Familial aggregation of renal calcium stone disease.
The question of a familial predisposition towards stone formation in primary nephrolithiasis has not been explored completely. In a sample of 214 calcium stone patients, and 428 age and sex-matched controls we observed a higher frequency of stones among the first degree relatives of stone patients compared to the relatives of controls. A family history of renal stones was more common among the female (45 per cent) than among the male patients (31 per cent). There was no relationship between family history of renal stones, and abnormal calcium and oxalate excretion rates. A significant association between a family history and a higher urinary pH was observed among the female calcium stone patients. A genetic defect in urinary acidification with variable expressivity might be associated with a high frequency of stone formation. Moreover, uric acid excretion was higher in male stone patients with a family history of stones. Finally, the parents and siblings of the renal stone patients were affected more by calculi than were the corresponding relatives of their spouses.


The biochemical properties of Rosmarinus officinalis L. affected by irrigation water amount and quality.
Water deficiency, especially in the arid and semi-arid areas, necessitates the proper water use and recycling. The objective was to investigate the effects of deficit irrigation as well as treated wastewater on the biochemical properties of Rosmarinus officinalis L., grown in the arid area of Iranshahr, Iran. A split-split plot design on the basis of a complete randomized block design with three replicates was conducted in 2017. Irrigation water treatments of (I1 = 100% of field capacity, FC), 75% of FC (I2), and 50% of FC (I3) as main plots, reduced (S1), and partial irrigation (S2), as sub-plots, and well water (Q1), treated wastewater (Q2), and the combination of Q1 and Q2 (Q3, 50% + 50%), as sub-sub plots, were tested. Plant biochemical properties including proline (Pr), soluble sugars (SS), and essential oil volume (V) and yield (Y) as well as water use efficiency (WUE) were determined. The I2, treatment, compared with I1, increased Pr, SS, V, Y and WUE by 34.4, 31.9, 52.6, 34.3, and 48.1%, respectively. The S2 treatment also increased plant biochemical properties more than 45% related to S1, and Q2 significantly enhanced the measured parameters compared with Q1 and Q3. Treated wastewater improved the essential oil yield of the plant in water deficit conditions. Accordingly, under deficit water conditions, treatment I2S2, and in the case of unfavorable water sources and deficit water conditions, treatment I2Q2 are recommendable to alleviate water stress and improve the biochemical properties of Rosmarinus officinalis L. in the arid areas.


Effect of beet flour on films made from biological macromolecules: Native and modified plantain flour.
Biological macromolecules such as starches of different amylaceous sources have been used in the formulation of edible films. However, there are few studies aimed at evaluating edible and intelligent films with response to pH changes from natural pigments, this despite the importance of these materials. In this context, films from native and modified plantain flour, plasticized with glycerol, with or without the addition of beet flour were developed. The chemical and structural composition of the flours, and its incidence on thickness, water solubility, contact angle, and mechanical and microstructural properties were evaluated, thus as its response to pH changes of the developed films. The observations showed that the incorporation of beet flour allowed to obtain intelligent films front to pH changes alkaline. Likewise, the betalains that were found in beet flour interacted more efficiently with the phosphated plantain flour, limiting well its immediate response to pH changes. In the same way, proteins and sugars of beet flour allowed to obtain more flexible films, due to the hydrogen bond interactions between these constituents and the plantain flours. This latter could justify the decrease of contact angle, and the increase on thickness and solubility of these films.


A short wholly inside-out reversed vascular graft facilitating difficult aortic anastomosis.
Aortic arch operations are sometimes very difficult because of their deep position, exposure limitation, and extensive involvement of the degenerative disease. We present a new technique derived from a modified elephant trunk technique to simplify some laborious situations.


Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials.
This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity. Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another. Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research.


Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for the treatment of patients with adenomyosis and prior abdominal surgical scars: A retrospective study.
The aim of this paper was to retrospectively compare the therapeutic efficacy and adverse effects of ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment for adenomyotic patients with or without prior abdominal surgical scars. From January 2011 to March 2014, 534 patients with adenomyosis were referred for HIFU treatment. Among them, 118 patients had prior abdominal surgical scars, 416 patients did not have prior abdominal surgical scars. Contrast-enhanced MRI was used to evaluate the treatment outcomes. All the adverse effects were recorded. All patients completed USgHIFU treatment. A fractional ablation of 74.8 ± 27.8% was achieved in the group of patients without abdominal scars; the fractional ablation was 75.6 ± 22.3% in the group of patients with prior abdominal surgical scars. No significant difference in fractional ablation between the two groups was observed (p > 0.05). The rate of skin burn in the group of patients with prior abdominal surgical scars was significantly higher than that in the group without abdominal scars (2.5% vs. 0.2%, p < 0.05), but it is still acceptable. The prior abdominal surgical scars have no significant influence on the effectiveness of HIFU treatment for adenomyosis. The risk of skin burn is higher in patients with abdominal scars than without, but the incidence rate is still acceptable.


Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study.
The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.


Down-regulation of microRNA-26a and up-regulation of microRNA-27a contributes to aggressive progression of human osteosarcoma.
Osteosarcoma is the most common primary bone malignancy with high local aggressiveness and rapid metastasizing potential, resulting in poor survival. Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression of miR-26a and miR-27a in osteosarcoma need further investigation in clinical samples. In our study, we evaluate the expression of these miRNAs in osteosarcoma tissues and compared with paired adjacent non-tumor bone tissues using RT-qPCR. Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues. Real-time PCR was applied to quantify the expression level of miR-26a and miR-27a. Moreover, the correlation of these markers with clinicopathological characteristics was also evaluated in osteosarcoma patients. A cox proportional hazards model was performed to assess multivariate analyses of prognostic values. Our result suggested that miR-26aexpression level in osteosarcoma bone tissue was significantly lower than that in the paired noncancerous bone tissues. MiR-27a expression was higher in osteosarcoma bone tissue in comparison with paired noncancerous bone tissues. The results indicated that low expression level of miR-26a and high expression of miR-27a were associated with high TNM stage (P = 0.001; P = 0.012), tumor grade (P = 0.007; P = 0.016), and distant metastasis (P = 0.004; P = 0.001). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-26a and high expression of miR-27a had shorter overall survival (log-rank test: P < 0.001). Multivariate Cox proportional hazards model analysis showed that low expression of miR-26a and high expression of miR-27a (P = 0.021; P = 0.011), high TNM stage (P = 0.001; P = 0.003), tumor grade (P = 0.005; P = 0.01), and distant metastasis.(P = 0.002; P = 0.005) were independent prognostic factors for overall survival patients with osteosarcoma cancer. In conclusion, our findings suggested that expression level of miR-26a and miR-27a contributes to aggressive progression of this malignancy. Therefore, may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.


EGF and NRG induce phosphorylation of HER3/ERBB3 by EGFR using distinct oligomeric mechanisms.
Heteromeric interactions between the catalytically impaired human epidermal growth factor receptor (HER3/ERBB3) and its catalytically active homologs EGFR and HER2 are essential for their signaling. Different ligands can activate these receptor pairs but lead to divergent signaling outcomes through mechanisms that remain largely unknown. We used stochastic optical reconstruction microscopy (STORM) with pair-correlation analysis to show that EGF and neuregulin (NRG) can induce different extents of HER3 clustering that are dependent on the nature of the coexpressed HER receptor. We found that the presence of these clusters correlated with distinct patterns and mechanisms of receptor phosphorylation. NRG induction of HER3 phosphorylation depended on the formation of the asymmetric kinase dimer with EGFR in the absence of detectable higher-order oligomers. Upon EGF stimulation, HER3 paralleled previously observed EGFR behavior and formed large clusters within which HER3 was phosphorylated via a noncanonical mechanism. HER3 phosphorylation by HER2 in the presence of NRG proceeded through still another mechanism and involved the formation of clusters within which receptor phosphorylation depended on asymmetric kinase dimerization. Our results demonstrate that the higher-order organization of HER receptors is an essential feature of their ligand-induced behavior and plays an essential role in lateral cross-activation of the receptors. We also show that HER receptor ligands exert unique effects on signaling by modulating this behavior.


Thunniform swimming: muscle dynamics and mechanical power production of aerobic fibres in yellowfin tuna (Thunnus albacares).
We studied the mechanical properties of deep red aerobic muscle of yellowfin tuna (Thunnus albacares), using both in vivo and in vitro methods. In fish swimming in a water tunnel at 1-3 L s(-1) (where L is fork length), muscle length changes were recorded by sonomicrometry, and activation timing was quantified by electromyography. In some fish a tendon buckle was also implanted on the caudal tendon to measure instantaneous muscle forces transmitted to the tail. Between measurement sites at 0.45 to 0.65 L, the wave of muscle shortening progressed along the body at a relatively high velocity of 1.7 L per tail beat period, and a significant phase shift (31+/-4 degrees ) occurred between muscle shortening and local midline curvature, both suggesting red muscle power is directed posteriorly, rather than causing local body bending, which is a hallmark of thunniform swimming. Muscle activation at 0.53 L was initiated at about 50 degrees of the tail beat period and ceased at about 160 degrees , where 90 degrees is peak muscle length and 180 degrees is minimum length. Strain amplitude in the deep red fibres at 0.5 L was +/-5.4%, double that predicted from midline curvature analysis. Work and power production were measured in isolated bundles of red fibres from 0.5 L by the work loop technique. Power was maximal at 3-4 Hz and fell to less than 50% of maximum after 6 Hz. Based on the timing of activation, muscle strain, tail beat frequencies and forces in the caudal tendon while swimming, we conclude that yellowfin tuna, like skipjack, use their red muscles under conditions that produce near-maximal power output while swimming. Interestingly, the red muscles of yellowfin tuna are slower than those of skipjack, which corresponds with the slower tail beat frequencies and cruising speeds in yellowfin.


