were highly associated with clinical status, and green module genes were significantly enriched in mitotic nuclear division, cell cycle, and p53 signaling pathway. Twenty-six candidates were subsequently screened out from the green module. Next, a 9-gene prognostic model (DLGAP5, NUF2, TOP2A, RRM2, HJURP, PLK1, AURKB, KIF18A, CCNB2) was constructed. The predicting ability of the model was optimal. Some cancer-related signaling pathways were differently activated between two risk score groups. Additionally, under-expression of some signature genes (AURKB, CCNB2, PLK1, RRM2, TOP2A) was associated with better survival rate for KIRC patients. Meanwhile, all 9 hub genes were substantially overexpressed in KIRC patients. A KIRC prognostic signature was screened in this study, contributing valuable findings to KIRC biomarker development.


Hyperpolarized 13C metabolic imaging detects long-lasting metabolic alterations following mild repetitive traumatic brain injury.
Career athletes, active military, and head trauma victims are at increased risk for mild repetitive traumatic brain injury (rTBI), a condition that contributes to the development of epilepsy and neurodegenerative diseases. Standard clinical imaging fails to identify rTBI-induced lesions, and novel non-invasive methods are needed. Here, we evaluated if hyperpolarized 13C magnetic resonance spectroscopic imaging (HP 13C MRSI) could detect long-lasting changes in brain metabolism 3.5 months post-injury in a rTBI mouse model. Our results show that this metabolic imaging approach can detect changes in cortical metabolism at that timepoint, whereas multimodal MR imaging did not detect any structural or contrast alterations. Using Machine Learning, we further show that HP 13C MRSI parameters can help classify rTBI vs. Sham and predict long-term rTBI-induced behavioral outcomes. Altogether, our study demonstrates the potential of metabolic imaging to improve detection, classification and outcome prediction of previously undetected rTBI.


Ultraviolet corneal photoablation.
The purpose of this article is to discuss missing information on the basic physical and biological processes of ultraviolet corneal photoablation and to evaluate its potential clinical implications. A physical description of ultraviolet laser corneal ablation that includes photothermal, photochemical, and radiative processes is proposed. Unresolved issues include the nature of the primary ablation process, the tissue and biological effects of the photothermal and photochemical components of the interaction, and the static and dynamic absorption process. A better understanding of the basic physics and biology of ultraviolet corneal photoablation may help us better understand, predict, and perhaps minimize the effect of tissue hydration, plume formation, and other factors that affect the predictability of ablation and the induced tissue damage.


Semi-physiological model of postprandial triglyceride response in lean, obese and very obese individuals after a high-fat meal.
To quantify the postprandial triglyceride (TG) response of chylomicrons and very-low-density lipoprotein-V6 (VLDL-V6) after a high-fat meal in lean, obese and very obese healthy individuals, using a mechanistic population lipokinetic modelling approach. Healthy individuals from three body mass index population categories: lean (18.5-24.9 kg/m2 ), obese (30-33 kg/m2 ), and very obese (34-40 kg/m2 ) were enrolled in a clinical study to assess the TG response after a high-fat meal, containing 60% fat. Non-linear mixed-effect modelling was used to analyse the TG concentrations of chylomicrons and large VLDL-V6 particles. The TGs in chylomicrons and VLDL-V6 particles had a prominent postprandial peak and represented the majority of the postprandial response; only the VLDL-V6 showed a difference across the populations. A turn-over model successfully described the TG concentration-time profiles of both chylomicrons and large VLDL-V6 particles after the high-fat meal. This model consisted of four compartments: two transit compartments for the lag between meal consumption and appearance of TGs in the blood, and one compartment each for the chylomicrons and large VLDL-V6 particles. The rate constants for the production of chylomicrons and elimination of large VLDL-V6 particles, along with the conversion rate of chylomicrons to large VLDL-V6 particles were well defined. This is the first lipokinetic model to describe the absorption of TGs from dietary fats into the blood stream and compares the dynamics of TGs in chylomicrons and large VLDL-V6 particles among lean, obese and very obese people. Such a model can be used to identify where pharmacological therapies act, thereby improving the determination of efficacy, and identifying complementary mechanisms for combinational drug therapies.


