Individuals at high-risk for pancreatic cancer development: management options and the role of surgery.
Pancreatic cancer (PC) is a highly lethal disease. Despite advances regarding the safety and long-term results of pancreatectomies, early diagnosis remains the only hope for cure. This necessitates the implementation of an intensive screening program (based mainly on modern imaging), which - given the incidence of PC - is not cost effective for the general population. However, this screening program is recommended for individuals at high-risk for PC development. Indications for screening include the following three clinical settings: hereditary cancer predisposition syndromes associated with PC, hereditary pancreatitis and familial pancreatic cancer syndrome. The aim of this strategy is to identify pre-invasive (precursor) lesions, which are curable. Surgery is recommended in the presence of recognizable lesion on imaging lesions. Partial (anatomic) pancreatectomy - depending on the location of the suspicious lesion - is the most widely accepted type of surgical intervention in this setting; occasionally, however, total pancreatectomy may be required, in carefully selected patients. Despite that experience still remains limited, there is evidence that this aggressive strategy allows early detection of neoplastic lesions, thereby improving the effectiveness of surgery and prognosis.


Differential palatability of leaf litter to four sympatric isopods in a Hong Kong forest.
The feeding behaviour of four sympatric isopods from a Hong Kong forest has been investigated. The study included two armadillids (Formosillo raffaelei and Orodillo maculatus) and two philosciids (Burmoniscus ocellatus and Burmoniscus sp.). When given a choice of eight types of litter, all isopod species showed significant dietary selection, and food preferences were similar. Berchemia racemosa (Rhamnaceae) was most readily consumed, followed by Celtis sinensis (Ulmaceac), while feeding rates on Cinnamomum camphora (Lauraceae) were low. The armadillids exhibited a narrower dietary spectrum than the philosciids. All isopods showed significant differences in consumption rates when each litter type was presented separately to them. Cinnamomum camphora was eaten the slowest, while Celtis sinensis and Berchemia racemosa were the top-ranked species. Although patterns of litter ranking based on percentage eaten or feeding rates were similar, all isopods ate more food when given a mixture of leaves than when presented with a single litter type. Assimilation rates were, in general, positively related to feeding rates. On this basis, it appears that assimilation may influence food preference. There were no clear relationships between food preference or feeding rates and ash, calcium, copper, soluble tannin or energy content of the litter. This finding may indicate the benefits of isopods maintaining a mixed diet, consuming certain litter species to meet their calcium or copper requirements and then switching to others so as to meet daily energy needs and to avoid excessive injection of tannins or plant allelochemicals.


Willingness of gynecologic cancer patients to participate in clinical trials.
Fewer than 5% of cancer patients enroll in clinical trials, delaying their completion and the progress of patient care. Patients who are elderly or members of ethnic minorities participate at even lower rates than the general population. The objective of this study was to identify the factors that motivate or inhibit patient enrollment specifically within the gynecologic oncology population. An anonymous, voluntary survey was administered to all new patients presenting in the outpatient gynecologic oncology office for an initial consultation. The questionnaire was developed based on prior surveys in the general oncology literature and included questions about age, demographic information, interest in participation in research, and reasons for declining or desiring participation. Groups were compared with Fisher's Exact Test. There were 98 surveys submitted, of which 79 surveys were completed and included for analysis. The median age of patients was 50 years and the majority (86%) was Caucasian. Only 38% stated they would be unwilling to participate in clinical research, while 20% of the patient population stated they would be willing to participate in clinical trials and 42% were unsure. Factors that reached statistical significance (p=.05) in willingness to participate were age less than 50 years, education level beyond high school, and possession of private insurance. The percentage of women with gynecologic malignancies willing to participate in clinical trials greatly exceeds the number enrolled. Increasing the use of educational materials, improving patient awareness of clinical trials, and offering enrollment to all patients may increase accrual.


A modified crossed radioimmunoelectrophoretic method for determination of allergen-specific IgG antibodies. Elimination of non-specific binding by use of F(ab')2-fragments of rabbit antibodies and 125I-labelled protein A.
A crossed radioimmunoelectrophoretic (CRIE) method for detection of specific IgG antibodies in patients' sera against horse hair and dander was developed. The unacceptably high non-specific binding encountered when substituting 125I-labelled antihuman IgG for 125I-labelled antihuman IgE in an ordinary CRIE was eliminated by the combined use of 125I-labelled Protein A as detector, and F(ab')2-fragments of the allergen-specific rabbit antibodies. The low background binding thus obtained makes the method useful for detection of specific IgG in sera where the ratio between specific and non-specific IgG is low. Therefore the method should also be applicable to other antigen/allergen systems.


Is Tranexamic Acid an Effective Prevention in the Formation of Epidural Fibrosis? Histological Evaluation in the Rats.
The present study aimed to determine the topical and systemic efficacy of tranexamic acid (TXA) on epidural fibrosis in a rat laminectomy model. Thirty-two 12-month-old adult Sprague-Dawley rats were used in this study. Each rat underwent bilateral laminectomy at the L1 and L2 vertebral levels. Rats were divided into four groups : in group I (control group, n=8), a laminectomy was performed and saline solution was applied into the surgical space. In group II (topical group, n=8), laminectomy was performed and 30 mg/ kg TXA was applied to the surgical site before skin closure. In group III (systemic group, n=8), 30 mg/kg TXA was administered intravenously via the tail vein in the same session as the surgical procedure. In group IV (topical and systemic group, n=8), TXA was administered 30 mg/kg both topical and intravenous. The rats were sacrificed at 4 weeks postoperatively. Masson's trichrome and hematoxylin and eosin were used to assess acute inflammatory cells, chronic inflammatory cells, vascular proliferation, and epidural fibrosis. Epidural fibrosis, acute inflammation, chronic inflammation, and sum histologic score value were significantly lower in the systemic TXA group, systemic and topical TXA groups than in the control group (p<0.05). In addion, the sum histologic score was significantly lower in the topical TXA group than in the control group (p<0.05). In this study, epidural fibrosis formation was prevented more by systemic application, but the topical application was found to be effective when compared to the control group. As a result, we recommend the systemic and topical use of TXA to prevent epidural fibrosis during spinal surgery.