Disynaptic effect of hilar cells on pattern separation in a spiking neural network of hippocampal dentate gyrus.
We study the disynaptic effect of the hilar cells on pattern separation in a spiking neural network of the hippocampal dentate gyrus (DG). The principal granule cells (GCs) in the DG perform pattern separation, transforming similar input patterns into less-similar output patterns. In our DG network, the hilus consists of excitatory mossy cells (MCs) and inhibitory HIPP (hilar perforant path-associated) cells. Here, we consider the disynaptic effects of the MCs and the HIPP cells on the GCs, mediated by the inhibitory basket cells (BCs) in the granular layer; MC → BC → GC and HIPP → BC → GC. The MCs provide disynaptic inhibitory input (mediated by the intermediate BCs) to the GCs, which decreases the firing activity of the GCs. On the other hand, the HIPP cells disinhibit the intermediate BCs, which leads to increasing the firing activity of the GCs. In this way, the disynaptic effects of the MCs and the HIPP cells are opposite. We investigate change in the pattern separation efficacy by varying the synaptic strength K ( BC , X ) [from the pre-synaptic X (= MC or HIPP) to the post-synaptic BC]. Thus, sparsity for the firing activity of the GCs is found to improve the efficacy of pattern separation, and hence the disynaptic effects of the MCs and the HIPP cells on the pattern separation become opposite ones. In the combined case when simultaneously changing both K ( BC , MC ) and K ( BC , HIPP ) , as a result of balance between the two competing disynaptic effects of the MCs and the HIPP cells, the efficacy of pattern separation is found to become the highest at their original default values where the activation degree of the GCs is the lowest. We also note that, while the GCs perform pattern separation, sparsely synchronized rhythm is found to appear in the population of the GCs. Hence, we examine quantitative association between population and individual firing behaviors in the sparsely synchronized rhythm and pattern separation. They are found to be strongly correlated. Consequently, the better the population and individual firing behaviors in the sparsely synchronized rhythm are, the more pattern separation efficacy becomes enhanced.


Telencephalic connections in lizards. II. Projections to anterior dorsal ventricular ridge.
Three distinct cytoarchitectonic regions were identified within the anterior dorsal ventricular ridge (ADVR) of two species of lizards, Gekko gecko and Iguana iguana. These regions have been named according to their general topographical positions: medial area, caudolateral area, and rostrolateral area. Injections of horseradish peroxidase throughout the ADVR demonstrated that each of the three areas of the ADVR receives projections from specific thalamic nuclei which are associated with specific sensory modalities. The medial area receives an auditory thalamic projection from nucleus medialis. The caudolateral area receives thalamic projections from nucleus medialis posterior and nucleus posterocentralis. The latter two nuclei were shown to receive projections from the spinal cord and, therefore, are presumed to be associated with body somatosensory information. The rostrolateral area receives a thalamic projection from nucleus rotundus, which receives visual information. In addition, the mesencephalic tegmentum and the thalamic nucleus dorsomedialis project to the entire ADVR. The latter projection is similar to the diffuse cortical projections of the intralaminar thalamic nuclei in mammals. These findings support previous suggestions that the ADVR is comparable to sensory regions of the mammalian neocortex.


Discrepancies between pharmacokinetic studies of amitriptyline.
In this article, studies on the disposition of amitriptyline after administration of a single dose, as well as following long term administration are reviewed. While long term studies showed bias towards a higher mean apparent oral clearance, studies in normal subjects nevertheless indicated a higher apparent oral clearance than that calculated from steady-state concentrations in depressed patients. Methodological issues could account for some of the discrepancies in mean values of the pharmacokinetic parameters of amitriptyline. Broad individual variability in the elimination rate of amitriptyline has been confirmed but could not be attributed to the clinical characteristics of the subjects.


Profiling the Somatic Mutational Landscape of Breast Tumors from Hispanic/Latina Women Reveals Conserved and Unique Characteristics.
Somatic mutational profiling is increasingly being used to identify potential targets for breast cancer. However, limited tumor-sequencing data from Hispanic/Latinas (H/L) are available to guide treatment. To address this gap, we performed whole-exome sequencing (WES) and RNA sequencing on 146 tumors and WES of matched germline DNA from 140 H/L women in California. Tumor intrinsic subtype, somatic mutations, copy-number alterations, and expression profiles of the tumors were characterized and compared with data from tumors of non-Hispanic White (White) women in The Cancer Genome Atlas (TCGA). Eight genes were significantly mutated in the H/L tumors including PIK3CA, TP53, GATA3, MAP3K1, CDH1, CBFB, PTEN, and RUNX1; the prevalence of mutations in these genes was similar to that observed in White women in TCGA. Four previously reported Catalogue of Somatic Mutations in Cancer (COSMIC) mutation signatures (1, 2, 3, 13) were found in the H/L dataset, along with signature 16 that has not been previously reported in other breast cancer datasets. Recurrent amplifications were observed in breast cancer drivers including MYC, FGFR1, CCND1, and ERBB2, as well as a recurrent amplification in 17q11.2 associated with high KIAA0100 gene expression that has been implicated in breast cancer aggressiveness. In conclusion, this study identified a higher prevalence of COSMIC signature 16 and a recurrent copy-number amplification affecting expression of KIAA0100 in breast tumors from H/L compared with White women. These results highlight the necessity of studying underrepresented populations. Comprehensive characterization of genomic and transcriptomic alterations in breast tumors from Hispanic/Latina patients reveals distinct genetic alterations and signatures, demonstrating the importance of inclusive studies to ensure equitable care for patients. See related commentary by Schmit et al., p. 2443.


A cross-sectional study of cryptorchidism in children: testicular volume and hormonal function at 18 years of age.
To evaluate the relationship between unilateral or bilateral criptorchidism, patient age, primary location of the gonad and modality of treatment with testicular volume and hormonal status at 18 years in patients diagnosed and treated for cryptorchidism during childhood. Testicular volume, LH, FSH, and testosterone were evaluated in 143 young men at 18 years treated in childhood for unilateral (n=103) or bilateral (n=40) cryptorchidism. Unilateral cryptorchidism: Location of testis was prescrotal in 36 patients, inguinal in 52 and non-palpable in 15. The mean volume was 9.7 mL compared to 16.2 L. for the spontaneously descended testicle in unilateral cryptorchidism. However, 22 patients who received HCG had a significantly bigger testis (11.8 mL.) than those treated with primary surgery (9.2 mL). The results showed a significant positive correlation between testicular volume and patient age at treatment. Bilateral cryptorchidism: Location of testis was prescrotal in 34 cases, inguinal in 40 and 6 patients with non-palpable testicles. Mean volume at 18 years was 12.9 mL, greater than unilateral cryptorchid testis (9.7 mL) but smaller than healthy contralateral in unilateral cases (16.2 mL). There were significant differences in the testicular growth for bilateral patients with testicular descent after being treated with HCG (14.4 mL) in respect with those untreated (11.1 mL) or those who underwent primary surgery (11.4 mL). There was a significant positive correlation between the testicular volume and palpable (12.4 mL) or non-palpable testis (10.4 mL). There was a correlation between unilateral or bilateral cryptorchidism and levels of FSH. Testicular volume and hormonal function at 18 years for patients diagnosed and treated for cryptorchidism during childhood are strongly influenced by whether the undescended testis was unilateral or bilateral. Location of the testes at diagnosis or age of initial treatment exerts no definite effect on testicular volume improvement r hormonal levels at 18 years of age.


Test-retest reliabilities of State-Trait Anxiety Inventory in a stressful social analogue situation.
The State-Trait Anxiety Inventory asserts that state anxiety varies with situational stress and that trait anxiety is related to relatively stable individual differences in proneness to anxiety. This study investigated test-retest reliabilities related to an anxiety-provoking social analogue involving a female confederate. The results, obtained from the perspective of a nonacademic anxiety situation, supported the state and trait concepts.


Interactions between sucrose, pain and isolation distress.
Two experiments were conducted that establish an opioid-based, functional-relationship between the taste of sucrose, pain threshold and distress vocalization in isolated 10-day-old albino rats. In the first experiment intraoral infusion of sucrose virtually doubled heat-withdrawal latencies. This elevation was naltrexone (0.5 mg/kg b.wt.) reversible. In the second experiment sucrose infusions caused a rapid and sustained diminution of distress vocalizations in rats totally isolated from dam and siblings. These are the first demonstrations of a causal relationship between a positive affective system and ones mediating pain and stress.


Atomic force microscopy measurements probing the mechanical properties of single collagen fibrils under the influence of UV light in situ.
Collagen plays a decisive role as a functional substrate in tissue engineering. In particular, the rigidity of the collagen influences the behaviour of the attached cells. Thus, modification and controlled adjustment of collagen's characteristics are essential. To this end, controlled exposure to ultraviolet (UV) light is a promising process because it can be temporally and spatially well defined. In this study, we investigated the effect of UV exposure on surface supported single collagen fibrils in situ. This procedure allowed for a direct comparison between the untreated and modified states of type I collagen. Atomic force microscopy was used to map the mechanical properties. Exposure to UV light was used to influence the mechanical properties of the fibrils in varied liquid environments (deionized water and phosphate-buffered saline (PBS)). The results led to the assumption that combined UV/thermal treatment in deionized water continuously lowers the elastic modulus. In contrast, experiments performed in PBS-based solutions in combination with UV-B and UV-C light or thermal treatment up to 45 °C suggested an increase in the modulus within the first 30-40 min that subsequently decreased again. Thus, the wavelength, exposure, temperature, and chemical environment are relevant parameters that need to be controlled when modifying collagen using UV light.


Clinical correlates of phosphene perception in migraine without aura: an Asian study.
Although controversy exists with regard to the presence of hypoexcitability versus hyperexcitability of the visual cortex in migraine patients, there remain a group who do not perceive phosphenes (P-). However, its clinical implications have not been systematically addressed. In this study, we hypothesize that P- patients classified as migraine without aura (MO) have distinct clinical features. Twenty-nine Asian MO patients (7 men; mean age: 44; median: 45; range: 25 to 65) were consecutively entered into the study. Visual cortex transcranial magnetic stimulation (TMS) was performed in the migraine interictum. Of the 19 patients, 19 (66%) were able to perceive phosphenes (P+), while 10 (34%) were not able to after repeated TMS (P-). P- patients had significantly higher headache frequency (p=0.008) and pain score (p=0.002) compared with P+ patients. In addition, there was significant positive correlation of phosphene threshold with pain score (r=0.52, p=0.02) in P+ patients. There was no significant difference between P+ and P- patients in terms of age (t-test, p=0.6). Our study is inkeeping with the hypothesis that interictal visual cortex excitability is reduced in relation to the severity of migraine in Asian MO patients, and lack of phosphene perception may be related to significantly elevated thresholds beyond the output of TMS stimulators.


