The state of health in Belgium, 1990-2019: a benchmarking analysis based on the Global Burden of Disease 2019 study.
In a context of decreasing resources and growing health needs, evidence-based health and care policies are essential. This study aims to assess the health trends in Belgium between 1990 and 2019, to compare the Belgian health status to that of the EU-15 countries, and to identify the main drivers in trends over time and country differences within the EU-15. We extracted estimates from the GBD 2019 study via the GBD results tool and visualization tools. We compared the Belgian health status with 14 European Union comparator countries between 1990 and 2019, and decomposed the time trends and country differences into the unique contributions of the different underlying causes of death and disability. Life expectancy (LE) in Belgium improved significantly between 1990 and 2019 for both men and women. Belgium age-standardised mortality rates dropped significantly for men (-40%) and women (-33%) between 1990 and 2019. Overall, Belgium age-standardised disability-adjusted life year (DALY) rates dropped by 23%. This decrease is mainly due to decreasing trends in age-standardised years of life lost (YLL) rates while age-standardised years lived with disability (YLD) rates remained stable. Compared to EU-15, Belgium's ranking in terms of age-standardised DALY rates worsened for both men and women in 2019. Self-harm and falls are major causes of disease burden, with DALY rates that are higher than in many other EU-15 countries, indicating a realistic potential for improvement. Lung cancer DALY rates remain worrisome for men, and even show an increasing trend for women. Increasing trends of headache disorders, drug use disorders, and diabetes, require further attention. Non-communicable diseases remain the main contributors for health burden in Belgium, with disability accounting for an increasingly larger share of the disease burden. Despite considerable improvements, Belgium's ranking for DALYs decreased between 1990 and 2019 compared to the EU-15. This study identified priority causes of disease burden based on their contributions to current evolutions and EU-15 differences. Since many of these causes are considered to be avoidable, primary and secondary prevention are crucial elements for reducing the burden of disease on the healthcare system.


Nonlinear poroplastic model of ventricular dilation in hydrocephalus.
The mechanism of ventricular dilation in normal-pressure hydrocephalus remains unclear. Numerical finite-element (FE) models of hydrocephalus have been developed to investigate the biomechanics of ventricular enlargement. However, previous linear poroelastic models have failed to reproduce the relatively larger dilation of the horns of the lateral ventricles. In this paper the authors instead elaborated on a nonlinear poroplastic FE model of the brain parenchyma and studied the influence of the introduction of these potentially more realistic mechanical behaviors on the prediction of the ventricular shape. In the proposed model the elasticity modulus varies as a function of the distension of the porous matrix, and the internal mechanical stresses are relaxed after each iteration, thereby simulating the probable plastic behavior of the brain tissue. The initial geometry used to build the model was extracted from CT scans of patients developing hydrocephalus, and the results of the simulations using this model were compared with the real evolution of the ventricular size and shape in the patients. The authors' model predicted correctly the magnitude and shape of the ventricular dilation in real cases of acute and chronic hydrocephalus. In particular, the dilation of the frontal and occipital horns was much more realistic. This finding suggests that the nonlinear and plastic mechanical behaviors implemented in the present numerical model probably occur in reality. Moreover, the availability of such a valid FE model, whose mechanical parameters approach real mechanical properties of the brain tissue, might be useful in the further modeling of ventricular dilation at a normal pressure.


Array comparative genomic hybridization identifies a heterozygous deletion of the entire KCNJ2 gene as a cause of sudden cardiac death.
Large gene rearrangements, not detectable by standard molecular genetic sequencing techniques, are present in a minority of patients with long QT syndrome. We aimed to screen for large rearrangements in genes responsible for long QT syndrome as part of the molecular autopsy of a 36-year-old woman who died suddenly and had a negative autopsy. A retrospective analysis of an ECG identified a long QT interval, but sequencing of known LQT genes was uninformative. Array comparative genomic hybridization was used to screen for deletions and duplications in 101 genes implicated in cardiac disorders and sudden death using a postmortem blood sample. A 542 kb deletion encompassing the entire KCNJ2 gene was identified in the decedent. The mother had electrocardiographic U-wave changes consistent with Andersen-Tawil syndrome and exaggerated by exercise but none of the characteristic noncardiac features. Fluorescence in situ hybridization confirmed the deletion in the decedent and established its presence in the mother. A novel application of array comparative genomic hybridization and fluorescence in situ hybridization has identified that long QT syndrome and sudden cardiac death may occur as a result of a deletion of an entire gene. The case also supports recent research suggesting that noncardiac features of Andersen-Tawil syndrome occur only with missense or minor gene rearrangements in the KCNJ2 gene, resulting in a dominant negative effect on Kir2.x channels.


Evaluation of Commercial-off-the-Shelf Materials for the Preservation of Bacillus anthracis Vegetative Cells for Forensic Analysis.
Environmental surface sampling is crucial in determining the zones of contamination and overall threat assessment. Viability retention of sampled material is central to such assessments. A systematic study was completed to determine viability of vegetative cells under nonpermissive storage conditions. Despite major gains in nucleic acid sequencing technologies, initial positive identification of threats must be made through direct culture of the sampled material using classical microbiological methods. Solutions have been developed to preserve the viability of pathogens contained within clinical samples, but many have not been examined for their ability to preserve biological agents. The purpose of this study was to systematically examine existing preservation materials that can retain the viability of Bacillus anthracis vegetative cells stored under nonpermissive temperatures. The results show effectiveness of five of seventeen solutions, which are capable of retaining viability of a sporulation deficient strain of B. anthracis Sterne when stored under nonrefrigerated conditions.


The Altered Metabolic Molecular Signatures Contribute to the RAD001 Resistance in Gastric Neuroendocrine Tumor.
Although the inhibition of mTOR is a promising treatment for neuroendocrine tumors, several questions are still open for cell specificity and resistance. With the newly characterized gastric neuroendocrine tumor mouse model (CEA424-SV40 T antigen transgenic mice), the anti-tumor efficiency of RAD001 (Everolimus) was tested both in vitro and in vivo. Tumor samples were analyzed for the expression of RNA by cDNA microarrays and also signaling pathways to get more details on the local surviving or selected cells. RAD001 treatment dramatically slowed down tumor growth and prolonged the animals' survival. This inhibitory effect has a preference for tumor cells since gastrointestinal hormone and neuroendocrine tumor specific markers were more reduced than the epithelial ones. While phosphorylation of p70S6K was almost completely blocked both in vitro and in vivo, the phosphorylation of 4EBP1 was only partially inhibited in vitro and unaffected in vivo. RAD001 treatment induced feedback activation of metabolism related pathways like PI(3)K-Akt-mTOR and MEK/ERK signalings. An induction of senescence as well as differential expression of genes responsible for metabolism was also observed, which highlighted the contribution of metabolic molecular signatures to the escape of the tumor cells from the treatment. Together, our data revealed efficient anti-tumor ability of RAD001 in a new gastric neuroendocrine tumor mouse model system and offered new insights into the clinical aspects of the incomplete elimination of tumor cells in patients treated.


Risk factors for aggressive recurrent respiratory papillomatosis in adults and juveniles.
In this cohort study we examined whether gender, age at onset, observation time or human papillomavirus (HPV) genotype are risk factors for an aggressive clinical course in Recurrent Respiratory Papillomatosis (RRP). Clinical data from patient records comprised gender, age at onset, date of first endolaryngeal procedure with biopsy, date of last follow-up, total number of endolaryngeal procedures, and complications during the observation period. Disease was defined as juvenile (JoRRP) or adult onset (AoRRP) according to whether the disease was acquired before or after the age of 18. Aggressive disease was defined as distal spread, tracheostomy, four surgical operations annually or >10 surgeries in total. DNA was extracted from formalin-fixed paraffin-embedded tissue. HPV genotyping was performed by quantitative PCR assay identifying 15 HPV genotypes. The study included 224 patients. The majority were males (141/174 in AoRRPs and 31/50 in JoRRPs; p = 0.005). The median follow-up from initial diagnosis was 12.0 years (IQR 3.7-32.9) for JoRRPs and 4.0 years (IQR 0.8-11.7) for AoRRPs. The disease was more aggressive in juveniles than adults (p<0.001), a difference that disappeared after 10 years' observation. JoRRPs with aggressive disease were younger at onset (mean difference 4.6 years, 95%CI [2.4, 6.8], p = 0.009). HPV6 or -11 was present in all HPV-positive papillomas. HPV11 was more prevalent in aggressive disease, and HPV6 in non-aggressive disease (p<0.001). Multiple logistic regression revealed that only age at onset (OR = 0.69, 95% CI [0.53, 0.88], p = 0.003) was associated with aggressive disease in juveniles, while HPV11 (OR = 3.74, 95% CI [1.40, 9.97], p = 0.008) and observation time >10 years (OR = 13.41, 95% CI [5.46, 32.99[, p<001) were risk factors in adults. In conclusion, the only significant risk factor for developing aggressive disease in JoRRPs was age at onset, but both HPV11 and observation time >10 years were risk factors for an aggressive disease course in AoRRPs.


Glial heterotopia of the middle ear.
A choristoma is the presence of histologically normal tissue in an area where it is not normally located. The most frequently reported choristoma of the middle ear is salivary choristoma. Heterotopic brain tissue is very uncommon in the middle ear and mastoid. We present a rare case of glial choristoma of the middle ear, together with a review of the literature.


