Tactile perception of nonpainful unpleasantness in relation to perceived roughness: effects of inter-element spacing and speed of relative motion of rigid 2-D raised-dot patterns at two body loci.
Rigid surfaces consisting of spatially jittered 2-D raised-dot patterns with different inter-element spacings were moved back and forth across the skin at three different speeds (10-fold range). Within each psychophysical experiment, participants numerically estimated the perceived magnitude of either unpleasantness (nonpainful) or roughness of 2-D raised-dot surfaces applied to two stationary body sites (experiment 1: fingers; experiment 2: forearm). The psychophysical functions for the two types of perceptual judgment were highly similar at both body loci; more specifically, the perceived magnitude of unpleasantness and roughness both increased monotonically as a power function of increasing inter-element spacing, with the rate of growth declining at the upper end of the continuum. These results suggest that inter-element spacing is a critical determinant of the perceived magnitude of unpleasantness (nonpainful), as well as of roughness. Each perceptual judgment also increased as a function of increasing relative speed at both body loci. However, the magnitude of this effect was significantly greater for perceived unpleasantness than for perceived roughness; conversely, the speed effect was significantly greater on the forearm than on the fingers. Several possible explanations for these findings are considered.


Evaluation of the presence of a specific histocompatibility protein on equine embryonic cells.
An indirect immunofluorescence assay was used to detect the presence of H-Y antigen on equine blastocysts. A total of 33 blastocyst stage horse embryos were collected 6 to 7 days post-ovulation by trans-cervical flush and were immediately evaluated for the presence of H-Y antigen. Additionally, 17 embryos, were collected and cultured for 72 h to the expanded blastocyst stage and similarly evaluated. Embryos were placed in medium containing monoclonal antibodies to H-Y antigen followed by incubation in medium containing 1/10 (v/v) fluorescein isothiocyanate conjugated goat anti-mouse IgM Fc specific antiserum. Embryos were individually evaluated at 400X to identify cell specific fluorescence. Following evaluation, embryonic sex was independently verified with karyotypes to identify sex chromosomes. Of the 50 embryos evaluated, 29 were evaluated as non-fluorescent and 21 fluorescent. Expression of H-Y antigen was determined to be uniform in those embryos classified as fluorescent. Twenty-three of 28 (82%) readable karyotypes corresponded to the predicted sex. These results indicate a specific histocompatibility antigen is expressed and maintained at the blastocyst stage of development. In addition, no segregation of this protein on specific cell types occurs in this species.


Bis(glycylglycinium) oxalate at 100 K.
The structure of the title compound, 2C(4)H(9)N(2)O(3)(+).C(2)O(4)(2-), which has been determined by X-ray diffraction, contains discrete glycylglycine (HGly-Gly)(+) cations in general positions and oxalate anions which lie across centres of inversion. Although the geometry of the (HGly-Gly)(+) cation is not significantly different compared with other structures containing this residue, a few changes in conformation are observed which indicate the presence of molecular interactions. The molecular network in the crystal consists of one nearly linear O-H...O, five N-H...O and two weak C-H.O hydrogen bonds.


Clinical Applications of Artificial Intelligence in Glaucoma.
Ophthalmology is one of the major imaging-intensive fields of medicine and thus has potential for extensive applications of artificial intelligence (AI) to advance diagnosis, drug efficacy, and other treatment-related aspects of ocular disease. AI has made impressive progress in ophthalmology within the past few years and two autonomous AI-enabled systems have received US regulatory approvals for autonomously screening for mid-level or advanced diabetic retinopathy and macular edema. While no autonomous AI-enabled system for glaucoma screening has yet received US regulatory approval, numerous assistive AI-enabled software tools are already employed in commercialized instruments for quantifying retinal images and visual fields to augment glaucoma research and clinical practice. In this literature review (non-systematic), we provide an overview of AI applications in glaucoma, and highlight some limitations and considerations for AI integration and adoption into clinical practice.


Gluteal compartment syndrome after laparoscopic surgery in lateral jackknife position: a case report.
We present a case of a 42-year-old obese female with a body mass index of 38.4 kg/m2. Laparoscopic tumor resection of a left nonfunctioning adrenal tumor was performed in the lateral jackknife position, and the operative time was over 5 h. After awakening, she complained right buttock pain, and we suspected bursitis due to the surgical position and decided to follow up the patient. On the second postoperative day, spontaneous pain worsened, and the computed tomography scan of the hip showed significant swelling of the gluteal muscles, which led us to suspect a gluteal compartment syndrome. Intramuscular compartment pressure was measured under general anesthesia at 72 mmHg, and a fasciotomy was performed. The symptoms improved promptly after surgery and completely disappeared 2 months after surgery. Although the gluteal compartment syndrome is a rare condition in which circulation is impaired by compression of the gluteal muscles, treatment should be initiated promptly before serious complications arise.


Effect of respiratory syncytial virus-antibody complexes on cytokine (IL-8, IL-6, TNF-alpha) release and respiratory burst in human granulocytes.
The release of interleukin-8 (IL-8), IL-6, and tumour necrosis factor-alpha (TNF-alpha) from human polymorphonuclear granulocytes (PMN) after exposure to infectious respiratory syncytial virus (RSV) particles was investigated. Our data showed that PMN secreted IL-8 and IL-6 in a time- and RSV-dose-dependent manner. During the RSV exposure, TNF-alpha was not detected in the cell supernatant of PMN. Similar amounts of IL-8 were secreted after either incubation with infectious or UV-inactivated RSV particles. Obviously, PMN bind and phagocytose the viral particles, which leads to the secretion of cytokines. The increased IL-8 secretion was accompanied with an enhanced cytoplasmic IL-8 mRNA steady state level, as shown by Northern blot analysis. The IL-8 secretion pattern from PMN was also studied after its interaction with RSV--antibody complexes. Non-neutralizing monoclonal antibodies (mAb) directed to the RSV fusion protein and glycoprotein were used to generate immune complexes. Only the mAb directed to the RSV fusion protein enhanced the IL-8 release from PMN significantly. In addition, the chemiluminescence response from PMN was analysed after exposure of the cells to RSV particles, RSV-mAb complexes, Ca-ionophore A23187 or N-formyl-methionyl-leucyl-phenylalanine (FMLP). The phagocytosis of RSV inhibited the oxygen radical production induced by the Ca-ionophore A23187 or FMLP. Only RSV-anti-fusion protein mAb complexes generated a chemiluminescence response from PMN. Thus, PMN play an important role in the control of RSV infection.


Fluorinated Fe(III) salophene complexes: optimization of tumor cell specific activity and utilization of fluorine labeling for in vitro analysis.
Fluorine-substituted iron(III) salophene complexes (salophene = N,N'-bis(salicylidene)-1,2-phenylenediamine) were synthesized and evaluated for biological activity. All complexes showed growth inhibitory effects with IC50 values ranging from 0.05 to 2.45 μM against HT-29 colon carcinoma as well as MCF-7 and MDA-MB-231 mammary carcinoma cells (cisplatin: 5.75, 12.72, 5.81 μM, respectively). HR-CS MAS investigations revealed that the complexes were highly protein-bound already after an incubation period of 10 min and accumulated more effectively in tumor cells than cisplatin. Interestingly, the ligands were enriched in the cells too, indicating that the salophene moiety acts as a carrier ligand and mediates the uptake of the complexes. Furthermore, induction of apoptosis proved to be dependent on the substitution pattern as well as on the tumor cell line, as evidenced from the annexin V-FITC/PI assay. Most of the complexes, especially the highly active 5-Fe, showed tumor cell specific effects and no/less influence on the proliferation of T-cells generated from the peripheral blood of healthy individuals.


Novel aspect of neprilysin in kidney fibrosis via ACSL4-mediated ferroptosis of tubular epithelial cells.
Although inhibition of neprilysin (NEP) might be a therapeutic strategy with the potential to improve the outcome of chronic kidney disease (CKD), the versatile function of NEP with its mechanism remains obscure in kidney fibrosis. In the study, we found that NEP was abnormally increased in tubular epithelial cells of CKD patients, as well as unilateral ureteral obstruction and adenine diet-induced mice. Treatment with a United States Food and Drug Administration-approved NEP inhibitor Sacubitrilat (LBQ657) could alleviate ferroptosis, tubular injury, and delay the progression of kidney fibrosis in experimental mice. Similarly, genetic knockdown of NEP also inhibited tubular injury and fibrosis in transforming growth factor (TGF)-β1 -induced tubular cells. Mechanically, NEP overexpression aggravated the ferroptotic and fibrotic phenotype, which was restored by acyl-CoA synthetase long-chain family member 4 (ACSL4) knockdown. The NEP silencing attenuated TGF-β1-induced tubular cell ferroptosis and was exacerbated by ACSL4 overexpression. Collectively, for the first time, a novel aspect of NEP was explored in kidney fibrosis through ACSL4-mediated tubular epithelial cell ferroptosis. Our data further confirmed that NEP inhibition exerted a promising therapeutic against fibrotic kidney diseases.


Effects of dietary supplementation of arginine-silicate-inositol complex on absorption and metabolism of calcium of laying hens.
The effects of supplementation of arginine-silicate-inositol complex (ASI; 49.5-8.2-25 g/kg, respectively) to laying hens were investigated with respect to eggshell quality, calcium (Ca) balance, and expression of duodenal proteins related to Ca metabolism (calbindin and tight junction proteins). A total of 360 laying hens, 25 weeks old, were divided into 3 groups consisting of 6 replicate of cages, 20 birds per cage. The groups were fed a basal diet and the basal diet supplemented with 500 or 1000 mg ASI complex per kilogram for 90 days. Data were analyzed by ANCOVA using data during the first week of the adaptation period as covariates. As the ASI complex supplementation level increased, there were increases in feed intake (P < 0.0001), egg production (P < 0.001), egg weight (P < 0.0001) and eggshell weight (P < 0.001) weight, and shell thickness (P < 0.001) and decreases in feed conversion ratio and cracked egg percentage (P < 0.0001 for both). Concentrations of serum osteocalcin (P < 0.0001), vitamin D (P < 0.0001), calcium (P < 0.001), phosphorus (P < 0.001), and alkaline phosphatase (P < 0.008) as well as amounts of calcium retention (P < 0.0001) and eggshell calcium deposition (P < 0.001), and Ca balance (P < 0.0001) increased, whereas amount of calcium excretion (P < 0.001) decreased linearly in a dose-dependent manner. The ASI complex supplementation increased expressions of calcium transporters (calbindin-D28k, N sodium-calcium exchanger, plasma membrane calcium ATPase, and vitamin D receptor) and tight junction proteins (zonula occludens-1 and occludin) in the duodenum in a linear fashion (P < 0.0001 for all). In conclusion, provision of dietary ASI complex to laying hens during the peak laying period improved eggshell quality through improving calcium utilization as reflected by upregulation of genes related to the calcium metabolism. Further studies are needed to elucidate the contribution of each of the ASI complex ingredients.