The Circadian Clock Improves Fitness in the Fruit Fly, Drosophila melanogaster.
It is assumed that a properly timed circadian clock enhances fitness, but only few studies have truly demonstrated this in animals. We raised each of the three classical Drosophila period mutants for >50 generations in the laboratory in competition with wildtype flies. The populations were either kept under a conventional 24-h day or under cycles that matched the mutant's natural cycle, i.e., a 19-h day in the case of per s mutants and a 29-h day for per l mutants. The arrhythmic per 0 mutants were grown together with wildtype flies under constant light that renders wildtype flies similar arrhythmic as the mutants. In addition, the mutants had to compete with wildtype flies for two summers in two consecutive years under outdoor conditions. We found that wildtype flies quickly outcompeted the mutant flies under the 24-h laboratory day and under outdoor conditions, but per l mutants persisted and even outnumbered the wildtype flies under the 29-h day in the laboratory. In contrast, per s and per 0 mutants did not win against wildtype flies under the 19-h day and constant light, respectively. Our results demonstrate that wildtype flies have a clear fitness advantage in terms of fertility and offspring survival over the period mutants and - as revealed for per l mutants - this advantage appears maximal when the endogenous period resonates with the period of the environment. However, the experiments indicate that per l and per s persist at low frequencies in the population even under the 24-h day. This may be a consequence of a certain mating preference of wildtype and heterozygous females for mutant males and time differences in activity patterns between wildtype and mutants.


[The influence of nasal continual positive airway pressure on some vasoactive substances in patients with obstructive sleep apnea syndrome].
To investigate the influence of nasal continual positive airway pressure (nCPAP) on the plasma levels of thromboxane B(2) (TXB(2)), renin, angiotensin II (AT-II), endothelin 1 (ET-1), cyclic AMP (cAMP) and cyclic GMP (cGMP) and evaluate their clinical significance. 20 patients with OSAS without cardiovascular complications and 20 nromal controls were enrolled in the study, who were monitored with PSG, and then treated with nCPAP during the second night. All the plasma parameters were measured after PSG monitoring and nCPAP management with radio-immunoassay. Before nCPAP, plasma levels of TXB(2), renin, and AT-II were higher in patients with OSAS than those in control (P < 0.05); Meanwhile, the plasma levels of ET-1, cAMP, and cAMP/cGMP were significantly higher in patients group than those in control (P < 0.01). Patients with severe OSAS may have disturbances in neuro-regulation and changes in plasma level of TXB(2), renin, AT-II and ET-1, which indicates that the vasoactive substance might be related to the hypoxemia and disturbance in neuro-regulations, and might play an important role in the development of hypertension and other cardiovascular disorders. nCPAP therapy can correct the abnormalities of some vasoactive substances.


Safety and diagnostic accuracy of dipyridamole-thallium imaging in the elderly.
The noninvasive diagnosis of coronary artery disease in the elderly can occasionally be difficult. Intravenous dipyridamole-thallium imaging is a potentially useful diagnostic test to determine presence and severity of coronary disease; however, the safety of the procedure has not been determined in an older population. The side effect profile and frequency of severe ischemic responses after 0.56 mg/kg of intravenous dipyridamole were compared in 101 patients greater than or equal to 70 years old and 236 patients less than 70 years old. There were no side effects in 64% and 62% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). Among the 337 patients tested, there were no complications of myocardial infarction or death. The most common cardiac side effect was chest pain, which occurred in 21 (21%) of the 101 patients aged greater than or equal to 70 years and in 64 (27%) of the 236 patients less than 70 years (p = NS). Aminophylline was required to reverse cardiac or noncardiac side effects in 15 (15%) and 36 (15%) of the patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). A severe ischemic response occurred in 2% and 2.5% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). The sensitivity of intravenous dipyridamole-thallium imaging for obstructive coronary artery disease was 86% (25 of 29) and 83% (68 of 82) in older and younger patients, respectively (p = NS); the specificity was 75% (6 of 8) and 70% (16 of 23), respectively (p = NS). Thus, intravenous dipyridamole-thallium imaging is a safe noninvasive method for assessment of older patients with obstructive coronary disease; its side effect profile and diagnostic accuracy are similar to those seen in younger patients. The technique is associated with severe ischemic responses in only a small minority of patients.


Comparative assessment of three drug eluting stents with different platforms but with the same biodegradable polymer and the drug based on quantitative coronary angiography and optical coherence tomography at 12-month follow-up.
The aim of this study was to compare neointima proliferation in three drug-eluting stents (DES) produced by the same company (Balton, Poland) which are covered with a biodegradable polymer and elute sirolimus (concentration: 1.0 and 1.2 µg/mm2), but have different stent platforms and strut thickness: stainless steel Prolim® (115 µm) and BiOSS LIM® (120 µm) and cobalt-chromium Alex® (70 µm). We analyzed data of patients with quantitative coronary angiography (QCA) and optical coherence tomography (OCT) at 12 months from BiOSS LIM Registry, Prolim Registry and Alex OCT clinical trial. There were 56 patients enrolled, in whom 29 Prolim® stents were deployed, in 11-BiOSS LIM® and in 16-Alex stents. The late lumen loss was the smallest in Prolim® subgroup (0.26 ± 0.17 mm) and did not differ from Alex® subgroup (0.28 ± 0.47 mm). This parameter was significantly bigger in BiOSS® subgroup (0.38 ± 0.19 mm; p < 0.05). In OCT analysis there was no statistically significant difference between Prolim® and Alex® subgroups in terms of mean neointima burden (24.6 ± 8.6 vs. 19.27 ± 8.11%) and neointima volume (28.16 ± 15.10 vs. 24.51 ± 17.64 mm3). In BiOSS® group mean neointima burden (30.9 ± 6.2%) and mean neointima volume (44.9 ± 4.9 mm3) were significantly larger. The morphological analysis revealed that in most cases in all groups the neointima was homogenous with plaque presence only around stent struts. In the QCA and OCT analysis regular DES (Prolim® and Alex®) obtained similar results, whereas more pronounced response from the vessel wall was found in the BiOSS® subgroup.


Cadherins: actin with the cytoskeleton to form synapses.
Classic cadherins are calcium-dependent homophilic cell adhesion molecules that are enriched at synapses and thought to function in target recognition and adhesion at synaptic junctions. This brief review highlights evidence that cadherins and their associated catenins play a role in directing the development of pre- and postsynaptic specializations. In particular, the question of whether cadherin regulation of the actin cytoskeleton at discrete contact sites translates into the assembly of synaptic compartments will be explored.


A comparative analysis of selected European guidelines and recommendations for biobanks with special regard to the research / non-research distinction.
Classifying an activity as research has considerable normative consequences: On the one side research activities are especially protected ("freedom of research"), on the other side stricter ethical rules legal regulations may apply to such activities, e.g. compulsory review by ethics committees. It is therefore important to find criteria to delimit research from non-research activities. The aim of the present study is to analyse some European guidelines and recommendations for biobanks and to see whether these documents provide comments that help to elucidate the research/non-research distinction.


Four-wave mixing assisted stability enhancement: theory, experiment, and application.
Stability enhancement on the basis of four-wave mixing (FWM) is proposed and proved for the first time to our knowledge. This technique is applied to dual-wavelength erbium-doped fiber lasers. Significant uniformity and stability of the novel fiber lasers are demonstrated experimentally.


Improving elementary students' knowledge and behavior to prevent traumatic injury: the impact of a behavioral skills training model delivered by aspirational role models.
Trauma is the leading cause of childhood morbidity and mortality annually in the USA, accounting for 11% of deaths, most commonly due to car crashes, suffocation, drowning, and falls. Prevention is paramount for reducing the incidence of these injuries. As an adult level 1 and pediatric level 2 trauma center, there is a commitment to injury prevention through outreach and education. The Safety Ambassadors Program (SAP) was developed as part of this aim. Safety Ambassadors (SA) are high schoolers who teach elementary school students about safety/injury prevention. The curriculum addresses prevalent areas of injury risk: car/pedestrian safety, wheeled sports/helmets, and fall prevention. The study group hypothesized that participation in SAP leads to improved safety knowledge and behaviors and ultimately reduces childhood preventable injuries. Educational material was delivered by high school students (ages 16-18 years old). First and second-grade participants (ages 6-8 years old) completed pre- and post-course exams to assess knowledge (12 questions) and behavior (4 questions). Results were retrospectively reviewed, and pre/post training mean scores were calculated. Scores were calculated based on number of correct answers on pre/post exam. Comparisons were made using the Student t-test. All tests were 2-tailed with significance set at 0.05. Pre- and post-training results were assessed for 2016-2019. Twenty-eight high schools and 37 elementary schools were enrolled in the program with 8832 student participants in SAP. First graders demonstrated significant improvement in safety knowledge (pre 9 (95% CI 8.9-9.2) vs post 9.8 (95%CI 9.6-9.9), (p < 0.01)) and behavior modification (pre 3.2 (95%CI 3.1-3.2) vs post 3.6 (95% CI 3.5-3.6), (p < 0.01)). Similar findings were seen in 2nd graders: safety knowledge (pre 9.6 (95% CI 9.4-9.9) vs post 10.1 (95% CI 9.9-10.2), (p < 0.01)) and behavior (pre 3.3 (95% CI 3.1-3.4) vs post 3.5 (95%CI 3.4-3.6), (p < 0.01)). Conclusion: SAP is a novel evidence-based educational program delivered to elementary school students by aspirational role models. This model is impactful, relatable, and engaging when provided by participants' older peer mentors. On a local level, it has demonstrated improved safety knowledge and behavior in elementary school students. As trauma is the leading cause of pediatric death and disability, enhanced education may lead to life-saving injury prevention in this vulnerable population. What is Known: • Preventable trauma is the leading cause of pediatric death in the USA and education has contributed to improvements in both safety knowledge and behavior. • The ideal delivery method for injury prevention education in children continues to be under investigation. What is New: • Our data suggest that a peer-based injury prevention model is both an effective education delivery method and easily instituted within existing school systems. • This study supports implementation of peer-based injury prevention programs to improve safety knowledge and practices. • With more widespread institution and research, we hope to ultimately reduce preventable childhood injury.