Characterization, cloning, curing, and distribution in lactic acid bacteria of pLP1, a plasmid from Lactobacillus plantarum CCM 1904 and its use in shuttle vector construction.
A small 2.1-kb plasmid called pLP1 was extracted from Lactobacillus plantarum CCM 1904 (ATCC 8014) and cloned into the Escherichia coli pUC19 plasmid. As determined by DNA-DNA Southern hybridization with a pLP1-radioactively labeled probe, other lactic acid bacteria such as L. curvatus, L. sake, Carnobacterium, and Leuconostoc mesenteroides harbor pLP1-related plasmids. Shuttle vectors based on the pLP1 replicon were constructed by inserting the erythromycin-resistance gene from pVA891 into the various pUC19-pLP1 constructions. pLP1-based shuttle vector transformation efficiencies (TE) by electroporation were compared to TE of a broad-host-range plasmid pGK12 in different lactobacilli strains. Expression of the pUC19-pLP1 plasmids in Escherichia coli maxicells showed that pLP1 encodes for a 37,000 MW protein which can act in trans allowing the replication of plasmids in which this protein is truncated. The pLP1-based shuttle vectors producing this protein replicate in lactobacilli and also in Bacillus subtilis. A pLP1-free strain was obtained by incompatibility with a pLP1-based shuttle vector introduced in L. plantarum CCM 1904 by electroporation. The absence of pLP1 has no incidence on the strain phenotype suggesting that pLP1 is not essential for the strain in our laboratory conditions.


Using in silico techniques: Isolation and characterization of an insect cuticle-degrading-protease gene from Beauveria bassiana.
Cuticle-degrading-proteases (CDPs) secreted by Beauveria spp. are pivotal biocontrol substances, possessing commercial potential for developing bio-pesticides. Therefore, a thoughtful and contemplative understanding and assessment of the structural and functional features of these proteases would markedly assist the development of biogenic pesticides. Computational molecular biology is a new facile alternative approach to the tedious experimental molecular biology; therefore, by using bioinformatics tools, we isolated and characterized an insect CDP gene from Beauveria bassiana 70 s.l. genomic DNA. The CDP gene (1240 bp with GeneBank accession no. KT804651.1) consisted of three introns and four CDS exons, and shared 74-100% sequence identity to the reference CDP genes. Its phylogenetic tree results showed a unique evolution pattern, and the predicted amino acid peptide (PAAP) consisted of 344 amino acid residues with pI, molecular weight, instability index, grand average hydropathicity value and aliphatic index of 7.2, 35.4 kDa, 24.45, -0.149, and 76.63, respectively. The gene possessed 74-89% amino acid sequence similarity to the 12 reference strains. Three motifs (Peptidase_S8 subtilase family) were detected in the PAAP, and the computed 3D structure possessed 79.09% structural identity to alkaline serine proteases. The PAAP had four (three serine proteases and one Pyridoxal-dependent decarboxylase) conserved domains, a disulfide bridge, two calcium binding sites, MY domain, and three predicted active sites in the serine family domains. These results will set the groundwork for further exploitation of proteases and understanding the mechanism of disease caused by cuticle-degrading-serine-proteases from entomopathogenic fungi.


Effect of experimental infection of cattle with bovine herpesvirus-1 (BHV-1) on the ex vivo interaction of bovine leukocytes with Mannheimia (Pasteurella) haemolytica leukotoxin.
Mannheimia (Pasteurella) haemolytica A1 produces an extracellular leukotoxin (LKT) that is reported to bind the beta(2)-integrin CD11a/CD18 (LEA-1) on ruminant leukocytes. LKT binding induces activation, and subsequent cytolysis, of these cells. It is well known that active viral infection greatly increases the susceptibility of cattle to pasteurellosis. To better understand the mechanism by which this occurs, we investigated the effects of experimental in vivo infection of cattle with bovine herpes virus-1 (BHV-1) on the ex vivo interaction of bovine leukocytes with the M. haemolytica LKT. In this study, we demonstrated that active BHV-1 infection increased the expression of the beta(2)-integrin CD11a/CD18 (as defined by the mAb BAT75) on bovine peripheral blood neutrophils, enhanced the binding of LKT to bronchoalveolar lavage (BAL) leukocytes and peripheral blood neutrophils, and increased the killing of BAL leukocytes and peripheral blood leukocytes by LKT. In addition, BHV-1 greatly increased the number of BAL, resulting in many more LKT-responsive cells being present in the lungs. These findings might explain in part the increased susceptibility of BHV-1 infected cattle to pneumonic pasteurellosis.


Comparative proteomic analysis of seed embryo proteins associated with seed storability in rice (Oryza sativa L) during natural aging.
Seed storability is considered an important trait in rice breeding; however, the underlying regulating mechanisms remain largely unknown. Here, we carried out a physiological and proteomic study to identify proteins possibly related to seed storability under natural conditions. Two hybrid cultivars, IIYou998 (IIY998) and BoYou998 (BY998), were analyzed in parallel because they share the same restorer line but have significant differences in seed storability. After a 2-year storage period, the germination percentage of IIY998 was significantly lower than that of BY998, whereas the level of malondialdehyde was reversed, indicating that IIY998 seeds may suffer from more severe damage than BY998 during storage. However, we did not find correlation between activities of antioxidant enzymes of superoxide dismutase, peroxidase, and catalase and seed storability. We identified 78 embryo proteins in embryo whose abundance varied more than 3-fold different during storage or between IIY998 and BY998. More proteins changed in abundance in IIY998 embryo (67 proteins) during storage than in BY998 (10 proteins). Several redox regulation proteins, mainly glutathione-related proteins, exhibited different degree of change during storage between BY998 and IIY998 and might play an important role protecting embryo proteins from oxidation. In addition, some disease/defense proteins, including DNA-damage-repair/toleration proteins, and a putative late embryogenesis abundant protein were significantly downregulated in IIY998, whereas their levels did not change in BY998, indicating that they might be correlated with seed storability. Further studies on these candidate seed storage proteins might help improve our understanding of seed aging.