A cooperative role for Atf1 and Pap1 in the detoxification of the oxidative stress induced by glucose deprivation in Schizosaccharomyces pombe.
In Schizosaccharomyces pombe, glucose concentrations below a certain threshold trigger the stress-activated protein kinase (SAPK) signal transduction pathway and promote increased transcription of Atf1-dependent genes coding for the general stress response. Removal of glucose specifically induces the nuclear accumulation of green fluorescent protein-labeled Pap1 (GFP-Pap1) and the expression of genes dependent on this transcription factor. In contrast, depletion of the nitrogen source triggers the SAPK pathway but does not activate Pap1-dependent gene transcription, indicating that carbon stress rather than growth arrest leads to an endogenous oxidative condition that favors nuclear accumulation of Pap1. The reductant agents glutathione or N-acetylcysteine suppress the nuclear accumulation of GFP-Pap1 induced by glucose deprivation without inhibiting the activation of the MAPK Sty1. In addition, cells expressing a mutant GFP-Pap1 unable to accumulate into the nucleus upon hydrogen peroxide-mediated oxidative stress failed to show this protein into the nucleus in the absence of glucose. These results support the concept of a concerted action between the SAPK pathway and the Pap1 transcription factor during glucose exhaustion by which glucose limitation induces activation of the SAPK pathway prior to the oxidative stress caused by glucose deprivation. The ensuing induction of Atf1-dependent genes (catalase) decreases the level of hydroperoxides allowing Pap1 nuclear accumulation and function. Congruent with this interpretation, glucose-depleted cells show higher adaptive response to exogenous oxidative stress than those maintained in the presence of glucose.


GXT responses in altitude-acclimatized cyclists during sea-level simulation.
This study examined the effects of gender on graded exercise stress test (GXT) response in moderate-altitude (MA)-acclimatized cyclists during sea-level (SL) simulation. It was hypothesized that alterations in arterial saturation would relate to changes in VO2peak. Twenty competitive cyclists (12 males, 8 females) who were residents of MA locations underwent two randomized bicycle GXTs: one under local normoxic hypobaria, and the other under simulated SL conditions. Under the SL condition, the cyclists demonstrated a significant increase (2-3%) in absolute and relative VO2peak, improved (4%) economy at lactate threshold (LT), and time-adjusted peak power (7%); the range of improvement between individuals varied from -6% to +25%. Simulated SL also resulted in a greater arterial saturation (S(a)O2) at rest and VO2peak, and significantly less desaturation (4 vs 8%) from rest to VO2peak. The individual variability in the change (Delta) in VO2peak was not significantly correlated to SL S(a)O2 or any other S(a)O2 variable analyzed, regardless of whether we examined each gender individually or combined. Significant correlations were found between Delta-peak power and Delta-economy as well as Delta-VO2peak and Delta-GXT time. These correlations as well as degree of improvement varied by gender. These data suggest that chronic residence at MA may attenuate the occurrence of exercise-induced arterial hypoxemia and eliminate the relationship between S(a)O2 and Delta-VO2peak that has been reported among SL residents acutely exposed to altitude. Additionally, the improvements that occur in predictors of aerobic performance when MA residents are exposed acutely to SL conditions have a large degree of individual variability, and the mechanism(s) for improvement may vary by gender.


Genicular Nerve Pulsed Dose Radiofrequency (PDRF) Compared to Intra-Articular and Genicular Nerve PDRF in Knee Osteoarthritis Pain: A Propensity Score-Matched Analysis.
Chronic knee osteoarthritic (OA) pain is a common and debilitating complaint in elderly patients. Despite numerous pharmaceutical options, the majority of patients still experience long-term pain. Genicular nerve (GN) radiofrequency has become increasingly popular as a treatment for knee pain. This retrospective study aimed to evaluate the effects of pulse dose radiofrequency (PDRF) in patients with chronic knee OA pain. Propensity score matching analysis was performed in a retrospective cohort of 78 patients with moderate-severe knee OA pain unresponsive to conservative treatment who underwent PDRF GN or intra-articular (IA) and PDRF GN. Pain relief was measured using the numeric rating scale (NRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Patient Global Impression of Change (PGIC) at 3 and 6 months post-intervention. A significant reduction in NRS scores was reported at 3 (p<0.001) and 6 months (p<0.001) after PDRF in both groups. NRS was lower in PDRF IA + GN than PDRF GN (p<0.0001). WOMAC pain was significantly reduced at 3 months in PDRF IA + GN group (baseline: 10.12±3.14, 3 months: 6.25±2.44, p=0.0001). WOMAC stiffness and function were improved only at 3 months in PDRF IA + GN compared to baseline (p=0.007 and p=0.006, respectively). A longer period of pain relief was reported after PDRF IA + GN (6.75±2.42 months) compared to PDRF GN (4.31±2.85 months, p<0.001) in association with higher PGIC scores. This is the first study that compared two different PDRF techniques. PDRF GN and PDRF IA + GN were both effective in reducing pain at 3 and 6 months follow-up. However, only PDRF IA + GN was able to improve WOMAC scores at 3 months after the treatment with a longer period of efficacy compared to PDRF GN alone.


[Protective effect of glucose-insulin-potassium solutions in myocardial damage caused by emetine].
This study was carried out on 170 dogs. Cardiotoxic effects of doses of 15 mg/kg of emetine hydrochloride were studied in 20 dogs. 20 mg/kg of emetine hydrochloride were administered intravenously over 60 min. to the remaining 150 animals. These dogs were distributed in groups of 25. One group received emetine alone. Phleboclyses with saline serum, glucose-insulin-potassium, glocose-insulin, glucose-potassium and glucose serum alone, respectively, were administered to the other 5 groups during the emetine infusion and cardial contraction and several electrograms were recorded. Mean systolic blood pressure was measured continuously in the femoral artery. Observations covered a 4 hour period. During the infusion of emetine alone, ventricular myocardial contraction and systemic arterial pressure decreased abruptly. Intra-atrial, atrio-ventricular and intraventricular conduction disorders, as weel as primary ventricular repolarization changes, were also observed. At the end of this infusion, the Q-T interval increased 25% and the heart rate decreased 26% of the control values. In the group also receiving glucose-insulin-potassium solution, the fall of the ventricular contraction amplitude was significantly less than in animals given emetine alone. Primary ventricular repolarization changes were less evident. The mortality rate reached only 4 per cent. In conclusion, the doses of emetine hydrochloride employed here have depressive cardiocirculatory effects. Glucose-insulin-potassium solution, administered simultaneously with emetine, seems to have a favorable metabolic effect against the emetine cardiotoxicity. This protective action of the G-I-K solution is superior to that obtained with each component, administered separately, and with saline serum.


PHYSIOLOGY OF INSECT ECDYSIS. II. THE ASSAY AND OCCURRENCE OF THE ECLOSION HORMONE IN THE CHINESE OAK, SILKMOTH, ANTHERAEA PERNYI.
1. A semi-quantitative biological assay for the eclosion hormone is described. 2. In the pharate moth hormonal activity is confined to the brain and the corporacardiaca (CC). 3. During the life history of the moth, activity is practically absent from the brain and CC of larval and pupal stages and appears only in preparation for adult emergence. 4. The titer of eclosion hormone in the brain and CC of Pernyi moths was followed through adult development. In both structures activity first appeared on about day 7. Titers then increased for the next 3 to 5 days followed by a plateau. On the morning of the day of emergence, the titer in the brain fell and that in the CC correspondingly reached its highest level. At the time of eclosion in the evening, the CC titer then dropped and hormone appeared in the blood. 5. Tests on brains and CC from cockroaches and bugs failed to show activity. 6. It was concluded that the eclosion hormone is used only for the pupal-adult ecdysis and, thus, is probably restricted to the holometabolous orders of insects.


[Application of 13-cis-retinoic acid in patients with 131I scintigraphically-negative metastases of differentiated thyroid carcinoma].
The loss of iodine uptake by differentiated thyroid carcinoma (DTC) cells is a major therapeutic problem especially in patients with nonsurgical metastatic foci or local recurrence. Using 13-cis-retinoic acid, it was attempted to retain iodine uptake as a result of redifferentiation (influence by retinoic acid receptors present in DTC cells). Between 1999 and 2005, 13-cis-retinoic acid was used in 11 patients with disseminated PTC and high serum level of thyroglobulin (Tg) before (131)I treatment (2 patients were treated twice - 13 treatment cycles in total). Side effects in skin and mucous membranes were observed in all the patients, however, their intensity did not require termination of the therapy. Increase of iodine uptake was observed in 5 patients (45%). Decreased Tg concentration was observed in 9 patients. In that group, increased (131)I uptake was observed in 4 patients with distant metastases. All determinations of Tg concentrations were carried out under TSH stimulation. 13-cis-retinoic acid causes an increase of radioiodine uptake in around half of treated patients, however, the follow-up of these patients indicates that this increase does not result in either full remission or even stabilisation of neoplastic disease. The possibility should be considered to use cis-retinoic acid as an independent therapeutic approach in patients with radioiodine non-avid foci of thyroid carcinoma especially those showing high expression of RARb and RXRg receptors.


Can a shoe-mounted IMU identify the effects of orthotics in ways comparable to gait laboratory measurements?
Footwear and orthotic research has traditionally been conducted within laboratories. With increasing prevalence of wearable sensors for foot and ankle biomechanics measurement, transitioning experiments into the real-world is realistic. However wearable systems must effectively detect the direction and magnitude of response to interventions to be considered for future usage. RunScribe IMU was used simultaneously with motion capture, accelerometers, and force plates during straight-line walking. Three orthotics (A, B, C) were used to change lower limb biomechanics from a control (SHOE) including: Ground reaction force (GRF) loading rate (A), pronation excursion (A and B), maximum pronation velocity (A and B), and impact shock (C) to test whether RunScribe detected effects consistent with laboratory measurements. Sensitivity was evaluated by assessing: 1. Significant differences (t-test) and effect sizes (Cohen's d) between measurement systems for the same orthotic, 2. Statistical significance (t-test and ANOVA) and effect size (Cohen's d & f) for orthotic effect across measurement systems 3. Direction of orthotic effect across measurement systems. GRF loading rate (SHOE: p = 0.138 d = 0.403, A: p = 0.541 d = 0.165), impact shock (SHOE: p = 0.177 d = 0.405, C: p = 0.668 d = 0.132), pronation excursion (A: p = 0.623 d = 0.10, B: p = 0.986 d = 0.00) did not significantly differ between measurement systems with low effect size. Significant differences and high effect sizes existed between systems in the control condition for pronation excursion (p = 0.005 d = 0.68), and all conditions for pronation velocity (SHOE: p < 0.001 d = 1.24, A: p = 0.001 p = 1.21, B: p = 0.050 d = 0.64). RunScribe (RS) and Laboratory (LM) recorded the same significant effect of orthotic but inconsistent effect sizes for GRF loading rate (LM: p = 0.020 d = 0.54, RS: p = 0.042 d = 0.27), pronation excursion (LM: p < 0.001 f = 0.31, RS: p = 0.042 f = 0.15), and non-significant effect of orthotic for impact shock (LM: p = 0.182 d = 0.08, RS: p = 0.457 d = 0.24). Statistical significance was different between systems for effect of orthotic on pronation velocity (LM: p = 0.010 f = 0.18, RS: p = 0.093 f = 0.25). RunScribe and Laboratory agreed on the direction of change of the biomechanics variables for 69% (GRF loading rate), 40%-70% (pronation excursion), 47%-65% (pronation velocity), and 58% (impact shock) of participants. The RunScribe shows sensitivity to orthotic effect consistent with the laboratory at the group level for GRF loading rate, pronation excursion, and impact shock during walking. There were however large discrepancies between measurements in individuals. Application of the RunScribe for group analysis may be appropriate, however implementation of RunScribe for individual assessment and those including pronation may lead to erroneous interpretation.


