Latency to respond and conjugate lateral eye movements: a methodological and theoretical note.
The relationship between latency to first response and lateral eye movements was investigated for 52 preschool and primary grade children. Latency to respond correlated significantly with number of eye movements observed for each child. Significantly greater latency occurred for spatial questions than for verbal reasoning questions. Methodological and theoretical implications of latency to first response in relation to the study of conjugate lateral eye movements are briefly described.


The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab.
The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice. A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD. There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001). The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice.


Cervical hematomyelia after traditional Chinese massage: a case report.
Hematomyelia is rare, and usually related to major trauma. Non-traumatic causes are much rarer and include underlying vascular malformations and cord tumors. We present the case of a previously well 44-year-old woman who developed severe acute neck pain and right-sided motor deficit after a session of traditional Chinese massage that entailed minimal neck manipulation. Emergent MRI confirmed hematomyelia of the right cervical hemicord, notably without associated bony or ligamentous injury. Follow-up spinal angiography and MRIs revealed no underlying vascular malformation or tumor. We highlight this case as there has been no reported case of hematomyelia occurring after mild trauma, although two cases of idiopathic hematomyelia have been reported. Though exceedingly rare, hematomyelia should be considered in the list of differential diagnoses in any case of neck pain and motor deficit after seemingly trivial injury.


Transconjunctival XEN45 implantation for secondary open-angle glaucoma management in a pediatric patient with WAGR syndrome.
To report a case of XEN45 gel stent implantation in a pediatric patient with WAGR syndrome as a successful surgical intervention in the management of multifactorial secondary open-angle glaucoma. A 6-year-old female with a history of WAGR syndrome, bilateral congenital aniridia, pseudophakia OD and glaucoma OD, was referred for a XEN45 gel stent OD. IOP was persistently elevated at 24 mm Hg despite two glaucoma medications. Implantation of the XEN45 gel stent was performed using a transconjunctival ab externo approach. There were no significant intra-or-postoperative adverse events associated with the stent. The patient achieved good IOP-lowering control without glaucoma medications across the 18-month follow-up period. A XEN45 stent through a transconjunctival ab externo approach may be an effective surgical intervention in pediatric patients with secondary open-angle glaucoma associated with aniridia and aphakia.


Deep learning-guided postoperative pain assessment in children.
Current automated pain assessment methods only focus on infants or youth. They are less practical because the children who suffer from postoperative pain in clinical scenarios are in a wider range of ages. In this article, we present a large-scale Clinical Pain Expression of Children (CPEC) dataset for postoperative pain assessment in children. It contains 4104 preoperative videos and 4865 postoperative videos of 4104 children (from 0 to 14 years of age), which are collected from January 2020 to December 2020 in Anhui Provincial Children's Hospital. Moreover, inspired by the dramatic successful applications of deep learning in medical image analysis and emotion recognition, we develop a novel deep learning-based framework to automatically assess postoperative pain according to the facial expression of children, namely Children Pain Assessment Neural Network (CPANN). We train and evaluate the CPANN with the CPEC dataset. The performance of the framework is measured by accuracy and macro-F1 score metrics. The CPANN achieves 82.1% accuracy and 73.9% macro-F1 score on the testing set of CPEC. The CPANN is faster, more convenient, and more objective compared with using pain scales according to the specific type of pain or children's condition. This study demonstrates the effectiveness of deep learning-based method for automated pain assessment in children.


Endodermal sinus tumour of the ovary: serum alpha fetoprotein dynamics and immunohistochemical localization of marker in tumour tissue.
The apparent successful treatment of endodermal sinus tumour of ovary is reported. The patient, after surgery and adjuvant chemotherapy, has remained in remission, and the serum alpha fetoprotein has been less than 10 micrograms/1 over a period of 9 months.


Mechanical and Electronic Properties of XC₆ and XC12.
A series of carbon-based superconductors XC₆ with high Tc were reported recently. In this paper, based on the first-principles calculations, we studied the mechanical properties of these structures, and further explored the XC12 phases, where the X atoms are from elemental hydrogen to calcium, except noble gas atoms. The mechanically- and dynamically-stable structures include HC₆, NC₆, and SC₆ in XC₆ phases, and BC12, CC12, PC12, SC12, ClC12, and KC12 in XC12 phases. The doping leads to a weakening in mechanical properties and an increase in the elastic anisotropy. C₆ has the lowest elastic anisotropy, and the anisotropy increases with the atomic number of doping atoms for both XC₆ and XC12. Furthermore, the acoustic velocities, Debye temperatures, and the electronic properties are also studied.


A new coding system for metabolic disorders demonstrates gaps in the international disease classifications ICD-10 and SNOMED-CT, which can be barriers to genotype-phenotype data sharing.
Data sharing is essential for a better understanding of genetic disorders. Good phenotype coding plays a key role in this process. Unfortunately, the two most widely used coding systems in medicine, ICD-10 and SNOMED-CT, lack information necessary for the detailed classification and annotation of rare and genetic disorders. This prevents the optimal registration of such patients in databases and thus data-sharing efforts. To improve care and to facilitate research for patients with metabolic disorders, we developed a new coding system for metabolic diseases with a dedicated group of clinical specialists. Next, we compared the resulting codes with those in ICD and SNOMED-CT. No matches were found in 76% of cases in ICD-10 and in 54% in SNOMED-CT. We conclude that there are sizable gaps in the SNOMED-CT and ICD coding systems for metabolic disorders. There may be similar gaps for other classes of rare and genetic disorders. We have demonstrated that expert groups can help in addressing such coding issues. Our coding system has been made available to the ICD and SNOMED-CT organizations as well as to the Orphanet and HPO organizations for further public application and updates will be published online (www.ddrmd.nl and www.cineas.org).


Molecular Dynamics Study on the Binding of an Anticancer DNA G-Quadruplex Stabilizer, CX-5461, to Human Telomeric, c-KIT1, and c-Myc G-Quadruplexes and a DNA Duplex.
DNA G-quadruplex (G4) stabilizer, CX-5461, is in phase I/II clinical trials for advanced cancers with BRCA1/2 deficiencies. A FRET-melting temperature increase assay measured the stabilizing effects of CX-5461 to a DNA duplex (∼10 K), and three G4 forming sequences negatively implicated in the cancers upon its binding: human telomeric (∼30 K), c-KIT1 (∼27 K), and c-Myc (∼25 K). Without experimentally solved structures of these CX-5461-G4 complexes, CX-5461's interactions remain elusive. In this study, we performed a total of 73.5 μs free ligand molecular dynamics binding simulations of CX-5461 to the DNA duplex and three G4s. Three binding modes (top, bottom, and side) were identified for each system and their thermodynamic, kinetic, and structural nature were deciphered. The molecular mechanics/Poisson Boltzmann surface area binding energies of CX-5461 were calculated for the human telomeric (-28.6 kcal/mol), c-KIT1 (-23.9 kcal/mol), c-Myc (-22.0 kcal/mol) G4s, and DNA duplex (-15.0 kcal/mol) systems. These energetic differences coupled with structural differences at the 3' site explained the different melting temperatures between the G4s, while CX-5461's lack of intercalation to the duplex explained the difference between the G4s and duplex. Based on the interaction insight, CX-5461 derivatives were designed and docked, showing higher selectivity to the G4s over the duplex.


Study on growth hormone and insulin secretion in myotonic dystrophy.
Growth hormone (GH) levels were measured in 12 patients with myotonic dystrophy (MD; 7 men and 5 women, aged 21-49 years) and 14 volunteers after administration of 100 micrograms GH-releasing hormone (GHRH; 1-29). A 75-g oral glucose tolerance test was carried out to determine glucose, insulin, plasma C-peptide, and urinary C-peptide. The GH level in six MD patients responded normally to GHRH (group I), with a peak of 17.1 +/- 1.46 micrograms/l, compared with controls (27.8 +/- 19.6 micrograms/l, NS), and that in the other six patients responded subnormally, with a peak of 3.15 +/- 1.46 micrograms/l, lower than in controls and in group I patients (P < 0.001). In group I the insulin response to the glucose tolerance test showed hyperinsulinism and was lower than that in group II patients; stimulated C-peptide was also higher in group II than in group I and in controls; urinary C-peptide levels were parallel to those in previous data. In all MD patients there were a negative correlation between absolute values of GH response to GHRH and insulin response to glucose tolerance test (r = -0.79, P < 0.001). Our data suggest that the failure in GH release and peripheral insulin action is due to a generalized defect in cellular membrane function in MD patients.


Using climate to model ancient human migration.
Modeling fills gaps in the fossil record of early hominin movement from Africa.


Elevation of ubiquinone content by peroxisomal inducers in rat liver during aging.
The effect of di(2-ethylhexyl)phthalate (DEHP) on the induction of peroxisomes and the content of ubiquinone in the liver was studied in rats between 25 and 496 days of age. During this period, peroxisomal beta-oxidation of fatty acids was greatly decreased but it could be induced many-fold in all ages. The ubiquinone (UQ) content was increased upon induction 6-fold in the first weeks of life, but the extent of this elevation continuously narrowed and no induction could be observed in the oldest animals, even after prolonged treatment with the plasticizer. In contrast, the treatment decreased the amount of liver cholesterol in all age groups. Treatment with this peroxisomal inducer increased the biosynthesis of UQ while the breakdown rate was found to be unaffected, as the half-life of this lipid was 103 and 106 h in control and treated rats, respectively. These results indicate that treatment with peroxisomal inducers increases the liver UQ content by increasing the rate of biosynthesis and that this effect is not apparent in aged rats.


Allosteric inhibitors against HIV-1 reverse transcriptase: design and synthesis of MKC-442 analogues having an omega-functionalized acyclic structure.
Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.