Preparation of CuSe-PDA/g-C3N4 and its visible-light photocatalytic performance to dye degradation.
CuSe as an excellent photocatalytic semiconductor material has wildly used in the field of photocatalysis. In this paper, CuSe-PDA/g-C3N4 was designed and synthesized, and the photocatalytic performance of CuSe was further enhanced by the addition of polydopamine (PDA) and graphite phase carbon nitride (g-C3N4). The as-prepared CuSe-PDA/g-C3N4 was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), and elemental mapping. The specific surface area and porous characteristics of the material were also studied by N2 adsorption-desorption isotherm, which the specific surface area were 186.6 m2/g and pore size were of 3.1 nm by BET data analysis. The photocatalytic conditions for the degradation of methylene blue (MB) by CuSe-PDA/g-C3N4 were optimized in the experiment. The results showed that the photocatalytic performance of CuSe-PDA/g-C3N4 under visible-light illumination were better than CuSe and PDA owing to the narrow band gap energy and delayed electron-hole recombination. Under the optimized conditions, the removal rate reach to 99% of 50 mg/L MB within 60 min irradiation time. Moreover, the MB removal rate was over 90% through six repeated experiments, which proved that the CuSe-PDA/g-C3N4 composite nanomaterials have good stability and reusability.


Calorimetric studies of elastin solvation.
The interaction of ox ligamentum nuchae elastin (native, purified and soluble) with four different solvents was investigated by Differential Scanning Calorimetry. The freezable solvent content was determined, at different total solvent contents, from the melting endotherms, and the amount of unfreezable solvent was obtained by extrapolation. For two bifunctional solvents, water and ethylene glycol, the molar ratio "bound solvent/elastin residue" was the same for all the elastin samples investigated, and very close to 1.5. This result is identical to that obtained by other workers for the "water/CO-NH group" of synthetic amorphous polyamides, and it can suggest that the hydration of elastin is interpretable on the basis of a similar model. The model is based on a direct interaction of water with the peptide group, and suggests that 0.5 moles of water are strongly bound, and 1.0 moles are loosely bound to the CO-NH group. The ratio "bound water/elastin residue" is larger for the soluble beta elastin. Different molar ratios are also obtained for monofunctional solvents such as methanol and trifluoroethanol.


Efficacy of PET/CT in the accurate evaluation of primary colorectal carcinoma.
This study was performed to assess in the accurate evaluation of primary colorectal carcinoma using PET/CT. One hundred patients with primary colorectal carcinoma were evaluated during 2004. All patients underwent PET/CT when their preoperative serum carcinoembryonic antigen was >or=10 ng/mL or when CT showed equivocal findings. The appropriateness of PET/CT-induced changes was noted by subsequent operative findings and follow-up. PET/CT more detected 15 intra-abdominal metastatic lesions than abdomino-pelvic CT scan. PET/CT showed true negative findings in 13 patients and false positive or negative findings in 10. Due to PET/CT results, management plans were altered in 27 patients; 9 had inter-modality changes, 10 received more extensive surgery, and 8 avoided unnecessary procedures. PET/CT altered management plan in 24% of patients with primary colorectal carcinoma in correct direction. These findings suggest that PET/CT should be considered a part of standard work up for preoperative evaluation in a subset of patients with colorectal carcinoma.


Rapid collaborative health impact assessment: a three-meeting process.
A three-meeting process for collaborative health (inequality) impact assessment [H(I)IA] of a proposed new road is described in which local residents worked with professionals to produce a jointly agreed evidence-based report. Collaborative H(I)IA provided a forum for people to express fears that they believed had been ignored, and for planners to understand the concerns of the community and the health impacts of developments on the most vulnerable. The report has been passed to those who will influence the future of the road development plan and a decision is awaited.


Facilitators and barriers to the increased supervisory role of senior charge nurses: a qualitative study.
To explore the experiences of senior charge nurses provided with 'increased supervisory hours'. Designated supervisory time is essential for senior charge nurses to provide effective clinical leadership. It is important to explore the impact arises of such an increase. An online questionnaire collected exploratory data from senior charge nurses (n = 60). Semi-structured interviews gathered in-depth qualitative data (n = 12). Findings were analysed for common themes associated with implementation of the increased senior charge nurse supervisory role. The majority of senior charge nurses were unable to use their full allocation of supervisory time. They struggled to accomplish leadership goals because of managing staffing levels, increased workload, time constraints and limited support. Factors that facilitated the role included preparation and support, adequate staff capacity, effective leadership skills and availability of supervisory time. The senior charge nurses took pride in providing clinical leadership, promoting staff development and delivering patient care. Support, in terms of preparation, capacity building and ongoing mentoring, was a key factor for achieving senior charge nurse goals. Senior charge nurses should be supported to maximise supervisory time through the provision of an induction programme, formal coaching and ongoing training and development. Preparation and support is essential for senior charge nurses to deliver enhanced clinical leadership through increased supervisory time.