[Molecular causes of thalassemia. IV. Cloning of the beta-globin gene in a patient with beta-thalassemia from Azerbaijan and determination of the point mutation in a minor intron].
On the basis of DNA from a beta-thalassemic patient, human gene library has been obtained using bacteriophage lambda EMBL4 as a vector. The recombinants contain human DNA insertions of 15 to 20 kb. The lambda A1 beta 1 clone has been isolated by the method of hybridization of phage plaque replicas to the HhaI fragment of JW102 plasmid containing human beta-globin cDNA. Restriction mapping revealed the presence of a 22 kb human DNA fragment comprising a portion of the beta-globin gene system. Subcloned fragments of beta-globin gene (within the pUC19 plasmid or phage MI3mp10) were sequenced using the Maxam and Gilbert method as well as that of Sanger. 2150 nucleotides in total were analysed. We have detected the point substitution G----A in the 110 nucleotide of minor intron, leading to the formation of an additional splicing site.


Prostaglandin E receptor-4 receptor mediates endothelial barrier-enhancing and anti-inflammatory effects of oxidized phospholipids.
Unlike other agonists that cause transient endothelial cell (EC) response, the products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) oxidation that contain cyclopenthenone groups, which recapitulate prostaglandin-like structure, cause sustained enhancement of the pulmonary EC barrier. The mechanisms that drive the sustained effects by oxidized PAPC (OxPAPC) remain unexplored. On the basis of the structural similarity of isoprostanoid moieties that are present in full-length oxygenated PAPC species, we used an inhibitory approach to perform the screening of prostanoid receptors as potential candidates that mediate OxPAPC effects. Results show that only prostaglandin E receptor-4 (EP4) was involved and mediated the sustained phase of the barrier-enhancing effects of OxPAPC that are associated with the activation of Rac GTPase and its cytoskeletal targets. EC incubation with OxPAPC also induced EP4 mRNA expression in pulmonary ECs and lung tissue. EP4 knockdown using gene-specific small interfering RNA did not affect the rapid phase of OxPAPC-induced EC barrier enhancement or the protective effects against thrombin-induced EC permeability, but abolished the advanced barrier enhancement phase and suppressed the protective effects of OxPAPC against more sustained EC barrier dysfunction and cell inflammatory response caused by TNF-α. Endothelial-specific knockout of the EP4 receptor in mice attenuated the protective effect of intravenous OxPAPC administration in the model of acute lung injury caused by intratracheal injection of LPS. Taken together, these results demonstrate a novel role for prostaglandin receptor EP4 in the mediation of barrier-enhancing and anti-inflammatory effects caused by oxidized phospholipids.-Oskolkova, O., Gawlak, G., Tian, Y., Ke, Y., Sarich, N., Son, S., Andreasson, K., Bochkov, V. N., Birukova, A. A., Birukov, K. G. Prostaglandin E receptor-4 receptor mediates endothelial barrier-enhancing and anti-inflammatory effects of oxidized phospholipids.


Expected and Experienced Pain Levels in Electromyography.
The aim of the present study was to assess pain using a visual analogue scale (VAS) in patients awaiting an EMG procedure (i.e., expected VAS) and after an EMG procedure (i.e., experienced VAS). Expected and experienced pain in response to nerve conduction studies (NCS) and needle EMG were assessed in 108 patients (61 females, 47 males; mean age 43.2±11.6) using a VAS. No significant correlations were noted between the expected or the experienced VAS in response to EMG and demographic features of the patients. The expected VAS was significantly higher than the experienced VAS in response to needle EMG (p=0.005). The highest VAS level was noted in the expected VAS in response to needle EMG (4.7±2.2). The lowest VAS level was noted in the experienced VAS in response to NCS (3.6±2.5). The present study demonstrated that neither the expected nor the experienced pain associated with EMG exceeded a moderate level. Interestingly, we found that expected pain levels in response to needle EMG were significantly higher than experienced pain levels. Therefore, it may be possible to increase compliance if patients are provided with this information before undergoing electrophysiological procedures.


Regulation of Na-K-ATPase gene expression by angiotensin II in vascular smooth muscle cells.
Na-K-adenosinetriphosphatase (Na-K-ATPase) activity profoundly influences vascular cell excitability, contractility, and volume regulation. We investigated the effect of angiotensin II on Na-K-ATPase gene expression in cultured rat vascular smooth muscle cells (VSMC). Na-K-ATPase alpha 1- and beta 1-isoform mRNAs, but not alpha 2- and alpha 3-isoform mRNAs, were expressed in cultured rat VSMC. Angiotensin II (1 microgram/ml) caused a threefold increase in alpha 1-mRNA accumulation and a fourfold increase in beta 1-mRNA accumulation; the peak increases for both alpha 1- and beta 1-mRNA were observed at 6 h. Angiotensin II induced alpha 1- and beta 1-mRNA expression in a dose-dependent manner. Pretreatment of VSMC with cycloheximide (20 micrograms/ml) or actinomycin D (5 micrograms/ml) completely inhibited angiotensin II-induced alpha 1-mRNA accumulation. Even after protein kinase C (PKC) activity was functionally depleted by treating VSMC with phorbol 12-myristate 13-acetate (10(-6) M) for 24 h, angiotensin II increased alpha 1-mRNA accumulation. The angiotensin II-induced increase in alpha 1-mRNA accumulation was associated with an increase in alpha 1-subunit protein accumulation. These results indicate that angiotensin II stimulates Na-K-ATPase alpha 1- and beta 1-isoform gene expression in VSMC and that the effect is mediated not via activation of PKC but needs synthesis of intermediate regulatory protein(s).


Correlation of body mass index with thoracic and abdominal panniculus.
Obesity can play a significant role in chronic diseases, sudden unexpected death, and morbid obesity may be important as a cause of death for forensic pathologists. Our study attempted to determine if there is a correlation between panniculus measurements and body mass index (BMI) since BMI has been used in most studies to categorize obesity. Using data obtained from a review of 524 adult autopsies conducted at the University of Michigan from 1990 to 1992 we were able to show a correlation between both thoracic and abdominal panniculus and BMI (r2 = 0.335 and 0.296 respectively) which is statistically significant (p = 10(-47) and 10(-41) respectively). A prospective study confirmed the correlation (r2 = 0.552 for thoracic and 0.436 for abdominal panniculus) when the measurements were taken at the xyphoid process and 3 cm below the umbilicus. Using these data we calculated a panniculus index (PI) which is equal to the thoracic + abdominal panniculus in centimeters divided by the square of the height (in meters). The PI strongly correlated with BMI and was able to predict obesity. Using a BMI cutoff of 39 for morbid obesity, a PI value of 4.07 for females and 3.25 for males predicted morbid obesity with the probability of a false positive less than or equal to 2.5%. Mild and severe obesity could also be determined using the PI. Based on these data we've concluded that a concise mathematical relationship does exist between BMI and panniculus measurements. Therefore panniculus measurements can be used either as a surrogate measurement of morbid obesity or to support BMI calculations.


IgY antibody and human neurocysticercosis: a novel approach on immunodiagnosis using Taenia crassiceps hydrophobic antigens.
Human neurocysticercosis (NCC) is a worldwide neglected disease caused by Taenia solium metacestode and responsible for various complications and neurological disorders. This study aimed to evaluate the use of specific immunoglobulin Y (IgY) produced by laying hens immunized with a hydrophobic fraction of Taenia crassiceps metacestodes (hFTc) in NCC diagnosis. Egg yolk IgY antibodies were fractionated, purified and characterized. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the production kinetics and avidity maturation of anti-hFTc IgY antibodies throughout the IgY obtention process. Antigen recognition tests were carried out by Western blotting and immunofluorescence antibody test using purified and specific anti-hFTc IgY antibodies for detection of parasitic antigens of T. crassiceps and T. solium metacestodes. Sandwich ELISA was performed to detect circulating immune complexes formed by IgG and parasitic antigens in human sera. The results showed high diagnostic values (93.2% sensitivity and 94.3% specificity) for immune complexes detection in human sera with confirmed NCC. In conclusion, specific IgY antibodies produced from immunized hens with hFTc antigens were efficient to detect T. solium immune complexes in human sera, being an innovative and potential tool for NCC immunodiagnosis.


Vitamin D status and healthy Egyptian adolescents: Where do we stand?
Vitamin D deficiency is a worldwide public health problem. Low vitamin D and its consequences among children and adolescents could be considered as one of the most important health-related problems. This study aimed to estimate the prevalence of vitamin D deficiency in healthy Egyptian adolescents and investigate factors associated with vitamin D status.A cross-sectional study was conducted on 572 school children (270 males and 302 females) aged 14 to 18 years, who were randomly selected from high schools in one governorate in Egypt. Data were collected through a self-administered questionnaire. Vitamin D level, serum calcium, phosphorus, alkaline phosphates were measured.Vitamin D deficiency was almost present in all the studied Egyptian healthy adolescents (99%), 94.8% had vitamin D deficiency and 4.2% had vitamin D insufficiency. Girls had a higher prevalence of vitamin D deficiency than boys. There was a significant association between lack of physical activity, sun exposure, and vitamin D deficiency.Vitamin D deficiency and insufficiency are highly prevalent. In sunny countries, the special pattern of conservative clothing and the lack of outdoor physical activity might be the underlying factors for the high prevalence in females. Vitamin D supplementation seems to be mandatory to halt the problem.


WY 14,643 inhibits human aldose reductase activity.
Aldose reductase (AR) is implicated to play a critical role in diabetes and cardiovascular complications because of the reaction it catalyzes. Our data reveal that peroxisome proliferator WY 14,643, follows a pure non-competitive inhibition pattern in the aldehyde reduction activity as well as in the alcohol oxidation activity of AR. This finding communicates for the first time a novel feature of WY 14,643 in regulating AR activity. In addition, this observation indicates that AR, AR-like proteins and aldo-keto reductase (AKR) members may be involved in the WY 14,643 mechanism of action when it is administered as PPAR agonist.