Low p53 expression of acute myelocytic leukemia cells with t(8;21) chromosome abnormality: association with low p14(ARF) expression.
In this study, the mRNA expression of p14(ARF) in t(8;21)AML cells was found to be significantly lower than acute myelocytic leukemia (AML) cells without t(8;21) chromosome abnormality, which was concordant with previous observation by Linggi et al. that AML1-MTG8 represses the transcription of p14(ARF). Although p53 mRNA expression level of t(8;21)AML cells was not low, p53 protein expression was reduced in t(8;21)AML cells. Genotoxic damage by ionizing radiation did not induce p53 upregulation in t(8;21)AML cells. Since p14(ARF) has been demonstrated to inhibit p53 degradation by binding to MDM2, repression of p14(ARF) expression in t(8;21)AML may facilitate the degradation of p53 by MDM2. Low p14(ARF) in t(8;21)AML may also account for the absence of upregulation of p53 by ionizing radiation. Then, we have shown that p53 expression level was inversely correlated with S/G2/M population of cell cycle in AML cells. Most of the t(8;21)AML are considered to be in p53(low) S/G2/M(high). It is now widely known that formation of AML1-MTG8 by t(8;21) translocation is a very early event in leukemogenesis, and AML1-MTG8 alone might have limited proliferative potential. Then, secondary oncogenic events such as activated receptor tyrosine kinase (like c-kit mutation), is necessary to become full-blown leukemia. Low p53 protein expression and insufficient induction of p53 by genotoxic damage might increase the opportunity to obtain additional oncogenic events, since genome guard function of p53 does not work in t(8;21)AML cells.


Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.
To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT. Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi). Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands. Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands.


ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes.
ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATM-deficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm(-/-) astrocytes, like Atm(-/-) lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATM-deficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.


EMP2 regulates angiogenesis in endometrial cancer cells through induction of VEGF.
Understanding tumor-induced angiogenesis is a challenging problem with important consequences for the diagnosis and treatment of cancer. In this study, we define a novel function for epithelial membrane protein-2 (EMP2) in the control of angiogenesis. EMP2 functions as an oncogene in endometrial cancer, and its expression has been linked to decreased survival. Using endometrial cancer xenografts, modulation of EMP2 expression resulted in profound changes to the tumor microvasculature. Under hypoxic conditions, upregulation of EMP2 promoted vascular endothelial growth factors (VEGF) expression through a HIF-1α-dependent pathway and resulted in successful capillary-like tube formation. In contrast, reduction of EMP2 correlated with reduced HIF-1α and VEGF expression with the net consequence of poorly vascularized tumors in vivo. We have previously shown that targeting of EMP2 using diabodies in endometrial cancer resulted in a reduction of tumor load, and since then we have constructed a fully human EMP2 IgG1. Treatment of endometrial cancer cells with EMP2-IgG1 reduced tumor load with a significant improvement in survival. These results support the role of EMP2 in the control of the tumor microenvironment and confirm the cytotoxic effects observed by EMP2 treatment in vivo.


Three-dimensional sonographic measurement of fetal renal volume.
The objective of this longitudinal study was to evaluate the growth of the fetal kidney in normal pregnancies using three-dimensional ultrasound. Three-dimensional sonographic examinations were performed on 13 appropriate-for-gestational-age fetuses. Fetal renal volume was measured every 2 to 3 weeks after 20 weeks gestational age until delivery. There was a good linear correlation between left and right renal volumes (r = 0.9614, P < 0.0001). Curvilinear relationships were found between gestational age and left and right renal volume (left: R(2) = 79.1%, P < 0.0001; right: R(2) = 74.2%, P < 0.0001), and normal ranges of left and right renal volume measurements for estimating the growth of the fetal kidney during normal pregnancy were generated. There was a difference for each predicted value of the fetal renal volume in the third trimester of pregnancy in our study and in two other previous studies. The left and right fetal renal volume to estimated fetal weight ratios were constant during the pregnancies studied. Our findings suggest that fetal renal volume measurement plays a role in assessment of the growth of fetal kidneys. However, we are doubtful about the reproducibility of fetal renal volume measurements made by using three-dimensional ultrasound in utero. Further studies involving larger sample sizes are needed to reevaluate the usefulness and reproducibility of fetal renal volume measurements.


A high-throughput screening system targeting the nuclear export pathway via the third nuclear export signal of influenza A virus nucleoprotein.
Two classes of antiviral drugs, M2 channel inhibitors and neuraminidase (NA) inhibitors, are currently approved for the treatment of influenza; however, the development of resistance against these agents limits their efficacy. Therefore, the identification of new targets and the development of new antiviral drugs against influenza are urgently needed. The third nuclear export signal (NES3) of nucleoprotein (NP) is the most important for viral replication among seven NESs encoded by four viral proteins, NP, M1, NS1, and NS2. NP-NES3 is critical for the nuclear export of NP, and targeting NP-NES3 is therefore a promising strategy that may lead to the development of antiviral drugs. However, a high-throughput screening (HTS) system to identify inhibitors of NP nuclear export has not been established. Here, we developed a novel HTS system to evaluate the inhibitory effects of compounds on the nuclear export pathway mediated by NP-NES3 using a MDCK cell line stably expressing NP-NES3 fused to a green fluorescent protein from aequorea coerulescens (AcGFP-NP-NES3) and a cell imaging analyzer. This HTS system was used to screen a 9600-compound library, leading to the identification of several hit compounds with inhibitory activity against the nuclear export of AcGFP-NP-NES3. The present HTS system provides a useful strategy for the identification of inhibitors targeting the nuclear export of NP via its NES3 sequence.


Nitrogen-Based Fuels: A Power-to-Fuel-to-Power Analysis.
What are the fuels of the future? Seven representative carbon- and nitrogen-based fuels are evaluated on an energy basis in a power-to-fuel-to-power analysis as possible future chemical hydrogen-storage media. It is intriguing to consider that a nitrogen economy, where hydrogen obtained from water splitting is chemically stored on abundant nitrogen in the form of a nontoxic and safe nitrogen-based alternative fuel, is energetically feasible.


Insulin sensitivity assessment with euglycemic insulin clamp in adult beta-thalassaemia major patients.
To assess insulin sensitivity in young adult normoglycemic beta-thalassaemia major patients. We measured insulin sensitivity with the euglycemic insulin clamp in 10 young adult (mean age 24.85 +/- 2.45 yrs) normoglycemic beta-thalassaemia major patients and 10 sex- & age-matched controls. Liver iron accumulation was assessed by magnetic resonance imaging (MRI). Glucose infusion rate (M) required to maintain euglycemia was significantly reduced in thalassaemic patients compared to controls (261.5 +/- 63.5 mg/m2 x min vs. 355.6 +/- 35.3 mg/m2 x min, P = 0.008). Consequently, significantly reduced in the thalassaemic group were also tissue sensitivity to insulin (M/I(s-s)) and glucose metabolic clearance rate (M/G(s-s)). There was significant negative correlation between ferritin levels and glucose infusion rate (r = -0.918 P = 0.004). No significant correlations were observed between age, body mass index, daily transfusional iron accumulation, liver iron content and any of the euglycemic clamp parameters. Fasting insulin levels were significantly increased in patients with beta-thalassaemia major compared to controls (P = 0.01), and had significant negative correlation to MRI-derived liver iron content (r = -0.733, P = 0.03). Our data indicate that reduced insulin sensitivity resulting in hyperinsulinaemia precedes the manifestation of glucose intolerance in patients with beta-thalassaemia major. Insulin resistance seems to correlate with increased serum ferritin levels.


Increasing social support for individuals with serious mental illness: evaluating the compeer model of intentional friendship.
We conducted a quasi-experimental study of Compeer, which matches community volunteers and people with SMI to increase social support. Seventy-five adults with SMI received community psychiatric treatments-usual (TAU) while 79 adults received Compeer services plus TAU. Compeer clients reported significant improvements in social support and a trend towards improved subjective well-being. After 6 months, social support increased >1 SD for 13%, increasing to 23% at 12 months, supporting qualitative research suggesting the "active ingredient" in intentional friendships often takes more than 1 year to develop. This subgroup of responders showed significant gains in subjective well-being and reductions in psychiatric symptoms.


Microbiological findings in erythema (chronicum) migrans and related disorders.
In order to evaluate the virtual advantage of proving borrelial infection in dermatoses clinically diagnosed as erythema (chronicum) migrans (ECM), acrodermatitis chronica atrophicans (ACA) or lymphadenosis cutis benigna (LCB) by means of histological, cultural or serological trials, skin and serum samples obtained from altogether 99 patients suffering from these dermatoses were examined. Serum and--to some extent--skin specimens gained from healthy individuals (n = 36), patients with not tick bite associated disorders of skin, internal organs and nervous system (n = 121) were used as controls. In addition, serum specimens from patients enduring circumscribed scleroderma (morphea), n = 31, and sera of Bavarian forest workers (n = 211) were proven for the presence of borrelial antibodies. Using an indirect immunofluorescence assay with borrelial strains, propagated in inbred mice, as antigens, elevated IgM- and/or IgG antibody titers were found in 51 (84%) out of 61 ECM-, in 17 (100%) ACA- and in 2 (33%) out of 6 LCB-sera. Antibody titers decreased significantly after adequate antibiotic therapy. The groups in comparison yielded spirochetal serum antibodies as follows: Healthy individuals and patients with various diseases 7 out of 157 (4.5%), morphea patients 7 out of 31 (23%) and forest workers 71 out of 211 (34%). Borrelia burgdorferi was cultivated from 6 out of 32 skin and from 1 blood specimen obtained from ECM patients and from 1 out of 5 ACA skin specimens. Borreliae could also be detected in the blood of 3 out of 11 thymusaplastic nude mice after intraperitoneal implantation of ECM-tissue. More frequently than borreliae spindle-shaped bacteria resembling fusobacterium sp. were detected not only by in vitro cultivation of ECM and ACA skin samples, but also in the blood of thymusaplastic mice after implantation of ECM-tissue. By Warthin-Starry silver strain borrelia-like structures were detected in 9 out of 28 ECM, in 3 out of 12 ACA and in 1 out of 5 LCB skin specimens. Therefore in our experience serological examinations turned out to be the most productive diagnostic tool.