Seasonal variations and public search interests in Toxoplasma: a 16-year retrospective analysis of big data on Google Trends.
This study aims to understand whether there is a seasonal change in the internet search interest for Toxoplasma by using the data derived from Google Trends (GT). The present study searched for the relative search volume (RSV) for the search term 'Toxoplasma' in GT within six major English-speaking countries (Australia, New Zealand [Southern Hemisphere] and Canada, Ireland, the UK and the USA [Northern Hemisphere] from 1 January 2004 to 31 December 2019, utilizing the category of 'health'. Data regarding the RSV of Toxoplasma was obtained and further statistical analysis was performed in R software using the 'season' package. There were significantly seasonal patterns for the RSV of the search term 'Toxoplasma' in five countries (all p<0.05), except for the UK. A peak in December-March and a trough in July-September (Canada, Ireland, the UK and the USA) were observed, while a peak in June/August and a trough in December/February (Australia, New Zealand) were also found. Moreover, the presence of seasonal patterns regarding RSV for 'Toxoplasma' between the Southern and Northern Hemispheres was also found (both p<0.05), with a reversed meteorological month. Overall, our study revealed the seasonal variation for Toxoplasma in using internet search data from GT, providing additional evidence on seasonal patterns in Toxoplasma.


Galectins and their involvement in ocular disease and development.
Galectins are carbohydrate binding proteins with high affinity to ß-galactoside containing glycoconjugates. Understanding of the functions of galectins has grown steadily over the past decade, as a result of substantial advancements in the field of glycobiology. Galectins have been shown to be versatile molecules that participate in a range of important biological systems, including inflammation, neovascularisation and fibrosis. These processes are of particular importance in ocular tissues, where a major theme of recent research has been to divert diseases away from pathways which result in loss of function into pathways of repair and regeneration. This review summarises our current understanding of galectins in the context important ocular diseases, followed by an update on current clinical studies and future directions.


Paradoxical vocal cord motion--a case report.
Paradoxical vocal cord motion (PVCM) is an unusual cause of stridor, which is associated with some underlying causes, such as central nervous system lesion, gastroesophageal reflux or psychogenic problem. Once a diagnosis of PVCM is made, acute management with reassurance and sedation instead of aggressive airway intervention is required. Speech therapy, psychotherapy combination with anti-reflux medication is considered to be useful in long-term management. We present a 58 year-old male patient who had suffered from several episodes of acute onset of stridor, short of breath and tachypnea since one year ago. He was initially treated as an asthmatic patient with poor response. Aneurysm of ascending aorta by angiography, and mild gastroesophageal reflux with hiatal hernia by panendoscopy were noted. Then, the paradoxical vocal cord motion during inspiration phase was confirmed by flexible fiberoptic nasopharyngoscope after the consultation with an otolaryngologist. The emergency of his air-hunger was relieved quickly after psychological intervention. Now, he is free of stridor attack under anti-reflux therapy and psychotherapy.


Multiple assessment methodologies in determining the antibiofilm actions of sodium hypochlorite mixed with clodronate or etidronate in endodontic irrigation.
This study aimed to use multiple methodologies, including a novel usage of scanning electron microscopy (SEM), to evaluate the antimicrobial actions of sodium hypochlorite (NaOCl) admixed with clodronate or etidronate in root canal irrigation. The study also examined the usefulness of colony counting as a biofilm assessment methodology. Seven day Enterococcus faecalis biofilms were grown on hydroxyapatite discs. The discs were disinfected with 0.26 M clodronate-5% NaOCl, 0.26 M etidronate-5% NaOCl, 5% NaOCl, or treated with phosphate buffered saline (PBS). Assessments were performed using colony counting, SEM and the XTT reduction assay. The XTT assessment used the same groups but with 2.5% NaOCl. For colony counting, bacteria were removed from the discs by vortex mixing, followed by plating. The discs were subsequently fixed for SEM imagining and evaluators scored the SEM micrographs for remaining bacteria. Antibiofilm actions were assessed with the Kruskal-Wallis and Dunn's multiple comparison tests. SEM micrographs and the XTT assay revealed no differences between the NaOCl controls and the clodronate or etidronate mixtures with NaOCl (P > 0.05). It was concluded that the chelator mixtures with NaOCl had antibiofilm actions comparable to NaOCl. Furthermore, vortex mixing incompletely removed biofilm from HA discs in the PBS controls and hence colony counting using E. faecalis biofilms on hydroxyapatite discs could not be used for intergroup comparisons involving PBS. Additionally, colony counting could not be used for comparisons between the NaOCl treatment groups because the removal of bacteria from the substrate by vortex mixing was affected by the irrigant type.


[Cellular composition of lymphoid nodules in the trachea wall in rats with different resistance to emotional stress in a model of hemorrhagic stroke].
To reveal regularities of changes in cellular composition of lymphoid nodules in the tracheal wall in male Wistar rats resistant and not resistant to emotional stress in a model of hemorrhagic stroke. Lymphoid formations of the tracheal wall (an area near the bifurcation of the organ) were investigated in 98 male Wistar rats using histological methods. Significant changes in the cellular composition of lymphoid nodules were found. The pattern of changes depends on the stress resistance of rats and the period of the experiment. The active cell destruction in lymphoid nodules was noted both in stress resistant and stress susceptible animals. The changes in the structure of lymphoid nodules found in the experimental hemorrhagic stroke suggest a decrease in the local immune resistance, which is most pronounced in rats not resistant to stress, that may contribute to the development of severe inflammatory complications of stroke such as pneumonia.