Characterization of drug metabolism enzymes in estrogen-induced kidney tumors in male Syrian hamsters.
In an attempt to characterize metabolism enzymes of the estrogen-induced kidney tumor in male Syrian hamsters, the activities of enzymes involved in drug and glutathione metabolism were determined in tumor tissue. Kidney tumors were induced in male Syrian hamsters by treatment with estradiol for 8 months. Cytochrome P-450 and cytochrome b5 concentrations in tumors were below detectable levels. However, when cytochrome P-450-mediated oxidation was analyzed by product formation assays, the oxidation of E-diethylstilbestrol to diethylstilbestrol-4',4"-quinone by tumor microsomes was 10-20% of the rate found in control microsomes. In kidney tissue surrounding estrogen-induced tumors, cytochrome P-450 and b5 contents were 50-60% less than those in untreated kidney. Activities of reducing enzymes of drug metabolism (cytochrome P-450, cytochrome b5 and NADH:cytochrome c reductases), glutathione metabolism enzymes (glutathione peroxidase, glutathione transferase, glutathione reductase, and gamma-glutamyl transpeptidase), and free radical scavenging enzymes (superoxide dismutase, catalase, and quinone reductase) in tumor were significantly lower than in untreated kidney tissue. The activities of these enzymes in renal tumor surrounding tissue were between those observed in tumor and control kidney. Glucose-6-phosphate dehydrogenase activity was increased by 50% in surrounding tissue and 430% in tumor compared to values in untreated controls. The decreased enzyme activity levels in hormone-exposed tissue surrounding tumors likely represented an adaptation of this tissue to the neoplastic environment induced by chronic estrogen treatment.


A story description task in children with Down's syndrome: lexical and morphosyntactic abilities.
A story description task was used to elicit short stories by 10 Italian children and adolescents with Down's syndrome and 10 normal children matched on mean length of utterance (MLU). Data analysis focused on a subset of lexical, morphological and syntactic aspects of language use. The results show that the subjects with Down's syndrome and their normal matches use a similar lexical repertoire. However, the two groups differ with respect to omissions of free morphemes, and some aspects of syntactic and pragmatic abilities. These data on Italian subjects corroborate and extend previous findings on other languages: despite an extensive repertoire of lexical and grammatical items, subjects with Down's syndrome seem unable to use such elements appropriately and consistently across contexts.


Paraplegia with lumbar artery compression by the diaphragmatic crus.
The authors report three cases of transient and recurrent paraplegia due to compression of the second right lumbar artery by the diaphragmatic crus. Circumstances of appearance are suggestive when paraplegia occurs in dorsolumbar hyperlordosis and low cardiac output is an associated hemodynamic risk factor. Selective medullary arteriography is indispensable for diagnosis and can demonstrate three signs: an anterior spinal dorsolumbar artery (artery of Adamkiewicz) that does not descend to the conus medullaris; posterior spinal arteries arising from the second lumbar arteries that vascularize the conus medullaris; existence of a tight stenosis on the second right lumbar artery that is aggravated during dynamic maneuvers. Section of the right diaphragmatic crus and release of the second right lumbar artery from the aorta to the fibrous arcade of the psoas permits definitive cure of symptoms.


Nucleoporin 50 proteins affect longevity and salinity stress tolerance in seeds.
Nucleoporin 50 (Nup50) is an evolutionarily conserved protein that is a constituent of the nuclear pore complex (NPC); however, its physiological role in plants is unclear. Arabidopsis has two Nup50 proteins, Nup50a and Nup50b, which are highly expressed in developing seeds. GFP-fused Nup50a and Nup50b are localized exclusively in the nucleopolasm, implying an additional function beyond the NPC in the nuclear envelope. To investigate the function of Nup50s, we employed the CRISPR/Cas9 system to generate a nup50a nup50b double mutant, which exhibited premature translation termination of both Nup50 proteins. While the mutant showed no significant abnormal phenotype during vegetative growth, the nup50a nup50b seeds had an abnormal shape compared to wild type. Comparative transcriptomics using immature seeds revealed that Nup50s regulate the expression of various genes, including cell-wall-related genes. The nup50a nup50b seeds exhibited reduced seed longevity and salinity-stress tolerance. Tetrazolium uptake and mucilage release assays implied that the nup50a nup50b seeds had greater water permeability than the wild type. Taken together, our results imply that Nup50s play a critical role in seed formation by regulating gene expression.


[A community-based case-control study on risk factors of hyperuricemia among residents in the community].
To investigate the risk factors of hyperuricemia among residents aged >/= 20 years. A community based case-control study was conducted in 286 patients with 858 controls without hyperuricemia. Available data were analyzed by mono-factorial and multi-factorial logistic regression methods using SPSS 10.0 software. 17 factors related to exposure were identified for hyperuricemia the mono-factorial analysis when; five factors were selected through multiple factoral logistic regression model at P = 0.05 level. The risk factors on hyperuricemia were: hypertriglyceridemia (OR = 3.069), alcohol consumption (OR = 2.032), obesity (OR = 1.802), taste of spicy food (OR = 1.877) and hyperglycemia (OR = 1.622). Hyperuricemia is a disease associated with environment and style-life. Changing lifestyle, such as decreasing alcohol consumption and adopting proper structure of diet may prevent or decrease the chance of getting hyperuricemia and gout.


[Notes on electrocardiograms of patients over 70].
A survey of 504 ECGs from persons over 70 years old revealed a considerable percentage of perfectly normal tracings. Among the pathological tracings, there was a marked predominance of rhythm as opposed to conduction disturbances, and a large percentage of ischaemic atypias and left axial deviations. A comparison with other reported series indicated that discrepancies in the values presented can primarily be attributed to differences in the composition of the series themselves.


Matching the chirality of monodentate N-heterocyclic carbene ligands: a case study on well-defined palladium complexes for the asymmetric alpha-arylation of amides.
N-Heterocyclic carbene ligands derived from C(2)-symmetric diamines with naphthyl side chains are introduced as chiral monodentate ligands, and their palladium complexes (NHC)Pd(cin)Cl are prepared. These compounds exist as a mixture of diastereomers, and the palladium complexes can be successfully separated and their absolute stereochemistry assigned. When used in the asymmetric intramolecular alpha-arylation of amides, oxindoles with quaternary carbon centers can be obtained in high yield and selectivity when correctly matching the chirality of the NHC complexes.


Mutual-Attention Net: A Deep Attentional Neural Network for Keyphrase Generation.
Neural keyphrase generation (NKG) is a recently proposed approach to automatically extract keyphrase from a document. Unlike the traditional keyphrase extraction, the NKG can generate keyphrases that do not appear in the document. However, as a supervised method, NKG is hindered by noise. In order to solve the problem that the existing NKG model does not consider denoising the source document, in this work, this paper introduces a new denoising architecture mutual-attention network (MA-net). Considering the structure of documents in popular datasets, the multihead attention is applied to dig out the relevance between title and abstract, which aids denoising. To further accurate generation of high-quality keyphrases, we use multihead attention to compute the content vector instead of Bahdanau attention. Finally, we employ a hybrid network that augments the proposed architecture to solve OOV (out-of-vocabulary) problem. It can not only generate words from the decoder but also copy words from the source document. Evaluation using five benchmark datasets shows that our model significantly outperforms the state-of-the-art ones currently in the research field.


Bifunctional Role of LiNO3 in Li-O2 Batteries: Deconvoluting Surface and Catalytic Effects.
Out of the many challenges in the realization of lithium-O2 batteries (LOB), the major is to deal with the instability of the electrolyte and the cathode interface under the stringent environment of both oxygen reduction and evolution reactions. Lithium nitrate was recently proposed as a promising salt for LOB because of its capability to stabilize the lithium anode by the formation of a solid electrolyte interphase, its low level of dissociation in aprotic solvents, and its catalytic effect toward oxygen evolution reaction (OER) in rechargeable LOB. Nevertheless, a deeper understanding of the influence of nitrate on the stability and electrochemical response of the cathode in LOB is yet to be realized. Additionally, it is well accepted that carbon instability toward oxidation is a major reason for early failure of LOB cells; therefore, it is essential to investigate the effect of electrolyte components on this side of the battery. In the present work, we show that nitrate leads to interfacial changes, which result in the formation of a surface protection domain on the carbon scaffold of LOB cathode, which helps in suppressing the oxidative damage of the carbon. This effect is conjugated with an additional electrocatalytic effect of the nitrate ion on the OER. Using in operando online electrochemical mass spectroscopy, we herein deconvolute these two positive effects and show how they are dependent on nitrate concentration and the potential of cell operation. We show that a low amount of nitrate can exhibit the catalytic behavior; however, in order to harness its ability to suppress the oxidative damage and passivate the carbon surface, an excess of LiNO3 is required.


Effects of Adverse Childhood Experiences on Sleep Quality in People With Drug Addiction and Non-Addicts and the Role of Resilience Between Them.
People with drug addiction are more likely to suffer from sleep disorders than non-addicts. The roles that childhood adversity experiences and resilience play in the development of sleep disorders will be explored in this study. A total of 459 participants with drug addiction and 400 non-addicts were investigated with the Adverse Childhood Experiences (ACEs) Scale, Pittsburgh Sleep Quality Index (PSQI), and Connor-Davidson Resilience Scale from April 2019 to December 2020. Our results suggested that participants with drug addiction had worse sleep quality compared to non-addicts. Resilience acted as a mediator and significantly affected the relationship between ACEs and sleep quality. For all participants who experienced ACEs, individuals with high resilience reported lower PSQI score, the regulatory effect of medium and high resilience on sleep quality was better than that of low resilience. Moreover, comparing to the non-addicts who experienced mild ACEs, high resilience showed a good buffer effect on the sleep quality for people with drug addiction. And high resilience played a stronger regulatory role in females as compared to males. The results help to broaden the relevant research in the field of sleep and we should pay attention to the role of resilience in regulating sleep quality.