The effects of the electromagnetic fields on the biochemical components, enzymatic and non-enzymatic antioxidant systems of tea Camellia sinensis L.
The electromagnetic fields (EMFs) by wide range of the frequency spectrum, have capability to cause crucial alternation and deleterious effects in biological systems. The aim of the present study is to assay the biochemical components, enzymatic and non-enzymatic antioxidant systems of the electromagnetic fields treated samples of tea which is the most ancient non-alcoholic drink, containing different types of flavonols. Rutin, Quercetin, Myricetin, and Kaempferol as flavonoid components markers are also to be analyzed using high-performance liquid chromatography. The results show that The EMF's treatments brought about distinct alternations in biochemical components of tea, so that regardless of the intensity of the EMF's, less duration of exposure (30 min) caused more content of those mentioned flavonoid components (except Myricetin) than that of 60 min of exposure. A 30 min of 4 miliTesla (mT) exposure of the EMF's, resulted in the highest amount of Rutin, Quercetin, Myricetin, and Kaempferol. It is concluded that less duration of the EMF's treatments induces more production and also accumulation of enzymatic and non-enzymatic antioxidant components. In higher intensity of the EMF's (more than 4 mT), the concentrations of the mentioned biochemical components decreased.


Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced/metastatic melanoma who have failed prior anti-PD-1 therapy.
Modulating the DNA damage response and repair (DDR) pathways is a promising strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related protein, which is crucial for DDR. This phase II trial evaluated ceralasertib plus durvalumab for the treatment of patients with metastatic melanoma who had failed anti-programmed cell death protein 1 therapy. Among the 30 patients, we observed an overall response rate of 31.0% and a disease control rate of 63.3%. Responses were evident across patients with acral, mucosal, and cutaneous melanoma. The median duration of response was 8.8 months (range, 3.8-11.7 months). The median progression-free survival was 7.1 months (95% confidence interval, 3.6-10.6 months), and the median overall survival was 14.2 months (95% confidence interval, 9.3-19.1 months). Common adverse events were largely hematologic and manageable with dose interruptions and reductions. Exploratory biomarker analysis suggested that tumors with an immune-enriched microenvironment or alterations in the DDR pathway were more likely to respond to the study treatment. We conclude that ceralasertib in combination with durvalumab has promising antitumor activity among patients with metastatic melanoma who have failed anti-programmed cell death protein 1 therapy, and constitute a population with unmet needs.


Characterization of apyrase activity from the salivary glands of the cat flea Ctenocephalides felis.
Apyrase activity (ATP diphosphohydrolase, EC 188.8.131.52) was detected in salivary glands of the cat flea Ctenocephalides felis. Whole extracts of salivary glands contain approximately 21 ng of protein, 145 U/mg ADP'ase and 158 U/mg ATP'ase activity; AMP is not hydrolysed by salivary gland extracts. DEAE-Sepharose CL-6B anion exchange chromatography, and Cibacron Blue affinity chromatography each give a single coincident peak of ADP/ATP'ase activity. Biogel P-100 gel filtration of salivary gland homogenates made in buffer containing Triton and protease inhibitors, separated enzymatic activity into 57 kD and 44 kD peaks of ADP/ATP'ase activity. Partially purified ADP/ATP'ases are dependent on divalent cations and activation increases between 0.125 mM and 5.0 mM calcium. At 5 mM, magnesium is almost equally effective as calcium in activating ADP/ATP'ase but manganese and zinc are less so, and EDTA abolishes activity. ADP/ATP'ases have a pH optima of 7-9. The Km for ADP hydrolysis by whole extracts and partially purified enzyme is approximately 66 microM ADP. The co-purification of ADP'ase and ATP'ase activity by three physiochemical techniques and parallelism between ADP and ATP hydrolysis under varying conditions of pH and activating cation indicates enzymatic activity is attributable to true apyrase(s).


Antioxidant activity of polyphenolic extracts of Ichnocarpus frutescens.
In the present study antioxidant activities by (1,1-diphenyl-2-picrylhydrazyl radical (DPPH), hydrogen peroxide, hydroxyl radical inhibition, hemolysis by hydrogen peroxide assay, reducing power and total antioxidant activities of polyphenolic extract of Ichnocarpus frutescens leaves were investigated. The flavonoids and total polyphenolic contents of the extract were also determined using standard methods. Phytochemical analyses revealed the presence of flavonoids, polyphenols, anthocyanins and simple phenolic acids. The results of antioxidant activities of polyphenol extract obtained by different in vitro methods were varied depending on the method used. Nevertheless, polyphenol extract showed significant inhibitory activities in all in vitro reactive oxygen species scavenging, might be attributed due to the high level of polyphenolic compound. Also, these various antioxidant activities were compared to α-tocopherol and l-ascorbic acid as reference antioxidant compounds. These findings provide evidence that the polyphenolic extract of I. frutescens is a natural source of antioxidant against oxidative damage.


Beyond LDL-C lowering: distinct molecular sphingolipids are good indicators of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency.
Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been proposed to be a potential new therapeutic target for treatment of hypercholesterolaemia. However, little is known about the effects of PCSK9 inhibition on the lipidome. We performed molecular lipidomic analyses of plasma samples obtained from PCSK9-deficient mice, and serum of human carriers of a loss-of-function variant in the PCSK9 gene (R46L). In both mouse and man, PCSK9 deficiency caused a decrease in several cholesteryl esters (CE) and short fatty acid chain containing sphingolipid species such as CE 16:0, glucosyl/galactosylceramide (Glc/GalCer) d18:1/16:0, and lactosylceramide (LacCer) d18:1/16:0. In mice, the changes in lipid concentrations were most prominent when animals were given regular chow diet. In man, a number of molecular lipid species was shown to decrease significantly even when LDL-cholesterol was non-significantly reduced by 10% only. Western diet attenuated the lipid lowering potency of PCSK9 deficiency in mice. Plasma molecular lipid species may be utilized for characterizing novel compounds inhibiting PCSK9 and as sensitive efficacy markers of the PCSK9 inhibition.


[Cost-effectiveness--limits between optimization and rationing].
Although rationing is an important feature in the German health care system, this topic is not discussed in an explicit and structured way. Currently, most rationing decisions are not based on systematic data on costs and outcomes of diseases and medical interventions. A major task of future research will be to provide health policy makers with data on direct costs, indirect costs, effectiveness, and utility of medical interventions and to integrate these data into decision analysis models. Interdisciplinary work-groups should be set up, combining clinical and economic knowledge. On the other hand, official grants are needed to perform unbiased research in this field covering the various areas of medical care.


The ATPase inhibitor protein in oxidative phosphorylation. The rate-limiting factor to phosphorylation in submitochondrial particles.
1. Purified luciferase and luciferin were used to study the time course of phosphorylation in submitochondrial particles. The light emitted was detected by a single-photon counter, using a multichannel analyser, and the results were analysed by an 'on-line' digital computer. 2. Using NADH as substrate, phosphorylation showed, in general, four phases. These were (i) a period of increasing rate ('lag'); (ii) a period of constant (positive) rate; (iii) a period of zero net rate (plateau), when the phosphorylation potential was maintained at its equilibrium value, and (iv) a period of negative rate (atp hydrolysis) after all the oxygen has been consumed. 3. The lag phase, several seconds in length, was a function of the inhibitor protein content of the particles. It was decreased in particles treated to remove the inhibitor protein, either by prior energisation of the particles with NADH, or by addition of aurovertin, which competes with the inhibitor protein for the ATPase. It was concluded that the ATPase inhibitor inhibits both ATP synthesis and hydrolysis by the ATPase. 4. The rate constant for the release of the inhibitor protein from the energised membrane was determined from the time course of ATP production during the lag phase. The activation energy of this process was measured from the temperature dependence of the lag, and was shown to be 13.3 kcal/mol, lower than the activation energy of ATP synthesis or NADH oxidation. 5. The rate constant for inhibitor release was dependent on 'energisation' of the membrane, being lower in the presence of uncouplers. However, it was possible to decrease the rate constant considerably with agents that collapsed the membrane potential without uncoupling the membrane. It was concluded that the inhibitor protein responded to the membrane potential component of the energisation. 6. A kinetic model for energy-dependent dissociation of the ATPase-inhibitor complex is proposed.


Evidence for calcium regulation of spinal cord motoneuron death in the chick embryo in vivo.
We have studied in living chick embryos the effects of an extracellular calcium load on the induction of apoptosis in spinal cord motoneurons. The action of a calcium ionophore, A23187, that does not raise extracellular calcium was also evaluated in order to explore the role of endogenous calcium in determining developmentally-regulated cell death of motoneurons. The application of a single dose of 50 microliters of 1.8 M CaCl2 onto the chorioallantoic membrane of E7 chick embryos produce a transient elevation of intraembryonic calcium concentration that was followed by a transitory rise in the number of apoptotic cells in the lateral motor column. Administration of 250 microM of the ionophore A23187 (100 microliters), also results in an increase in apoptosis of motoneurons in the lateral motor column on E6 and E7 but this effect is progressively lost following treatment at more advanced stages of development. Neither of these effects can be explained by unspecific calcium cytotoxicity since they can be inhibited by prior administration of the protein synthesis inhibitor cycloheximide or the neuromuscular blocking agent (+)-tubocurarine. After calcium loading, degenerating cells display similar ultrastructural characteristics as during physiologically occurring motoneuron death and exhibit histochemically detectable DNA fragmentation. Chronic administration of CaCl2 or A23187 does not reduce the total number of surviving motoneurons at the end of the normal period of naturally occurring motoneuron death (E10). It is suggested that calcium loading stimulates and accelerates the physiological degeneration of a restricted subpopulation of motoneurons which will undergo the process of natural cell death.