Aluminum Trichloride Induces Hypertension and Disturbs the Function of Erythrocyte Membrane in Male Rats.
Aluminum (Al) is the most abundant metal in the earth's crust. Al accumulates in erythrocyte and causes toxicity on erythrocyte membrane. The dysfunction of erythrocyte membrane is a potential risk to hypertension. The high Al content in plasma was associated with hypertension. To investigate the effect of AlCl3 on blood pressure and the function of erythrocyte membrane, the rats were intragastrically exposed to 0, 64(1/20 LD50), 128(1/10 LD50), and 256(1/5 LD50) mg/kg body weight AlCl3 in double distilled water for 120 days, respectively. Then, we determined the systolic and mean arterial blood pressures of rats, the osmotic fragility, the percentage of membrane proteins, the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-pX), and malondialdehyde (MDA) content of the erythrocyte membrane in this experiment. The results showed that AlCl3 elevated the systolic and mean arterial blood pressure of rats, increased the osmotic fragility, decreased the percentage of membrane protein, inhibited the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, CAT, SOD and GSH-pX, and increased the MDA content of erythrocyte membrane. These results indicate that AlCl3 may induce hypertension by disturbing the function of erythrocyte membrane.


Multidetector CT angiography of pediatric vascular malformations and hemangiomas: utility of 3-D reformatting in differential diagnosis.
Vascular malformations can be difficult to diagnose and classify. Accurate classification is important because treatments and prognosis vary based on the type of lesion. Diagnosis is based on a combination of clinical features with a variety of imaging techniques, including US, MRI/MRA, CT, and conventional angiography. We hypothesized that imaging features seen on 3-D reformatted images obtained with multidetector CT angiography (CTA) would aid in differential diagnosis of types of vascular anomalies. We retrospectively reviewed CT scans of 11 patients with vascular lesions and pathologically proven diagnoses in which 3-D reformatting was obtained. The 3-D images accurately diagnosed hemangiomas and lymphangiomas in all cases, in contrast to diagnosis by clinical criteria and planar CT, which was difficult or inaccurate. The 3-D CTA did not aid in the distinction between venous malformations and arteriovenous malformations (AVM), which appeared similar. Our preliminary observations suggest that volume-rendered reformatting is helpful in categorizing clinically significant vascular head and neck lesions, resulting in more diagnostic value than planar CT imaging alone. In particular, 3-D CTA might allow accurate differentiation of hemangiomas from AVM, and of lymphangiomas from other types of lesions, which was, in our series, not possible using clinical examination or conventional planar CT angiography.


Culturing of specialized glial cells (olfactory ensheathing cells) of human olfactory epithelium.
A monolayer of dissociated glial cells of human olfactory epithelium was cultured in Petri dishes and 12-well plates using a polylysine-laminin substrate. Primary cultures were subcultured after 10-15 days. The cell cultures were analyzed by phase contrast microscopy at all stages of culturing. A cytological study involved histological methods (trypan blue staining) and immunocytochemical visualization of GFAP, nestin, and low-affinity nerve growth factor receptors. At the final stage of culturing (5 passages) the monolayer cultures included 2 types of cells: GFAP- and p75-positive glial cells and nestin-positive fibroblasts.


Protein-coding regions prediction combining similarity searches and conservative evolutionary properties of protein-coding sequences.
The gene identification procedure in a completely new gene with no good homology with protein sequences can be a very complex task. In order to identify the protein-coding region, a new method, 'SYNCOD', based on the analysis of conservative evolutionary properties of coding regions, has been realized. This program is able to identify and use the coding region homologies of the non-annotated (unknown) protein-coding sequences already present in the nucleotide sequence databases by using the alignment produced by BLASTN. The ratio of number mismatches resulting in synonymous codons to the number of mismatches resulting in non-synonymous codons is estimated for each open reading frame. Monte Carlo simulations are then used to estimate the significance of the ratio deviation from random behavior. The SYNCOD program has been tested on generated random sequences and on different control sets. The high accuracy of predicting protein-coding regions (the correlation coefficient, CC, varies from 0.67 to 0.79) and the high specificity (the portion of wrong exons, WE, varies from 0.06 to 0.07) have proved to be important features of the suggested approach. The SYNCOD program is resident on the ITBA-CNR Web Server and can be used via the Internet (URL: www.itba.mi.cnr.it/webgene).


Bile acid sulfates. III. Synthesis of 7- and 12-monosulfates of bile acids and their conjugates using a sulfur trioxide-triethylamine complex.
The 7- and 12-monosulfates of chenodeoxycholic acid, deoxycholic acid, and cholic acid were prepared by sulfation of the protected bile acids with sulfur trioxide-triethylamine in pyridine overnight and were isolated by precipitation as the p-toluidinium salt after removing the protecting group(s). The taurine conjugates were obtained by conjugating the bile acid sulfates with taurine in hot dimethylformamide (DMF) in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). A new procedure of preparing glycine conjugated bile acid sulfates by direct conjugation of the bile acid sulfate triethylammonium salt with ethyl glycinate in boiling chloroform in the presence of EEDQ is also described. The advantage of these procedures over other procedures are their simplicity and their higher yields (tyically above 90%) The thin layer chromatographic mobilities of these sulfates are presented. The influence of side chain and hydroxyl group configurations on the properties of bile acid sulfates is briefly discussed.