α5β1 integrin mediates pulmonary epithelial cyst formation.
Formation of the epithelial cyst involves the establishment of apical-basolateral polarity through a series of cellular interactions that are in part mediated by the extracellular matrix (ECM). We report that in a three-dimensional multi-cellular self-assembly model of lung development, α5 integrin regulates epithelial cyst formation through organization of soluble fibronectin matrix into insoluble fibrils through a process called fibrillogenesis. Dissociated murine embryonic lung cells self-assemble into three-dimensional pulmonary bodies that are dependent on α5β1 integrin mediated fibrillogenesis for cell-cell mediated self-assembly: compaction and epithelial cyst formation. Knockdown of α5 integrin resulted in a significant increase in another mediator of fibrillogenesis, αV integrin. Compensatory increased expression of another mediator of fibrillogenesis, αV integrin, was not sufficient to normalize epithelial cyst formation. Loss of α5 integrin-mediated fibrillogenesis perturbed the ability of clustered epithelial cells to establish clear polarity, loss of epithelial cell pyramidal shape, and disrupted apical F-actin-rich deposition. Lack of rich central epithelial localization of F-actin cytoskeleton and Podocalyxin suggests that loss of α5 integrin-mediated fibrillogenesis interferes with the normal cytoskeleton organization that facilitates epithelial cysts polarization. We conclude that lung epithelial cyst formation in development is mediated in part by α5β1 integrin dependent fibrillogenesis. Developmental Dynamics 246:475-484, 2016. © 2017 Wiley Periodicals, Inc.


Recombineering to homogeneity: extension of multiplex recombineering to large-scale genome editing.
Recombineering has been an essential tool for genetic engineering in microbes for many years and has enabled faster, more efficient engineering than previous techniques. There have been numerous studies that focus on improving recombineering efficiency, which can be divided into three main areas: (i) optimizing the oligo used for recombineering to enhance replication fork annealing and limit proofreading; (ii) mechanisms to modify the replisome itself, enabling an increased rate of annealing; and (iii) multiplexing recombineering targets and automation. These efforts have increased the efficiency of recombineering several hundred-fold. One area that has received far less attention is the problem of multiple chromosomes, which effectively decrease efficiency on a chromosomal basis, resulting in more sectored colonies, which require longer outgrowth to obtain clonal populations. Herein, we describe the problem of multiple chromosomes, discuss calculations predicting how many generations are needed to obtain a pure colony, and how changes in experimental procedure or genetic background can minimize the effect of multiple chromosomes.


Measurement in group interventions for women with breast cancer.
Instrumentation is a critical component of intervention research. This article discusses a review of measurement tools used in research on group interventions for women with breast cancer. The wide variety of instruments used in research studies is listed. The criteria for instrument selection are compared with the most commonly used instrument, the Profile of Mood States. The authors summarize directions for future research related to instrumentation use.


Corticotropin and angiotensin induce dephosphorylation of a Mr-20,000 protein in bovine adrenal cells.
ACTH (1-24) and Angiotensin II, both able to activate steroidogenesis in bovine fasciculata-reticularis cells, each reduced the [32P] incorporation in a cytosolic Mr-20,000 pI 6.8 protein in this cell. Cells preincubated with Sar1-Angiotensin prevented the effect of Angiotensin. Angiotensin 10(-8)M and ACTH 10(-10)M led to an almost complete disappearance of the corresponding radioactive spot on the autoradiograph. The effect was observed as soon as 2 minutes after addition of hormones to the cells. Other activators of steroidogenesis such as 8-bromocyclicAMP (8-BrcAMP), 4 beta-Phorbol-12 beta-Myristate-13 alpha-acetate (PMA) and [9-tryptophan (o-nitrophenylsulfenyl)] substituted ACTH (NPS-ACTH), also reduced the labeling of the Mr-20,000 polypeptide. On the other hand, this effect was not reproduced by insulin or human growth hormone (hGH). On 2-D gels from control, the coincidence of this polypeptide with phosphorylated myosin light chain was not observed. We suggest that the apparent dephosphorylation of this polypeptide may represent a common effect of all steroidogenic agents regardless of their seemingly distinct early actions.


Clinically diagnosed nonocclusive mesenteric ischemia after cardiopulmonary bypass: retrospective study.
This retrospective study evaluates our experience with clinically diagnosed nonocclusive mesenteric ischemia after cardiopulmonary bypass. Twenty-three of 3,600 consecutive patients suffered from splanchnic malperfusion. Symptoms developed between day 2 and 6 postoperatively in 18 of 23 patients. Four of 23 patients had no abdominal symptoms. Laboratory evaluation revealed significantly higher serum lactate and creatine phosphokinase levels in the 18 symptomatic patients compared with those of a control group. Arteriography was performed in 20 cases and revealed nonocclusive splanchnic hypoperfusion. Risk factors for development of mesenteric ischemia include arrhythmias and low cardiac output. Patients with angiographically proven nonocclusive mesenteric ischemia were treated with intra-arterial bolus injection and subsequent intra-arterial infusion of tolazoline combined with heparin sodium. The overall mortality rate was 30% (7 of 23). Infusion therapy with tolazoline and heparin seems to be a successful treatment modality for clinically diagnosed mesenteric ischemia.


In search of a comprehensive value model for assessing supplementary person-organization fit.
In this study, the authors tested the comprehensiveness of the S. H. Schwartz (1992) value model as a conceptual framework for assessing supplementary person-organization fit. They conducted an extensive literature search in which they identified 42 value instruments or typologies that are used to measure life, work, or organizational values. Experts judged whether each of 1,578 items from these 42 instruments could be regarded as an indicator of 1 of the 10 value types identified by S. H. Schwartz (1992). The authors found that (a) 92.5% of the items could be classified into 1 of the 10 value types and (b) the remaining items suggested 2 possible new types (goal orientedness and relations). The authors also found indications that 2 value types could be split to obtain a more univocal meaning. Overall, these findings suggest that the S. H. Schwartz (1992) value model might be an appropriate comprehensive framework for studying supplementary person-organization fit.


Adaptive Physiological and Morphological Adjustments Mediated by Intestinal Stem Cells in Response to Food Availability in Mice.
Several studies have evaluated plastic changes in the morphology of the digestive tract in rodents subjected to caloric restriction or restricted availability. Nevertheless, studies that link these morphological responses to physiological consequences are scarce. In order to investigate short-term plastic responses in the intestine, we acclimated adult Mus musculus (BALB/c) males for 20 days to four distinctive treatments: two caloric regimens (ad libitum and 60% of calorie ingestion) and two levels of periodicity of the regimens (continuous and stochastic treatment). At the end of the treatment we analyzed the cell proliferation and cell death dynamics of small intestinal crypts in these animals. In addition, we measured organ masses and lengths, hydrolytic digestive enzyme activities, and energy output from feces. Finally, in order to explore the metabolic changes generated by these dietary conditions we assessed the catabolic activity (i.e., enzymes) of the liver. Our results show that individuals acclimated to a continuous and 60% regimen presented longer intestines in comparison to the other treatments. Indeed, their intestines grew with a rate of 0.22 cm/day, generating a significant caloric reduction in the content of their feces. Besides, both mass and intestinal lengths were predicted strongly by the stabilization coefficient of BrdU+ proliferating cells per crypt, the latter correlating positively with the activity of n-aminopeptidases. Interestingly, by using pharmacological inhibition of the kinase mammalian target of rapamycin complex 1 (mTORC1) by Rapamycin, we were able to recapitulate similar changes in the proliferation dynamics of intestinal stem cells. Based on our results, we propose that the impact of caloric restriction on macroscopic variation in morphology and functional changes in digestive n-aminopeptidases occurs through synchronization in the proliferation rate of stem and/or progenitor cells located in the small intestinal crypts and requires mTORC1 as a key mediator. Hence, we suggest that an excessive stem and progenitor activity could result in increased crypts branching and might therefore underlie the reported intestinal tissue expansion in response to short-term caloric restriction. Summarizing, we demonstrate for the first time that short-term caloric restriction induces changes in the level of cell proliferation dynamics explaining in part digestive tract plasticity in adaptive performance.


Insulin Resistance and Vitamin D Deficiency: A Link Beyond the Appearances.
Vitamin D is a steroid hormone that plays a key role in the regulation of body homeostasis, including cardiovascular function. Although the chronic deficiency of vitamin D is associated with cardiovascular risk factors, as well as with an adverse prognosis, randomized controlled trials have failed in demonstrating that dietary vitamin D supplementation could ameliorate the prognosis of patients with cardiovascular diseases, and suggested that vitamin D deficiency is the expression of the effects of other determinants of cardiovascular risk. Thus, the supplementation of vitamin D is not sufficient to improve the cardiovascular risk profile and prognosis. Insulin resistance is a complex phenomenon that plays a key role in the pathogenesis of conventional cardiovascular risk factors. Interestingly, defects of vitamin D and insulin resistance have a superimposable epidemiological distribution. According to the common view, Insulin resistance is considered the direct or indirect consequence of vitamin D deficiency. However, it is also reasonable to speculate that the deficit or the impaired action of vitamin D, in some circumstances, could be the result of the same pathogenic mechanisms responsible of insulin resistance development. In this case, vitamin D deficiency could be considered an epiphenomenon of insulin resistance. Insulin resistance is a reversible condition, being possibly ameliorated by physical activity and hypocaloric diets. Notably, both physical exercise and energy-restricted dietary regimens are associated with an increase of vitamin D levels. These findings indicate that improving insulin resistance condition is a necessary step to ameliorate vitamin D supplementation-based strategies in cardiovascular prevention.


A Victim of the Great East Japan Earthquake Identified with the Preserved Medical Samples of Her Deceased Mother.
On March 11, 2011, a magnitude 9.0 earthquake and huge tsunami occurred near the Pacific coast of northeast Japan, in which more than 18,000 people died or went missing and more than 120,000 buildings were destroyed. In Taro district, one of the areas struck hardest by the tsunami, a middle-aged woman was found deceased in the rubble. Generally, a family physician can recognize victims based on their appearance; the place where they were found; their home or work address; their belongings; the identifying marks on their clothes; their dental charts; and their living biological parents, children, or multiple siblings through DNA analysis. However, in this case, the middle-aged woman remained the area's sole unidentified person for months, because her appearance was different, her body was slightly swollen, and she was missing some teeth. The district's medical and dental facilities were destroyed and almost all medical records and dental charts lost. Fortunately, a family physician who had worked in the district for many years survived the disaster, and was available to provide background information about the victim, her family, and their relationship. He recalled the existence of tissue samples of her mother who had died several years earlier. Subsequently, the individual was identified through the DNA analysis of her blood and mother's tissue samples. As demonstrated in the case, appropriately managed medical information and samples from previously deceased relatives can aid disaster victim identification. The destruction caused by the Great East Japan Earthquake forms our investigation's background.