Easy Preparation Method for 2-Thioxopyrrolidine Derivatives Including 3-Hydroxy- methylene-2-thioxopyrrolidine, an Antimicrobial Degradation Product of Radish Pungent Principle, via (E,Z)-4-Ylethoxy-3-butenyl Isothiocyanate.
An easy preparation method was developed for 3-hydroxymethylene-2-thioxopyrrolidine (TPC), an antimicrobial degradation product of radish pungent principle. The key intermediate, 4- methoxy-3-butenyl-isothiocyanate (MBI), which was prepared from 3-cyanopropionaldehyde dimethyl acetal in 3 reaction steps, was easily converted to TPC in acidic (pH 3.0-4.0) aqueous media. In methanol or ethanol with a few drops of acetic acid, MBI afforded corresponding 3-(α,α-dialkoxy)methyl-2-thioxopyrrolidines as the major products.


Inositol lipid binding and membrane localization of isolated pleckstrin homology (PH) domains. Studies on the PH domains of phospholipase C delta 1 and p130.
The relationship between the ability of isolated pleckstrin homology (PH) domains to bind inositol lipids or soluble inositol phosphates in vitro and to localize to cellular membranes in live cells was examined by comparing the PH domains of phospholipase Cdelta(1) (PLCdelta(1)) and the recently cloned PLC-like protein p130 fused to the green fluorescent protein (GFP). The prominent membrane localization of PLCdelta(1)PH-GFP was paralleled with high affinity binding to inositol 1,4,5-trisphosphate (InsP(3)) as well as to phosphatidylinositol 4,5-bisphosphate-containing lipid vesicles or nitrocellulose membrane strips. In contrast, no membrane localization was observed with p130PH-GFP despite its InsP(3) and phosphatidylinositol 4,5-bisphosphate-binding properties being comparable with those of PLCdelta(1)PH-GFP. The N-terminal ligand binding domain of the type I InsP(3) receptor also failed to localize to the plasma membrane despite its 5-fold higher affinity to InsP(3) than the PH domains. By using a chimeric approach and cassette mutagenesis, the C-terminal alpha-helix and the short loop between the beta6-beta7 sheets of the PLCdelta(1)PH domain, in addition to its InsP(3)-binding region, were identified as critical components for membrane localization in intact cells. These data indicate that binding to the inositol phosphate head group is necessary but may not be sufficient for membrane localization of the PLCdelta(1)PH-GFP fusion protein, and motifs located within the C-terminal half of the PH domain provide auxiliary contacts with additional membrane components.


A pair of ionic 1D Cu(II) chain enantiomers simultaneously displaying large second- and third-harmonic generation responses.
By employing enantiomerically pure mono-bidentate N-donors (LR/LS) as chiral bridging ligands to react with Cu(ClO4)2(H2O)6 in CH3CN-DMF mixed solvent, respectively, a pair of ionic one-dimensional (1D) Cu(II) chain enantiomers formulated as {[CuLR(CH3CN)(DMF)H2O](ClO4)2}n/{[CuLS(CH3CN)(DMF)H2O](ClO4)2}n (D-1/L-1) were isolated and structurally characterized, where LR/LS = (-)/(+)-4,5-pinenepyridyl-2-pyrazine. They crystallize in the noncentrosymmetric (NCS) P212121 space group of an orthorhombic system due to the introduction of chiral LR/LS, and the ClO4- groups as counteranions reside in crystal lattices, thus leading to charge separation with large dipole moments in their molecular structures. Based on crystal samples, investigation on their nonlinear optical (NLO) behaviors showed that D-1 and L-1 display simultaneously much larger second- and third-harmonic generation (SHG and THG) responses than their analogues based on the same chiral N-donors (LR/LS) and Cu(NO3)2(H2O)3 with NO3- acting as the coordination group to bind Cu(II) ions. The SHG intensities of D-1/L-1 are 0.62/0.60 × KDP (KH2PO4), and THG intensities of D-1/L-1 are 238/228 × α-SiO2. Our finding indicates that coordination polymers (CPs) with charge separation and NCS structures, i.e., ionic CPs with NCS arrangements are the ideal NLO crystalline materials for the simultaneous observation of large SHG and THG responses, thus providing a new approach to obtain NLO-active CP crystalline materials with high-performance SHG and THG responses.


[Medically indicated preterm birth. Maternal and fetal consequences].
One of the principal challenges of obstetrics is to reduce the percentage of perinatal mortality. Preterm birth is considered the main cause of neonatal morbidity and mortality. Preterm birth by medical indication, is a condition rarely documented in medical literature, but it requires analysis to determine the effect in perinatal health. In a third care hospital setting, a prospective study was performed on 154 pregnant women that delivered preterm babies between 25 and 36 weeks of gestation. The Relative Risk (RR) was obtained to compare the association between the medical indication of the preterm birth, the use of fetal pulmonary maturants, type of delivery, the health status of the newborn at birth and hospital discharge. The main causes of preterm birth by medical indication were: premature rupture of membranes, preeclampsia, intrauterine growth retardation and fetal distress. Neonatal mortality was 13%. The rate of cesarean section was higher than expected. Despite the various types of delivery, there were no significant differences between mortality, length of hospital stay or hospital complications. The probability of death to preterm born was explained to gestational age and was not modified for medical decision to interrupt pregnancy.


Evaluating Technology-Enhanced Continuing Medical Education.
Technology is changing the face of continuing medical education (CME). However, will it improve the quality of CME? No longer is it sufficient to count heads or ask if participants liked the experience. It is time to look at CME's influence on performance, habits, and perhaps even outcomes, and to use data to continuously improve CME programs and practices. As CME experiences integrate into professional life in the forms of online knowledge tools streamed to the bed side, mobile advice and e-coaching, all of which pay scant attention to time or place, evaluation methods and questions must evolve to provide meaningful feedback.


Identification and Characterization of Circulating Naïve CD4+ and CD8+ T Cells Recognizing Nickel.
Allergic contact dermatitis caused by contact sensitizers is a T-cell-mediated inflammatory skin disease. The most prevalent contact allergens is nickel. Whereas, memory T cells from nickel-allergic patients are well-characterized, little is known concerning nickel-specific naïve T-cell repertoire. The purpose of this study was to identify and quantify naïve CD4+ and CD8+ T cells recognizing nickel in the general population. Using a T-cell priming in vitro assay based on autologous co-cultures between naïve T cells and dendritic cells loaded with nickel, we were able to detect a naïve CD4+ and CD8+ T-cell repertoire for nickel in 10/11 and 7/8 of the tested donors. We calculated a mean frequency of 0.49 nickel-specific naïve CD4+ T cells and 0.37 nickel-specific naïve CD8+ T cells per million of circulating naïve T cells. The activation of these specific T cells requires MHC molecules and alongside IFN-γ production, some nickel-specific T-cells were able to produce granzyme-B. Interestingly, nickel-specific naïve CD4+ and CD8+ T cells showed a low rate of cross-reactivity with cobalt, another metallic hapten, frequently mixed with nickel in many alloys. Moreover, naïve CD4+ T cells showed a polyclonal TCRβ composition and the presence of highly expanded clones with an enrichment and/or preferentially expansion of some TRBV genes that was donor and T-cell specific. Our results contribute to a better understanding of the mechanism of immunization to nickel and propose the T-cell priming assay as a useful tool to identify antigen-specific naïve T cells.


High Maternal Blood Mercury Level Is Associated with Low Verbal IQ in Children.
The objective of the present study was to investigate the relationship of IQ in children with maternal blood mercury concentration during late pregnancy. The present study is a component of the Mothers and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 553 children whose mothers underwent testing for blood mercury during late pregnancy. The children were given the Korean language version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R) at 60 months of age. Multivariate linear regression analysis, with adjustment for covariates, was used to assess the relationship between verbal, performance, and total IQ in children and blood mercury concentration of mothers during late pregnancy. The results of multivariate linear regression analysis indicated that a doubling of blood mercury was associated with the decrease in verbal and total IQ by 2.482 (95% confidence interval [CI], 0.749-4.214) and 2.402 (95% CI, 0.526-4.279), respectively, after adjustment. This inverse association remained after further adjustment for blood lead concentration. Fish intake is an effect modifier of child IQ. In conclusion, high maternal blood mercury level is associated with low verbal IQ in children.


Platelet activating factor (PAF) as a mediator of injury in nephrotoxic nephritis.
Release of acetyl glyceryl ether phosphorylcholine, platelet-activating factor (PAF), has been demonstrated to be associated with glomerular inflammatory damage in acute serum sickness. Moreover, PAF can increase glomerular permeability to proteins and induce mesangial contraction. Thus PAF might be a good candidate as a mediator of glomerular damage. However the in vivo evidence that PAF might cause glomerular injury is lacking. To evaluate if PAF has a major role in promoting glomerular inflammatory reaction and fibrin deposition, we studied the effect of a molecule, L-652,731, which blocks the PAF receptor, on the evolution of an experimental model of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN). GN was initiated by sheep-anti-rabbit nephrotoxic serum. A proliferative GN regularly occurred in which heavy proteinuria, intra and extracapillary proliferation of resident and inflammatory cells and fibrin deposition in Bowman's capsule were the prominent findings. Our results showed that the PAF receptor antagonist reduces the glomerular damage in anti-GBM GN, supporting the hypothesis that PAF is indeed a mediator of glomerular inflammatory reaction. PAF receptor blocking prevented renal function deterioration in the early phase of the disease, probably preserving glomerular hemodynamics. In the delayed phase of the disease the PAF receptor antagonist reduced proteinuria and prevented renal function deterioration and fibrin deposition. These effects appear to be mediated by an inhibitory action of PAF receptor blocking on macrophage accumulation and activation.