Rheumatic Mitral Valve Stenosis: Diagnosis and Treatment Options.
This review provides an update on rheumatic mitral stenosis. Acute rheumatic fever (RF), the sequela of group A β-hemolytic streptococcal infection, is the major etiology for mitral stenosis (MS). While the incidence of acute RF in the Western world had substantially declined over the past five decades, this trend is reversing due to immigration from non-industrialized countries where rheumatic heart disease (RHD) is higher. Pre-procedural evaluation for treatment of MS using a multimodality approach with 2D and 3D transthoracic and transesophageal echo, stress echo, cardiac CT scanning, and cardiac MRI as well as hemodynamic assessment by cardiac catheterization is discussed. The current methods of percutaneous mitral balloon commissurotomy (PMBC) and surgery are also discussed. New data on long-term follow-up after PMBC is also presented. For severe rheumatic MS, medical therapy is ineffective and definitive therapy entails PMBC in patients with suitable morphological mitral valve (MV) characteristics, or surgery. As procedural outcomes depend heavily on appropriate case selection, definitive imaging and interpretation are crucial. It is also important to understand the indications as well as morphological MV characteristics to identify the appropriate treatment with PMBC or surgery.


Decolourisation of dyes under electro-Fenton process using Fe alginate gel beads.
This study focuses on the application of electro-Fenton technique by use of catalytic activity of Fe alginate gel beads for the remediation of wastewater contaminated with synthetic dyes. The Fe alginate gel beads were evaluated for decolourisation of two typical dyes, Lissamine Green B and Azure B under electro-Fenton process. After characterization of Fe alginate gel beads, the pH effect on the process with Fe alginate beads and a comparative study of the electro-Fenton process with free Fe and Fe alginate bead was done. The results showed that the use of Fe alginate beads increases the efficiency of the process; moreover the developed particles show a physical integrity in a wide range of pH (2-8). Around 98-100% of dye decolourisation was obtained for both dyes by electro-Fenton process in successive batches. Therefore, the process was performed with Fe alginate beads in a bubble continuous reactor. High color removal (87-98%) was attained for both dyes operating at a residence time of 30 min, without operational problems and maintaining particle shapes throughout the oxidation process. Consequently, the stable performance of Fe alginate beads opens promising perspectives for fast and economical treatment of wastewater polluted by dyes or similar organic contaminants.


Chemical modification by polyethylene glycol of the anti-tumor enzyme arginine deiminase from Mycoplasma arginini.
Amino acid-degrading enzymes are known to inhibit the growth of tumor cells in culture by depleting amino acids in the medium. Here we demonstrate that arginine deiminase (EC 126.96.36.199) from Mycoplasma arginini had stronger growth-inhibitory activity against all 4 kinds of tumor cell lines tested than L-asparaginase and arginase, which are well-known anti-tumor enzymes. Next, chemical modification of the arginine deiminase molecule with polyethylene glycol was shown to enhance its potency as an anti-tumor enzyme. The percentage of modified amino groups per molecule was estimated to be 51% of the total amino groups, and the average molecular weight was estimated to be about 400,000 by gel-filtration HPLC. The enzymic activity of the modified enzyme was 25.5 units/mg protein, which was equivalent to 57% of that of the native enzyme. The modified enzyme strongly inhibited growth of a mouse hepatoma cell line, MH134, at a concentration of more than 10 ng/ml, showing almost the same dose-response curve as the native enzyme. When a bolus of 5 units of the modified enzyme was intravenously injected into male BDF1 mice, L-arginine in the blood completely disappeared within 5 min, and remained undetectable for more than 8 days. On the other hand, in the case of bolus injection of the same number of units of native enzyme, the plasma L-arginine level recovered up to 66% of the control level at 8 days. These results suggest that this modified enzyme has a longer plasma clearance time and may be more effective as a new anti-tumor agent than the native enzyme.


Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing.
C/D box small nucleolar RNAs (SNORDs) are small noncoding RNAs, and their best-understood function is to target the methyltransferase fibrillarin to rRNA (for example, SNORD27 performs 2'-O-methylation of A27 in 18S rRNA). Unexpectedly, we found a subset of SNORDs, including SNORD27, in soluble nuclear extract made under native conditions, where fibrillarin was not detected, indicating that a fraction of the SNORD27 RNA likely forms a protein complex different from canonical snoRNAs found in the insoluble nuclear fraction. As part of this previously unidentified complex,SNORD27 regulates the alternative splicing of the transcription factor E2F7p re-mRNA through direct RNA-RNA interaction without methylating the RNA, likely by competing with U1 small nuclear ribonucleoprotein (snRNP). Furthermore, knockdown of SNORD27 activates previously "silent" exons in several other genes through base complementarity across the entire SNORD27 sequence, not just the antisense boxes. Thus, some SNORDs likely function in both rRNA and pre-mRNA processing, which increases the repertoire of splicing regulators and links both processes.


Fatty acid desaturase 2 (FADS2) but not FADS1 desaturates branched chain and odd chain saturated fatty acids.
Branched chain fatty acids (BCFA) and linear chain/normal odd chain fatty acids (n-OCFA) are major fatty acids in human skin lipids, especially sebaceous gland (SG) wax esters. Skin lipids contain variable amounts of monounsaturated BCFA and n-OCFA, in some reports exceeding over 20% of total fatty acids. Fatty acid desaturase 2 (FADS2) codes for a multifunctional enzyme that catalyzes Δ4-, Δ6- and Δ8-desaturation towards ten unsaturated fatty acids but only one saturate, palmitic acid, converting it to 16:1n-10; FADS2 is not active towards 14:0 or 18:0. Here we test the hypothesis that FADS2 also operates on BCFA and n-OCFA. MCF-7 cancer cells stably expressing FADS1 or FADS2 along with empty vector control cells were incubated with anteiso-15:0, iso-16:0, iso-17:0, anteiso-17:0, iso-18:0, or n-17:0. BCFA were Δ6-desaturated by FADS2 as follows: iso-16:0 → iso-6Z-16:1, iso-17:0 → iso-6Z-17:1, anteiso-17:0 → anteiso-6Z-17:1 and iso-18:0 → iso-6Z-18:1. anteiso-15:0 was not desaturated in either FADS1 or FADS2 cells. n-17:0 was converted to both n-6Z-17:1 by FADS2 Δ6-desaturation and n-9Z-17:1 by SCD Δ9-desaturation. We thus establish novel FADS2-coded enzymatic activity towards BCFA and n-OCFA, expanding the number of known FADS2 saturated fatty acid substrates from one to six. Because of the importance of FADS2 in human skin, our results imply that dysfunction in activity of sebaceous FADS2 may play a role in skin abnormalities associated with skin lipids.


Impact of sentinel lymph node biopsy through the axillary cribriform fascia approach on intraoperative indicators and postoperative complications.
The aim of this study was to compare intraoperative indicators and postoperative complications of sentinel lymph node biopsy (SLNB) via the axillary cribriform membrane and traditional axillary fold with blue dye to make a priority choice. This single-center, retrospective cohort study enrolled 330 eligible breast cancer patients with stage of cTis ~ 2N0M0 in our hospital from August 2018 to July 2021. Multiple linear and binary logistic regression were used to evaluate the effects of different surgical approaches on intraoperative indicators (drainage volume, tube time, intraoperative bleeding, operative time and the number of sentinel lymph nodes (SLNs)) and postoperative complications (upper limb edema and dysfunction). All statistical tests were two sided. Multiple linear and logistic regression results after adjusting the covariate showed that the axillary cribriform fascia approach could render more greater intraoperative indictors and reduce the risk of upper limb dysfunction (P = 0.038, OR 0.32, 95%CI 0.11-0.94). High BMI could increase the drainage volume, tube time and operative time. There was no significant difference in the number of SLNs between the two approaches and it also had no relationship with intraoperative indicators and postoperative complications. Overall, 6 (1.8%) experienced upper limb edema and 18 (5.5%) experienced upper limb dysfunction. Univariate logistic regression analysis showed that radiotherapy increased the risk of upper limb edema (P = 0.032, OR = 12.76, 95%CI 1.25-130.06). SLNB through the axillary cribriform fascia approach produces more satisfied intraoperative indictors, a lower risk of upper limb dysfunction.


Influence of ultrasonic in low thermal expansion Fe-Ni electrodeposition process for micro-electroforming.
The electrochemical mechanism of Fe-Ni electrodeposition under ultrasonic was investigated by electrochemistry methods. Linear scanning voltammetry and cyclic voltammetry were used to show that the deposition process changed from the diffusion control under static conditions to an electrochemical control under ultrasonic conditions. Chronoamperometry curves showed that the Fe-Ni deposit occurred by a mechanism that instantaneous nucleation is followed by three-dimensional growth under charge transfer control. Chronopotentiogram indicated that because of the intensity of the ultrasound stripping effect, high ultrasonic power is unsuitable for electroforming Fe-Ni alloy, and a high current density is also not appropriate. Thus, the optimum parameters for Fe-Ni electrodeposition under ultrasonic conditions are ultrasonic power between 80 and 100 W (power density 0.28-0.35 W/cm2), and a current density lower than 10 mA/cm2 with temperature 323 K and pH 3. Experiments were performed to verify that the Fe-Ni masks prepared by ultrasonic-assisted electroforming had a good surface quality. The increase in ultrasonic power can obtain a larger grain size, thus got a low thermal expansion coefficient and a high hardness. Therefore, ultrasonic-assisted electrodeposition technology provides an effective and practically feasible manufacturing method for OLED Fe-Ni mask preparation.