Real-world bone turnover marker use: impact on treatment decisions and fracture.
The use of bone turnover marker (BTM) testing for patients with osteoporosis in the USA has not been well characterized. This retrospective US-based real-world data study found BTM testing has some association with treatment decision-making and lower fracture risk in patients with presumed osteoporosis, supporting its use in clinical practice. The purpose of this study was to characterize bone turnover marker (BTM) testing patterns and estimate their clinical utility in treatment decision-making and fragility fracture risk in patients with osteoporosis using a retrospective claims database. Data from patients aged ≥ 50 years with newly diagnosed osteoporosis enrolled in the Truven MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Co-ordination of Benefits databases from January 2008 to June 2018 were included. Osteoporosis was ascertained by explicit claims, fragility fracture events associated with osteoporosis, or prescribed anti-resorptive or anabolic therapy. BTM-tested patients were 1:1 propensity score matched to those untested following diagnosis. Generalized estimating equation models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for testing versus no testing on both treatment decision-making and fragility fracture. Of the 457,829 patients with osteoporosis, 6075 were identified with ≥ 1 BTM test following diagnosis; of these patients, 1345 had a unique treatment decision made ≤ 30 days from BTM testing. The percentage of patients receiving BTM tests increased significantly each year (average annual % change: + 8.1%; 95% CI: 5.6-9.0; p = 0.01). Patients tested were significantly more likely to have a treatment decision (OR: 1.14; 95% CI: 1.13-1.15), and testing was associated with lower odds of fracture versus those untested (OR: 0.87; 95% CI: 0.85-0.88). In this large, heterogeneous population of patients with presumed osteoporosis, BTM testing was associated with treatment decision-making, likely leading to fragility fracture reduction following use.


Childhood acute lymphoblastic leukemia associated with parental alcohol consumption and polymorphisms of carcinogen-metabolizing genes.
Limited information is available on the association of parental consumption of alcohol prior to and during pregnancy with the risk of childhood leukemia, as well as for the potentially modifying role of genetic polymorphisms. We conducted a population-based, case-control study of 491 incident cases of acute lymphoblastic leukemia age 0-9 years and matched on age and sex to 491 healthy controls. Cases were identified at tertiary care centers in the Province of Québec between 1980 and 1993. Each parent was interviewed separately about alcohol consumption habits. We also used a case-only design with 186 cases to estimate interaction odds ratios between prenatal exposure and child DNA variants in the GSTM1 and CYP2E1 genes. The adjusted odds ratio for any maternal consumption during pregnancy was 0.7 (95% confidence interval = 0.5-0.9). The interaction odds ratios for the GSTM1 null genotype during third pregnancy trimester was 2.4 (95% confidence interval = 1.1-5.4); the interaction odds ratio for CYP2E1 variant G-1295C (or allele *5) during the nursing period was 4.9 (95% confidence interval = 1.5-16.7). The observed association with maternal alcohol consumption during pregnancy could be due to the potential chemopreventive effects of flavonoids found in wine and beer. These possible effects of alcohol may be at least partially genetically determined, although data are preliminary.


Establishment of a direct quantitative method for measurement of microRNA-224 in serum by UHPLC/MS/MS.
MicroRNAs (miRNAs) are known as potential noninvasive biomarkers for cancer diagnosis. Previous studies have been reported that miR-224 is upregulated in hepatocellular carcinoma (HCC) tissues and sera samples. However, current available methods of miRNA detection typically require pre-enrichment, amplification and labeling steps, and mostly they are semi-quantitative. Herein, we developed an isotope dilution mass spectrometry approach to convert the signal of miR-224 into the mass response of a reporter peptide. Specifically, the newly formed DNA-peptide probe was hybridized with miR-224, which was biotinylated and attached to streptavidin agarose in advance. After through trypsinization, solid phase extraction and blow drying, it used a UHPLC/MS/MS-based quasi-targeted proteomics assay for miR-224 quantification and determines the peak area or peak height ratio of labeled and non-labeled analytes to which an isotope label was added to estimate the concentration of the analyte in the sample. Moreover, this method showed good linearity, precision, accuracy and recovery in the calibration range. In addition, it also demonstrated good performance in comparison with qRT-PCR. Taken together, this study may offer a novel direct quantitative method for serum miRNA analysis applied in clinical practice.


A case of traumatic penile fracture with simultaneous rupture of both corpora cavernosa and complete urethral transection.
Penile fracture is a rare injury to the penis caused by blunt trauma. The presence of urethral injuries sustained during fracture is less than 10%, but very few cases involve complete circumferential urethral transection. We present a case of a patient who presented with traumatic penile fracture involving bilateral corporal cavernosa injury and complete urethral transection.


Limiting efficiencies of the non-parametric median method for A exp(-kt) data.
Weighted least squares analysis and the median method are used to extract A and k from simulated single exponential decays. The standard deviations of these parameters (sigma p) depend upon the method of analysis. The sigma p are compared as efficiencies (= sigma 2p[least squares]/sigma 2p[median]). These efficiencies depend upon the range of the decay and the underlying error structure. These include errors independent of the data, approximately equal to the data and approximately equal to the square root of the data. Some efficiencies fall well below 25% for the median method. Such instances reflect the large cost of not knowing or not using the weights; they amount to ignoring greater than 75% of the data we strive to collect.


A theory of the electric field-induced phase transition of phospholipid bilayers.
Improving the statistical mechanical model of Jacobs et al. (Jacobs, R.E., Hudson, B. and Andersen, H.C. (1975) Proc. Natl. Acad. Sci. U.S. 72, 3993--3997) we have constructed a model which describes not only the temperature but also the external field dependence of the membrane structure of phospholipid bilayers. In addition to the interactions between head groups, between hydrocarbon chains, and the internal conformational energy of the chains (which were considered in Jacobs' model), our model includes the energy of deformation and the field energy as well. By the aid of this model we can explain the phenomenon of dielectric breakdown, the non-linearity of current-voltage characteristics, and the mechanism of membrane elasticity. The free energy of the membrane, the average number of the gauche conformations in the hydrocarbon interior and at the membrane surface, gauche distribution along the chain, the membrane thickness, area and volume are calculated at different temperatures and voltages. The calculation also gives the temperature dependence of Young's modulus and that of the linear thermal expansion coefficient.