Annihilation limit of a visible-to-UV photon upconversion composition ascertained from transient absorption kinetics.
Noncoherent sensitized green-to-near-visible upconversion has been achieved utilizing palladium(II) octaethylporphyrin (PdOEP) as the triplet sensitizer and anthracene as the energy acceptor/annihilator in vacuum degassed toluene. Selective 547 nm excitation of PdOEP with incident irradiance as low as 600 μW/cm(2) results in the observation of anthryl fluorescence at higher energy. Stern-Volmer analysis of the dynamic phosphorescence quenching of PdOEP by anthracene possesses an extremely large K(SV) of 810,000 M(-1), yielding a triplet-triplet energy transfer quenching constant of 3.3 × 10(9) M(-1) s(-1). Clear evidence for the subsequent triplet-triplet annihilation (TTA) of anthracene was afforded by numerous experiments, one of the most compelling was an excitation scan illustrating that the Q-band absorption features of PdOEP are solely responsible for sensitizing the anti-Stokes fluorescence. The upconverted emission intensity with respect to the excitation power was shown to vary between quadratic and linear using either coherent or noncoherent light sources, illustrating the expected kinetic limits for the light producing photochemistry under continuous wave illumination. Time-resolved experiments directly comparing the total integrated anthracene intensity/time fluorescence data produced through upconversion (λ(ex) = 547 nm, delayed signal) and with direct excitation (λ(ex) = 355 nm, prompt signal) under conditions where the laser pulse is completely absorbed by the sample reveal annihilation efficiencies of approximately 40%. Similarly, the delayed fluorescence kinetic analysis reported by Schmidt and co-workers (J. Phys. Chem. Lett. 2010, 1, 1795-1799) was used to reveal the maximum possible efficiency from a model red-to-yellow upconverting composition and this treatment was applied to the anthryl triplet absorption decay transients of anthracene measured for the PdOEP/anthracene composition at 430 nm. From this analysis approximately 50% of the anthryl triplets that decay by TTA produce singlet fluorescence, consistent with the notion that annihilation spin statistics does not impose efficiency limits on upconversion photochemistry.


Deconstructing the root system of grasses through an exploration of development, anatomy and function.
Well-adapted root systems allow plants to grow under resource-limiting environmental conditions and are important determinants of yield in agricultural systems. Important staple crops such as rice and maize belong to the family of grasses, which develop a complex root system that consists of an embryonic root system that emerges from the seed, and a postembryonic nodal root system that emerges from basal regions of the shoot after germination. While early seedling establishment is dependent on the embryonic root system, the nodal root system, and its associated branches, gains in importance as the plant matures and will ultimately constitute the bulk of below-ground growth. In this review, we aim to give an overview of the different root types that develop in cereal grass root systems, explore the different physiological roles they play by defining their anatomical features, and outline the genetic networks that control their development. Through this deconstructed view of grass root system function, we provide a parts-list of elements that function together in an integrated root system to promote survival and crop productivity.


The effects of ionizing radiation on the growth plate in rat tibiae.
The deleterious effects of ionizing radiation on the growth plate continue to be cause for concern. This study evaluated the ionizing radiation effects on bone development and growth plate in the tibia of rats. All animals were submitted to ionizing radiation on the left leg. The animals were divided into two groups and euthanized 30 and 60 days after radiation. The tibiae were removed and separated into groups: control 30 days, irradiated 30 days, control 60 days and irradiated 60 days. Animals in each group (n = 7) were used for macroscopic and histological analysis. The irradiated tibiae showed arrested growth, angular deformity and limb length discrepancy when compared with nonirradiated tibiae. There was statistical difference between control and radiation groups in all the parameters analyzed, except in the lateral-medial thickness of the distal epiphysis. Histological analysis showed evident changes in the growth plate, which was thicker in the Groups irradiated for 30 days, and irradiated for 60 days, compared with their respective controls. The growth plate showed wide areas with disorganized zones of chondrocytes and severely reduced calcification zone. It was concluded that ionizing radiation damaged the growth plate, compromised the endochondral ossification process, and resulted in complete arrest of bone development.