Suppression of experimental atherosclerosis in rabbits by interferon-inducing agents.
The effects of two chemically different interferon inducers on the suppression of atherosclerosis were studied in rabbits fed an atherogenic chow diet. One group (10 rabbits per group) was fed normal rabbit chow, and three groups were fed an atherogenic chow. One of the latter groups received the atherogenic feeding alone; the other two were treated with either polyinosinic-polycytidylic acid (poly I:C) or 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP). Neither of the drugs reduced significantly the hypercholesterolemia induced by the feeding. However, both poly I:C and ABPP treatment significantly reduced the percent area of the aortic intimal surface lesions, stained for lipid with Sudan IV, compared with that in untreated rabbits fed atherogenic chow. Microscopic sections of typical aortic plaques showed that both drug treatments significantly reduced the size and number of intimal lipid deposits compared with those observed in the aortas of untreated animals. Chemical analysis for cholesterol and collagen content revealed that interferon-inducing agents significantly reduced cholesterol deposits in the aorta, with little effect on fibrous protein deposition. The results indicate that two unrelated interferon-inducing drugs suppressed atherogenesis without reducing serum cholesterol and low density lipoprotein levels. Whether the protection against atherosclerosis is exerted by endogenous interferon production remains to be determined.


[Antigenic variants among street rabies virus isolates from France, Africa, Madagascar and Asia. Preliminary results with antinucleocapsid monoclonal antibodies].
A panel of monoclonal antibodies directed against the nucleocapsid antigens of rabies virus allowed a rapid characterization of isolates by an indirect immunofluorescence test on brain smears of infected animals. Analysis of 77 isolates (71 from animals and 6 from humans) showed a great diversity. Isolates from different areas showed different patterns of reactivity. No relation was found between animal species and antigenic patterns specificity.


A technique for atraumatic scrotal pouch orchiopexy in the management of testicular torsion.
Scrotal pouch orchiopexy without suture fixation will result in strong atraumatic fixation of the testis in the management of undescended testis. We describe a similar technique that is effective in the management of testicular torsion. A total of 19 scrotal pouch orchiopexies was performed in 11 boys with testicular torsion. Age ranged from 10 to 17 years (mean 14). Orchiopexy was done using a scrotal pouch without transparenchymal suture fixation of the testis. The partial serosal sac was obliterated, placing the testis in a secured extravaginal position. Followup ranged from 17 to 33 months (mean 25.6). There were no instances of infection, hematoma, wound dehiscence, atrophy or recurrent torsion. Scrotal pouch orchiopexy as described is recommended to prevent torsion of the testis.


Assessment of room temperature influence on finger blood flow response induced by short-term grasping of vibrating handle.
To investigate the influence of room temperature on finger blood flow (FBF) change in healthy subjects exposed to short-term grasping of a vibrating handle under different room temperatures. FBF was measured using a blood flowmeter in six male subjects on the dorsum of the middle phalanx of third finger in both hands once at the end of every minute for an equal duration of 5 min at pre-exposure, during exposure to grasping of vibrating handle with sinusoidal vibration and after exposure. Vibration was generated with a frequency of 125 Hz and an rms acceleration of 40 m/s(2). Measurements were conducted in four room temperatures of 15+/-1, 20+/-1, 25+/-1 and 30+/-1 degrees C. Compared with the baseline measurements in the exposed hand during grasping of vibrating handle most significant increase in FBF was observed at 15+/-1 degrees C (P<0.001) and least at 30+/-1 degrees C (P<0.05), and after vibration least significant FBF was found at 25+/-1 degrees C (P<0.05). In case of the unexposed hand significant increase in FBF was exhibited at 20+/-1 degrees C (P<0.01) and 30+/-1 degrees C (P<0.01) during vibration, and only at 15+/-1 degrees C (P<0.05) after vibration. Response in FBF due to grasping of vibrating handle was of different patterns from the baseline measurement under different room temperature conditions in both exposed and unexposed hands and it was influenced by room temperature. Overall, the influence was greater at lower test room temperature, inducing more significant increase in FBF.


Inference of selection pressures that drive insecticide resistance in Anopheles and Culex mosquitoes in Korea.
Pyrethroids are primarily used for mosquito control in Korea. However, high frequencies of mutations conferring resistance to not only pyrethroids but also to other insecticides have been found in mosquito populations. This study aimed to examine the hypothesis that insecticides used outside of public health may play a role in selection. Briefly, the resistance mutation frequencies to three insecticide groups (pyrethroids, organophosphates, and cyclodienes) were estimated in two representative groups of mosquito species (Anopheles Hyrcanus Group and Culex pipiens complex). The relationship between these frequencies and the land-use status of the collection sites was investigated through multiple regression analysis. In the Anopheles Hyrcanus Group, the frequencies of both ace1 (organophosphate resistance) and rdl (cyclodiene resistance) mutations were positively correlated with 'proximity to golf course', possibly be due to the insecticides used for turf maintenance. They also showed positive correlations with field area and rice paddy area, respectively, suggesting the role of agricultural insecticides in the selection of these resistance traits. For the Cx. pipiens complex, the kdr (pyrethroid resistance), ace1, and rdl mutations were positively correlated with the residential area, field, and rice paddy, respectively. Therefore, pyrethroids used for public health could serve as a direct source of resistance selection pressure against kdr, whereas non-public health insecticides may pose primary selection pressure against the ace1 and rdl traits. The current findings suggest that the insecticides used in agriculture and the golf industry play a significant role in mosquito selection, despite variations in the extent of indirect selection pressure according to the mosquito groups and insecticide classes.


NIR-FT-Raman spectroscopic analytical characterization of the fruits, seeds, and phytotherapeutic oils from rosehips.
In this study nondestructive Raman spectroscopic analysis of rosehips has been conducted by laser excitation at 1064 nm, with the objective of direct measurement of different parts of the fruit, including the inside and outside of the seeds, while preserving the integrity of the more representative chemicals. Carotenoid substances are responsible for the major Raman features in the spectra of the fruit parts; analysis of the nu(1) mode (1520 cm(-1)) strongly indicates the presence of a C(9) carotene, and analysis of the main characteristic carotene band set (C=C, C-C, and C-CH(3) stretching modes at 1520, 1157, and 1007 cm(-1), respectively) suggests the presence of beta-carotene as the main constituent. Raman spectra of the seed parts show the presence of unsaturated fatty acids, which are predominant inside the seed; these spectra also reveal the fatty products content comprises cis isomers. Analysis of the CH-stretching region bands and comparison with those in the spectra obtained from linoleic acid and commercial rosehip oil indicate that the relative band intensity of the CH-stretching mode is strongly affected by the chemical environment of the fatty acid esters present in both parts (inside and outside) of rosehips seeds.


Forward masking and unmasking of the offset cochlear compound action potential of the gerbil: comparison with suppression areas of the onset cochlear compound action potential.
Simultaneous and forward maskers were used to generate 'onset' and 'offset' compound action potential tuning curves (TCs) in the gerbil. The simultaneously masked offset TC, generated in response to a 16 kHz, 65 dB SPL probe stimulus, is W-shaped, with a low frequency tip at 11 kHz, a high frequency tip at 20 kHz, and a peak which occurs at 16 kHz. The 16 kHz forward masked onset TC has a single tip which occurs at 11 kHz. Although it lacks the finely tuned peak and high frequency tip of the stimultaneously masked offset TC, its single tip is more finely tuned than the low frequency tip of the simultaneously masked offset TC. Normalizing these two TCs [(1977) J. Acoust. Soc. Am. 62, 1048-1051] produces a figure which resembles 11 kHz onset TCs with their nonoverlapping regions which are analogs of two-tone suppression (2TS). A similar pattern occurs when probe stimuli at frequencies from 13 to 24 kHz are used to generate offset TCs; i.e., the forward masked offset TC resembles an onset TC and normalizing it to a simultaneously masked offset TC produces areas which resemble analogs of 2TS. Unmasking of the forward masked onset TCs [(1979) Hear, Res. 1, 133-154] produces regions of 2TS which are very similar to those produced by unmasking the forward masked offset TC which is generated by a higher frequency tone. These regions of 2TS for the Offset TC, as determined by unmasking, are very similar to the analogs of 2TS described above.


Demographic, clinical and etiological profile of pericardial effusion in India: A single centre experience.
Pericardial effusion (PE) is a life-threatening condition. However, there are very few Indian studies which determined etiological distribution. The current retrospective observational study was carried out to assess etiological factors responsible for PE in a tertiary care centre in India. The study enrolled consecutive 55 patients with the diagnosis of moderate to large PE as established by echocardiography between January 2018 and December 2018. The echocardiography guided percutaneous pericardiocentesis was performed by the standard procedure. Amongst the enrolled PE patients in the study, 30 (54.55%) were males and 25 (45.45%) were females, with the average age of 43.00 ± 15.54 years. In clinical assessment, tamponade was found in 52 (94.54%) patients. Tuberculosis was the most common etiology for PE (n=35, 63.64%) followed by hypothyroidism (n = 6, 10.9%), and malignancies (n = 4, 7.27%). Among 12.72% patients, the PE was of recurrent type. Additionally, no death or any complication was encountered during pericardiocentesis. Pericardial disease and effusion is a major cause of morbidity in India. Despite developments in the healthcare facilities, tuberculosis was the most common etiology for PE. Additionally, the raised number of hypothyroid and malignant PE cases demonstrates the changing etiological trends, similar to western countries.


Serum zinc and copper levels in ischemic cardiomyopathy.
Changes in the copper (Cu) and zinc (Zn) concentrations have been reported previously in ischemic cardiomyopathy (ISCMP). Due to controversial results, the aims of this study were to compare levels of Cu, Zn, and Zn/Cu ratio of ISCMP patients with healthy volunteers and also to investigate the possible relationship between trace elements status in ISCMP patients with the severity of clinical disease based on the New York Heart Association (NYHA) classification. The subjects of this study consisted of 30 ISCMP and 27 healthy volunteers. ISCMP was diagnosed with a history of previous myocardial infarction and also coronary artery disease was confirmed by coronary angiography. Exclusion criteria were renal or hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or Zn within 1 week. Cu and Zn levels have been assayed with atomic absorption spectrophotometry. Statistical analysis was performed with the SPSS 10 software using independent sample t test for comparing the levels of Cu and Zn between ISCMP and normal subjects. The mean Cu level of the ISCMP group (1.54 +/- 0.52 mg/L) was significantly more than the Cu levels of the healthy volunteers (1.31 +/- 0.24 mg/L; p = 0.048). The mean Zn levels of the ISCMP and healthy volunteers were 1.05 +/- 0.28 and 1.12 +/- 0.42, respectively, without any significant difference between groups. There was a trend for higher Cu level, lower Zn level, and lower Zn/Cu ratio in NYHA III patients in comparison with NYHA II group. Considering the results of this study, Cu may have a role in the development of ISCMP. Interventions such as administration of Cu chelators to relieve the symptoms or to decrease the progression of ISCMP is needed to be examined in large clinical trials. In this study, the Zn level of ISCMP patients was not significantly different in comparison with the healthy volunteers.