Rates and Levels of Elite Sport Participation at 5 Years After Revision ACL Reconstruction.
There is a paucity of data regarding return to play (RTP), level of competition, and longevity of play after revision of anterior cruciate ligament (ACL) reconstruction (ACLR) in elite athletes. To report RTP rates and competition levels in elite athletes at the point of RTP, as well as at 2 and 5 years after revision ACLR, and the effect of meniscal and chondral pathology at revision surgery on these outcomes. Case series; Level of evidence, 4. A retrospective review of a consecutive series of all revision ACLRs undertaken by the senior author between 2009 and 2019, with a minimum 2-year follow-up, was carried out. Outcome measures were RTP rates and competition level. A total of 49 knees in 48 elite athletes met the inclusion criteria. After revision ACLR, 43 (87.8%) elite athletes achieved RTP, of whom 75.5% were at the same level. At 2 years after surgery, 39 (79.6%) were still playing, 25 (51%) at the same level; at 5 years after surgery, 20 (44.4%) were still playing, 9 (20%) at the same level. Elite athletes with <50% thickness or no articular cartilage lesions were more likely to RTP (94.6% vs 66.7%; P = .026), as well as return to the same competition level (83.8% vs 50%; P = .047), compared with those with ≥50% thickness chondral lesions. Those without medial meniscal pathology were more likely to RTP at the same level after revision surgery (94.4% vs 64.5%; P = .036). The median time elite athletes continued to play after revision ACLR was 73 months (95% CI, 43.4-102.6); 23 months at the same level (95% CI, 13.6-32.4). The probability of still playing at 5 years after surgery was 55.9%, with a 22.5% chance of maintaining preinjury competition level. In elite athletes, RTP rates and competition level decreased over time after revision ACLR. The presence of >50% thickness chondral pathology was associated with lower RTP rates and competition level at RTP time, while medial meniscal pathology was associated with lower competition level at RTP.


Detection of amide I signals of interfacial proteins in situ using SFG.
In this Communication, we demonstrate the novel observation that it is feasible to collect amide signals from polymer/protein solution interfaces in situ using sum frequency generation (SFG) vibrational spectroscopy. Such SFG amide signals allow for acquisition of more detailed molecular level information of entire interfacial protein structures. Proteins investigated include bovine serum albumin, mussel protein mefp-2, factor XIIa, and ubiquitin. Our studies indicate that different proteins generate different SFG amide signals at the polystyrene/protein solution interface, showing that they have different interfacial coverage, secondary structure, or orientation.


An overview of the causes of current practices in Pratinidhi Dravyas (substitution of drugs) in Ayurveda including newer techniques for their evaluation.
Many Pratinidhi Dravyas in Ayurvedic classics are mentioned and certainly are based on a methodical approach, which involves many aspects. These principles on which Pratinidhis were decided are quoted nowhere; so both to understand the established Pratinidhis and to find new ones a rational approach is the need of the hour. This article is an effort in the direction to study this concept meticulously in light of modern techniques for its better understanding and application. As there are very few established parameters, which help for selection and evaluation of Pratinidhi Dravyas. A rational technique like Fourier transform infrared spectroscopy may be incorporated to set a new dimension. As most of the routine analytical techniques are separation based, overall component load cannot be predicted. Thus, it is prime necessity to compare the drugs with a whole aspect, which goes in hand by hand with a holistic approach of Ayurveda "Treat the man as Whole - Take the drug as whole."


Leiomyoma of the urinary bladder.
Leiomyoma of the urinary bladder is a rarity but should be considered in the differential diagnosis of intramural neoplasm. We report a case illustrating clinical and pathological features in particular the immunohistochemistry. Etiology and differential diagnosis are discussed.


What Goes Wrong with Lon in Ageing?
We have shown previously that the product of the human lon gene, the Lon protease, selectively degrades oxidized mitochondrial proteins, thus preventing their aggregation and cross-linking. We have also shown that lon is a stress-responsive gene, whose protease product is a stress-responsive protein that is induced by multiple stressors, including heat shock, serum starvation, and oxidative stress. Lon induction, by pre-treatment with low-level stress, protects against oxidative protein damage, diminished mitochondrial function, and loss of cell proliferation, induced by toxic levels of hydrogen peroxide. Blocking Lon induction, with lon siRNA, also blocks this induced protection. All of these results were obtained in young, healthy cells. In senescent cells, and in older primary cells, however, Lon activity declines, and adaptational responses become sluggish or even ineffectual. Studies in Drosophila melanogaster flies and in mice now suggest that declining Lon activity and declining responsiveness to stress, may contribute to the ageing process, and to various age-associated diseases. We propose that Lon is a generalized stress-protective enzyme whose decline may contribute to the increased levels of protein damage and mitochondrial dysfunction observed in ageing and various age-related diseases. We further propose that impaired ability to induce lon, and other stress-responsive genes, now needs to be included in any Free Radical Theory of Ageing.


Factors Associated with Nursing Student Satisfaction with Their Clinical Learning Environment at Wolkite University in Southwest Ethiopia.
The clinical learning environment has been defined as "an interactive network of strengths within the clinical environment that influence the clinical learning outcomes of students. Understanding students' level of satisfaction with their clinical learning environment is crucial to ensuring the required teaching and learning process. Therefore, this study was designed to assess the level of satisfaction with the CLE among nursing students at the Wolkite University of Ethiopia. A cross-sectional study was conducted at Wolkite University. This study was carried out in March 2022 on 208 student nurses selected by purposive and convenient sampling techniques. This study used the English version of the Clinical Learning Environment and Supervision + Nurse Teacher (CLES + T) evaluation scale. The collected data were cleaned, coded, and entered into Epi data 3.1, and then, statistical analyses were performed using SPSS version 26. Bivariate and multivariable logistic regression models were used to identify factors associated with the satisfaction level of nursing students towards CLE. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated, and p values < 0.05 were considered to indicate statistical significance. More than half of the study participants were females, and nearly half (50.5%) of the participants were in year three of the nursing program. The study found that 39.9% (95%CI: 32.2%, 46.6%) of students were satisfied with their CLE. Factors that had a significant association with the satisfaction level of nursing students towards CLE were gender (female students) (AOR = 16.053 (6.397, 40.286)), year of study (4th year) (AOR = 6.296 (2.679, 14.796)), and the type of the hospital in which their last clinical placement was held (at a primary hospital) (AOR = 2.961 (1.122, 7.815)). Effective nursing education programs need to be developed to increase satisfaction with clinical practice and to promote positive emotional regulation in nursing students. Nurse practitioners and managers should be aware of their important role in the professional development of students and their satisfaction with clinical placements.