De novo transcriptome assembly reveals high transcriptional complexity in Pisum sativum axillary buds and shows rapid changes in expression of diurnally regulated genes.
The decision for a bud to grow into a branch is a key regulatory process affecting plant architecture. In order to study molecular processes regulating axillary bud outgrowth in the model plant garden pea (Pisum sativum), we sequenced the axillary bud transcriptome and performed de novo transcriptome assembly. We assembled a pea axillary bud transcriptome into 81,774 transcripts comprised of 194,067 isoforms. This new pea transcriptome resource is both comprehensive and representative, as shown by comparison to other available pea sequence resources. Over half of the transcriptome could be annotated based on sequence homology to Arabidopsis thaliana proteins, while almost one quarter of the isoforms were identified as putative long non-coding RNAs (lncRNAs). This transcriptome will be useful in studies of pea buds because it includes genes expressed specifically in buds which are not represented in other transcriptome studies. We also investigated the impact of a short time collection series on gene expression. Differential gene expression analysis identified 142 transcripts changing within the short 170 min time frame that the buds were harvested within. Thirty-three of these transcripts are implicated in diurnal fluctuations in other flowering plants, while the remaining transcripts include 31 putative lncRNA. Further investigation of the differentially expressed transcripts found an enrichment of genes involved in post-transcriptional regulation, including RNA processing and modification, as well as genes involved in fatty acid biosynthesis and oxidative phosphorylation. We have sequenced and assembled a high quality pea bud transcriptome containing both coding and non-coding RNA transcripts that will be useful for further studies into axillary bud outgrowth. Over the short sample collection time frame of just 170 min, we identified differentially expressed coding and non-coding RNA, some of which are implicated in diurnal regulation, highlighting the utility of our transcriptome resource in identifying gene expression changes and informing future experimental designs.


Combined Haplotypes of CaSR Gene Sequence Variants and Their Associations with Growth Traits in Cattle.
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor that regulates food intake and assimilation. However, studies on the relationship between CaSR gene and growth traits in cattle are deficient. The aim of this study was to examine the association of the CaSR polymorphism with growth traits in cattle breeds. Four novel single nucleotide polymorphisms (SNPs) and one previously reported SNP (NC_007299.5: g.67630865T>C, 67638409G>C, 67660395G>C, 67661546C>G, and 67661892A>C) were identified in the bovine CaSR gene using DNA sequencing and PCR-SSCP methods in 520 individuals from three representative breeds. The three SNP P4_2, P7_1, and P7_4 in LX, QC, and JX cattle populations belonged to intermediate genetic diversity (0.25 < PIC < 0.5). In addition, we evaluated the haplotype frequency and linkage disequilibrium coefficient of five sequence variants in the three cattle breeds. LD and haplotype structure of CaSR were different between breeds. LD analysis showed that the P4_2 and P7_4 loci were in complete LD in JX cattle population (r2 = 0.99 and D' = 1). Only 11 haplotypes were listed except for those with a frequency of <0.03. Hap1 (-TGGGC-) had the highest haplotype frequencies in LX (27.30%), Hap6(-TGGCC-) had the highest haplotype frequencies in QC (21.70%) and JX (32.30%). Association analysis indicated that P2, P4_2, and P7_4 loci were all significantly associated with growth traits and combined genotype TTGCGC was highly significantly associated with Chest circumference and body weight than the other genotype in JX cattle population. The results of this study suggest that the CaSR gene possibly is a strong candidate gene that affects growth traits in the Chinese cattle breeding program.


Phospholipid dependence of rat brain microsomal glucose-6-phosphate phosphohydrolase.
Partial lipid removal of rat brain microsomes by acetone-butanol extraction resulted in 32% loss of activity of glucose-6-phosphate phosphohydrolase (G-6-Pase) and an increase in Km and energy of activation (Ea) of the enzyme while the Vmax was lowered. The activity was restored by supplementation of microsomal total phospholipid (PL) and phosphatidylcholine (PC) in sonicated dispersions but not with neutral lipids, phosphatidyl ethanolamine, sphingomyelin, phosphatidylglycerol and cholesterol. In both intact and delipidated membranes, the activity was decreased by sodium deoxycholate and enhanced by dimethylsulfoxide. Egg yolk PC and asolectin influenced the activity to the extent of that produced by microsomal PC. PC increased the Km of the enzymatic reaction in intact microsomes but decreased the same in disrupted membrane while the Vmax was not affected in both the membranes. Addition of PC into the assay system lowered Ea of the reaction in both the membrane systems. However, there was no break observed in the Arrhenius plot. Ability of liver nonspecific lipid transfer proteins to introduce alien PL into brain microsomes was used to study lipid dependence of G-6-Pase and investigation of membrane-enzyme interrelationship. Protein catalyzed transfer of egg PC from a donor PC-cholesterol unilamellar liposomes resulted in substantial increase in microsomal membrane PC and total PL and a net reduction in the enzyme activity was observed in intact and delipidated membranes.(ABSTRACT TRUNCATED AT 250 WORDS)


Major Depression in Chinese Medicine Outpatients with Stagnation Syndrome: Prevalence and the Impairments in Well-Being.
Stagnation syndrome, a diagnostic entity in traditional Chinese medicine (TCM), has been long regarded as the TCM counterpart of major depression in Western medicine. The study investigated the prevalence of major depression among stagnation syndrome patients and evaluated their well-being and functioning outcomes. In total, 117 patients diagnosed with stagnation syndrome were measured using Stagnation Scale, the Patient Health Questionnaire-9 (PHQ-9), and the Body-Mind-Spirit Well-Being Inventory. Results indicate major depression among stagnation syndrome patients was characterized by a high co-occurrence rate and worse physical, mental, and functional outcomes. More than one-quarter (26.5%) of the patients met the DSM-V diagnostic criteria for major depression and over half (53%) exceeded the PHQ-9 cutoff (score above 10) for moderate/severe depression symptoms. The wellness of the stagnation syndrome patients was worse (M = 298.2, SD = 66.5) than that of the general population (M = 360.9, SD = 79.9), with a large Cohen's d value of 0.9. The "wellness outlook" of the depressed stagnation syndrome patients appeared grimmer (M = 252.3, SD = 52.2). The correlation between stagnation and depression was higher for affective symptoms than somatic symptoms. Physical distress did not mediate the relationship between stagnation and daily functioning. These might suggest that stagnation syndrome and major depression may share some similar psychological mechanisms.


[Prevalence of visual, hearing, speech, physical, intellectual and mental disabilities in China, 2006].
To explore the prevalence of visual, hearing, speech, physical, intellectual and mental disabilities in China, 2006. The reference time of the Second National Sample Survey on Disability was zero hour, April 1, 2006, and 2,526,145 individuals were investigated from 31 provinces autonomous regions or municipalities under the "Disability Classification and Standards for the Second National Sampling Survey on Disability". The classified prevalence rates of 6 types of disability was analyzed. (1)The overall prevalence of disabilities was 6.39%, which was 1.49 percent higher than the prevalence rate in 1987. The prevalence of physical disability was the highest (2.34%), while the speech disability was the lowest (0.53%). (2)29.49% of all the disabled persons were classified as severe who suffered grade-1 and grade-2 while 70.51% of them were moderately and mildly disabled suffering from grade-3 and grade-4. Over 65% of the speech disability and over 45% of the mental disability were identified, which were much higher than the other 4 types of disability. (3) The correlation between age, gender, residential place and each of 6 types of disability were statistically significant (P < 0.001). (4) Among all the disabling factors of speech disability and mental retardation disability, congenital factors made great contribution (22.67% and 22.41% respectively). According to the analysis results,the characteristics of disabled persons in China were as follows: ageing population had high prevalence rate of disability; all the population mainly suffered moderate and mild disability, but the proportion of severe disability was not low; the prevalence rate was higher and the main reasons caused disability were diversification in rural area.


Children's Oncology Group's 2023 blueprint for research: Rare tumors.
The Children's Oncology Group (COG) Rare Tumor Committee includes the Infrequent Tumor and Retinoblastoma subcommittees, encompassing a wide range of extracranial solid tumors that do not fall within another COG disease committee. Current therapeutic trial development focuses on nasopharyngeal carcinoma, adrenocortical carcinoma, pleuropulmonary blastoma, colorectal carcinoma, melanoma, and thyroid carcinoma. Given the rarity of these tumors, novel strategies and international collaborative efforts are necessary to advance research and improve outcomes.


Optimization of fibrinogen isolation for manufacturing autologous fibrin glue for use as scaffold in tissue engineering.
Numerous manufacturing techniques for autogenous fibrin glue used as scaffold material have been described. As there is no consensus regarding the influence of chemical additives on cell biology, it was the aim of this study to establish a method for manufacturing autologous fibrin glue without any additives. The serum part was separated from whole blood. After fibrinogen precipitation, centrifugation was performed to obtain the fibrinogen pellet. Various experimental series were run to examine influences of various temperatures or substituting centrifugation for sedimentation. The method as described here is effective, simple, and performed without any additives, which could potentially influence cell biology.


Optical mapping of the atrioventricular junction.
In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles, and is responsible for the appropriate atrial-ventricular delay. Under normal physiological conditions, the AVN controls appropriate frequency-dependent delay of contractions. The AVN also plays an important role in pathology: it protects ventricles during atrial tachyarrhythmia, and during sinoatrial node failure the atrioventricular (AV) junction assumes the role of pacemaker. Finally, the AV junction provides an anatomic substrate for AV nodal reentrant tachycardia, which is the most prevalent supraventricular tachycardia in humans. Using fluorescent imaging with voltage-sensitive dye and immunohistochemistry, we have investigated the structure-function relationship of the atrioventricular (AV) junction during normal conduction, reentry, and junctional rhythm. We identified the site of origin of junctional rhythm at the posterior extension of the AV node (AVN) in 78% (n=23) of the studied hearts and we found that this pacemaker is sensitive to autonomic control. For instance, when the autonomic nervous system was activated using subthreshold stimulation, a transient accelerated junctional rhythm was observed when subthreshold stimulation was terminated. A very similar phenomenon is observed clinically during slow pathway ablations treating AV nodal reentrant tachycardia (AVNRT). The autonomic control of the AV junction was investigated using immunohistochemistry, showing that the AV junction of the rabbit is very densely innervated with both cholinergic and adrenergic neurons. The posterior AV nodal extension was similar to the compact AVN as determined by morphologic and molecular investigations. In particular, both the posterior extension and the compact node express the pacemaking channel HCN4 (responsible for the IF current) and neurofilament 160. In the rabbit heart, AV junction conduction, reentrant arrhythmia, and spontaneous rhythm are governed by heterogeneity of expression of several isoforms of gap junctions and ion channels, and these properties are regulated by the autonomic nervous system. Uniform neurofilament expression suggests that AV nodal posterior extensions are an integral part of the cardiac pacemaking and conduction system.