[Studies on the flavonoids in stem of Rhododendron anthopogonoide II].
To further investigate the flavonoids of Rhododendron anthopogonoide. The compounds were isolated and purified by Sephadex LH-20, polyamide and silica gel column chromatography. Their chemical structures were elucidated on the basis of physicochemical properties and spectral data. Six compounds were isolated and identified as: taxifolin (I), guaijaverin (II), reynoutrin (III), quercitrin (IV), polystachoside (V) and quercetin-4'-O-beta-D-galactoside (VI). For the first time, compound VI was separated from Ericaceae plant, compounds II and V were isolated from Rhododendron plant, and compounds I and II were obtained from this plant.


Heterodimers of alpha1B- and alpha1D-adrenergic receptors form a single functional entity.
Heterologous expression of alpha(1D)-adrenergic receptors (alpha(1D)-ARs) in most cell types results in intracellular retention and little or no functionality. We showed previously that heterodimerization with alpha(1B)-ARs promotes surface localization of alpha(1D)-ARs. Here, we report that the alpha(1B)-/alpha(1D)-AR interaction has significant effects on the pharmacology and signaling of the receptors, in addition to the effects on trafficking described previously. Upon coexpression of alpha(1B)-ARs and epitope-tagged alpha(1D)-ARs in both human embryonic kidney 293 and DDT(1)MF-2 cells, alpha(1D)-AR binding sites were not detectable with the alpha(1D)-AR selective antagonist 8-[2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-8-azaspiro[4,5]decane-7,9-dione (BMY 7378), despite the ability to detect alpha(1D)-AR protein using confocal microscopy, immunoprecipitation, and a luminometer cell-surface assay. However, the alpha(1B)-AR-selective mutant F18A conotoxin showed a striking biphasic inhibition in alpha(1B)/alpha(1D)-AR-expressing cells, revealing that alpha(1D)-ARs were expressed but did not bind BMY 7378 with high affinity. Studies of norepinephrine-stimulated inositol phosphate formation showed that maximal responses were greatest in alpha(1B)/alpha(1D)-AR-coexpressing cells. Stable coexpression of an uncoupled mutant alpha(1B)-AR (Delta12) with alpha(1D)-ARs resulted in increased responses to norepinephrine. However, Schild plots for inhibition of norepinephrine-stimulated inositol phosphate formation showed a single low-affinity site for BMY 7378. Thus, our findings suggest that alpha(1B)/alpha(1D)-AR heterodimers form a single functional entity with enhanced functional activity relative to either subtype alone and a novel pharmacological profile. These data may help to explain why alpha(1D)-ARs are often pharmacologically undetectable in native tissues when they are coexpressed with alpha(1B)-ARs.


Mice lacking the plasminogen activator inhibitor 1 are protected from trabecular bone loss induced by estrogen deficiency.
Bone turnover requires the interaction of several proteases during the resorption phase. Indirect evidence suggests that the plasminogen activator/plasmin pathway is involved in bone resorption and turnover, and recently we have shown that this cascade plays a role in the degradation of nonmineralized bone matrix in vitro. To elucidate the role of the plasminogen activator inhibitor 1 (PAI-1) in bone turnover in vivo, bone metabolism was analyzed in mice deficient in the expression of PAI-1 gene (PAI-1-/-) at baseline (8-week-old mice) and 4 weeks after ovariectomy (OVX) or sham operation (Sham) and compared with wild-type (WT) mice. PAI-1 inactivation was without any effect on bone metabolism at baseline or in Sham mice. However, significant differences were observed in the response of WT and PAI-1-/- mice to ovariectomy. The OVX WT mice showed, as expected, decreased trabecular bone volume (BV/TV) and increased osteoid surface (OS/BS) and bone formation rate (BFR), as assessed by histomorphometric analysis of the proximal tibial metaphysis. In contrast, no significant change in any of the histomorphometric variables studied was detected in PAI-1-/- mice after ovariectomy. As a result, the OVX PAI-1-/- had a significantly higher BV/TV, lower OS/BS, lower mineral apposition rate (MAR) and BFR when compared with the OVX WT mice. However, a comparable decrease in the cortical thickness was observed in OVX PAI-1-/- and WT mice. In addition, the cortical mineral content and density assessed in the distal femoral metaphysis by peripheral quantitative computed tomography (pQCT), decreased significantly after ovariectomy, without difference between PAI-1-/- mice and WT mice. In conclusion, basal bone turnover and bone mass are only minimally affected by PAI-1 inactivation. In conditions of estrogen deficiency, PAI-1 inactivation protects against trabecular bone loss but does not affect cortical bone loss, suggesting a site-specific role for PAI-1 in bone turnover.


Minute-Ventilation Variability during Cardiopulmonary Exercise Test is Higher in Sedentary Men Than in Athletes.
The occurrence of minute-ventilation oscillations during exercise, named periodic breathing, exhibits important prognostic information in heart failure. Considering that exercise training could influence the fluctuation of ventilatory components during exercise, we hypothesized that ventilatory variability during exercise would be greater in sedentary men than athletes. To compare time-domain variability of ventilatory components of sedentary healthy men and athletes during a progressive maximal exercise test, evaluating their relationship to other variables usually obtained during a cardiopulmonary exercise test. Analysis of time-domain variability (SD/n and RMSSD/n) of minute-ventilation (Ve), respiratory rate (RR) and tidal volume (Vt) during a maximal cardiopulmonary exercise test of 9 athletes and 9 sedentary men was performed. Data was compared by two-tailed Student T test and Pearson´s correlations test. Sedentary men exhibited greater Vt (SD/n: 1.6 ± 0.3 vs. 0.9 ± 0.3 mL/breaths; p < 0.001) and Ve (SD/n: 97.5 ± 23.1 vs. 71.6 ± 4.8 mL/min x breaths; p = 0.038) variabilities than athletes. VE/VCO2 correlated to Vt variability (RMSSD/n) in both groups. Time-domain variability of Vt and Ve during exercise is greater in sedentary than athletes, with a positive relationship between VE/VCO2 pointing to a possible influence of ventilation-perfusion ratio on ventilatory variability during exercise in healthy volunteers.


Therapeutic improvements of nifedipine controlled-release tablets combined with sacubitril valsartan on patients with diabetic nephropathy complicated with hypertension.
This study aimed to evaluate the efficacy of nifedipine controlled-release tablets combined with sacubitril valsartan in diabetic nephropathy (DN) patients with hypertension. One hundred and twelve DN patients with hypertension were enrolled. They were randomly divided into the control group (treated with nifedipine controlled-release tablets combined with valsartan) and the observation group (treated with nifedipine controlled-release tablets combined with sacubitril valsartan). Renal function, endothelial function and inflammatory response were examined. After three-months treatment, the levels of clinical indexes (glycosylated hemoglobin, fasting blood glucose, systolic and diastolic blood pressure), renal function indicators (urinary albumin excretion rate, blood urea nitrogen, serum creatinine and cystatin C), endothelial function indicators (microalbumin, angiotensin II, thrombomodulin and cartilage oligomeric matrix protein) and inflammatory response factors (interleukin-6 and tumor necrosis factor-α) in the observation group were significantly lower than those in the control group. Nifedipine controlled-release tablets combined with sacubitril valsartan could effectively alleviate the progression of DN combined with hypertension.


Possible existence of a higher coverage quasi-one-dimensional phase of argon adsorbed on bundles of single-walled carbon nanotubes.
We present results of Ar adsorption isotherms at very low coverages in the first layer and, beyond monolayer completion, on bundles of close-ended single-walled carbon nanotubes. The low coverage results were used to determine the isosteric heat of adsorption and the binding energy of Ar in the groove sites in the first layer. The higher coverage results show evidence of the possible formation of a second-layer groove phase, beyond monolayer completion. Our results for higher coverages are compared with recent computer simulations for this system.


Multiple Chemosensory Neurons Mediate Avoidance Behavior to Rare Earth Ions in Caenorhabditis elegans.
As rare earth (RE) metals are abundantly present in the soil, in spite of their name, it is conceivable that organisms may encounter and interact with RE ions. In the present study, we demonstrated that the soil nematode Caenorhabditis elegans avoids RE ions, such as yttrium and all examined lanthanide ions, which exhibit toxic effects on nematodes. We also demonstrated that the chemosensory system of this animal mediates avoidance behavior toward RE ions similar to heavy metal (HM) ion avoidance. The C. elegans dyf-11(pe554) mutant is unable to respond to chemosensory cues because it lacks all ciliated endings of the chemosensory neurons required for the detection of environmental chemicals. Cell-specific rescue of the dyf-11 mutant and cell-specific genetic ablation studies revealed that the avoidance behavior toward HM and RE ions was mediated by a partially overlapping but distinct subset of chemosensory neurons (ASH, ADL, ASE, ADF, and ASK). With the help of multiple chemosensory neurons, worms may improve the fidelity of avoidance behavior to evade RE ions. Among the chemosensory neurons in C. elegans, ADF and ASK neurons were involved in RE avoidance, but not in HM avoidance. These results suggested that ADF and ASK neurons in C. elegans have RE-selective mechanisms to mediate the avoidance response.


Spatial distributions, source apportionment and ecological risks of C9-C17 chlorinated paraffins in mangrove sediments from Dongzhai Harbor, Hainan Island.
The spatial distributions, possible sources of C9-C17 chlorinated paraffins (CPs), and the ecological risks posed in mangrove sediment in Dongzhai Harbor (Hainan Island, China) were investigated. Comprehensive two-dimensional gas chromatography combined with electron capture negative ionization mass spectrometry was used to determine 50 C9-C17 CP congener groups. The concentrations of C9-CPs, short-chain CPs (SCCPs), and medium-chain CPs (MCCPs) in the mangrove sediment samples were 8.28-79.7, 89.2-931, and 58.8-834 ng g-1 dry weight, respectively. The CPs concentrations in the mangrove sediment samples were moderate compared with those found in other regions worldwide. The spatial distributions and congener patterns of the CPs indicated that the CP concentrations were mainly controlled by local emissions and that wastewater discharged from livestock and shrimp breeding facilities and domestic sewage were the main sources of CPs in mangrove sediment in Dongzhai Harbor. C10Cl6-7 and C14Cl7-8 were the dominant SCCP and MCCP congener groups, respectively. The MCCP concentrations and total organic carbon contents significantly correlated (R2 = 0.607, P < 0.05). Hierarchical cluster analysis and principal component analysis indicated that the SCCP and MCCP congeners were from different commercial CP formulations and sources. Risk assessments suggested that SCCPs and MCCPs in mangrove sediment in Dongzhai Harbor do not currently pose marked risks to sediment-dwelling organisms.