An empirical study of the psychodynamics of suicide: a preliminary report.
Preliminary results from a study of psychodynamic constructs are presented based on data from inpatients following a suicide attempt. The study examines the association between four psychodynamic constructs, severity of suicidal intent, and severity of depressive symptomatology in a sample of hospitalized suicide attempters. Higher levels of suicidal intent were associated with less differentiated self and object representations and less emotional investment in relationships. More severe depressive symptoms in suicide attempters were correlated with more self-targeted anger, less eternally directed anger, higher levels of shame and guilt, more affectively negative views of relationships, greater use of maladaptive and self-sacrificing defenses, and more impaired reality testing. These findings offer some preliminary empirical support for the validity of psychodynamic theories of suicidal behavior.


Purine signaling and potential new therapeutic approach: possible outcomes of NTPDase inhibition.
Interest for extracellular nucleotides has increased since the pioneer work of Burnstock in the early seventies. Research on cellular functions modulated by purines and pyrimidines has led to the identification and characterization of the different components of purine signaling, namely purinoceptors and ecto-nucleotidases. Receptors for tri- and diphosphonucleosides, known as P2 nucleotide receptors, are designated either P2Y receptors, for those coupled to G-proteins, or P2X for those which are ligand gated-ion channels. Ecto-nucleoside triphosphate diphosphohydrolase (NTPDase; EC 18.104.22.168), previously identified as ecto-ATPase, ecto-ATPDase or CD39, is now considered as the main ecto-nucleotidase responsible for the sequential hydrolysis of beta and gamma phosphates of tri- and diphosphonucleosides. More recently, research has been focused on the development of specific agonists and antagonists to P2 purinoceptors. The need to develop specific inhibitors for NTPDase to understand the role of this enzyme has clearly emerged. This paper covers the development of specific molecules targeting purinergic signaling, more specifically the inhibition of NTPDase and their impact on the different physiological systems.


Prospective randomized trial of standard versus highly crosslinked tibial polyethylene in primary posterior-stabilized total knee arthroplasty: clinical and radiological follow-up at 2 to 11 years.
There is insufficient evidence to recommend the use of alternative polyethylene bearings in modular, fixed-bearing total knee arthroplasty (TKA). The purpose of this study was to compare standard polyethylene (SP) and highly crosslinked polyethylene (XLP) tibial liners in posterior-stabilized TKA, with osteolysis as the primary outcome and clinical results and the rate of re-operation as the secondary outcomes. This is a single-surgeon, prospective randomized study involving one design of modular posterior-stabilized TKA. An analysis of 122 TKAs with an SP compression moulded liner and 123 with an XLP liner was performed, with a mean follow-up of six years (2 to 11). Patients were evaluated clinically using the Knee Society score, Lower Extremity Activity Score (LEAS), and the presence of an effusion, and standard radiographs were assessed for radiolucent lines and osteolytic lesions. Osteolysis was present in four TKAs (3.3%) in the SP group, and no knees in the XLP group (p = 0.06). There were no significant differences between the Knee Society total score, change in total score, knee function score, change in function score, LEAS, and change in LEAS in the two groups. There was a significant difference in the presence of an effusion (10/122 with SP liners, 1/123 with XLP liners; p = 0.02). There was no significant difference in the rate of re-operation between the two groups (p = 0.36). There were no complications related to the XLP liner. At this length of follow-up, there were no advantages and no complications related to the use of this XLP tibial liner. The presence of effusion and small osteolytic lesions was more frequent with SP than XLP liners, but of unknown clinical significance. Cite this article: Bone Joint J 2019;101-B(7 Supple C):33-39.


Biomarkers of drug-induced acute kidney injury: a regulatory perspective.
Biomarkers are one of the drug development tools that are being developed through collaborative efforts among multiple stakeholder communities to enhance the drug development process. Biomarkers of acute drug-induced renal injury as used in drug development are more commonly referred to as renal safety biomarkers, the focus of this manuscript. Areas covered: This manuscript provides an overview of the history and evolution of the United States Food and Drug Administration's Center for Drug Evaluation and Research's Biomarker Qualification Program. In addition, a regulatory perspective on the potential for renal safety biomarkers to accelerate medical and pharmaceutical research is presented. The first qualification submissions (acute kidney injury biomarkers) are discussed, including how the FDA review process affected the evolution of the biomarker qualification process and the future of biomarker discovery, development, and use. This manuscript also discusses a new repository for data on novel translational safety biomarkers from drug development programs. Expert opinion: In addition to the qualification of novel biomarkers, a key achievement of the first submission for qualification was the bringing together of multiple stakeholder communities to optimize the process. Early qualification reviews provided valuable lessons that informed an overarching approach of how to develop a biomarker for regulatory use.


Wear characteristics of trimethylolpropane trimethacrylate filler-containing resins for the full crown restoration of primary molars.
Although the demand for aesthetic restoration of primary molars has increased, the full-crown restorations using resin and the details of the wear characteristics of trimethylolpropane trimethacrylate (TMPT) filler containing resins for primary molars are not well understood. This study was conducted to determine whether new light-cured composite resin (Fantasista) and 4-META/MMATBB resin (Bondfill SB) are appropriate for full crown restoration of primary molars by evaluating their wear characteristics. Both resins products contain TMPT filler. The properties of the resins were evaluated through in vitro impacting-sliding wear tests; the wear properties of the opposing enamel specimens used in the tests were also studied. The properties of the resins were compared with those of Litefill, MetafilC, and Clearfil FII, which had been evaluated previously. Fantasista exhibited simple shape of wear that was suggestive of a higher wear resistance than that of Litefill. Fantasista caused the least damage to the antagonistic primary enamel.


The prevalence of molar incisor hypomineralization: evidence from 70 studies.
A growing number of studies have investigated the prevalence of Molar Incisor Hypomineralization (MIH) around the world. The aim of this study was to systematically estimate the pooled prevalence of MIH. A comprehensive literature research was completed in English and Chinese databases. Random effect models were used to calculate the pooled prevalence. To address the heterogeneity, meta-regression, and sensitivity analyzes were conducted. Publication bias was estimated by trim and fill method. Seventy eligible studies were included. The pooled prevalence of MIH was 14.2% globally. In subgroup analysis, South America (18.0%, 95% CI: 13.8-22.2) and Spain (21.1%, 95% CI: 17.7-24.6) had the highest prevalence. There was no significant difference between males (14.3%, 95% CI: 12.0-16.6) and females (14.4%, 95% CI: 12.8-15.9). The prevalence of MIH among children 10 years of age or younger (15.1%, 95% CI: 12.1-18.2) was much higher than the prevalence of MIH among older children (12.1%, 95% CI: 8.0-16.3). Sample size explained 15.7% heterogeneity. MIH has a high incidence globally, especially among children <10 years old. It is, therefore, imperative to develop more appropriate dental healthcare strategies to care for these children and to identify the etiology of MIH to prevent it occurring.


Shared Y chromosome repetitive DNA sequences in stallion and donkey as visualized using whole-genomic comparative hybridization.
The genome of stallion (Spanish breed) and donkey (Spanish endemic Zamorano-Leonés) were compared using whole comparative genomic in situ hybridization (W-CGH) technique, with special reference to the variability observed in the Y chromosome. Results show that these diverging genomes still share some highly repetitive DNA families localized in pericentromeric regions and, in the particular case of the Y chromosome, a sub-family of highly repeated DNA sequences, greatly expanded in the donkey genome, accounts for a large part of the chromatin in the stallion Y chromosome.


Impact of mindfulness training and yoga on injury and pain-related impairment: a group randomized trial in basic combat training.
Service members are at risk for pain-related difficulties in functioning and physical injury. Previous studies suggest that mindfulness training (MT) and yoga may prevent these outcomes. The present study was designed to determine the impact of MT and yoga on the health, pain, and injury of Army trainees completing 10 weeks of basic combat training (BCT). Platoons (≈40 trainees per platoon) were randomized to MT and yoga or training-as-usual in October to December 2020 at a large installation in the US. Self-reported outcomes were health, pain level, and pain impact on training, sleep, mood, and stress. Objective outcomes were injury-related medical encounters and number of diagnoses. The trial was registered at ClinicalTrials. Gov (NCT05550610). Intervention trainees reported significantly better health (OR = 1.05, 95% CI [1.00, 1.10]) and less impact of pain on training (OR = 0.81, 95% CI [0.74, 0.90]), sleep (OR = 0.88, 95% CI [0.81, 0.95]), mood (OR = 0.86, 95% CI [0.78, 0.96]), and stress (OR = 0.88, 95% CI [0.79, 0.98]). There was no significant difference in injury-related medical encounters (AOR = 0.70, 95% CI [0.48, 1.03]), but intervention trainees had fewer diagnoses (OR = 0.67, 95% CI [0.47, 0.95]) and were 30% less likely to have a first medical encounter at any time during BCT. This difference emerged 3 weeks into BCT. A combined MT and yoga intervention resulted in better trainee health. The US Army and other organizations requiring resilience under extreme stress should consider implementing MT and yoga to offset risks to employee health.


Isolated bilateral uveitis in child with hypereosinophilic syndrome.
The ocular involvement has rarely been described in hypereosinophilic syndrome (HES). We report an 8-year-old girl with HES and isolated bilateral uveitis as end-organ damage. Almost 20 months after detection of persistent asymptomatic eosinophilia, she developed complete loss of vision in right eye due to retinal detachment and decreased vision in left eye. We treated this organ-threatening condition with prednisolone and imatinib mesylate, although she was negative for FIP1L1-PDGRFA fusion gene. The vision in her left eye returned to normal. At present, the child is on alternate-day low-dose prednisolone and daily imatinib. Early recognition and aggressive treatment is essential in HES with ocular involvement to save vision. Imatinib is a useful adjuvant drug even in PDGRFA/FIP1L1-negative HES.