[CHEK2 c.1100delC may not contribute to genetic background of hereditary breast cancer from Shanghai of China].
To investigate the prevalence of CHEK2 c.1100delC mutation among non-BRCA1/BRCA2 familial/early-onset breast cancer patients in Shanghai. One hundred and fourteen non-BRCA1/BRCA2 hereditary breast cancer patients were analyzed, among whom 76 cases had at least one first-degree relative affected with breast cancer and 38 cases were diagnosed as breast cancer below the age of 40 years without family history. The mutation genotyping of CHEK2 c.1100delC were carried out through long-range PCR amplifying of exons 10-14, and followed by amplification of exon 10 and then DNA direct sequencing. No c.1100delC frame-shift mutation was identified in our studied population. One novel missense mutation 1111C>T (p.His371Tyr), located in kinase catalytic domain, was found in 3 familial breast cancer cases but no one in control group. CHEK2 c.1100delC is rare variant for Chinese population and may not contribute to predisposition for hereditary breast cancer in Shanghai. Novel variant -1111C>T could be in association with genetic susceptibility to breast cancer. A further study is needed to confirm the results.


Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to ⁶⁰Co γ-rays and p(66)+ Be(40) neutrons.
To investigate both the formation of micronuclei (MN) and the induction and subsequent loss of phosphorylated histone H2AX foci (γH2AX foci) after in vitro exposure of human lymphocytes to either (60)Co γ-rays or p(66)+ Be(40) neutrons. MN dose response (DR) curves were obtained by exposing isolated lymphocytes of 10 different donors to doses ranging from 0-4 Gy γ-rays or 0-2 Gy neutrons. Also, γH2AX foci DR curves were obtained following exposure to doses ranging from 0-0.5 Gy of either γ-rays or neutrons. Foci kinetics for lymphocytes for a single donor exposed to 0.5 Gy γ-rays or neutrons were studied up to 24 hours post-irradiation. Micronuclei yields following neutron exposure were consistently higher compared to that from (60)Co γ-rays. All MN yields were over-dispersed compared to a Poisson distribution. Over-dispersion was higher after neutron irradiation for all doses > 0.1 Gy. Up to 4 hours post-irradiation lower yields of neutron-induced γH2AX foci were observed. Between 4 and 24 hours the numbers of foci from neutrons were consistently higher than that from γ-rays. The half-live of foci disappearance is only marginally longer for neutrons compared to that from γ-rays. Foci formations were more likely to be over-dispersed for neutron irradiations. Although neutrons are more effective to induce MN, the absolute number of induced γH2AX foci are less at first compared to γ-rays. With time neutron-induced foci are more persistent. These findings are helpful for using γH2AX foci in biodosimetry and to understand the repair of neutron-induced cellular damage.


Classification of Vertebral Osteomyelitis and Associated Judgment Applied during Post-Mortem Inspection of Swine Carcasses in Portugal.
Vertebral osteomyelitis (VO) it is often a suppurative lesion that, in Portugal, represents the main cause of total condemnation of slaughtered finishing pigs. Based on the EU Meat Inspection legislation, meat from generalized VO cases presenting signs of pyemia should be declared unfit for human consumption. For that reason, the main objective of this study is to establish a classification scheme to differentiate between localized and generalized VO cases using macroscopic findings and validate it based on the presence of pyemia. To assist in, a combination of macroscopic characteristics of gross lesions (e.g., presence of pyaemia-related lesions (PRL), acute/chronic characteristics of VO) was used to create a classification scheme to differentiate between localized and generalized VO cases. The scheme was applied to 40 VO cases that had been totally condemned in an undifferentiated way. In those 40 cases, histopathological analysis was used to validate acute/chronic macro-criteria, and microbiological analysis was performed to identify the pyemia cases. From the 40 selected VO cases, 20 were macroscopically classified as chronic and 20 as acute. Cohen's kappa coefficient (κ = 0.80; p < 0.001), revealed a substantial agreement between macroscopic and histopathology classification. Microbiological analyses identified 13 pyemia cases (13/40; 32.5%). Among those, 12 were macroscopically classified as acute, this association being highly significant (p < 0.001). By using the proposed VO classification scheme, 14 possible cases out of 40 could have been spared from total condemnation. This scheme can be used to harmonize the classification of VO and meat inspection decisions in Portuguese abattoirs. The output would lead to avoidance of unnecessary carcasses condemnation (food waste/economic losses), under an evidence-based approach, without compromising food safety and public health as demanded by the EU Meat Inspection legislation.