Hysteresis effects of meteorological variation-induced algal blooms: A case study based on satellite-observed data from Dianchi Lake, China (1988-2020).
As one of three top-priority eutrophic lakes in China, Dianchi Lake has received national attention due to its severe eutrophication in recent decades. Meteorological factors are the main factors driving the formation and persistence of algae blooms. In addition, meteorological variation-induced algal blooms usually have a hysteresis effect. However, there have been few quantitative studies on this hysteresis effect. In the present study, Landsat images were used to extract the dynamic characteristics of changes in algal blooms in Dianchi Lake from 1988 to 2020. The hysteresis effect of meteorological factors driving algal blooms was studied by employing the modified lag-correlation method. The results showed that the algal blooms in Dianchi Lake were most severe between 1998 and 2008. During the periods of algal blooms, the values of air temperature (AT) and precipitation (PP) were significantly higher, while those wind velocity (WV) and sunshine duration (SSD) were obviously lower, than the corresponding annual mean values. AT and PP were significantly positively correlated with algal bloom factors in both the formation and persistence stages of algal blooms, while SSD and WV both promoted their regression, but these effects were less significant in the persistence period than in the formation period. Moreover, rainfall led to a decrease in SSD and WV, indirectly contributing to algal blooms. Furthermore, AT, PP and SSD are the main factors impacting the duration of persistent blooms. The time periods during which each meteorological factor was most influential were as follows: 1) AT - 25-30 days before the maximum bloom. 2) PP - within the first 10 days before the maximum bloom. 3) Both SSD and WV - 15-20 days before the maximum bloom. The results of this study support the prediction of algal blooms in Dianchi Lake.


Remote sensory assessment of beer quality based on visual perception of foamability and biometrics compared to standard emotional responses from affective images.
The social isolation settings derived from the COVID-19 pandemic affected the standard sensory evaluation techniques used in the food and beverage industry. This situation forced companies and researchers to assess other options to continue conducting these tests in remote contactless locations. This study aimed to evaluate two sets of samples (i) six images from Geneva affective picture database (GAPED) and (ii) six videos of beer pouring using traditional self-reported sensory data and emotional response from consumers biometrics. Specifically, four research questions (RQ) arouse from this study: RQ1: are there significant differences between GAPED images and beers in unconscious and self-reported responses from consumers?, RQ2: are there any correlations between subconscious and self-reported responses from consumers when assessing beer?, RQ3: can consumers differentiate positive, neutral and negative images based on subconscious and self-reported responses?, RQ4: are there any relationships between subconscious and self-reported responses when assessing GAPED images and beers, and how are samples associated with variables? A total of 113 Mexican beer consumers participated in the virtual sensory session using an online videoconference software to record videos of participants during the session. Results showed there were significant differences (p < 0.05) between samples, especially for self-reported responses (RQ1), and several correlations between variables, such as positive correlations between the perceived quality of beers and happy emoji (r = 0.84), and negative correlation with confused emoji (r = -0.97; RQ2). Besides, using the proposed methods, consumers were able to correctly differentiate through elicited emotions the positive, neutral and negative GAPED images (RQ3). Regarding RQ4, several relationships were found between variables in both GAPED images and beers; however, it was found that different emotions were elicited depending of the stimuli used. The proposed method showed to be a reliable and practical option to conduct visual and potentially tasting sensory tests in isolation and recruit participants from different countries without travelling to collect their responses.


Changes in the soft tissue facial profile following orthodontic extractions: a geometric morphometric study.
The aim of this study is to test the null hypothesis that changes in soft tissue facial profile in children who undergo orthodontic treatment, using either an extraction or non-extraction technique, do not differ. Longitudinal, retrospective. San Juan, PR and Aberdeen, UK. Fifty-eight consecutively treated children using fixed appliances with a mean age of 13.2 (+/- 2.1) years. Extraction of the upper and lower, first or second premolars. The mean pre- and post-treatment, extraction and non-extraction configurations were compared using finite-element scaling analysis (FESA), incorporating a thin-plate spline interpolation. Post-treatment the two groups differed statistically in the premaxillary region (p < 0.05) with the non-extraction group being relatively larger in that region by 25%. For the non-extraction group after treatment, localized increases in relative size in the naso-maxillary region size of 25% (p < 0.01) were present. For the extraction group after treatment, a non-significant reduction in relative size of 15% was localized in the putative bicuspid area. Soft tissue facial differences in non-extraction and extraction cases prior to treatment may be accentuated following orthodontic treatments that elect non-extraction or extraction protocols. Robust diagnosis and treatment planning, incorporating the judicious use of extractions if appropriate, may yield optimal orthodontic outcomes.


CC-1065 functional analogues possessing different electron-withdrawing substituents and leaving groups: synthesis, kinetics, and sequence specificity of reaction with DNA and biological evaluation.
Antitumor agent CC-1065 functional analogues possessing different electron-withdrawing substituents and leaving groups have been synthesized. The extent and the relative rates of DNA cleavage following alkylation by these CPI structures and thermal treatment were determined independently by an ethidium binding assay and by agarose gel electrophoresis experiments. The anticipated preferential covalent binding to adenine sites within the minor groove was confirmed by sequencing determination of selected agents on high-resolution gels. Certain of the synthetic agents, unlike CC-1065, also bind covalently to G sites with weaker intensity. The cytotoxicities of these compounds were also determined against KB cells in vitro. Compounds bearing a bromo or nitro group in the benzene ring and a methylsulfonyl as a leaving group are 10 and 5 times more potent than their unsubstituted counterparts, respectively. Compounds bearing a methylsulfonyl as a leaving group are more potent than those bearing a chlorine.


Possibilities to group nanomaterials across different substances - A case study on organic pigments.
Grouping concepts to reduce the testing of NFs have been developed for regulatory purposes for different forms of the same substance. Here we explore possibilities to group nanomaterials across different substances for non-regulatory applications, using the example of 16 organic pigments from six chemical classes. Organic pigments are particles consisting of low-molar-mass organic molecules, and rank by tonnage among the most important substances manufactured in nanoform (NF). Tiered testing strategies relevant to the inhalation route included Tier 1 (deposition, dissolution, reactivity, inflammation) and if available Tier 3 data (in vivo). A similarity assessment of the pigment NF data was conducted in a quantitative (Tier 1 and Tier 3 in vivo potency) or qualitative (Tier 3 in vivo effects) manner. We observed that chemical similarity of organic pigments was predictive for their similarity of reactivity and dissolution, but that additional NF descriptors such as surface area or size, modulate the similarity in inflammation or cytotoxicity. We applied the concept of biologically relevant ranges to crop the values of the Tier 1 data matrix before applying similarity algorithms. The Tier 3 assessment by in vivo inhalation confirmed the IATA methodical choices and IATA assessment criteria as consistent and conservative. We suggested limits of acceptable similarity for Tier 1 data and demonstrated their application to support the grouping of some candidate NFs (subsequently confirmed by Tier 3 data). Four candidate NFs exceeded the limits of acceptability for Tier 1 and were escalated from Tier 1 to Tier 3, but were then included in the group, demonstrating the conservative Tier 1 criteria. The resulting group of low-solubility, low-reactivity materials included both NFs and non-NFs of various substances, and could find use for risk management purposes in the occupational handling of pigment powders.


The value of edema fluid protein measurement in patients with pulmonary edema.
Alveolar fluid and plasma proteins were analyzed in 24 patients with florid pulmonary edema, in 21 of whom pulmonary capillary wedge pressure (Pcw) was also measured. In all patients with Pcw less than 20 mm Hg, the edema fluid to plasma protein ratio exceeded 0.6; the mean edema fluid to plasma protein ratio in the four patients with cardiogenic edema (increased Pcw) was 0.46. In the 21 patients in whom full data were available, the net intravascular filtration force (Pcw - plasma colloid osmotic pressure) was less than -4 mm Hg, the value at which (according to others) pulmonary edema should occur, in only 10. When the interstitial colloid osmotic pressure, approximated by the osmotic pressure of edema fluid protein, was added, the net filtration force became positive in 17 of 21 patients. Comparison of the protein concentrations of edema fluid and plasma aids in the diagnostic separation of increased permeability from high hydrostatic pressure edema and adds to our understanding of the relative osmotic and hydrostatic forces that contribute to pulmonary edema when the alveolar-capillary membrane is damaged.


Comparison of the 40 kDa hematopoietic cell antigens bound by monoclonal antibodies IV.3, 41H.16 and KB61.
A study is presented which compares the properties of antigens with relative mol. mass of about 40,000, detected by three different monoclonal antibodies: IV.3, 41H.16 and KB61. Antibody IV.3 has been shown (in work by other investigators) to detect the Fc receptor for IgG. It recognizes this molecule on neutrophils, macrophages and platelets. Antibody 41H.16 precipitates a molecule of mol. wt of approximately 40,000, which is present on B cells, neutrophils and macrophages. The antigens precipitated by IV.3 and 41H.16 have been compared by isoelectric focusing, sequential antibody-mediated affinity chromatography and trypsin hydrolysis. The results indicate that these two antibodies bind different molecules of similar relative mol. mass. A third antibody, KB61, has been reported, which also reacts with a 40,000 mol. wt molecule and has a distribution of cellular reactivity which is similar to 41H.16. Sequential preclearing experiments have shown that these molecules recognize the same antigen.