Frequency self deconvolution in the quantitative analysis of near infrared spectra.
In this paper a new model based on frequency self deconvolution (FSD) is proposed for the quantitative analysis of a near infrared (NIR) spectrum. The model couples FSD and partial least square regression (PLS). The grid search optimization method is used to select the optimal values of the full width at half height (FWHH) and the truncation point of the apodization function. The proposed FSD-PLS provides a significant improvement in the prediction ability of the PLS model. Furthermore, a modification of the new FSD-PLS method is introduced to enable the removal of the baseline variations from the NIR spectra. The proposed models were validated using absorbance spectra of mixtures composed from glucose, urea and triacetin in a phosphate buffer solution where the concentrations of the components are selected to be within their physiological range in blood. The whole experiments were carried out in a non-controlled environment to show that the model can suppress effectively most of the experimental variations. The results show that the standard error of prediction (SEP) decreases from 35.58 mg dL(-1) using 8 factors for the PLS model to 15.53 mg dL(-1) by using 12 factors for the modified FSD-PLS model. The proposed models are also shown to yield a slightly improved performance than a newly developed second derivative-PLS model without incurring the shortcoming associated with the derivative approach in not providing interpretable results and in degrading the SNR of the spectra at a faster rate.


Diabetes mellitus associated with cystic fibrosis.
The prevalence of overt diabetes mellitus and carbohydrate intolerance was studied in 448 patients with cystic fibrosis (CF). Insulin-dependent diabetes (IDDM) developed in 7.6% of patients (13 male and 21 female). Survival was significantly lower (P less than 0.01) in the IDDM-CF group, with fewer than 25% surviving to age 30 years, whereas nearly 60% of the nondiabetic CF population reached this age. A significant deterioration in CF clinical status, based on NIH score, became apparent 2 years before onset of overt IDDM (P less than 0.05 at 2 years prior, P less than 0.01 at IDDM diagnosis). Total glycosylated hemoglobin (HbA1) was significantly (P less than 0.001) higher for the total CF population (7.3% +/- 1.2%) than for the general non-CF population (6.5% +/- 0.7%), and in the IDDM-CF group (P less than 0.05) compared with normoglycemic CF control patients. Female patients had a higher mean HbA1 after 12 years of age than their male counterparts did (P less than 0.02). HBA1 did not predict the development of IDDM, but there was a weak inverse relationship between HbA1 and both NIH clinical score (r = -0.41, P less than 0.02) and standard pulmonary function tests (forced vital capacity, r = -0.25, P less than 0.01) in the general CF population. Therefore, impaired carbohydrate tolerance in CF is associated with progressive clinical deterioration.


Development of generalized Fourier and Fick's law of electro-osmotic MHD flow of sodium alginate based Casson nanofluid through inclined microchannel: exact solution and entropy generation.
Electro-osmotic flow via a microchannel has numerous uses in the contemporary world, including in the biochemical and pharmaceutical industries. This research explores the electroosmotic flow of Casson-type nanofluid with Sodium Alginate nanoparticles through a vertically tilted microchannel. In addition, the transverse magnetic field is also considered. In this flowing fluid, the influence of heat and mass transmission is also explored. The aforementioned physical process is represented by partial differential equations. Utilizing suitable dimensionless variables for nondimensionalized. Furthermore, the non-dimensional classical system is fractionalized with the use of generalized Fourier and Fick's law. Generalizations are made using the Caputo derivative's description. The analytical solution of the velocity, temperature, and concentration profiles is obtained by combining the methods of Laplace and Fourier. Interestingly, the influence of several physical characteristics such as the fractional parameter, Casson fluid parameter, the thermal and mass Grashof numbers, and the zeta potential parameter is displayed. Moreover, the results show that the volume fractional of nanoparticles enhances the rate of heat transfer up to 39.90%, Skin friction up to 38.05%, and Sherwood number up to 11.11%. Also, the angle of inclination enhances the fluid velocity.


Antiamylase-pullulanase enzyme monoclonals which specifically inhibit amylase or pullulanase activity.
Monoclonal antibodies against amylase-pullulanase enzyme from Bacillus circulans F-2 have been produced to locate and characterize the catalytic sites of the enzyme. The antibodies have been examined for inhibition of both enzyme activities of amylase and pullulanase and then classified into four types: Type I which inhibited amylase activity, Type II which inhibited pullulanase activity, Type III which inhibited both enzyme activities, and Type IV which had no effect on either enzyme activity. Only two monoclonal antibodies (MAP-12 and MAP-17) as Type I and two antibodies (MAP-3 and MAP-5) as Type II were isolated. The inhibitory activities of the antibodies were characterized and compared. In Type II antibodies, the maximal demonstrated inhibition on the pullulanase activity was 88% for MAP-3 with 1 microg of antibody and 90% for MAP-5 with 2 microg of antibody, but did not inhibit the amylase activity. In Type I antibodies, in contrast, the maximal demonstrated inhibition on the amylase activity was 94% for MAP-12 and 97% for MAP-17 with 1 microg of antibody, respectively, but no inhibition of the pullulanase was noted. MAP-12 recognized sequential epitope, while MAP-17 recognized conformation-dependent epitope of amylase activity-related regions. However, both MAP-3 and MAP-5 recognized the conformation-dependent epitope of the pullulanase activity-related region. Furthermore, the antibodies of MAP-3, MAP-5, MAP-12, and MAP-17 did not compete with one another for binding to the enzyme, indicating that they have different target epitopes on the enzyme. Antibody binding of MAP-12 and MAP-17 to the enzyme was not specifically affected by any of the antiamylase compounds tested: (a) nojirimycin; and (b) 1-deoxynojirimycin. Kinetic analysis of their effects provides evidence that both antibodies of MAP-12 and MAP-17 decrease the catalytic rate of enzyme activity and have little or no effect on substrate binding.


Immediate- and medium-term effects of balloon pulmonary valvuloplasty in infants with critical pulmonary stenoses during the first year of life: A prospective single center study.
Balloon pulmonary valvuloplasty (BPV) represents the standard of management for all patients with severe pulmonary stenosis (PS) irrespective of their age. Nevertheless neonates and infants with critical PS represent a high-risk group that needs to be studied. The study population included 72 infants with severe congenital valvular PS and four infants with imperforate pulmonary valve (PV) who were subjected to detailed history taking, full clinical examination, resting 12-lead ECG, Chest roentgenogram and transthoracic echocardiography. BPV was attempted in all infants with a peak-to-peak gradient across the PV of 50 mmHg or greater at catheterization-laboratory. Full echocardiographic evaluation was done 24 hours after the procedure as well as 3 and 6 months later. Seventy-six infants with severe PS or imperforate PV with a mean age of 5.63 ± 2.99 months were subjected to BPV with or without wire perforation. Immediately after the procedure patients had a significant reduction of the right ventricular systolic pressure (RVSP) (104.69 ± 24.98 mm Hg Vs 43.6 ± 13 mm Hg, p < 0.001) and RV-PA systolic pressure gradient (PG) (82.5 ± 23.76 mm Hg Vs 17.35 ± 8.96 mm Hg, p < 0.001). The immediate success rate defined as the drop in the RVSP to less than or equal to 50% of the baseline measurement was achieved in 85% of the cases. There was a progressive drop in the PG across the PV by Doppler echocardiogram throughout a follow-up period of six months from a mean of 93.3 ± 28.2 mm Hg to a mean of 17.4 ± 10.42 mm Hg (p < 0.001). There was a significant increase of the mean PV annulus diameter after balloon dilatation (p < 0.001). There was also a highly significant inverse correlation between the growth of the pulmonary annulus and the annular size at the baseline before dilatation (r = -0.74, p value <0.001). The incidence of PR significantly increased immediately after BPV to 64% followed by a progressive decline over a 6 months period of follow-up to 20%. There was a significant decrease in the incidence of tricuspid regurgitation (TR) over the same period of follow-up (from 55.6% at baseline to less than 20% at follow-up). BPV is safe and effective to relieve critical PS in infants during the first year of life. The balloon promotes advantageous changes in both, pulmonary annulus and PG across the RVOT. In addition, the Doppler gradient observations during the follow-up support the expectation that BPV is a "curative" therapy.


Solitary primary amyloidosis of urinary bladder. Light and electron microscopic study.
A fifty-four-year-old white woman with a history of episodic gross hematuria was diagnosed as having solitary primary amyloidosis of the urinary bladder involving a large segment of the dome and anterior wall. A segmental resection of the bladder was performed with good results. Electron microscopic examination of the lesion revealed evidence to indicate that amyloid in this case was produced by the fibroblasts within the lamina propria of the bladder. The mode of amyloidogenesis is identical to that noted in some of the previously published electron microscopic studies on localized amyloidosis of skin. Solitary primary amyloidosis of the urinary bladder is a rare lesion with only 46 cases having been previously reported in the literature.


Relationship between sarcopenia and sleep status in female patients with mild to moderate Alzheimer's disease.
Sleep disorders and sarcopenia could contribute to the development of Alzheimer's disease (AD), which are risk factors that rapidly deteriorate cognitive functions. However, few studies have evaluated the relationship between sarcopenia and sleep disorders in female AD patients, who have a higher prevalence than male patients. This study aimed to investigate the relationship between sarcopenia and sleep status in female patients with mild to moderate AD. This cross-sectional study recruited 112 female outpatients aged between 60 and 85 years. Demographic characteristics, appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were assessed. Sarcopenia was diagnosed according to criteria of the Asian Working Group for Sarcopenia. Pittsburgh Sleep Quality Index (PSQI) assessed sleep variables. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessed cognitive function. Binary logistic regression models explored the relationship between sleep variables and cognitive function and sarcopenia, adjusting for potential cofounders. The outpatients were divided into 36 AD patients with sarcopenia (ADSa) and 76 AD patients without sarcopenia (ADNSa), with a prevalence of 32.1%. ADSa had lower ASMI, weaker grip strength, slower gait speed, a higher incidence of poor sleep quality and poorer cognitive function. Multivariate binary logistic regression analysis showed that high total scores of PSQI (odds ratio (OR) = 1.13), poor sleep quality (OR = 2.73), poor subjective sleep quality (OR = 1.83), low MMSE (OR = 0.77) and MoCA (OR = 0.76) scores were associated with high odds of sarcopenia. Compared to sleep time ≤ 15 min, >60 min (OR = 5.01) were associated with sarcopenia. Sleep duration <6 h (OR = 3.99), 8-9 h (OR = 4.48) and ≥9 h (OR = 6.33) were associated with sarcopenia compared to 7-8 h. More sleep symptoms and cognitive impairment exist in female patients with sarcopenia. The higher total scores of PSQI, poorer subjective sleep quality, longer sleep latency, excessive and insufficient sleep duration and poorer cognitive function are associated with higher odds of sarcopenia in female patients with mild to moderate AD.