[Nursing education in Spain: background and current program].
Spanish nursing has experienced many changes since the early twentieth century. At first, the nurse was simply a medical assistant, then they studied at university, and nowadaysthey are able to specialize in seven different areas.In the last decade, Spanish nurses have had access to master studies in different fields of the scope of nursing to reach the doctoral degree. This has stimulated research in nursing as well as nurse autonomy.


Fluorescent and dispersion experiments on biological membranes under micro-gravity.
Almost all biological processes, especially those involved in signal reception and signal transduction, depend on the physical and physiological properties of biological membranes. It has been shown, that neuronal tissue and the speed of the action potential (AP) which is the basic neuronal unit of all nervous activity, is sensitive to changes in gravity as well as to other weak external forces. We strongly suppose the membrane to be the most important factor in gravitational responses although it is very difficult to observe the effects of gravity changes on these fragile thermodynamic systems. Therefore we developed two different experiments to measure the structural changes and the lateral membrane tension of spheroid cells under microgravity.


[Leu7 (HNK-1)-positive cells in peripheral blood and natural killer cell activity in patients with atopic dermatitis].
To clarify the immunologic abnormalities in patients with atopic dermatitis (AD), the percentages of Leu7 (HNK-1)-positive cells and natural killer (NK) cell activity were measured in peripheral blood lymphocytes isolated from 25 AD patients (8 males and 17 females, mean age of 20.8 years old) and 69 healthy non-atopic persons (46 males and 23 females, mean age of 27.4 years old). The percentage of Leu7-positive cells was significantly reduced in AD patients compared with that in controls (AD patients: 11.6 +/- 7.0%, controls: 19.5 +/- 8.3%, p less than 0.01). Although the difference was not statistically significant, reduction of the percentage was slighter in patients with mild AD than in moderate and severe AD patients (mild AD: 14.3 +/- 6.6%, moderate AD: 10.1 +/- 4.4%, severe AD: 10.5 +/- 8.3%). There was also a significant inverse correlation between the percentage of Leu7-positive cells and log IgE levels in patients with AD (r = -0.537, p less than 0.01). No differences in NK cells activity or NK cell activities augmented by interferon-beta and interleukin-2 were observed between in AD patients and in controls. These results suggest that the Leu7-positive cells in AD patients may be closely associated with the regulation of serum IgE production.


Psychological status of patients with alopecia areata.
Alopecia areata is not painful or life-threatening, but its aesthetic repercussions can lead to profound changes in patients' psychological status and relationships. The psycho-logical status and personality traits of 73 patients and 73 controls were evaluated with the Minnesota Multi-phasic Personality Inventory (MMPI-2). Analysis of the MMPI-2 profile showed that scores for some scales (i.e. Depression, Anxiety, Family relationships) were higher for patients with alopecia areata than for controls. Patients with alopecia appeared to experience more depressive, hysterical and anxiety feelings, have more hypo-chondriac tendencies, and to be more in conflict with their social environment. In order to provide more effective management, the psychological status of patients with alopecia areata should be evaluated in dermatological settings.


Spectral modification of whispering-gallery-mode resonances in spheroidal resonators due to interaction with ultra-small particles.
The recently developed general ab initio theory of nanoparticle-induced modifications of the spectrum of whispering gallery modes of optical spheroidal resonators is applied to the case in which distinct particle-induced resonances overlap and cannot be resolved. This situation occurs in the case of resonances with low Q-factors and/or ultra-small particles. The position of the single resonance observed in these situations depends on the strengths and widths of the overlapping resonances. We determine this position by considering the spectral characteristics of the total power scattered by the resonator. The obtained theoretical results are compared against the available experimental data and heuristic theories.


Predicting outcomes of conservative treatment for patients with carpal tunnel syndrome: Group- and individual-based rehabilitation.
To identify predicting factors of treatment outcomes of a two stage group-based and then individual-based intervention programme for patients with carpal tunnel syndrome (CTS). A prospective cohort study where patients diagnosed with CTS were recruited from an out-patient occupational therapy clinic to join the two-stage CTS programme. The Stage-One programme consisted of splinting and educational talks in a group format, while the Stage-Two programme consisted of four weekly individual sessions providing psychosocial support, reinforcing correct ergonomics and mobilization. Baseline assessment on six potential predicting factors and four outcome measures was done for all patients. Patients were re-assessed at the end of the Stage-One and the Stage-Two programme. Analysis was done by binary logistic regression adjusted for baseline covariates. One hundred and sixty-six patients completed the Stage-One programme and 46 patients also completed the Stage-Two programme. Results showed that the Chinese Symptom Severity Scale (SSS) baseline score was the only significant predictor for the Stage-One programme outcomes (AUC for ROC was 0.708) with an optimum cut-off score of 23.5. On the other hand, the Chinese QuickDASH baseline score was the only significant predictor for the Stage-Two programme outcomes (AUC for ROC was 0.801) with an optimum cut-off score of 27.4. The significant predictor for the Stage One Programme was the Chinese SSS baseline score and that for the Stage Two Programme was the Chinese QuickDASH baseline score. The optimum cut-off scores identified may be applied clinically to guide client-centered treatment planning.


P066 Real-World Experience of Ustekinumab in Crohn's Disease Patients With Prior Anti-TNF Therapy at a Tertiary Care Hospital.
Ustekinumab (UST) is a monoclonal antibody against the p40 subunit of IL-12/23. It is approved for the treatment of moderate to severe Crohn's disease (CD) and Ulcerative Colitis. We performed a retrospective study to demonstrate the efficacy and outcomes of UST in CD patients who received prior anti-TNF therapies. We collected a list of all patients who received UST until May 2021. In addition, the list was screened for patients who were on anti-TNFs for treatment of CD in the past. Data was collected for patient demographics, disease characteristics, comorbidities, disease phenotype, age of initiation of UST, prior biologic therapy, time since last biologic therapy, concomitant use of steroids or immunomodulator, inflammatory markers, induction of remission, deep remission. Chi-square tests were used for statistical analysis. We identified 34 patients (59% females) with CD on UST who failed at least one anti-TNFs before induction with UST. Clinical remission was documented in 70.5% of patients. 29 percent of patients who achieved clinical remission were on concomitant steroids or immunomodulators at the time of induction of remission along with UST. Fifty percent of patients had a fistulizing disease, of which 70% achieved clinical remission with UST. C-reactive protein (CRP) was reported in 70 percent of patients. Mean CRP prior to initiation of UST was 2.4. CRP trended down to 1.98 (p = 0.079, 95% CI: -0.064-1.08). Eighteen percent of patients had fecal calprotectin reported. Mean fecal calprotectin before initiation of UST was 386, and it trended down 175 while on UST (p = 0.148, 95% CI: -106.25-528.46). Our study demonstrates that remission rates in CD patients who have failed prior anti-TNF therapy are high, including for patients with perianal disease. In patients with fistulizing CD, we suggest using UST for higher rates of remission after induction. We also found that for fecal calprotectin, although an excellent surrogate of colon inflammation, compliance amongst patients remains low.


[Faecal incontinence - serious medical and social issue].
Faecal incontinence presents gastrointestinal disorder with high prevalence (more than 2% of population) and serious impact on the quality of life. General practitioners, gastroenterologists and colorectal surgeons play the principal role in screening, diagnostics and providing health care to patients who suffer from faecal incontinence. Insufficient knowledge about faecal incontinence and minimal training aimed at its diagnostics and therapy lead to the low quality of provided health care.Authors offer comprehensive up-to-date review focused on faecal incontinence - its definition, prevalence, seriousness, consequences, pathophysiology, diagnostics and management. Detailed anatomical and physiological assessment of each patient is fundamental in determining correct cause of faecal incontinence and consequent selection of the most appropriate therapeutic modality.Broad spectrum of available therapeutic options comprises conservative management (lifestyle modification, diet, medications, and absorbent tools), biofeedback and surgical interventions (sphincter augmentation, sphincter reconstruction, sacral nerve stimulation, sphincter substitution and stools diversion). Application of the most appropriate treatment can lead in majority of patients to significant improvement in faecal incontinence and quality of life. Early diagnosis prevents possible complications, which would possibly deteriorate patients quality of life.


Validity and Responsiveness of the Portable Warrior Test of Tactical Agility After Rehabilitation in Service Members With Mild Traumatic Brain Injury.
The Portable Warrior Test of Tactical Agility (POWAR-TOTAL) is a performance-based test designed to assess active-duty service members diagnosed with mild traumatic brain injuries (mTBIs) and could potentially inform return to duty decisions. To examine the validity and responsiveness of the POWAR-TOTAL measure, this study collected self-reported and performance measures by active-duty service members before and after an episode of physical therapist care. Seventy-four individuals, enrolled in care for mTBI symptoms at 1 of 2 concussion specialty Intrepid Spirit Centers, were examined the week that they initiated physical therapy with the intention to return to active duty. Self-reported measures of concussion symptoms, pain, posttraumatic stress, headache, dizziness, and sleep quality were used, as were concurrent measures of mobility and balance. The POWAR-TOTAL task (motor and cognitive skills in single and dual-task conditions) was administered. Forty-nine active-duty service members returned for posttherapy testing using the same test battery. Effect sizes for change in measures were calculated. Construct validity was assessed by correlating change scores on POWAR with concurrent self-report and mobility measures. Responsiveness was evaluated using an anchor-based approach. Significant improvements in self-reported and performance-based measures, including POWAR, were observed after therapy with moderate to large effect sizes. Improvement in POWAR performance correlated with improvement in both performance and self-reported measures. After therapy, individuals who registered improvement on the Patient Global Impression of Change scale demonstrated significantly faster POWAR motor performance than those who rated little or no improvement in their condition. The POWAR-TOTAL captured improvement on a military-specific task after completing physical therapy for mTBI and could serve as an indicator of physical recovery and readiness for return to duty. Challenging cognitive and motor measures for service members may aid in the assessment of recovery and the ability to successfully return to duty after concussion as part of a comprehensive examination approach.