Does bicarbonate correct coagulation function impaired by acidosis in swine?
Coagulopathy is an important contributor to morbidity and mortality in trauma patients. Acidosis contributes to coagulopathy. Acidosis can be neutralized with intravascular bicarbonate, but it is unclear if the coagulation defect is rapidly reversed. The effects of acidosis and bicarbonate neutralization on coagulation function were investigated in vivo. Acidosis was induced in 12 pigs by infusing 0.2 mol/L HCl to pH 7.1. Pigs were then infused with either LR to maintain a pH of 7.1 (A-LR, n = 6) or 0.3 mol/L bicarbonate to a pH of 7.4 (A-Bi, n = 6). Blood samples were taken at baseline, 15 minutes after acidosis induction, and 15 minutes after bicarbonate neutralization. Coagulation function was assessed by prothrombin time (PT), partial thromboplastin time (PTT), thrombin generation, initial clot formation time (R), clotting rapidity (alpha), and clot strength (MA). Compared with baseline values, acidosis reduced fibrinogen concentration to 66% +/- 2% in A-LR and to 71% +/- 3% in A-Bi, and decreased platelet counts to 49% +/- 4% in A-LR and to 53% +/- 4% in A-Bi. Thrombin generation decreased to 60% +/- 4% in A-LR and to 53% +/- 7% in A-Bi. Acidosis prolonged PT and PTT about 20% and decreased alpha and MA. After pH neutralization, fibrinogen and platelet levels remained depleted and no reversal of acidosis-induced changes in thrombin generation, PT, PTT, alpha, and MA were observed. Acidosis impaired coagulation by depleting fibrinogen and platelets and by inhibiting clotting kinetics. The deficit associated with acidosis was not reversed with bicarbonate pH neutralization.


Open Versus Arthroscopic Latarjet for Recurrent Anterior Shoulder Instability: A Systematic Review and Meta-analysis.
The open Latarjet (OL) procedure and arthroscopic Latarjet (AL) procedure are able to treat recurrent anterior shoulder instability (RASI) with high success rates. To evaluate the clinical efficacy and postoperative revisions and complications between the OL and AL procedures in the treatment of RASI. Systematic review; Level of evidence, 3. MEDLINE, Embase, and the Cochrane Library were searched to retrieve and include cohort studies comparing the OL and AL procedures for RASI. Clinical outcomes were compared, and results were reported as odds ratios (ORs) or mean differences (MDs) with 95% CIs. Eleven clinical trials with 1217 patients were included. There were no differences between the procedures in pain score, Rowe score, Walch-Duplay score, external rotation, persistent apprehension, instability, recurrence, revisions attributed to recurrent instability, overall complications, wound infection, hematoma, graft complications, screw-related complications, or osteoarthritis. When compared with the OL procedure, the AL procedure had a significantly lower nonunion rate (OR, 9.92; 95% CI, 1.71 to 57.71; P = .01); however, the AL procedure had a longer operation time (MD, -24.49; 95% CI, -48.44 to -0.54; P = .05), lower Western Ontario Shoulder Instability Index score (MD, 97.27; 95% CI, 21.91 to 172.63; P = .01), higher revision rate (OR, 0.39; 95% CI, 0.16 to 0.95; P = .04), and greater screw deviation (MD, -6.41; 95% CI, -10.25 to -2.57; P = .001). For most outcome measures, no difference was seen between the OL and AL procedures. The AL procedure had a lower Western Ontario Shoulder Instability Index score and a higher revision rate and appeared to have a significant learning curve. However, the AL procedure resulted in a lower nonunion rate.


Estimation of personal exposure to ambient nicotine in daily environment.
To evaluate the actual exposure level of nonsmokers to environmental tobacco smoke (ETS) in their daily life, the exposure level of ambient nicotine was measured with a nicotine personal monitor carried by a nonsmoker. Average exposure levels of nicotine, even in such smoky places as cars, coffee shops and pubs, were less than 45 micrograms/m3. As a result of all-day monitoring, the highest amount of nicotine inhaled in a day was estimated, in this study, to be up to 310 micrograms, equivalent to actively smoking 0.31 ordinary cigarettes.


Evaluation of epilepsy and burn patterns in a tertiary hospital in southwestern Iran.
Based on the high rates of burn injuries in patients with epilepsy, it is crucial to evaluate the epidemiological factors, etiology, types of burns, and outcome of these certain individuals and to enhance knowledge about the possible risks of epilepsy-related burns by preventive actions and programs. Our retrospective study was carried out from September 2013 to February 2017 in Amir-al Momenin Hospital, a tertiary referral burns and plastic surgery healthcare center. Because of the fact that a number of patients with burns had experienced their trauma at the time of convulsion or in postconvulsion phase, it is necessary to evaluate the outcome, burn patterns, etiology of injury, and related epidemiological factors in order to develop a greater understanding of possible risks of epilepsy-related burns by preventive actions and programs. In our study, 2715 patients who referred to burn centers and hospitalized with a mean age of 26.838 (standard deviation (SD) = 21.186) were enrolled, in which 29 patients were involved in burn accidents due to epilepsy and seizure, resulting in a 1.1% epilepsy incidence in these individuals. In patients with seizure disorder, there was a mean rate of 5.8 (SD = 1.923) cases per year. Eighteen (62.1%) were male, and 11 (37.9%) were female. There were no cases of seizure-induced burn injury in pediatrics (<15 years) in our study. Among the patients with seizure-induced burns, 11 (out of 1101; 37.9%) were from rural areas, while 18 (out of 1570; 62.1%) were from urban locations. The occurrence of accidents due to seizure was also categorized based on the season, with the highest occurrence during winter (12 out of 683; 41.4%) and lowest during spring (3 out of 659; 10.3%). The mechanism of burn in patients with seizures was also documented, in which 12 (41.4%) were due to liquid, 12 (41.4%) due to fire, 1 (3.4%) due to explosion, and 1 (3.4%) due to other objects. Out of patients with seizure-induced burns, 21 (72.4%) were discharged, 2 released with their own will, 1 was transferred, and 5 (17.2%) died in the course of hospitalization. This study demonstrates that burn injuries by epilepsy are a public health concern in low- and middle-income countries. Therefore, we suggest the execution of a strong national epilepsy preventive actions and programs, as well as proper education for both medical practitioners and patients of the possible dangers as part of an injury control program.


Thalamic stimulation in absence epilepsy.
The site specific effects of two different types of electrical stimulation of the thalamus on electroencephalic epileptic activity as generated in the cortico-thalamo-cortical system were investigated in genetic epileptic WAG/Rij rats, a well characterized and validated absence model. First, 12 male rats received low frequency (double-pulse pairs of 2.5Hz, 150 μA intensity and 30s inter-pair-interval) open-loop stimulation to either the Ventral-Postero-Medial (VPM) or the Anterior Thalamic Nucleus (ATN) for 8h. Second, rats received high frequency (130Hz, pulse train of 1s) closed-loop stimulation applied to either VPM or ATN whenever a spike-wave discharge (SWD) was automatically detected. Low frequency stimulation induced 8Hz SWD-like afterdischarges (AD). AD were frequently seen in VPM but rarely in ATN stimulated rats. AD, recorded in cortex and thalamus, showed a strong temporal coherence (visually assessed) and opposite spike polarities. Properties of AD and spontaneous SWD were equally affected by the stimulation. Closed-loop high frequency stimulation disrupted spontaneous SWD with no difference between ATN and VPM stimulated rats. 89% of SWD could be disrupted leading to a decrease in average SWD duration from 9 to 1.5s. Low frequency stimulation induced AD, which strongly mimic SWD. Moreover, the effects were site-specific. High frequency thalamic stimulation disrupts ongoing SWD probable by interfering with the slow firing pattern of cortico-thalamo-cortical neurons seen during SWD cycle. The absence of stimulation site specificity for high frequency stimulation might be due to the fact that stimulation only started on average 1s after SWD onset when SWD are already fully expressed in the bidirectional cortico-thalamo-cortical resonance system.


Serum and platelet lipoamide dehydrogenase in Friedreich's ataxia.
Pyruvate dehydrogenase (PDH), alpha-keto glutarate dehydrogenase (alpha-KGDH) and lipoamide dehydrogenase (LAD) were measured in platelets of 11 patients with typical Friedreich's ataxia and 10 normal control subjects. Serum LAD was also evaluated in the same patients. No statistically significant changes were found in platelets for the group as a whole, although some patients had low values (more than one standard deviation below control mean). Serum LAD was significantly reduced in the patients with Friedreich's ataxia. This was not due to associated diabetes.


Vinexin: a novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization.
Using the yeast two-hybrid system and an in vitro binding assay, we have identified a novel protein termed vinexin as a vinculin-binding protein. By Northern blotting, we identified two types of vinexin mRNA that were 3 and 2 kb in length. Screening for full-length cDNA clones and sequencing indicated that the two mRNA encode 82- and 37-kD polypeptides termed vinexin alpha and beta, respectively. Both forms of vinexin share a common carboxyl-terminal sequence containing three SH3 domains. The larger vinexin alpha contains an additional amino-terminal sequence. The interaction between vinexin and vinculin was mediated by two SH3 domains of vinexin and the proline-rich region of vinculin. When expressed, vinexin alpha and beta localized to focal adhesions in NIH 3T3 fibroblasts, and to cell-cell junctions in epithelial LLC-PK1 cells. Furthermore, expression of vinexin increased focal adhesion size. Vinexin alpha also promoted upregulation of actin stress fiber formation. In addition, cell lines stably expressing vinexin beta showed enhanced cell spreading on fibronectin. These data identify vinexin as a novel focal adhesion and cell- cell adhesion protein that binds via SH3 domains to the hinge region of vinculin, which can enhance actin cytoskeletal organization and cell spreading.


Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis.
TRIM/RBCC are a large family of proteins that include more than 80 proteins, most of which act as E3 ligases and catalyze the direct transfer of Ubiquitin, SUMO and ISG15 on specific protein substrates. They are involved in oncogenesis processes and in cellular immunity. On this topic, we focus on TRIM8 and its multiple roles in tumor pathologies. TRIM8 inhibits breast cancer proliferation through the regulation of estrogen signaling. TRIM8 downregulation in glioma is involved in cell proliferation, and it is related to patients' survival. Several studies suggested that TRIM8 regulates the p53 suppressor signaling pathway: it is involved in the NF-kB pathway (Nuclear Factor kappa light- chain-enhancer of activated B cells) and in STAT3 (Signal Transducer and Activator of Transcription 3) of the JAK-STAT pathway. In this review, we summarize how the association between these different pathways reflects a dual role of TRIM8 in cancer as an oncogene or a tumor suppressor gene.