Postinfarction left-ventricular aneurysm: regional stress, function, and remodeling after aneurysmectomy.
Left-ventricular (LV) aneurysm formation after myocardial infarction (MI) leads to LV remodeling with global and regional cardiac dysfunction. LV aneurysmectomy (LVA) can often improve LV function, but changes of regional wall stress and systolic function in the noninfarcted segment before and after the operation remain poorly understood. The purpose of this study was to assess the effects of LVA on regional stress and systolic function in the noninfarcted region and to examine this procedure's impact on the LV remodeling in patients with LV aneurysm after myocardial infarction (MI). Using quantitative left ventriculography and pressure measurements, 11 patients with an anterior LV aneurysm were studied before and 8 months after standard linear repair (LVA group), and 10 patients with an anterior transmural infarction who received coronary artery bypass grafting were also studied (CABG group) in an attempt to separate the effects of aneurysmectomy from the effects of bypass surgery. Regional end-systolic (ESS) and end-diastolic (EDS) stresses of the contractile segment (CS) were computed by Janz's method. The total ejection fraction (EF) increased (p < 0.01) in the LVA group, whereas it did not change in the CABG group at 8 months after surgery. Both the end-diastolic and end-systolic volume indices of CS decreased (p < 0.01 and p < 0.01, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The mean velocity of circumferential fiber shortening (mean Vcf) of CS increased substantially (p < 0.01) in the LVA group and, less significantly (p < 0.05), in the CABG group. Regional ESS and EDS decreased (p < 0.01 and p < 0.05, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The increase in mean Vcf correlated strongly with the magnitude of decrease in ESS (r = -0.63, p < 0.01) in the LVA group but not in the CABG group. LVA can reduce regional afterload and improve ejection performance of the noninfarcted myocardium in many patients with a large anterior LV aneurysm and, moreover, may favorably affect the LV remodeling process after MI.


Cryo-EM structure of the DNA-dependent protein kinase catalytic subunit at subnanometer resolution reveals alpha helices and insight into DNA binding.
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) regulates the nonhomologous end joining pathway for repair of double-stranded DNA (dsDNA) breaks. Here, we present a 7A resolution structure of DNA-PKcs determined by cryo-electron microscopy single-particle reconstruction. This structure is composed of density rods throughout the molecule that are indicative of alpha helices and reveals structural features not observed in lower resolution EM structures. Docking of homology models into the DNA-PKcs structure demonstrates that up to eight helical HEAT repeat motifs fit well within the density. Surprisingly, models for the kinase domain can be docked into either the crown or base of the molecule at this resolution, although real space refinement suggests that the base location is the best fit. We propose a model for the interaction of DNA with DNA-PKcs in which one turn of dsDNA enters the central channel and interacts with a resolved alpha-helical protrusion.


Association between miR-34b/c rs4938723 polymorphism and risk of cancer: An updated meta-analysis of 27 case-control studies.
Several studies investigated the association between miR-34b/c rs4938723 polymorphism and the risk of several human cancers, but the findings remain inconclusive. To evaluate the impact of miR-34b/c rs4938723 on cancer risk, we performed a meta-analysis on all available studies including 12 361 cancer cases and 14 270 controls. Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Google scholar databases. Pooled odds ratios with 95% confidence intervals were calculated in codominant, dominant, recessive, overdominant, and allele models to quantitatively estimate the association. The overall findings showed no significant association between miR-34b/c rs4938723 polymorphism and cancer risk in codominant, dominant, recessive, overdominant, and allele inheritance model. However, in stratified analysis by cancer types, the rs4938723 polymorphism significantly increased the risk of gastrointestinal cancer, hepatocellular carcinoma. In addition, the rs4938723 polymorphism was associated with decreased risk of esophageal squamous cell carcinoma, colorectal cancer, and acute lymphoblastic leukemia. The findings did not support an association between rs4938723 variant and digestive tract as well as gastric cancer. In summary, the findings of this meta-analysis indicated that the miR-34b/c rs4938723 polymorphism might be associated with some cancer development. Larger and well-designed studies are necessary to estimate this association in detail.


Expression and regulation of Schlafen (SLFN) family members in primary human monocytes, monocyte-derived dendritic cells and T cells.
Schlafen (SLFN/Slfn) family members have been investigated for their involvement in fundamental cellular processes including growth regulation, differentiation and control of viral replication. However, most research has been focused on the characterization of Slfns within the murine system or in human cell lines. Since little is known about SLFNs in primary human immune cells, we set out to analyze the expression and regulation of the six human SLFN genes in monocytes, monocyte-derived dendritic cells (moDCs) and T cells. Comparison of SLFN gene expression across these three cell types showed high mRNA expression of SLFN11 in monocytes and moDCs and high SLFN5 expression in T cells, indicating functional importance within these cell types. Differentiation of monocytes to moDCs leads to the gradual upregulation of SLFN12L and SLFN13 while SLFN12 levels were decreased by differentiation stimuli. Stimulation of moDCs via human rhinovirus, lipopolysaccharide, or IFN-α lead to strong upregulation of SLFN gene expression, while peptidoglycan poorly stimulated regulation of both SLFNs and the classical interferon-stimulated gene MxA. T cell activation was found to downregulate the expression of SLFN5, SLFN12 and SLFN12L, which was reversible upon addition of exogenous IFN-α. In conclusion, we demonstrate, that SLFN gene upregulation is mainly dependent on autocrine type I interferon signaling in primary human immune cells. Rapid decrease of SLFN expression levels following T cell receptor stimulation indicates a role of SLFNs in the regulation of human T cell quiescence.


Cytochemical and cytological properties of perineuronal oligodendrocytes in the mouse cortex.
Neuronal cell bodies are associated with glial cells collectively referred to as perineuronal satellite cells. One such satellite cell is the perineuronal oligodendrocyte, which is unmyelinating oligodendrocytes attaching to large neurons in various neural regions. However, little is known about their cellular characteristics and function. In this study, we identified perineuronal oligodendrocytes as 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive cells attaching to neuronal perikarya immunostained for microtubule-associated protein 2, and examined their cytochemical and cytological properties in the mouse cerebral cortex. 2',3'-Cyclic nucleotide 3'-phosphodiesterase-positive perineuronal oligodendrocytes were immunonegative to representative glial markers for astrocytes (brain-type lipid binding protein and glial fibrillary acidic protein), microglia (Iba-1) and NG2(+) glia. However, almost all perineuronal oligodendrocytes expressed glia-specific or glia-enriched metabolic enzymes, i.e. the creatine synthetic enzyme S-adenosylmethionine:guanidinoacetate N-methyltransferase and L-serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase. As to molecules participating in the glutamate-glutamine cycle, none of the perineuronal oligodendrocytes expressed the plasmalemmal glutamate transporters GLAST and GLT-1, although nearly half of the perineuronal oligodendrocytes were immunopositive for glutamine synthetase. Cytologically, perineuronal oligodendrocytes were mainly distributed in deep cortical layers (layers IV-VI), and attached directly and tightly to neuronal cell bodies, making a long concave impression to the contacting neurons. Interestingly, they attached more to glutamatergic principal neurons than to GABAergic interneurons, and this became evident at postnatal day 14, when the cerebral cortex develops and maturates. These cytochemical and cytological properties suggest that perineuronal oligodendrocytes are so differentiated as to fulfill metabolic support to the associating principal cortical neurons, rather than to regulate their synaptic transmission.


Efficacy and safety of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults: A pooled analysis of two phase 2 clinical trials.
There is a need for new treatment options for moderate-to-severe atopic dermatitis (AD) in adults. Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, has recently been approved for this indication. A pooled analysis of a phase 2a (NCT01548404) and a phase 2b (NCT01859988) study and a subanalysis of the 2b study evaluated the efficacy and safety of subcutaneous dupilumab 300 mg once weekly (qw) and every 2 weeks (q2w) in adults with moderate-to-severe AD. Dupilumab significantly improved clinical outcomes in both analyses at week 12. Itch was significantly improved in the pooled analysis as measured by peak pruritus Numerical Rating Scale, 5-dimension pruritus scale, and SCORing Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) pruritus scores (all p < .0001 vs. placebo at week 12). Sleep loss was significantly improved (SCORAD VAS sleep loss score; p < .0001 vs. placebo at week 12); similar results were shown for the q2w dose. Dupilumab had an acceptable safety profile. Consistent with previous studies, dupilumab qw and q2w significantly improved signs and symptoms of AD at week 12, including improvements in itch and sleep loss. Subcutaneous dupilumab is an effective new treatment option for adults with moderate-to-severe AD.


Miliary tuberculosis: a severe opportunistic infection in juvenile systemic lupus erythematosus patients.
One of the main issues in juvenile systemic lupus erythematosus (JSLE) patients is infection, such as tuberculosis (TB). Of note, SLE patients are susceptible to pulmonary and extrapulmonary TB. However, to our knowledge, this contagious disease was rarely reported in pediatric lupus population, particularly diffuse or miliary TB. Therefore, from January 1983 to December 2011, 5,635 patients were followed-up at our Pediatric Rheumatology Unit and 285 (5%) of them met the American College of Rheumatology classification criteria for SLE. Four (1.4%) of our JSLE patients had disseminated TB and were described herein. All of them were female gender, received BCG vaccination and did not have a history of TB household contact. The median of current age at TB diagnosis and the period between JSLE and TB diagnosis were 17 years old (range 14-20) and 5.5 years (range 2-7), respectively. All patients developed miliary TB during the course of the disease. The median of SLE Disease Activity Index 2000 (SLEDAI-2K) was 4 (2-16) and the patients were treated with immunosuppressive agents (glucocorticoid, azathioprine and/or intravenous cyclophosphamide). Two of them presented sepsis and TB diagnosis was only established at autopsy, especially with lungs, central nervous system and abdominal involvements. Anti-TB therapy (isoniazid, rifampicin and pyrazinamide) was indicated in the other two TB cases, however they deceased. Miliary TB is a rare and severe opportunist infection in pediatric lupus population. This study reinforces the importance of routine searches for TB in JSLE patients.