Advanced gastric cancer with brain metastasis effectively treated by arterial infusion chemotherapy: A case report.
The current report presents a case of advanced gastric cancer with brain metastasis effectively treated by intra-left gastric arterial and internal carotid arterial infusions of tegafur, epirubicin and lobaplatin. The patient was a 73-year-old male complaining of headache, nausea/emesis and discomfort in the upper abdomen for six months and was found to have advanced gastric cancer with brain metastasis. The patient was treated by intra-left gastric arterial infusion of 800 mg tegafur, 20 mg epirubicin hydrochloride and 30 mg lobaplatin; and intra-left internal carotid arterial infusion of 400 mg tegafur, 10 mg epirubicin hydrochloride and 20 mg lobaplatin. Following four cycles of intra-arterial infusion chemotherapy, the patient's brain metastasis and discomfort in the upper abdomen had disappeared. The treatment appeared effective for advanced gastric cancer with brain metastasis. However, further investigation in a large-sample study is required to confirm its validity.


Using memory strategies to improve 24-hour dietary recalls among older adults.
Dietitians commonly use 24-hour recall to obtain estimates of the typical food intakes for a population. This study was designed to determine whether using an encoding strategy or support at the time of retrieval improves older adults' 24-hour recall of food items and amounts consumed. The study included 17 older adults ranging from 74 to 91 years of age. Lunch was served to these individuals, and 24-hour dietary recall and recognition of food items consumed at the meal were conducted the following day. Portion sizes for five food items served at the meal, as well as memory tests for recall and recognition and a visual perceptual test, were also administered. Among older adults, use of an encoding strategy did not enhance memory of food items and amounts consumed. However, when the adults were provided support with a visual recognition aid at the time of food item recall, individuals remembered more food items but not amounts consumed. Performance on the Wechsler Memory Scale I and II, Verbal Paired Associates, was found to be a predictor of subjects' performance on 24-hour recall.


Versatile gold catalyzed transglycosidation at ambient temperature.
Glycosidation with stable alkyl glycosyl donors using a catalytic amount of gold salts is promising. Herein, 1-ethynylcyclohexanyl glycosides are identified as novel donors at room temperature and mechanistic investigation showed that the leaving group simply extrudes out.


MTA1 modulated by miR-30e contributes to epithelial-to-mesenchymal transition in hepatocellular carcinoma through an ErbB2-dependent pathway.
MTA1 is a metastasis-associated protein, which is essential to epithelial-to-mesenchymal transition (EMT). However, information concerning its up- and downstream regulation is rare. We investigated its upstream regulation and downstream effector in human hepatocellular carcinoma (HCC). In total, 94 paired HCC and adjacent tissue samples were involved in the study, and the results indicated that decreased miR-30e levels were associated with increased MTA1 levels in human HCC. miR-30e exerted its regulation of MTA1 transcription by binding to its 3'-untranslated region, and was negatively associated with EMT. Furthermore, significantly higher expression of MTA1 was associated with overexpression of v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ErbB2) in human HCC, and MTA1 can promote transcription of ErbB2 by binding with histone deacetylase 2 (HDAC2) and acting as a promoter. The EMT promotion effect caused by MTA1 largely depended on ErbB2, and reducing the activity of ErbB2 can significantly attenuate EMT promotion by causing overexpression of MTA1 both in vitro and in vivo. In general, downregulation of miR-30e can increase levels of MTA1 in human HCC, and furthermore promote cell invasion and metastasis by promoting ErbB2.


Visualization and quantitative analysis of complex formation between E. coli RNA polymerase and an rRNA promoter in vitro.
We have established conditions that stabilize the interaction between RNA polymerase and the rrnB P1 promoter in vitro. The requirements for quantitative complex formation are unusual for E. coli promoters: (1) The inclusion of a competitor is required to allow visualization of a specific footprint. (2) Low salt concentrations are necessary since complex formation is salt sensitive. (3) The addition of the initiating nucleotides ATP and CTP, resulting in a low rate of dinucleotide production, is required in order to prevent dissociation of the complexes. The complex has been examined using DNAase I footprinting and filter binding assays. It is characterized by a region protected from DNAase I cleavage that extends slightly upstream of the region protected by RNA polymerase in most E. coli promoters. We find that only one mole of active RNA polymerase is required per mole of promoter DNA in order to detect filter-bound complexes. Under the conditions measured, the rate of association of RNA polymerase with rrnB P1 is as rapid as, or more rapid than, that reported for any other E. coli or bacteriophage promoter.


The Attitudes About Parenting Strategies for Anxiety Scale: A Measure of Parenting Attitudes About Protective and Intrusive Behavior.
Protective and intrusive parenting behaviors consistently relate to children's anxiety development. We present two studies describing the development of the Attitudes about Parenting Strategies for Anxiety (APSA) scale, which assesses parent distress about children's displays of anxiety and shyness as well as parent attitudes about the effectiveness of protective and intrusive responses across several domains. Study 1 included 594 parents who completed the APSA and additional measures online and established the factor structure, internal reliability, and validity of the measure. We also performed a latent profile analysis of the attitude items to understand common patterns and their correlates. Study 2 comprised 108 mothers participating in a laboratory-based study and provided additional evidence for the factor structure, reliability, and validity, as well as 1-year stability. The APSA appears to be a reliable and valid measure that could have utility for understanding the determinants of parenting behaviors relevant to child anxiety development.


Phylogenetic footprints of an Antarctic radiation: the Trematominae (Notothenioidei, Teleostei).
The teleost suborder Notothenioidei is restricted to the Southern Ocean and has been described as a species flock spanning the whole of it. Within the suborder, the subfamily Trematominae is important for coastal Antarctic ecosystems. The eleven Trematomus species occupy a large range of ecological niches. The genus is monophyletic if the genus Pagothenia (two additional species) and Cryothenia amphitreta, also nested within it, are included. Although the Trematominae have received much interest, the relationships among these fourteen species are still unclear. Several recent studies have tried to resolve these interrelationships; however no complete and clear picture has emerged, probably because of the use of a low number of insufficiently variable markers. The only common results places T. scotti as the sister-group of the rest of the subfamily and T. loennbergi close to T. lepidorhinus. We use here more variable markers. Four nuclear markers, two of which are new, and a mitochondrial marker for the biggest trematomine sampling ever gathered (14 species, 78 specimens). We found that several nuclear haplotypes are shared by several species (mostly in very closely related species). The haplotype patterns coupled with the cytogenetics of the subfamily suggest that a phenomenon of incomplete lineage sorting (ILS) is likely to be at play. Using a calibration linked to fossil evidence, we evaluate the relative ages of each clade within the Trematominae to assess the proximity of the speciation events to one another. The main trematomine diversification was recent and sudden.


Regio- and Stereoselective Synthesis of Functionalized Cyclopentene Derivatives via Mizoroki-Heck Reactions.
Pd(0)-catalyzed Mizoroki-Heck alkenylations and arylations of protected aminocyclopentenes, prepared in a few steps from Vince lactam, afforded functionalized cyclopentenes in high yields and stereoselectivities. DFT calculations were performed to rationalize the high diastereoselectivities. Functionalized cyclopentene products were transformed into valuable chiral building blocks, such as cyclic γ-amino acids and carbocyclic nucleoside precursors.


Physicians' usefulness ratings of family-oriented clinical tools.
Family-oriented patient care is a cornerstone of family practice. Family practice educators have proposed various methods to help the physician to better assess and treat families. Little is known, however, of the usefulness of family-oriented clinical tools to practicing physicians. On a mailed survey questionnaire, 595 members of the Wisconsin Academy of Family Physicians were asked to rate the usefulness of 10 family-oriented tools and indicate the frequency of use and level of training received for each item. In addition, physicians rated their current and desired level of competency for involving families in patient care. Two hundred ninety-nine (50%) physicians responded. Most of the tools were rated as useful but used infrequently. Identifying the effects of chemical dependency on the health of families and conducting family conferences were rated as highly useful and frequently used skills. Clinical tools rated as least useful were record keeping by family charts and folders and family function assessment by the Family APGAR: Physicians who had received training in the use of a tool rated it as more useful, except for the Family APGAR and family charts or folders. Physicians with busier practices rated some of the tools as less useful than did other physicians. Respondents indicated a desire to develop their family counseling skills. Most family-oriented tools were reported to be useful but used infrequently by practicing physicians. Residency programs should continue to provide training for assessing and treating families, particularly in the areas of family systems theory, self-awareness of the physician's own family background, and the effect of chemical dependency on families. Future research should target larger and more varied groups of family physicians.


Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline.
Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation.


Effects of parathyroid hormone and related polypeptides on the heart and coronary circulation of dogs.
The effects of parathyroid hormone and related polypeptides on the heart were examined using the canine heart-lung preparation supported by a donor. Synthetic bovine parathyroid hormone (PTH) containing 34 amino acids [PTH-(1--34)] and natural bovine PTH containing 84 amino acids [PTH-(1--84)] showed slight positive chronotropic and inotropic action and prominent coronary vasodilator action. The effects of the two compounds were very similar. The cardiac stimulatory action was not blocked by pindolol. The coronary vasodilation occurred without increase in the myocardial oxygen consumption, suggesting that it is due to a direct action on the coronary vasculature. All effects occurred soon after intra-arterial injection, lasted only about 20 min, and were not accompanied by changes in plasma Ca and Pi levels. Fragments of PTH, PTH-(24--34) containing 11 amino acids. PTH-(24--28) containing 5 amino acids, and PTH-(25--27) containing 3 amino acids showed very weak transient coronary dilatory action without cardiac stimulatory effects.