Amelioration of Danhong injection on the lipopolysaccharide-stimulated systemic acute inflammatory reaction via multi-target strategy.
Systemic inflammatory response syndrome (SIRS), leading to dire consequences, is a serious and fatal disease in clinic. Danhong injection (DHI), one of the most popular medications for coronary heart disease and cerebral ischemia, plays pharmacological actions through inhibiting local inflammation. Nevertheless, the anti-inflammatory effect of DHI has not been reported before and has not been fully clarified. In this study, a model of systemic acute inflammatory reaction was induced by lipopolysaccharide (LPS) to investigate whether DHI could be applied to SIRS through the anti-inflammatory effect. The anti-inflammatory effect of DHI in vivo was evaluated in ICR mice pretreated intraperitoneally (i.p.) with LPS (1mg/kg) and the serum, liver and kidney were collected. Interleukin (IL)-6, tumor necrosis factor (TNF)-α and monocyte chemotactic protein (MCP-1) in serum were measured by enzyme-linked immunosorbent assay (ELISA) and the mRNA expressions of inducible NO synthase (iNOS), IL-6, interleukin (IL)-1β, MCP-1 in mice liver and kidney were analyzed by quantitative real-time reverse-transcription polymerase chain reaction (real-time RT-PCR). Meanwhile, Proteome profiler array was used to screen the acute phase proteins, cytokines and chemokines activated in the acute inflammation. The inflammatory model of macrophages stimulated by LPS (0.2μg/mL) was used to evaluate the anti-inflammatory mechanism of DHI in vitro. The secretion of nitric oxide (NO) was measured by the Griess reagent system. The productions of prostaglandin E2 (PGE2), IL-6, TNF-α and MCP-1 were detected using ELISA, and the protein expression of cyclooxygenase (COX)-2 was determined by cell-based ELISA. As well, the mRNA expressions of these inflammatory factors were detected by real-time RT-PCR. DHI could attenuate the inflammatory reaction via decreasing 20 cytokines and acute phase proteins analyzed by Proteome profile array in serum. The secretions of IL-6, TNF-α and MCP-1 in serum were coincidence with the result of Proteome profile array. Meanwhile, the mRNA expressions of iNOS, IL-6, IL-1β, MCP-1 in mice liver and kidney were significantly reduced by DHI. Experiments performed in vitro further revealed that the productions of NO, PGE2 and the mRNA expressions of iNOS, COX-2 were notably inhibited by DHI. Cell-based ELISA revealed that the COX-2 protein expression was diminished by DHI. The results of ELISA demonstrated that DHI significantly down-regulated the protein productions of IL-6 and MCP-1. Furthermore, the mRNA expressions of iNOS, COX-2, TNF-α, IL-1β, IL-6 and MCP-1 analyzed by real-time RT-PCR were suppressed by DHI. These results demonstrate that DHI exerts the protective effect through inhibiting the expressions of iNOS, COX-2, IL-1β, IL-6, MCP-1 and TNF-α, which elucidate that DHI may be a strongly multi-target Chinese medicine injection on improving the inflammatory diseases.


Pathophysiology of antiphospholipid antibodies: absence of prostaglandin-mediated effects on cultured endothelium.
Antiphospholipid antibodies are associated with recurrent pregnancy loss and thrombosis. Studies suggest that antiphospholipid antibodies may inhibit the production of prostacyclin by vascular tissues. We incubated sera from women with moderate to high levels of antiphospholipid antibodies with primary human umbilical vein endothelial cell cultures. Intact confluent, subconfluent, hydrogen peroxide-damaged, and mechanically damaged endothelial cell monolayers were evaluated for the production of the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in the presence of sera that were positive and negative for antiphospholipid antibodies. All sera were assayed for baseline concentrations of 6-keto-prostaglandin F1 alpha before incubation with endothelial monolayers. Additionally, the extent of binding of antiphospholipid antibodies to intact and damaged endothelium was studied by immunofluorescent techniques and enzyme-linked immunosorbent assay. Our results indicate that prostacyclin production is not impaired by sera containing antiphospholipid antibodies, regardless of the condition of the endothelium. Further, we were unable to demonstrate binding of immunoglobulin from sera containing antiphospholipid antibodies to intact or damaged endothelium. However, the baseline concentration of 6-keto-prostaglandin F1 alpha was nearly fourfold higher in sera containing antiphospholipid antibodies. The finding of elevated baseline serum concentrations of prostacyclin metabolite in patients with antiphospholipid antibodies suggests a condition of long-term stimulation or altered metabolism of prostacyclin.


Endocrine carcinoma of the stomach: clinicopathological analysis of 27 surgically treated cases in a single institute.
Gastric endocrine carcinoma (EC) is an uncommon tumor of the stomach and the clinical features are not well known. Additionally, the classification and staging systems of this tumor are not yet unified worldwide. In this study, we reviewed 27 patients with gastric EC to evaluate the clinicopathological characteristics of this tumor. We retrospectively reviewed 27 patients with gastric EC among 6466 patients who had undergone gastrectomy between 1986 and 2008 at our institute. Clinicopathological features including immunohistochemistry of Ki-67 were investigated to evaluate the malignant potential of the tumor. Furthermore, survivals were compared between the 7th edition of the International Union Against Cancer (UICC)-TNM (7th TNM) classification for gastric cancer (GC) and the new TNM classification for foregut neuroendocrine tumors (NET). The median survival of the patients was 19.0 months. The 5-year survival rate was 100% in pathological stage (pStage) I, 40% in pStage II, 38% in pStage III, and 11% in pStage IV according to the 7th TNM classification for GC. Survivals by stage showed great difference between the 7th TNM classification for GC and the new TNM classification for foregut NET, but each system correlated with survival. The Ki-67 labeling index was more than 20% in most of the patients. Univariate analysis revealed that maximum tumor diameter, tumor depth, lymph node metastasis, lymphatic invasion, pStage, and curability had significant correlations with survival. Early detection and curative operations are essential for improving the prognosis of gastric EC. However, some adjuvant chemotherapies are required for advanced-stage tumors. Classification and staging systems may need to be unified worldwide for further analysis.


Mass Spectrometry Study of Coumarins: Correlation Between Charges of Atoms and Fragmentation Processes.
The mass spectrometry of a number of 6-substituted coumarins was studied in the context of correlating fragmentation pathways and electronic charges of atoms performed by AM1 semiempirical method. The atomic charges of atoms are found to be good predictors of the fragmentation pathways.


Obesity-related protein biomarkers for predicting breast cancer risk: an overview of systematic reviews.
Based on the biological mechanisms underlying the obesity-breast cancer connections, potential protein biomarkers involved in breast cancer development have been identified, which may be helpful for the estimation of breast cancer risk. This study aimed to carry out a comprehensive overview of systematic reviews on circulating levels of obesity-related protein biomarkers for female breast cancer risk to provide a solid reference for potential breast cancer predictors. Comprehensive literature searches were conducted in MEDLINE, EMBASE and Cochrane Database of Systematic Reviews up to Dec 2019. The AMSTAR tool was used for the methodological quality assessment of the included systematic reviews. Evidence was reported narratively. A total of 28 relevant systematic reviews which were mostly of moderate quality were included in the overview. Protein biomarkers relating to adipokines, insulin/insulin-like growth factor-1 (IGF-1) axis, inflammatory cytokines and sex hormones were investigated. Higher levels of circulating IGF-1, IGF-binding protein-3, leptin and resistin were found to be associated with an increased risk of premenopausal breast cancer; lower levels of circulating adiponectin and higher levels of circulating c-reactive protein, leptin, and resistin were found to be associated with an increased risk of postmenopausal breast cancer. We found sufficient evidence on the positive associations between certain obesity-related protein biomarkers with pre- and/or postmenopausal breast cancer risk. These biomarkers could be used jointly as predictors, so as to build a comprehensive risk predictive score for female breast cancer. CRD42020175328.


Estrogen and testosterone attenuate extracellular matrix loss in collagen-induced arthritis in rats.
Rheumatoid arthritis (RA) is a sexually dimorphic, autoimmune inflammatory disorder affecting the joints. Joint disability in RA results primarily from loss of matrix components (collagen and glycosoaminoglycan) in the cartilage and synovium. This study was carried out to understand the effect of physiological levels of testosterone, estrogen, and progesterone on oxidative stress-induced changes in matrix composition in rat synovium in arthritis. Arthritis induction in castrated and ovariectomized rats resulted in enhanced oxidative stress and this was assessed by lipid peroxidation levels and depletion of antioxidants. This, in turn, led to significantly (p < 0.01) increased levels of TNF-alpha and matrix metalloproteinase-2 (MMP-2), subsequently resulting in loss of collagen, elastin, and glycosoaminoglycan (GAG) and disorganization of reticulin as evidenced by biochemical quantitation and also by staining for collagen, reticulin, and elastin. Treatment with physiological doses of dihydrotestosterone (25 mg topically) and estrogen (5 microg/0.1 ml subcutaneously) restored the antioxidant levels significantly (p < 0.05) and reduced the levels of TNF-alpha and MMP-2, with estrogen exhibiting a higher potency. This, in turn, attenuated the damage to reticulin organization as well as the loss of collagen and GAG in the articular tissues. However, elastin loss could not be attenuated by either treatment. Progesterone (2 mg/0.1 ml subcutaneously) was not shown to have any significance in disease modification, and on the contrary, it inhibited the protective effects of estrogen. However, progesterone contributed to increased collagen levels in the tissues.


Fibrin glue and transanal rectal advancement flap for high transsphincteric perianal fistulas; is there any advantage?
In recent decades, fibrin glue has appeared as an alternative treatment for high perianal fistulas. Early results seemed promising, with high success rates being reported. However, with increasing follow-up, the enthusiasm was tempered because of disappointing results. The aim of this retrospective study was to assess the additional value of fibrin glue in combination with transanal advancement flap, compared to advancement flap alone, for the treatment of high transsphincteric fistulas of cryptoglandular origin. Between January 1995 and January 2006, 127 patients were operated for high perianal fistulas with an advancement flap. After exclusion of patients with inflammatory bowel disease or HIV, 80 patients remained. A consecutive series of 26 patients had an advancement flap combined with obliteration of the fistula tract with fibrin glue. Patients were matched for prior fistula surgery, and the advancement was performed identically in all patients. In the fibrin glue group, glue was installed retrogradely in the fistula tract after the advancement was completed and the fistula tract had been curetted. Minimal follow-up after surgery was 13 months [median of 67 months (range, 13-127)]. The overall recurrence rate was 26% (n=21). Recurrence rates for advancement flap alone vs the combination with glue were 13% vs 56% (p=0.014) in the group without previous fistula surgery and 23% vs 41% (p=0.216) in the group with previous fistula surgery. Obliterating the fistula tract with fibrin glue was associated with worse outcome after rectal advancement flap for high perianal fistulas.