Repetitive negative thinking in daily life and functional connectivity among default mode, fronto-parietal, and salience networks.
Repetitive negative thinking (RNT) is a maladaptive response to sadness and a transdiagnostic risk-factor. A critical challenge hampering attempts to promote more adaptive responses to sadness is that the between-person characteristics associated with the tendency for RNT remain uncharacterized. From the perspective of the impaired disengagement hypothesis, we examine between-person differences in blood-oxygen-level-dependent (BOLD) functional networks underlying cognitive conflict signaling, self-referential thought, and cognitive flexibility, and the association between sadness and RNT in daily life. We pair functional magnetic resonance imaging with ambulatory assessments deployed 10 times per day over 4 consecutive days measuring momentary sadness and RNT from 58 participants (40 female, mean age = 36.69 years; 29 remitted from a lifetime episode of Major Depression) in a multilevel model. We show that RNT increases following sadness for participants with higher than average between-network connectivity of the default mode network and the fronto-parietal network. We also show that RNT increases following increases in sadness for participants with lower than average between-network connectivity of the fronto-parietal network and the salience network. We also find that flexibility of the salience network's pattern of connections with brain regions is protective against increases in RNT following sadness. Our findings highlight the importance of functional brain networks implicated in cognitive conflict signaling, self-referential thought, and cognitive flexibility for understanding maladaptive responses to sadness in daily life and provide support for the impaired disengagement hypothesis of RNT.


MANAGEMENT OF EMOTIONAL DISORDERS IN ELDERLY PATIENTS UNDERGOING SURGICAL TREATMENT OF PROXIMAL FEMORAL FRACTURES.
The goal of our research was to study the to identify key aspects of the management of emotional disorders in the practice of operative treatment of proximal femoral fractures in elderly patients. The study was conducted with 24 patients who needed surgical treatment of proximal femoral fracture and were at risk for the development of psycho-emotional disorders due to the presence of emotional disorders of an anxiety-depressive nature were examined. The presence of such disorders was recorded at the time of admission, before and after surgical treatment using specialized psychodiagnostic techniques. Mini Mental State Examination, modified Hachinski ischemic scale, Frontal assessment battery, Spielberg-Khanin Scale of Reactive and Trait Anxiety, The Zung Self-Rating Depression Scale were used. Results of the clinical study of the Most patients at risk had a high level of reactive anxiety - 14 (58.33%) patients (equally in subgroups I and II - 7 (29.17%) patients in each) compared with moderate levels (10 (41.67%) patients) - equally I and II subgroups (5 (20.83%) patients in each). In the subgroups I and II with moderate and high levels of reactive anxiety, a predominance of female patients was noted: subgroup I - female patients with a moderate level - 3 (12.50%), and with a high level -5 (20.83%); subgroup II - 3 (12.50%) and 4 (16.67%) female patients respectively. As a result of determining the key aspects of the management of emotional disorders in the practice of operative treatment of proximal femoral fractures in elderly patients:the presence of moderate (41.67%) and high (58.33%) levels of reactive and trait anxiety in elderly patients with proximal femoral fractures and emotional disorders is noted. The presence of a depressive state of varying severity was recorded: a subdepressive state (75.00%) and mild depression (25.00%). The general levels of reactive and trait anxiety and depressive disorders showed the presence of limit levels between moderate, high (reactive and trait anxiety) and mild depression and sub-depressive state (depressive disorders): reactive anxiety (42.52±0.05), trait anxiety (42.23±0.07) and depressive disorders (51.41±0.07). It is proved that the treatment of emotional disturbances of the anxiety-depressive spectrum lead to a significant levelling in existing psychological changes.The deterioration of the existing emotional disorders of the anxiety-depressive spectrum among patients at risk in the absence of drug treatment has been established.