[Successful treatment of adult Still's disease with tofacitinib in a HIV-2 positive female patient].
A 46-year-old female patient with a known HIV-2-infection suffered from adult onset Still's disease, which was initially complicated by a macrophage activation syndrome (MAS). The required glucocorticoid treatment induced a psychosis and the patient developed an aversion to glucocorticoids. After failure of treatment with anakinra, an alternative option with the JAK-inhibitor tofacitinib was introduced because of the short half-life and to reduce glucocorticoid exposure. A switch to tofacitinib was only successful after an overlapping treatment with anakinra and tofacitinib for 3 weeks. The patient is currently being treated with monotherapy with tofacitinib as well as NSAID on demand, is in stable remission and can continue working as normal.


Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials.
Patients who have acute myocardial infarction remain at major risk of cardiovascular events. We aimed to assess the effects of either human atrial natriuretic peptide or nicorandil on infarct size and cardiovascular outcome. We enrolled 1216 patients who had acute myocardial infarction and were undergoing reperfusion treatment in two prospective, single-blind trials at 65 hospitals in Japan. We randomly assigned 277 patients to receive intravenous atrial natriuretic peptide (0.025 microg/kg per min for 3 days) and 292 the same dose of placebo. 276 patients were assigned to receive intravenous nicorandil (0.067 mg/kg as a bolus, followed by 1.67 microg/kg per min as a 24-h continuous infusion), and 269 the same dose of placebo. Median follow-up was 2.7 (IQR 1.5-3.6) years for patients in the atrial natriuretic peptide trial and 2.5 (1.5-3.7) years for those in the nicorandil trial. Primary endpoints were infarct size (estimated from creatine kinase) and left ventricular ejection fraction (gauged by angiography of the left ventricle). 43 patients withdrew consent after randomisation, and 59 did not have acute myocardial infarction. We did not assess infarct size in 50 patients for whom we had fewer than six samples of blood. We did not have angiographs of left ventricles in 383 patients. Total creatine kinase was 66,459.9 IU/mL per h in patients given atrial natriuretic peptide, compared with 77,878.9 IU/mL per h in controls, with a ratio of 0.85 between these groups (95% CI 0.75-0.97, p=0.016), which indicated a reduction of 14.7% in infarct size (95% CI 3.0-24.9%). The left ventricular ejection fraction at 6-12 months increased in the atrial natriuretic peptide group (ratio 1.05, 95% CI 1.01-1.10, p=0.024). Total activity of creatine kinase did not differ between patients given nicorandil (70 520.5 IU/mL per h) and controls (70 852.7 IU/mL per h) (ratio 0.995, 95% CI 0.878-1.138, p=0.94). Intravenous nicorandil did not affect the size of the left ventricular ejection fraction, although oral administration of nicorandil during follow-up increased the left ventricular ejection fraction between the chronic and acute phases. 29 patients in the atrial natriuretic peptide group had severe hypotension, compared with one in the corresponding placebo group. Patients with acute myocardial infarction who were given atrial natriuretic peptide had lower infarct size, fewer reperfusion injuries, and better outcomes than controls. We believe that atrial natriuretic peptide could be a safe and effective adjunctive treatment in patients with acute myocardial infarction who receive percutaneous coronary intervention.


Human calcitonin radioimmunoassay: characterization and application.
A radioimmunoassay of human calcitonin (HCT) has been developed, employing antibodies formed in response to a HCT-bovine gamma globulin conjugate. The assay is sensitive (lower limits of detection 30 pg/ml serum), reproducible, and specific for intact HCT and carboxyl-terminal fragments of HCT. Serum HCT was detected in 76% of 63 normal subjects (mean +/- S.E.M. = 72 +/- 7 pg/ml), and was increased in cord sera, as well as sera from patients with chronic renal disease and medullary thyroid cancer. Increased levels were observed during calcium infusion into normal subjects, but not in sera from pregnant women or subjects with chronic hypercalcemia. No significant correlation was observed between serum ionized calcium and HCT in sera from 147 hospitalized patients. These findings suggest the usefulness of this assay for further studies of conditions affecting calcitonin homeostasis.


Pedalium murex Linn.: an overview of its phytopharmacological aspects.
Pedalium murex Linn (family: Pedaliaceae) (P. murex) commonly known as Large Caltrops and Gokhru (India) is a shrub found in the Southern part, Deccan region of India and in some parts of Ceylon. Different parts of the plant are used to treat various ailments like, cough, cold and as an antiseptic. Interestingly, P. murex is reported traditionally to have an excellent cure in patients with reproductive disorders which are mainly impotency in men, nocturnal emissions, gonorrhoea as well as leucorrhoea in women. The plant has also benifited in complications like urinary track disorder as well as gastro intestinal tract disorders. Phytochemically the plant is popular for the presence of a considerable amount of diosgenin and vanillin which are regarded as an important source and useful starting materials for synthesizing steroidal contraceptive drugs and isatin alkaloids. Other phytochemicals reported in the plant includes quercetin, ursolic acid, caffeic acid, amino acids (glycine, histidine, tyrosine, threonine, aspartic acid and glutamic acid) and various classes of fatty acids (triacontanoic acid, nonacosane, tritriacontane, tetratriacontanyl and heptatriacontan-4-one). Pharmacologically, the plant have been investigated for antiulcerogenic, nephroprotective, hypolipidemic, aphrodisiac, antioxidant, antimicrobial and insecticidal activities. From all these reports it can be concluded that the plant were found to have a better profile with potential natural source for the treatment of various range of either acute or chronic disease. The overall database of our review article was collected from the scientific sources in regards with all the information of the research article for P. murex published so far.


A graphics-oriented personal computer-based microscope charting system for neuroanatomical and neurochemical studies.
This report describes a computerized microscope charting system based on the IBM personal computer or compatible. Stepping motors are used to control the movement of the microscope stage and to encode its position by hand manipulation of a joystick. Tissue section contours and the location of cells labeled with various compounds are stored by the computer, plotted at any magnification and manipulated into composites created from several charted sections. The system has many advantages: (1) it is based on an industry standardized computer that is affordable and familiar; (2) compact and commercially available stepping motor microprocessors control the stage movement. These controllers increase reliability, simplify implementation, and increase efficiency by relieving the computer of time consuming control tasks; (3) the system has an interactive graphics interface allowing the operator to view the image during data collection. Regions of the graphics display can be enlarged during the charting process to provide higher resolution and increased accuracy; (4) finally, the digitized data are stored at 0.5 micron resolution and can be routed directly to a multi-pen plotter or exported to a computer-aided design (CAD) program to generate a publication-quality montage composed of several computerized chartings. The system provides a useful tool for the acquisition and qualitative analysis of data representing stained cells or chemical markers in tissue. The modular design, together with data storage at high resolution, allows for potential analytical enhancements involving planimetric, stereologic and 3-D serial section reconstruction.


The effects of age-bias on neural correlates of successful and unsuccessful response inhibition.
Response inhibition is important for adherence to social norms, especially when norms conflict with biases based on one's social identity. While previous studies have shown that in-group bias generally modulates neural activity related to stimulus appraisal, it is unclear whether and how an in-group bias based on age affects neural information processing during response inhibition. To assess this potential influence, young adults completed a Go/NoGo task incorporating younger face (in-group) and older face (out-group) stimuli while undergoing functional magnetic resonance imaging (fMRI). Our results replicated previous findings by demonstrating higher accuracy in successful Go compared to NoGo trials, as well as the engagement of nodes of the response inhibition network during successful response inhibition, and brain regions comprising the salience network during unsuccessful response inhibition. Importantly, despite a lack of behavioural differences, our results showed that younger and older face stimuli modulated activity in the response inhibition and salience networks during successful and unsuccessful inhibition, respectively. Interestingly, these effects were not uniform across networks. During successful response inhibition, in-group stimuli increased activity in medial prefrontal cortex and temporo-parietal junction, whereas out-group stimuli more strongly engaged pre-supplemental motor area. During unsuccessful response inhibition, in-group stimuli increased activity in posterior insula, whereas out-group stimuli more strongly engaged angular gyrus and intraparietal sulcus. Consequently, the results infer the presence of an age-bias effect in the context of inhibitory control, which has substantial implications for future experimental design and may also provide the means of investigating the neural correlates of implicit beliefs that contribute to ageism.


Molecular detection of tick-borne protozoan parasites in a population of domestic cats in midwestern Brazil.
Some tick-borne pathogens that infect domestic cats have been considered emergent in veterinary medicine. Occurrences of Hepatozoon spp., Babesia spp. and Cytauxzoon spp. have been described in several regions of Brazil. This paper offers a comprehensive analysis of the 18S rRNA gene of a Hepatozoon sp. strain detected in domestic cats in the metropolitan area of Cuiabá, in Midwestern Brazil. Based on a molecular analysis, we detected the presence of Hepatozoon species circulating among cats in this region. The aforementioned strain is closely related to other isolates of H. felis detected in wild felids. Moreover, a phylogenetic analysis indicates that this genotype is grouped into a clade of 18S rRNA sequences previously described for the genus Hepatozoon in wild felids around the world. Hepatozoon felis strains detected in cats from Spain and Israel showed, respectively, 98% and 97% identity to our sequence and are clustered on a separate branch of the phylogenetic tree. This finding suggests a high diversity of Hepatozoon genotypes occurring in cats in Europe and South America. None of the analyzed cats were positive for Babesia spp. or Cytauxzoon spp. by PCR analysis.


A progress report on the New Zealand Multicentre Parkinson's disease trial. A comparison of low-dose treatment with bromocriptine or L-dopa.
A short-term and long-term prospective trial comparing 'low-dose' bromocriptine with L-dopa in the de novo treatment of Parkinson's disease began in 1983. One hundred and twenty-eight patients entered the trial by early 1987. One hundred and seven have remained on one drug. Statistical analysis indicates that a hundred patients in each treatment group will be necessary to avoid a type II statistical error in the comparison of these treatments.