The information continuum model of evolution.
Most biologists agree that evolution is contingent on inherited information shaped by natural selection. This apparent consensus could be taken to indicate agreement on the forces shaping evolution, but vivid discussions reveal divergences on how evolution is perceived. The predominant Modern Synthesis (MS) paradigm holds the position that evolution occurs through random changes acting on genomic inheritance. However, studies from recent decades have revealed that evolutionary inheritance also includes DNA-methylation, RNA, symbionts, and culture, among other factors. This has fueled a demand of a broader evolutionary perspective, for example from the proponents of the Extended Evolutionary Synthesis (EES). Despite fundamental disagreements the different views agree that natural selection happens through dissimilar perpetuation of inheritable information. Yet, neither the MS, nor the ESS dwell extensively on the nature of hereditary information. We do - and conclude that information in and of itself is immaterial. We then argue that the quality upon which natural selection acts henceforth is also immaterial. Based on these notions, we arrive at the information-centric Information Continuum Model (ICM) of evolution. The ICM asserts that hereditary information is embedded in diverse physical forms (DNA, RNA, symbionts etc.) representing a continuum of evolutionary qualities, and that information may migrate between these physical forms. The ICM leaves theoretical exploration of evolution unrestricted by the limitations imposed by the individual physical forms wherein the hereditary information is embedded (e.g. genomes). ICM bestows us with a simple heuristic model that adds explanatory dimensions to be considered in the evolution of biological systems.


Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study.
Pneumocystis jirovecii pneumonia (PJP) and pulmonary cytomegalovirus (CMV) infection are common opportunistic infections among immunocompromised patients. However, few studies have evaluated their co-infection, especially among non-HIV patients. Therefore, we aimed to evaluate the outcomes and prognostic factors among non-HIV patients with PJP according to their CMV infection status. This retrospective study evaluated non-HIV patients who were diagnosed with PJP between January 2009 and January2016.The patients were classified and compared according to their pulmonary CMV infection status (positive infection: bronchoalveolar lavage fluid [BALF] CMV DNA loads of >500copies/mL). Among 70 non-HIV patients with PJP, we identified 38 patients (54.3%) with pulmonary CMV infection. There was no significant difference in the mortality rates for the two groups (p = 0.15). Pulmonary CMV infection was significantly more common among patients who were receiving glucocorticoids and immunosuppressants, compared to corticosteroids only (p = 0.02). Pulmonary CMV infection was also significantly associated with severe dyspnea, a lower PaO2/FiO2, and the presence of centrilobular nodules (p = 0.008). Higher CMV DNA loads in the BALF were positively associated with mortality (p = 0.012). Combined therapy using corticosteroids and other immunosuppressants may be a risk factor for pulmonary CMV co-infection among patients with PJP. In addition, CMV pneumonia should be considered when centrilobular nodules and/or severe hypoxemia are observed in non-HIV patients with PJP. Furthermore, antiviral treatment should be promptly initiated for patients with a high CMV DNA load in BALF, based on their poor prognosis.


Fluorescence Detection of Prostate Cancer by an Activatable Fluorescence Probe for PSMA Carboxypeptidase Activity.
Prostate cancer (PCa) is a common malignant tumor among adult males, and convenient intraoperative detection of PCa would reduce the risk of leaving positive surgical margins, especially during nerve-sparing procedures. To achieve rapid, fluorescence-based visualization of PCa, we focused on the glutamate carboxypeptidase (CP) activity of prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein that is attracting attention as a PCa biomarker. Based on our finding that aryl glutamate conjugates with an azoformyl linker are recognized by PSMA and have a sufficiently low LUMO (lowest unoccupied molecular orbital) energy level to quench the fluorophore through photoinduced electron transfer, we designed and synthesized a first-in-class activatable fluorescence probe for CP activity of PSMA. The developed probe allowed us to visualize the CP activity of PSMA in living cells and in clinical specimens from PCa patients and is expected to be useful for rapid intraoperative detection and diagnosis of PCa.


Study of the diclofenac/phospholipid interactions with liposomes and monolayers.
The interaction of diclofenac sodium (SD) with soya phosphatidylcholine (SPC) has been studied with floating Langmuir monolayers and liposomes. SD was either introduced into the subphase of SPC monolayers or co-spread with SPC on an aqueous subphase. In both cases, SD caused the surface pressure isotherm to become more expanded, thus demonstrating the affinity between SD and SPC. The incorporation of SD caused SPC liposomes to have a decreased diameter according to light scattering experiments. When SPC liposomes were injected into an aqueous subphase, their destruction yielding surface-active monomers could be monitored by changes in surface pressure. SD-loaded liposomes displayed a much faster kinetics when the surface density of surface-active monomers was plotted against time, with rate constants increasing significantly with the SD concentration. The kinetic profile can be quantitatively analyzed by plotting ln[1 - (gamma/gamma infinity)] versus t1/2.


Type 1a glycogen storage disease with hepatoblastoma in siblings.
Clinical and histologic details of the two siblings with type 1a glycogen storage disease (GSD-1a) who developed hepatoblastoma are presented. The light microscopic studies on hepatic tumor in both siblings revealed fetal type of hepatoblastoma. Ultrastructural findings in Patient 2 showed markedly altered mitochondria, which were frequently surrounded by the rough endoplasmic reticulum. This is the first known occurrence with this association, and the third report on the familial occurrence of this neoplasm. Glycogen storage disease may increase the risk of hepatocellular carcinoma and hepatoblastoma.


Heritability of personality traits in adult male twins.
Personality test data from the California Psychological Inventory were collected on 99 pairs of identical and 99 pairs of fraternal adult male twins. Heritabilities were comuted for all 18 scales and compared to the heritabilities for "pure" scales with overlapping items omitted. Two of the pure scales, Responsibility and Femininity, had zero heritabilities, whereas all of the full scales had moderate to high heritabilities. It was concluded that item overlap has contributed significantly to previous failures to find evidence for the differential heritability of personality traits as measured by the CPI. CPI items were classified into genetic or environmental categories and separate factor analyses of items in these categories revealed more differences than similarities in factor structure. The genetic personality factors included Conversational Poise, Compulsiveness, and Social Ease. Environmental factors included Confidence in Leadership, Impulse Control, Philosophical Attitudes, Intellectual Interest, and Exhibitionism. Compared to the genetic factors, each of the environmental factors accounted for only a very small percentage of the variance.


Endoscopic ultrasound guided vascular access and therapy: A promising indication.
Endoscopic ultrasound (EUS) is an imaging technique that has consolidated its role as an important tool for diagnosis and therapeutics. In recent years we have seen a dramatic increase in the number of EUS-guided therapeutic indications (celiac plexus neurolysis/block, pseudocyst drainage, etc). Preliminary reports have suggested EUS may also be used to guide vascular access for both imaging and treating different vascular diseases. This review aims to objectively describe the existing evidence in the field.


Overdose and substance-related mortality after release from prison in Washington State: 2014-2019.
Persons released from prison are at an increased risk of mortality compared to the non-incarcerated population, particularly from drug- and opioid-related overdose. Contributors to overdose mortality vary with changing patterns of substance use and updating overdose and mortality statistics may help focus resources for persons released from prison. In this retrospective cohort study, records for 33,811 people released from Washington State Department of Corrections prisons between 2014 and 2018 were linked to Washington State death records from 2014 to 2019. We calculated post-release mortality rates by cause of death, including overdose and substance-related mortality. Hazard ratios for risk factors for all-cause, non-overdose, and overdose mortality were estimated using Cox proportional hazards regression. 862 deaths were identified among persons released from prison. The all-cause mortality rate was 747 per 100,000 person-years (95 % CI: 699-800), and drug overdose was the leading cause of death (216 per 100,000 person-years; 95 % CI: 190-244). Psychostimulant-related mortality (152 per 100,000 person-years; 95 % CI: 131-177) and opioid-related mortality (138 per 100,000 person-years; 95 % CI: 118-161) were the most prevalent among substance-related causes of death, with the greatest mortality risk occurring within two weeks after release. Older age at most recent release, previous incarceration, and drug-related convictions were significant risk factors for all-cause and overdose mortality within six years after release. Psychostimulants were the greatest contributors to substance-related mortality for persons released from Washington State prisons. Greater efforts to prevent psychostimulant- and opioid-related overdose are needed.


Health education to diabetic patients before the start of Ramadan: Experience from a teaching hospital in Dammam.
Studies have shown that pre-Ramadan structured educational program for patients with diabetes mellitus (DM) is beneficial. In this study, our aim was to evaluate the degree of adherence of treating physicians to such programs and their influence on the patient's knowledge and behavior. This cross-sectional study was carried out on adult patients with DM attending a university hospital, who were observed while fasting during Ramadan 1436/2015. Data was collected using a questionnaire-based interview. Baseline characteristics were obtained, and patients were asked whether they had had pre-Ramadan education or not and who the provider was. Patients' knowledge of the components of the recommended structured pre-Ramadan educational program was also tested. Comparison between patients who had the education and those who did not was done using Chi-square test and independent samples Student's t-test; p ≤ 0.05 was considered statistically significant. A total of 298 patients with type 1 or type 2 DM were included in the study; 75.5% of the patients were aged 40 years or older. Only 30% had pre-Ramadan education delivered mainly by diabetic educators or the treating physicians (52% and 44%, respectively). Patients who had the education were younger (mean age: 45.6 ± 17.4 vs. 50.3 ± 14.4, respectively, p = 0.0048), had higher educational qualifications, were more likely to be employed, and self-monitored their blood glucose more frequently (p = 0.0001). There was no difference between the two groups with regard to their knowledge of diet and exercise. The adherence to the pre-Ramadan educational program by the treating physician was low. It is necessary to increase the awareness about the importance of these programs among health-care professionals. The programs should target the less educated, the unemployed, and older patients.


[Monteggia injuries].
Sixty-three recent Monteggia lesions are reported, which were all treated operatively. In 52 patients, the ulna was stabilized by a compression plate. Dislocation of the radial head was reduced by a closed procedure in 24 patients and 38 patients an open operation was performed (including fractures, sutures of the annular ligament, and resections of the radial head). After 38 months, the results were better in comparison to series using conservative or medullary pinning (88% good and very good). Poor results must be expected if the operation is delayed for 2 or more weeks, if the radial head has to be resected, or in posterior Monteggia lesions. The late reconstruction of a neglected Monteggia lesion by means of an osteotomy of the ulna shaft and plate fixation is described in a child.