Blood pressure load in adults with treated hypertension.
To assess blood pressure (BP) load in a population of treated hypertensive patients. The study group consisted of 137 hypertensive adults, including 75 (54.75%) men and 62 (45.25%) women, with either formerly or newly diagnosed hypertension based on office BP measurements. The median age in the whole study group was 52 years (47 and 56 years among men and women, respectively). The mean body mass index (BMI) was 27 ± 4 kg/m², and median duration of hypertension was 3 years. We divided the study group into subgroups depending on age, gender, BMI, and duration of hypertension. All patients underwent single 24-h ambulatory BP monitoring. We calculated 24-h, daytime and nighttime BP loads separately for systolic and diastolic BP. Statistical analysis was carried out using the SPSS 15.0 environment. Men were significantly younger than women (48.17 vs. 55.48 years, p < 0.02). Mean BMI was higher in men than women (28 vs. 26 kg/m², p < 0.044). There were no differences in the mean values of BP load depending on gender, BMI and, duration of hypertension (p = NS). Twenty-four hour and daytime diastolic BP load was higher in patients aged 41-65 years than in patients above 65 years (32.4 vs. 20.8%, p < 0.04; and 29.6 vs. 17.5%, p < 0.03). A negative correlation was found between daytime diastolic BP load and age (r = -0.19, p < 0.026) and a positive correlation was found between night time systolic BP load and age (r = 0.24, p < 0.005). There was no relationship between BP load and gender, BMI, and duration of hypertension. Diastolic BP load was age-related. Middle-aged patients were characterised by significantly higher values of 24-h and daytime diastolic BP load than the elderly patients.


Using Nanoliposomes To Construct a FRET-Based Ratiometric Fluorescent Probe for Sensing Intracellular pH Values.
Nanoliposomes were first used to encapsulate two fluorophores, fluorescein and cresyl violet, to construct a FRET-based ratiometric fluorescent probe, for sensing intracellular pH values. The morphology, stability, interference factors, biocompatibility, and performance were investigated in detail. The fluorophores-encapsulated nanoliposomes (FEN) probe can be uptaken by cells within 30 min, which is faster than any other nanosensor, and cell viability was not significantly changed upon treatment with the FEN probe for 24 h, showing the low cytotoxicity and good biocompatibility of the probe. Quantitative determinations of intracellular pH of MCF-7 cells and the pH fluctuations associated with inflammation have been successfully performed with our probe. This work demonstrated that nanoliposomes could be served as an emerging approach for constructing useful fluorescent nanosensors with low toxicity.


A New Generation of Arachidonic Acid Analogues as Potential Neurological Agent Targeting Cytosolic Phospholipase A2.
Cytosolic phospholipase A2 (cPLA2) is an enzyme that releases arachidonic acid (AA) for the synthesis of eicosanoids and lysophospholipids which play critical roles in the initiation and modulation of oxidative stress and neuroinflammation. In the central nervous system, cPLA2 activation is implicated in the pathogenesis of various neurodegenerative diseases that involves neuroinflammation, thus making it an important pharmacological target. In this paper, a new class of arachidonic acid (AA) analogues was synthesized and evaluated for their ability to inhibit cPLA2. Several compounds were found to inhibit cPLA2 more strongly than arachidonyl trifluoromethyl ketone (AACOCF3), an inhibitor that is commonly used in the study of cPLA2-related neurodegenerative diseases. Subsequent experiments concluded that one of the inhibitors was found to be cPLA2-selective, non-cytotoxic, cell and brain penetrant and capable of reducing reactive oxygen species (ROS) and nitric oxide (NO) production in stimulated microglial cells. Computational studies were employed to understand how the compound interacts with cPLA2.