Dynamic human MutSα-MutLα complexes compact mismatched DNA.
DNA mismatch repair (MMR) corrects errors that occur during DNA replication. In humans, mutations in the proteins MutSα and MutLα that initiate MMR cause Lynch syndrome, the most common hereditary cancer. MutSα surveilles the DNA, and upon recognition of a replication error it undergoes adenosine triphosphate-dependent conformational changes and recruits MutLα. Subsequently, proliferating cell nuclear antigen (PCNA) activates MutLα to nick the error-containing strand to allow excision and resynthesis. The structure-function properties of these obligate MutSα-MutLα complexes remain mostly unexplored in higher eukaryotes, and models are predominately based on studies of prokaryotic proteins. Here, we utilize atomic force microscopy (AFM) coupled with other methods to reveal time- and concentration-dependent stoichiometries and conformations of assembling human MutSα-MutLα-DNA complexes. We find that they assemble into multimeric complexes comprising three to eight proteins around a mismatch on DNA. On the timescale of a few minutes, these complexes rearrange, folding and compacting the DNA. These observations contrast with dominant models of MMR initiation that envision diffusive MutS-MutL complexes that move away from the mismatch. Our results suggest MutSα localizes MutLα near the mismatch and promotes DNA configurations that could enhance MMR efficiency by facilitating MutLα nicking the DNA at multiple sites around the mismatch. In addition, such complexes may also protect the mismatch region from nucleosome reassembly until repair occurs, and they could potentially remodel adjacent nucleosomes.


Agarose gel electrophoresis pattern of serum creatine kinase and lactate dehydrogenase isoenzymes in zoo-managed Asian elephants (Elephas maximus).
Serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) isoenzymes were evaluated in nine zoo-managed Asian elephants (Elephas maximus) using a commercial agarose gel electrophoresis (AGE) kit. CK was separated into two major fractions, CK-BB and CK-MM, along with a small fraction of macroenzyme-CK type 2 (mCK2); CK-MM was the largest fraction. LDH was separated into five fractions (LDH1-5); LDH3 was the largest fraction. Age was negatively and positively correlated with the percentages of CK-BB and CK-MM, respectively, and negatively correlated with CK-BB and mCK2 activities. These results indicate that an AGE kit can be used to evaluate CK and LDH isoenzymes. Routine isoenzyme testing may enable early detection of disease and physiological changes.


HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells.
It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1-mediated downmodulation of HLA-C was associated with reduced binding to its respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed reduced antiviral activity compared to their unlicensed counterparts, potentially due to residual binding to the respective inhibitory receptors. Nevertheless, NK cells were able to sense alterations of HLA-C expression demonstrated by increased antiviral activity when exposed to viral strains with differential abilities to downmodulate HLA-C. These results suggest that the capability of HLA-C-licensed NK cells to control HIV-1 replication is determined by the strength of KIR/HLA-C interactions and is thus dependent on both host genetics and the extent of virus-mediated HLA-C downregulation.


Effects of exogenous and endogenous cannabinoids on GABAergic neurotransmission between the caudate-putamen and the globus pallidus in the mouse.
Globus pallidus neurons receive GABAergic input from the caudate-putamen via the striatopallidal pathway. Anatomical studies indicate that many CB(1) cannabinoid receptors are localized on terminals of striatopallidal axons. Accordingly, the hypothesis of the present work was that activation of CB(1) receptors presynaptically inhibits neurotransmission between striatopallidal axons and globus pallidus neurons. In sagittal mouse brain slices, striatopallidal axons were electrically stimulated in the caudate-putamen, and the resulting GABAergic inhibitory postsynaptic currents (IPSCs) were recorded in globus pallidus neurons. The synthetic cannabinoid receptor agonists R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)-methanone mesylate (WIN55212-2) and (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxy-propyl)-cyclohexanol (CP55940) decreased the amplitude of IPSCs. The CB(1) receptor antagonist rimonabant prevented the inhibition by WIN55212-2, pointing to involvement of CB(1) receptors. Depolarization of globus pallidus neurons induced a weak and short-lasting suppression of IPSCs [i.e., depolarization-induced suppression of inhibition (DSI) occurred]. Prevention of DSI by rimonabant indicates that endocannabinoids released from the postsynaptic neurons acted on CB(1) receptors to suppress synaptic transmission. WIN55212-2 did not modify currents in globus pallidus neurons elicited by GABA released from its chemically bound ("caged") form by a flash pulse, suggesting that WIN55212-2 depressed neurotransmission presynaptically. For studying the mechanism of the inhibition of GABA release, terminals of striatopallidal axons were labeled with a calcium-sensitive fluorescent dye. WIN55212-2 depressed the action potential-evoked increase in axon terminal calcium concentration. The results show that activation of CB(1) receptors by exogenous and endogenous cannabinoids leads to presynaptic inhibition of neurotransmission between striatopallidal axons and globus pallidus neurons. Depression of the action potential-evoked calcium influx into axon terminals is the probable mechanism of this inhibition.


Children use nonverbal cues to make inferences about social power.
Four studies (N = 192) tested whether young children use nonverbal information to make inferences about differences in social power. Five- and six-year-old children were able to determine which of two adults was "in charge" in dynamic videotaped conversations (Study 1) and in static photographs (Study 4) using only nonverbal cues. Younger children (3-4 years) were not successful in Study 1 or Study 4. Removing irrelevant linguistic information from conversations did not improve the performance of 3- to 4-year-old children (Study 3), but including relevant linguistic cues did (Study 2). Thus, at least by 5 years of age, children show sensitivity to some of the same nonverbal cues adults use to determine other people's social roles.


Cx43 gap junction gene expression and gap junctional communication in mouse neural crest cells.
Although gap junctions are not known to be important in mediating cell-cell interactions amongst migratory cells, our studies showed that the connexin 43 (Cx43) gap junction gene is widely expressed in mouse neural crest cell lineages. Using in situ hybridization analysis, Cx43 expression was detected in presumptive neural crest cells emerging from the neural folds of the early postimplantation embryo. Neural crest expression of the Cx43 gap junction gene was also indicated by the analysis of transgenic mice containing a lacZ reporter construct driven by the Cx43 promoter. In neural tube explant cultures of these transgenic mice, lacZ expression was observed in the emerging neural crest outgrowths. Whole mount X-gal staining of these transgenic embryos at various stages of development showed lacZ expression in neural crest cells distributed along the entire craniocaudal axis, with expression found in both cranial and trunk neural crest cells contributing to a wide range of embryonic tissues. This included presumptive cardiac neural crest cells localized in the heart. In light of the widespread expression of Cx43 in neural crest cell lineages, dye injection studies, were carried out to determine if neural crest cells are functionally coupled via gap junctions. Such studies revealed extensive dye coupling among presumptive neural crest cells, thus demonstrating that these migratory cells are indeed gap junctional communication competent. In total, these observations suggest that gap junctions may play a role in mouse neural crest development. This possibility is particularly intriguing given the recent finding that the Cx43 knockout mice die of defects associated with the outflow tract [Reaume et al., 1995], a region of the heart in which neural crest cells are required for normal development.


Multiphoton control of the 1,3-cyclohexadiene ring-opening reaction in the presence of competing solvent reactions.
Although physical chemistry has often concentrated on the observation and understanding of chemical systems, the defining characteristic of chemistry remains the direction and control of chemical reactivity. Optical control of molecular dynamics, and thus of chemical reactivity provides a path to use photon energy as a smart reagent in a chemical system. In this paper, we discuss recent research in this field in the context of our studies of the multiphoton optical control of the photo-initiated ring-opening reaction of 1,3-cyclohexadiene (CHD) to form 1,3,5- cis-hexatriene (Z-HT). Closed-loop feedback and learning algorithms are able to identify pulses that increase the desired target state by as much as a factor of two. Mechanisms for control are discussed through the influence of the intensity dependence, the nonlinear power spectrum, and the projection of the pulses onto low orders of polynomial phase. Control measurements in neat solvents demonstrate that competing solvent fragmentation reactions must also be considered. In particular, multiphoton excitation of cyclohexane alone is capable of producing hexatriene. Statistical analyses of data sets obtained in learning algorithm searches in neat cyclohexane and for CHD in hexane and cyclohexane highlight the importance of linear and quadratic chirp, while demonstrating that the control features are not so easily defined. Higher order phase components are also important. On the basis of these results the involvement of low-frequency ground-state vibrational modes is proposed. When the population is transferred to the excited state, momentum along the torsional coordinate may keep the wave packet localized as it moves toward the conical intersections controlling the yield of Z-HT.


Targeted Deletion of Interleukin-6 in a Mouse Model of Chronic Inflammation Demonstrates Opposing Roles in Aging: Benefit and Harm.
Chronic inflammation (CI) in older adults is associated with reduced health span and life span. Interleukin-6 (IL-6) is one CI marker that is strongly associated with adverse health outcomes and mortality in aging. We have previously characterized a mouse model of frailty and chronic inflammatory pathway activation (IL-10tm/tm, IL-10 KO) that demonstrates the upregulation of numerous proinflammatory cytokines, including IL-6. We sought to identify a more specific role for IL-6 within the context of CI and aging and developed a mouse with targeted deletion of both IL-10 and IL-6 (IL-10tm/tm/IL-6tm/tm, DKO). Phenotypic characteristics, cytokine measurements, cardiac myocardial oxygen consumption, physical function, and survival were measured in DKO mice and compared to age- and gender-matched IL-10 KO and wild-type mice. Our findings demonstrate that selective knockdown of IL-6 in a frail mouse with CI resulted in the reversal of some of the CI-associated changes. We observed increased protective mitochondrial-associated lipid metabolites, decreased cardiac oxaloacetic acid, improved myocardial oxidative metabolism, and better short-term functional performance in DKO mice. However, the DKO mice also demonstrated higher mortality. This work shows the pleiotropic effects of IL-6 on aging and frailty.