A Danish reference chart for assessment of psychomotor development based on the Ages & Stages Questionnaire.
The aim of this study was to obtain Ages and Stages Questionnaire (ASQ) scores from the background population so that these may be used as a reference group to extremely preterm children at nine and 18 months of corrected age. A total of 298 children were randomly chosen among the Danish population in three different groups: 9-, 18- and 21 month-old children. The parents received the 10-month ASQ when their child had reached a corrected age of nine months and the 24-month ASQ questionnaire when their child had reached the corrected age of 18 or 21 months. The total scores were normally distributed in both groups. There was a highly significant (p < 0.001) linear regression between ASQ total score and adjusted age for both the 10- and the 24-month ASQ. The results of the study show that the overall development can be assessed when the child is scored with an ASQ intended for older children. Screening for developmental delay in children in the age range of 8-10 months or 18-22 can be quickly assessed by reference to a chart. The chart can also be used as a reference when monitoring the quality in neonatal services by the developmental outcome and this ensures that children are classified according to Danish standards.


[A case of Fournier's gangrene in which Flexi-Seal was effective for evacuation management].
A 67-year-old male was referred to our hospital with septicemia from necrotizing fasciitis of the genitalia of unknown origin. He had a history of diabetes and cerebral infarction. Extensive debridement of necrotizing tissue was performed over an area extending from the lower abdomen to the light inguinal,scrotal and perianal regions. At a suitable point,Flexi-Seal was applied to the wound as a preventive measure against infection. There was no contamination of perianal wounds,allowing them to be closed without infection. The Flexi-Seal was successfully removed after around 3 weeks. This is the second case in which Flexi-Seal was used in Japan to treat Fourier's gangrene.


Accelerated wound repair in ADAM-9 knockout animals.
ADAM-9 belongs to a family of transmembrane, disintegrin-containing metalloproteinases (ADAMs) involved in protein ectodomain shedding and cell-cell and cell-matrix interactions. Although the functions of many ADAM family members are known, the specific biological function of ADAM-9 is still unclear. In this study, we have analyzed ADAM-9 temporal and spatial distribution during wound healing. We showed increased ADAM-9 transcript expression during the first 7 days post-wounding and, by immunolocalization, detected ADAM-9 in all migrating and proliferating keratinocytes from days 3 to 7. In older 14-day-old wounds, ADAM-9 expression was restored. We have investigated the role of this protein in the healing process following excisional wounding. Animals deficient in ADAM-9 showed accelerated wound repair compared with control littermates. No alterations in neutrophil, leukocyte, and macrophage infiltration were observed. However, re-epithelialization was significantly faster in Adam-9 -/- than control wounds. Although no differences in proliferation were observed in vivo and in vitro, increased migration of keratinocytes was responsible for this effect. These results show the previously unreported role of ADAM-9 in wound repair by regulating keratinocyte migration through modulation of collagen XVII shedding.


Honing in on the Social Difficulties Associated With Sluggish Cognitive Tempo in Children: Withdrawal, Peer Ignoring, and Low Engagement.
Sluggish cognitive tempo (SCT) symptoms are associated with social difficulties in children, though findings are mixed and many studies have used global measures of social impairment. The present study tested the hypothesis that SCT would be uniquely associated with aspects of social functioning characterized by withdrawal and isolation, whereas attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms would be uniquely associated with aspects of social functioning characterized by inappropriate responding in social situations and active peer exclusion. Participants were 158 children (70% boys) between 7-12 years of age being evaluated for possible ADHD. Both parents and teachers completed measures of SCT, ADHD, ODD, and internalizing (anxiety/depression) symptoms. Parents also completed ratings of social engagement and self-control. Teachers also completed measures assessing asociality and exclusion, as well as peer ignoring and dislike. In regression analyses controlling for demographic characteristics and other psychopathology symptoms, parent-reported SCT symptoms were significantly associated with lower social engagement (e.g., starting conversations, joining activities). Teacher-reported SCT symptoms were significantly associated with greater asociality/withdrawal and ratings of more frequent ignoring by peers, as well as greater exclusion. ODD symptoms and ADHD hyperactive-impulsive symptoms were more consistently associated with other aspects of social behavior, including peer exclusion, being disliked by peers, and poorer self-control during social situations. Findings provide the clearest evidence to date that the social difficulties associated with SCT are primarily due to withdrawal, isolation, and low initiative in social situations. Social skills training interventions may be effective for children displaying elevated SCT symptomatology.


Relationship between serum testosterone levels and features of the metabolic syndrome defining criteria in patients with type 2 diabetes mellitus.
There are increasing reports on the association between the testosterone deficiency syndrome (TDS) and increased risk of development of the metabolic syndrome - a well recognized cardiovascular risk factor in men with diabetes mellitus. To determine the relationship between serum testosterone levels and components of the metabolic syndrome in Type 2 diabetes mellitus in Nigerian men. A total of 203 men with type 2 DM aged 30-86 years were evaluated for the testosterone deficiency syndrome (TDS). The diagnosis of the TDS or hypogonadism was made using a combination of clinical features of hypogonadism and subnormal levels of total testosterone. The presence of the metabolic syndrome was sought for in those with and without the TDS. The metabolic syndrome was diagnosed using the new criteria by the International Diabetes Federation and related bodies. The overall prevalence rates of the TDS and the metabolic syndrome in the study subjects were 36% and 44% respectively. The proportion of the subjects with the Metabolic Syndrome (METS) was comparable in subjects with and without the TDS. (47% vs 43%, p = 0.6). Using the Mann Whitney U test, the mean rank of the testosterone level in the subjects with the METS was lower than that of those without the METS but this difference was not statistically significant (67.2 vs 66, p =0.9). The frequency of occurrence of the metabolic syndrome in men with type 2DM is comparable in those with hypogonadism and those without hypogonadism. There is no correlation between serum testosterone levels and the metabolic syndrome defining parameters.


Aspect on vortex lines in Euler flow.
A class of Euler flows of an ideal incompressible liquid is considered. Helical flow structures are classified by Hopf index, Brouwer degree, and linking number in geometry. A mechanism of generation and annihilation of vortex line is given. The evolution equation of the vortex line has been given and its bifurcation behavior at the critical points is also discussed in detail. Three kinds of length scales are given: l proportional to (t- t*)1/2, l proportional to t- t*, and l=const.


Neurotology Workforce in the United States: Gender Diversity and Geographic Distribution.
The workforce of neurotology has changed with increasing numbers of accredited programs and diverse representation among trainees over the past several decades. This study aims to describe the characteristics, density, and geographic variation of the current neurotology workforce in the United States. Cross-sectional study. American Board of Otolaryngology-Head and Neck Surgery portal and online search. The study cohort included physicians certified in Neurotology by the American Board of Otolaryngology as of 2021 (n = 372). Physician characteristics including years of practice, gender, practice setting, and location were collected. Geographic variation analysis was performed by the state, county, and hospital referral region. Associations between the number of neurotologists per population and socioeconomic characteristics were assessed using multivariable regression analysis. Among 372 neurotologists, 65% practiced in academic settings and 13% were female. The percentage of female neurotologists increased from 0% among neurotologists with ≥30 years of practice to 23% among <10 years of practice. There were no differences in a practice setting by gender. The geographical analysis demonstrated that the average number of neurotologists was 1.1 per 1 million Americans. In a multivariable model, the density of neurotologists was significantly higher within counties with the highest quartiles of college education (β = .6 [95% confidence interval, CI: 0.3-0.8]) and income (β = .3 [95% CI: 0.1-0.6]). The number of board-certified neurotologists has gradually increased and there have been trends toward greater gender diversity. The geographical distribution of neurotology practice was concentrated in counties with higher socioeconomic status as expected given the referral-based nature of the subspecialty. There should be efforts to reach out to low socioeconomic communities to ensure equivalent access to neurotological care.


[Intratesticular varicocele: Progress in research].
Intratesticular varicocele (ITV) is a relatively rare condition. Currently, there is no domestic literature available on this topic. This paper presents an overview of the epidemiology, diagnosis, differential diagnosis, impact on male reproductive health, and treatment of ITV with a review of recent foreign literature, aiming to gain a deeper insight into this condition.


Transient metabolic improvement in obese mice treated with navitoclax or dasatinib/quercetin.
Senescent cells accumulate with obesity in the white adipose tissue of mice and humans. These senescent cells enhance the pro-inflammatory environment that, with time, contributes to the onset of glucose intolerance and type 2 diabetes. Glucose intolerance in mouse models of obesity has been successfully reversed by the elimination of senescent cells with the senolytic compounds navitoclax or the combination of dasatinib and quercetin (D/Q). In this work, we generated obese mice by high-fat diet feeding, and treated them with five consecutive cycles of navitoclax or D/Q during 16 weeks. We observed an efficient reduction in the white adipose tissue of the senescence markers senescence-associated β-galactosidase activity, Cdkn2a-p16 and Cdkn2a-p19 at the end of the 5 cycles. Mice treated with both navitoclax and D/Q showed an improvement of their insulin sensitivity and glucose tolerance during a short period of time (cycles 3 and 4), that disappeared at the fifth cycle. Also, these mice tended to increase the expression at their adipose tissue of the adipogenic genes Pparg and, Cebpa, as well as their plasma adiponectin levels. Together, our work shows that two different senolytic treatments, acting through independent pathways, are transiently effective in the treatment of obesity-induced metabolic disorders.


A Systematic Approach for the Determination of B-Group Vitamins in Multivitamin Dietary Supplements by High-Performance Liquid Chromatography with Diode-Array Detection and Mass Spectrometry.
This paper describes a practical approach using an LC diode-array detector (DAD) and MS for the quantitation of B-group vitamins (thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxine, biotin, folic acid, and cyanocobalamin) in multivitamin supplements. The purpose of this study was to optimize the extraction and chromatographic conditions without application of internal standards to determine B-group vitamins in multivitamins. Chromatographic separation on a C18 column was optimized on the basis of chromatographic behavior depending on pH variation of the mobile phase. The optimized methods showed good r values, with RSD values lower than 2.44 and 3.09% for most of the B-group vitamins (except cyanocobalamin) using LC-DAD and LC-MS, respectively. The methods were also proved to be reproducible, with RSD values of 0.96 and 2.48% being obtained with LC-DAD and LC-MS, respectively. In addition, the developed analytical methods for B-group vitamins were validated using certified reference materials and were applied to commercially available multivitamin tablets.