Investigation of toxic effect of mercury on Microcystis aeruginosa: Correlation between intracellular mercury content at single cells level and algae physiological responses.
Single-cell studies can help to understand individual differences and obtain atypical cellular characteristics in view of cellular heterogeneity. Herein, the accumulation of mercury (Hg) in single algae cells was studied by droplet chip-time resolved inductively coupled plasma mass spectrometry analytical system, and the relation of Hg accumulation to the physiological responses of algae cell was explored. When low concentrations of Hg2+ (5-20 μg/L) were used in the exposure experiment, the content of Hg in single cells increased in first 2 h, then decreased with further increase of exposure time to 96 h, probably due to the growth dilution effect of the algae. When exposed to 30 μg/L Hg2+, the uptake of Hg by individual cells increased over time, which was associated with increased cell membrane permeability. The exposure to Hg2+ (5-30 μg/L) inhibited the growth of algae in a concentration-dependent manner and serious growth inhibition occurred under the exposure concentration of 30 μg/L. While the exposure concentration was lower than 20 μg/L, algal cells exhibited a recover tendency due to the self-protection mechanism of algal cells. Bivariate results showed that intracellular Hg accumulation was significantly negatively correlated with cells growth in terms of OD680, photosynthetic pigments, Fv/Fm and PIabs. On the contrast, reactive oxygen species content, superoxide dismutase activity, and cell membrane permeability were significantly positively correlated with the accumulation of intracellular Hg. These results are helpful to further understand the toxic effect of Hg on algae.


Effect of acetylcholine on single Ca2(+)-activated K+ channels in bovine chromaffin cells.
The single channel current amplitudes of "maxi" Ca2(+)-activated K+ channels from bovine chromaffin cell membranes are reduced when acetylcholine is applied to the internal surface of the membrane, which can be explained by a fast channel block. The block is concentration dependent with moderate affinity. It becomes progressively greater with depolarization although the voltage dependence is not pronounced. Acetylcholine reduces the probability of the open state in the same concentration range and in an essentially voltage independent manner. The changes in the channel kinetics are complex. Whilst the long component of the open intervals is shortened (by 48%; from 9.5 to 5.1 ms), the long component of the closed intervals is prolonged (by 96%; from 45 to 89 ms). The short components (open and closed) are essentially unaffected. Short open intervals are reduced by 4% (from 1.09 to 1.05 ms), whilst short closed intervals are reduced by 5% (from 2.3 to 2.2 ms). These changes in the channel kinetics can be explained at least partly if one assumes that acetylcholine, in addition to its fast channel blocking activity, acts also as a slow blocker. If so, both binding sites are expected to be located close to the mouth of the channel pore. Alternatively, acetylcholine may be affecting the gating mechanism, presumably by interfering with the Ca2+ binding.


Environmental VOSCs--formation and degradation of dimethyl sulfide, methanethiol and related materials.
Volatile organic sulfur compounds (VOSCs) play a major role in the global sulfur cycle. Two components, dimethyl sulfide (DMS) and methanethiol (MT) are formed in large amounts by living systems (e.g. algae, bacteria, plants), particularly in marine environments. A major route to DMS is by action of a lyase enzyme on dimethylsulfoniopropionate (DMSP). DMSP has other roles, for instance as an osmoprotectant and cryoprotectant. Demethiolation of DMSP and other materials leads to MT. A major transport process is release of DMS from the oceans to the atmosphere. Oxidation of DMS in the atmosphere by hydroxyl and nitrate radicals produces many degradation products including CO2, COS, dimethyl sulfoxide, dimethyl sulfone, organic oxyacids of sulfur, and sulfate. These materials also have roles in biotic processes and there are complex metabolic interrelationships between some of them. This review emphasizes the chemical reactions of the organic sulfur cycle. For biotic reactions, details of relevant enzymes are provided when possible.


NO donors potentiate the beta-adrenergic stimulation of I(Ca,L) and the muscarinic activation of I(K,ACh) in rat cardiac myocytes.
The effects of nitric oxide (NO) donors on the L-type Ca(2+) current (I(Ca,L)) and the muscarinic activated K(+) current (I(K,ACh)) were studied in isolated rat cardiac myocytes. The nitrosothiol S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1 pM-1 microM) strongly potentiated the stimulation of the I(Ca,L) elicited by subthreshold concentrations of isoprenaline (Iso, 0.1-0.5 nM) in ventricular myocytes. The effect of SNAP was mimicked by 2-(N,N-diethylamino)-diazenolate-2-oxide (DEANO, 1 pM-1 nM), a NONOate that spontaneously releases NO in a pH-controlled manner, and was blunted by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (100 microM), a NO trap. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxaline-1-one (10 microM), a guanylyl cyclase inhibitor, did not alter the effect of SNAP. SNAP (1 pM-1 microM) did not modify the effect of L858051 (0.1-0.3 microM), a forskolin analogue that activates adenylyl cyclase, on I(Ca,L) and did not enhance the basal I(Ca,L) in the presence of rolipram (1 microM), a phosphodiesterase type 4 inhibitor. Superfusion with Rp-CPT-cAMPS (500 microM), or internal dialysis with cAMP-dependent protein kinase (cA-PK) inhibitory peptide (PKI; 20 microM), inhibitors of the cA-PK, blunted the effect of SNAP (1 nM and 1 microM) on the Iso-stimulated (1-100 pM) I(Ca,L). SNAP (1 nM and 1 microM) potentiated the threshold stimulation of I(Ca,L) elicited by internal GTP-gammaS (10 microM), a non-hydrolysable analogue of GTP. SNAP (1 pM-1 microM) and DEANO (1 microM) potentiated the stimulation of I(K,ACh) elicited by low concentrations of ACh (1-2 nM) in rat atrial myocytes. The threshold stimulation of I(K,ACh) elicited by internal 5'-guanylylimidodiphosphate (10 microM) was also potentiated by NO donors. SNAP (1 microM) did not modify I(K,ACh) reconstituted in human embryonic kidney 293 cells, in the absence or in the presence of ACh (1 or 10 nM). Taken together, these data suggest that NO is a cGMP-independent modulator of G-protein-coupled muscarinic and beta-adrenergic receptor actions on cardiac ion channels. Although this action of NO seemed to occur at the level of G proteins, it appeared to require a component distinct from receptors, G proteins or their effectors.


Landscape ecological concepts in planning: review of recent developments.
Landscape ecology as an interdisciplinary science has great potential to inform landscape planning, an integrated, collaborative practice on a regional scale. It is commonly assumed that landscape ecological concepts play a key role in this quest. The aim of the paper is to identify landscape ecological concepts that are currently receiving attention in the scientific literature, analyze the prevalence of these concepts and understand how these concepts can inform the steps of the planning processes, from goal establishment to monitoring. We analyzed all empirical and overview papers that have been published in four key academic journals in the field of landscape ecology and landscape planning in the years 2015-2019 (n = 1918). Title, abstract and keywords of all papers were read in order to identify landscape ecological concepts. A keyword search was applied to identify the use of these and previously mentioned concepts in common steps of the planning cycle. The concepts Structure, Function, Change, Scale, Landscape as human experience, Land use, Landscape and ecosystem services, Green infrastructure, and Landscape resilience were prominently represented in the analyzed literature. Landscape ecological concepts were most often mentioned in context of the landscape analysis steps and least in context of goal establishment and monitoring. The current literature spots landscape ecological concepts with great potential to support landscape planning. However, future studies need to address directly how these concepts can inform all steps in the planning process. The online version of this article (10.1007/s10980-021-01193-y) contains supplementary material, which is available to authorized users.


Interventions to address parenting and parental substance abuse: conceptual and methodological considerations.
Parental substance abuse is a serious problem affecting the well-being of children and families. The co-occurrence of parental substance abuse and problematic parenting is recognized as a major public health concern. This review focuses on 21 outcome studies that tested dual treatment of substance abuse and parenting. A summary of theoretical conceptualizations of the connections between substance abuse and parenting provides a backdrop for the review. Outcomes of the dual treatment studies were generally positive with respect to reduction of parental substance use and improvement of parenting. Research in this area varied in methodological rigor and needs to overcome challenges regarding design issues, sampling frame, and complexities inherent in such a high-risk population. This area of work can be strengthened by randomized controlled trials, use of mixed-methods outcome measures, consideration of parent involvement with child protective services, involvement of significant others in treatment, provision of concrete supports for treatment attendance and facilitative public policies.


Expanding the injury definition: evidence for the need to include musculoskeletal conditions.
The objectives of the study are to quantify the proportion of cumulative microtraumatic overuse injuries in a physically active population, evaluate their impact in terms of lost work time, and link them to precipitating activities to inform prevention initiatives. The study design is retrospective cohort study. For a population of U.S. Army Soldiers, diagnoses from medical records (International Classification of Diseases [ICD]-9 800-999 and selected ICD-9 710-739) were matched with self-reported injury information. Common diagnoses, limited duty days, and activities and mechanisms associated with the injuries were summarized. Most self-reported injuries (65%) were classified by providers with diagnoses that described cumulative microtraumatic tissue damage, and these injuries led to a higher incidence of limited duty (85%) than acute traumatic injury diagnoses. Reported mechanisms and activities often indicated repetitive physical training-related onset. Because many diagnoses for cumulative microtraumatic musculoskeletal tissue damage are categorized as diseases to the musculoskeletal system in the International Classification of Diseases, they are often not included in definitions of injury. However, reported injury activities and mechanisms in this population provide evidence that cumulative microtraumatic injuries often arise from identifiable and preventable events. This finding confirms that these diagnoses should be classified as injuries in epidemiologic evaluations and surveillance to accurately represent injury burden.