[The relationship between the fracture site and etiology in mandibular fractures].
The aim of this study was to evaluate the relationship between the fracture site and etiology in mandibular fractures. The study included 37 patients (61 fracture sites) (29 males, 8 females; mean age 26 years; range 1.5 to 77 years) who underwent surgical treatment for mandibular fractures between May 2001 and November 2003. Data on epidemiological characteristics of patients, etiology and fracture sites were retrospectively reviewed. Of the patient group, 51.3% had a single, 48.6% had two or more fractures. Seventy-five percent of the assault victims had more than one fracture site. Motor vehicle accidents accounted for 36% of all the fracture sites. The most common locations of the fractures according to the etiology were as follows: fractures caused by motor vehicle accidents at the parasymphyseal area, by falls at the condyle, and by assaults at the parasymphyseal and angular areas. All the fractures resulting from bicycle accidents occurred at the condyle area. It is advisable to be more attentive for condyle fractures when confronted with any etiology of mandibular fractures. Etiology may be suggestive of the fracture site(s).


Local and Remote Effects of Mesenchymal Stem Cell Administration on Skin Wound Regeneration.
Wound healing is an important medical problem. We evaluated the efficacy of locally administered mesenchymal stem cells (MSCs) isolated from human umbilical cords on the dynamics of skin wound healing. The study was conducted on the backs of Wistar rats, where two square wounds were created by removing all layers of the skin. Four groups were studied in two series of experiments: (1) a Control_NaCl group (the wounds were injected with 0.9% NaCl solution) and a Control_0 group (intact wounds on the opposite side of the same rat's back); (2) an MSC group (injected MSCs, local effect) and a Control_sc group (intact wounds on the opposite side of the back, remote MSC effect). The area and temperature of the wounds and the microcirculation of the wound edges were measured. Histological and morphometric studies were performed on days 3 and 7 after the wounds were created. The results showed that the injection trauma (Control_NaCl) slowed the regeneration process. In both MSC groups (unlike in either control group), we observed no increase in the area of the wounds; in addition, we observed inhibition of the inflammatory process and improved wound regeneration on days 1-3 in the remote group and days 1-5 in the local (injected) group. The MSC and Control_sc groups demonstrated improved microcirculation and suppression of leukocyte infiltration on day 3. On day 7, all the studied parameters of the wounds of the Control_0 group were the same as those of the wounds that received cell therapy, although in contrast to the results of the Control_ NaCl group, fibroblast proliferation was greater in the MSC and Control_sc groups. The dynamics of the size of the wounds were comparable for both local and remote application of MSCs. Thus, even a one-time application of MSCs was effective during the first 3-5 days after injury due to anti-inflammatory processes, which improved the regeneration process. Remote application of MSC, as opposed to direct injection, is advisable, especially in the case of multiple wounds, since the results were indistinguishable between the groups and injection trauma was shown to slow healing.


A novel mutation of human liver alanine:glyoxylate aminotransferase causes primary hyperoxaluria type 1: immunohistochemical quantification and subcellular distribution.
A novel alanine:glyoxylate aminotransferase (AGT) mutation involved in primary hyperoxaluria type 1 (PH1) was studied in Japanese patients. Two mutations in exon 7, c.751T>A and c.752G>A, lead to a W251K amino acid substitution. Proband 1 (patient 1) was homozygous for the W251K mutation allele (DDBJ Accession No. AB292648), and AGT-specific activity in the patient's liver was very low. To reveal the cause of the low enzymatic activity, the intracellular localization of AGT (W251K) was studied using immunohistochemistry and immunoelectron microscopy. The latter analysis showed that patient 2 had only one-fifth of the normal AGT expression per catalase, suggesting impairment of AGT (W251K) dependent transport into peroxisomes. Peroxisomal transport of human AGT is believed to be dependent on the presence of the type 1 peroxisomal targeting sequence. The C-terminal tripeptide of AGT, KKL is necessary for peroxisomal targeting. In cultured cells, EGFP-AGT (W251K) localized both in the peroxisome and cytosol. These results were consistent with the data obtained from liver analysis of patient 2. The subcellular distribution of AGT (W251K) and the results from a random mutagenesis study suggest that KKL is necessary for peroxisomal targeting of human AGT, but additional signal other than KKL may be necessary.


Investigation of Salmonella Enteritidis Outbreak Associated with Truffle Oil - District of Columbia, 2015.
On September 8, 2015, the District of Columbia Department of Health (DCDOH) received a call from a person who reported experiencing gastrointestinal illness after eating at a District of Columbia (DC) restaurant with multiple locations throughout the United States (restaurant A). Later the same day, a local emergency department notified DCDOH to report four persons with gastrointestinal illness, all of whom had eaten at restaurant A during August 30-September 5. Two patients had laboratory-confirmed Salmonella group D by stool culture. On the evening of September 9, a local newspaper article highlighted a possible outbreak associated with restaurant A. Investigation of the outbreak by DCDOH identified 159 patrons who were residents of 11 states and DC with gastrointestinal illness after eating at restaurant A during July 1-September 10. A case-control study was conducted, which suggested truffle oil-containing food items as a possible source of Salmonella enterica serotype Enteritidis infection. Although several violations were noted during the restaurant inspections, the environmental, laboratory, and traceback investigations did not confirm the contamination source. Because of concern about the outbreak, the restaurant's license was suspended during September 10-15. The collaboration and cooperation of the public, media, health care providers, and local, state, and federal public health officials facilitated recognition of this outbreak involving a pathogen commonly implicated in foodborne illness.


Activation of the IL-6R/Jak/stat pathway is associated with a poor outcome in resected pancreatic ductal adenocarcinoma.
Chronic localized pancreatic inflammation in the form of chronic pancreatitis is an established risk factor for human pancreatic ductal adenocarcinoma (PDAC) development. Constitutive activation of inflammation-related signal transducer and activator of transcription (Stat)3 signaling has been implicated in the development and progression a number of malignancies, including PDAC. Although, the Janus Kinase (Jak)/Stat pathway is a potential drug target, clinicopathological, molecular, and prognostic features of Stat3-activated PDAC remain uncertain. Our aim was to determine the clinicopathological impact of this inflammatory pathway in resectable PDAC. Using a tissue microarray-based cohort of PDAC from 86 patients undergoing pancreaticoduodenectomy with curative intent and complete clinicopathological data available, we evaluated expression of the interleukin-6 receptor (IL-6R)/Jak/Stat pathway by immunohistochemistry. IL-6R, Jak, phospho (p)-Jak, Stat3, pStat3(Tyr705), and pStat3(Ser727) were assessed in PDAC and pancreatic intraepithelial neoplasia. A Cox regression multivariate analysis model was used to determine factors influencing survival. Activation of the IL-6R/Jak/Stat3 pathway was compared with the systemic inflammatory response as measured by serum C-reactive protein levels. High pJak was associated with reduced overall survival in multivariate analysis when compared with those with moderate or low expression (p = 0.036; hazard ratio (HR) = 1.68) as was pStat3(Tyr705) (p < 0.001; HR = 2.66) independent of lymph node status and tumor grade. Patients with a combination of pJakhigh/pStat3(Tyr705) high expression had an especially poor prognosis (median survival of 8.8 months; 95 % CI, 4.4-13.2). While the IL-6R/Jak/Stat pathway did not correlate with serum C-reactive protein levels, high pStat3 expression was associated with a reduction in the density of the local tumoral immune response. Activation of the Jak/Stat3 pathway via phosphorylation was associated with adverse outcome following resection of PDAC with curative intent supporting potential roles for pJak and pStat3 as prognostic biomarkers markers and therapeutic targets.


The impact of COVID 19 infection on HCV-induced thyroid disease.
As we progress into the COVID-19 pandemic, it has become apparent that this infection is associated with a multitude of systemic effects, some involving the thyroid gland. The thyroid is also frequently affected in the HCV chronic infection. The objective of this study is to determine the effects of COVID-19 infection on the presence and severity of thyroid disorders associated with chronic HCV infection, at short and mid-term follow-up. We prospectively evaluated patients with documented HCV- associated thyroid disease (with sustained virologic response after antiviral therapy). The study group consisted of 42 patients with HCV- associated thyroid disease, diagnosed with COVID -19 infection between April and October 2020. We determined serum values of thyroid-stimulating hormone, freeT3, free T4, anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies at one and three months after resolution of infection and compared them to the baseline characteristics of the patient. We also evaluated the changes in thyroid substitution treatments or antithyroid drugs. At baseline, out of the 42 patients, 5 presented hypothyroidism under levothyroxine substitution therapy, while 2 presented hyperthyroidism under methimazole therapy; 37 patients had positive antithyroid antibodies. At one month follow-up, we note an increase in serum values of antibodies, with a decrease in TSH, freeT3 and freeT4 levels, correlated with the severity of COVID-19 infection. Two patients required discontinuation of levothyroxine. At 3 months follow-up, lower levels of antithyroid antibodies were recorded, with an increase in TSH levels. No medication doses were adjusted at this time. Among the systemic effects of COVID-19, the impact of thyroid dysfunction should not be underestimated, especially in the presence of pre-existing conditions, such as HCV infection.


Photosystem II assembly: from cyanobacteria to plants.
Photosystem II (PSII) is an integral-membrane, multisubunit complex that initiates electron flow in oxygenic photosynthesis. The biogenesis of this complex machine involves the concerted assembly of at least 20 different polypeptides as well as the incorporation of a variety of inorganic and organic cofactors. Many factors have recently been identified that constitute an integrative network mediating the stepwise assembly of PSII components. One recurring theme is the subcellular organization of the assembly process in specialized membranes that form distinct biogenesis centers. Here, we review our current knowledge of the molecular components and events involved in PSII assembly and their high degree of evolutionary conservation.


Development of a diagnostic method for detecting increased muscle protein degradation in patients with catabolic conditions.
Muscle atrophy in catabolic illnesses is due largely to accelerated protein degradation. Unfortunately, methods for detecting accelerated muscle proteolysis are cumbersome. The goal of this study was to develop a method for detecting muscle protein breakdown and assess the effectiveness of anticatabolic therapy. In rodent models of catabolic conditions, it was found that accelerated muscle protein degradation is triggered by activation of caspase-3. Caspase-3 cleaves actomyosin/myofibrils to form substrates for the ubiquitin-proteasome system and leaves a characteristic 14-kD actin fragment in the insoluble fraction of a muscle lysate. Muscle biopsies were obtained from normal adults and three groups of patients: 14 who were undergoing hip arthroplasty, 28 hemodialysis patients who were participating in exercise programs, and seven severely burned patients. In muscle of patients who were undergoing hip arthroplasty, the 14-kD actin fragment level was correlated (r = 0.787, P < 0.01) with the fractional rate of protein degradation. In muscle of hemodialysis patients who were undergoing endurance exercise training, the 14-kD actin fragment decreased to values similar to levels in normal adults; strength training did not significantly decrease the actin fragment. Severely burned patients had increased muscle protein degradation and actin fragment levels, but the two measures were not significantly correlated. The experimental results suggest that the 14-kD actin fragment in muscle biopsies is increased in catabolic states and could be used in conjunction with other methods to detect and monitor changes in muscle proteolysis that occur in patients with mild or sustained increases in muscle proteolysis.


Caudal Epidural Injections in Lumbar Spinal Stenosis: Comparison of Nonimage, Ultrasonography-, and Fluoroscopy-Guided Techniques. A Randomized Clinical Trial.
Caudal epidural injections (CEIs) are widely used in the treatment of lumbar spinal stenosis (LSS). Imaging modalities, such as fluoroscopy and ultrasonography, are frequently employed to confirm proper needle placement and to prevent possible complications. This is a prospective, randomized, study aiming to compare the efficacy of nonimage, ultrasonography-, and fluoroscopy-guided CEIs for the management of LSS. A total of 45 patients were included based on their clinical symptoms and their magnetic resonance images indicative of LSS. Patients were randomized and allocated into 3 equal groups, the nonimage, the ultrasonography-guided, and the fluoroscopy-guided group. All patients received 12 mg betamethasone and 4 mg ropivacaine dissolved in 20 mL normal saline. The injections were administered twice, with a 30-day interval. Visual Analogue Scale (VAS) and Oswestry Disability Index were recorded before the injections and 1 month after the second injection. The procedure times for each group were also compared. Visual Analogue Scale scores and Oswestry Disability Index values were improved in all the groups compared to the baseline values (p < 0.001). The intergroup difference in Visual Analogue Scale scores and Oswestry Disability Index values before and after CEIs was not statistically significant (p = 0.836 and p = 0.438, respectively). The mean procedure time was higher for the fluoroscopy-guided group, followed by ultrasonography-guided, but the differences were not statistically significant (p = 0.067). CEIs are an effective analgesic method for patients suffering from LSS. Nonimage, ultrasonography-, and fluoroscopy-guided CEIs are similarly effective in terms of pain relief and functional improvement.


FEM numerical model study of heating in magnetic nanoparticles.
Electromagnetic heating of nanoparticles is complicated by the extremely short thermal relaxation time constants and difficulty of coupling sufficient power into the particles to achieve desired temperatures. Magnetic field heating by the hysteresis loop mechanism at frequencies between about 100 and 300 kHz has proven to be an effective mechanism in magnetic nanoparticles. Experiments at 2.45 GHz show that Fe3O4 magnetite nanoparticle dispersions in the range of 1012 to 1013 NP/mL also heat substantially at this frequency. An FEM numerical model study was undertaken to estimate the order of magnitude of volume power density, Qgen (W m-3) required to achieve significant heating in evenly dispersed and aggregated clusters of nanoparticles. The FEM models were computed using Comsol Multiphysics; consequently the models were confined to continuum formulations and did not include film nano-dimension heat transfer effects at the nanoparticle surface. As an example, the models indicate that for a single 36 nm diameter particle at an equivalent dispersion of 1013 NP/mL located within one control volume (1.0 × 10-19 m3) of a capillary vessel a power density in the neighborhood of 1017 (W m-3) is required to achieve a steady state particle temperature of 52 °C - the total power coupled to the particle is 2.44 μW. As a uniformly distributed particle cluster moves farther from the capillary the required power density decreases markedly. Finally, the tendency for particles in vivo to cluster together at separation distances much less than those of the uniform distribution further reduces the required power density.


Blue Nevi of the Ocular Surface: Clinical Characteristics, Pathologic Features, and Clinical Course.
Blue nevus is a melanocytic tumor that is commonly found in the skin. Extracutaneous presentations, including the ocular surface, are rare. As such, the purpose of this study was to characterize the clinical features and clinical course of congenital melanocytic tumor (blue nevus) of the conjunctiva. Retrospective, noncomparative case series. Twenty-one patients with 23 blue nevi of the ocular surface that were excised surgically between 2000 and 2016. Chart review of patients identified from a database search of the Florida Lions Ocular Pathology Laboratory records. Pathologic diagnoses were confirmed by 2 pathologists (S.R.D. and G.E.). All specimens were bleached and, tissue permitting, stained using SOX10 (MilliporeSigma, Darmstadt, Germany) and CD68 (Leica Biosystems, Nussloch, Germany). Clinical characteristics, pathologic features, and clinical course. Mean age of the population was 55±15 years; 71.4% (n = 15) were white and 57.1% (n = 12) were men. One patient had 3 lesions, for a total of 23 lesions examined. Clinically, 13 lesions were on the bulbar conjunctiva, 3 were on the tarsal conjunctiva, 3 were in the fornix, 2 were caruncular, 1 was episcleral, and 1 was at the limbus. Before excision, 8 patients were thought to have primary acquired melanosis, 4 with concern for primary conjunctival melanoma, and 1 thought to have metastatic disease from a plantar melanoma. Five lesions were thought to be benign, and in 8 patients, the lesions were identified incidentally after other ocular surgeries, with no diagnosis of the lesions before excision. Pathologic features were consistent with simple blue nevi in 21 lesions and cellular blue nevus in 2 lesions. No malignant transformations were noted in any patient over the mean 20.2-month follow-up period (range, 2 weeks-103 months). Blue nevus is a rare deeply pigmented congenital melanocytic lesion with a benign clinical course that can appear clinically similar to primary acquired melanosis or melanoma.


[Effects of olfactory deprivation on action potential and ankyrin-G expression in glutamatergic neurons in the barrel cortex of mice].
To investigate effect of upregulated touch sensation induced by olfactory deprivation on action potentials and ankyrin-G expression in the glutamatergic neurons in the barrel cortex of mice. Chloroform (40 μL) was dropped into the unilateral nasal cavity to induce olfactory deprivation in 40 C57 mice (12 days old), whose glutamatergic neurons were genetically labeled with yellow fluorescent protein (YFP). Behavioral experiments were carried out to assess the effects of olfactory deprivation on whisker tactile of the mice. The action potentials of the glutamatergic neurons in the barrel cortex on the side with or without chloroform treatment (olfactory deprivation group and control group, respectively) were recorded by patch-clamp electrophysiological recording, and ankyrin-G expression in the proximal axonal segment of the neurons was detected with immunohistochemistry. Compared with those on the control side, the inter-spike intervals of the barrel glutamatergic neurons were significantly decreased and the absolute refractory periods were significantly shortened on the side with olfactory deprivation (P < 0.01); the expression of ankyrin-G was also significantly increased in the proximal axonal segment of the glutamatergic neurons in the barrel cortex on the side with olfactory deprivation (P < 0.01). Olfaction deprivation induces up-regulation of touch sensation in mice possibly as a result of functional enhancement of the glutamatergic neurons and increased ankyrin-G expression in the barrel cortex.


Survey of the association of deoxyribonuclease I polymorphism with disease.
The deoxyribonuclease I (DNase I) system was studied in 120 unrelated Japanese patients with liver disease, malignant neoplasms, alimentary-canal disease and inflammatory conditions with respect to the distribution of phenotypes and gene frequencies in serum samples. In patients with alimentary-canal disease a significant deficit of the DNase I phenotype 1-2 was demonstrated, which suggests that heterozygosity may confer protection against such disease. Furthermore, a significant association between the DNase I phenotype 2 and liver disease was found. The possible involvement of these phenotypes in the response to these diseases would appear to merit further study.


Beta-blockers reduced the risk of mortality and exacerbation in patients with COPD: a meta-analysis of observational studies.
Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD). Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases. But the effects of beta-blockers on outcomes in patients with COPD remain controversial. The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD. An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD. The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD. Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included. The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD. The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71). In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively. The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD. Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients.


Rapidly progressing facial leishmaniasis: effective treatment with liposomal amphotericin B and a review of the management of Old World cutaneous leishmaniasis.
Cutaneous leishmaniasis (CL), a common condition in many parts of the world, is being increasingly encountered in non-endemic countries secondary to immigration. The clinical manifestations and course can vary substantially, with appropriate management ranging from observation for self-healing lesions to urgent treatment to prevent damaging anatomical and cosmetic sequelae. While there are now several effective medications, optimal therapy is not well defined, and decision-making can be challenged by the location of lesions and various drug issues, including availability, mode of delivery and adverse effects. A 7-year-old Afghani boy who presented shortly after arriving in the United States with a rapidly progressing crusting and ulcerative facial rash caused by Leishmania tropica is described. The various drugs currently available for CL and experience of using liposomal amphotericin B specifically are reviewed.


Temperature-dependent size exclusion chromatography for the in situ investigation of dynamic bonding/debonding reactions.
Polymers capable of dynamic bonding/debonding reactions are of great interest in modern day research. Potential applications can be found in the fields of self-healing materials or printable networks. Since temperature is often used as a stimulus for triggering reversible bonding reactions, an analysis operating at elevated temperatures is very useful for the in situ investigation of the reaction mechanism, as unwanted side effects can be minimized when performing the analyses at the same temperature at which the reactions occur. A temperature-dependent size exclusion chromatographic system (TD SEC) has been optimized for investigating the kinetics of retro Diels-Alder-based depolymerization of Diels-Alder polymers. The changing molecular weight distribution of the analyzed polymers during depolymerization gives valuable quantitative information on the kinetics of the reactions. Adequate data interpretation methods were developed for the correct evaluation of the chromatograms. The results are confirmed by high-temperature dynamic light scattering, thermogravimetric analysis, and time-resolved nuclear magnetic resonance spectroscopy at high temperatures. In addition, the SEC system and column material stability under application conditions were assessed using thermoanalysis methods, infrared spectroscopy, nitrogen physisorption, and scanning electron microscopy. The findings demonstrate that the system is stable and, thus, we can reliably characterize such dynamically bonding/debonding systems with TD SEC.