The burden of pneumoconiosis in China: an analysis from the Global Burden of Disease Study 2019.
Pneumoconiosis refers to a class of serious diseases threatening the health of workers exposed to coal or silicosis dust. However, the burden of pneumoconiosis is unavailable in China. Incident cases, deaths, and disability-adjusted life years (DALYs) from pneumoconiosis and its subtypes in China were estimated from the Global Burden of Disease Study 2019 using a Bayesian meta-regression method. The trend of the burden from pneumoconiosis was analyzed using percentage change and annualized rate of change (ARC) during the period 1990-2019. The relationship between subnational socio-demographic index (SDI) and the ARC of age-standardised death rate was measured using Spearman's Rank-Order Correlation. In 2019, there were 136.8 (95% uncertainty interval [UI] 113.7-162.5) thousand new cases, 10.2 (8.1-13.6) thousand deaths, and 608.7 (473.6-779.4) thousand DALYs from pneumoconiosis in China. Of the global burdens from pneumoconiosis, more than 60% were in China. Both the total number of new cases and DALYs from pneumoconiosis was keeping increasing from 1990 to 2019. In contrast, the age-standardised incidence, death, and DALY rates from pneumoconiosis and its subtypes, except for the age-standardised incidence rate of silicosis, and age-standardised death rate of asbestosis, experienced a significant decline during the same period. The subnational age-standardised death rates were higher in western China than in eastern China. Meanwhile, the subnational ARC of age-standardised death rates due to pneumoconiosis and its subtypes were significantly negatively correlated with SDI in 2019. China suffers the largest health loss from pneumoconiosis in the world. Reducing the burden of pneumoconiosis is still an urgent task in China.


Demonstration of capsules in Clostridium difficile.
In four strains of Clostridium difficile the formation of capsules was demonstrated by light and electron microscopy.


Estrogen-responsive genes encoding egg yolk proteins vitellogenin and apolipoprotein II in chicken are differentially regulated by selective estrogen receptor modulators.
In a hen, large quantities of the egg yolk proteins, apolipoprotein II (apo-II) and vitellogenin (VG), are expressed in the liver and transported to the oviduct during egg production. Estrogenic stimulation of the hepatic expression of apo-II and VG is due to both transcriptional increase and mRNA stabilization. The nucleolytic degradation of apo-II messenger RNA (mRNA) is prevented by estrogen-regulated mRNA-stabilizing factor (E-RmRNASF). Gene-specific effects of a select panel of selective estrogen receptor modulators (SERMs) on the hepatic expression of the estrogen-responsive genes encoding apo-II, VG, and E-RmRNASF in the chicken liver were investigated. In the present study, 6-week-old roosters were treated with the vehicle, estrogen, the SERMs genistein, resveratrol, tamoxifen, pterostilbene, raloxifene, catechin, and clomiphene or a combination of estrogen and a 200-fold excess of each of the SERMs. Results from mRNA stabilization studies conducted to investigate the stimulation of expression of E-RmRNASF in the liver by these agents showed that the expression of E-RmRNASF in the liver was stimulated by estrogen and the SERMs genistein, resveratrol, tamoxifen, pterostilbene, and catechin but not by the vehicle, clomiphene or raloxifene. The expression of apo-II and VG from the aforementioned treatments was determined by Northern blot analysis, RNase protection assays, and Western blot analysis. The transcription and protein expression of both apo-II and VG genes were seen in response to treatment with estrogen but not with the SERMs or combinations of estrogen and each of the SERMs. The SERMs that stimulated the expression of E-RmRNASF antagonized the stimulation of the expression of both apo-II and VG by estrogen, demonstrating a gene-specific, selective regulation of the aforementioned genes in the chicken liver by the SERMs. The above panel of SERMs may likely have adverse effects on egg production.


The genomic diversity and stability of field strains of suid herpesvirus 1 (Aujeszky's disease virus).
The genomic diversity among isolates of suid herpesvirus 1 (SHV-1) collected in the same herd and among clones from the same isolate was studied by restriction fragment pattern (RFP) analysis using BamHI. Tentatively defining a field strain as a transmissible entity, it was concluded that strains of SHV-1 commonly comprise distinguishable genomic variants. Contrary to the hypothesis of genomic lability, it is suggested that the pool of variants is sufficiently stable to specifically characterize a strain. The impact of the results on epizootiological methods based on identification of field isolates is discussed in connection with Aujeszky's disease in Denmark.


Effects of maternal feed intake restriction during pregnancy on the expression of growth regulation, imprinting and epigenetic transcription-related genes in foetal goats.
Maternal nutrition during gestation is a leading factor of modifying the foetal epigenome and phenotype for mammals. Imprinting genes have important roles in regulating foetal growth, programming and development. There, however, are limited data available on the effects of feed intake restriction on the expression of imprinting genes in pregnant goats. The present study, therefore, was conducted to assess the effects of maternal feed intake restriction on the relative abundance of mRNA for growth imprinting, DNA methyltransferase (DNMT) and epigenetic transcription-related genes in the liver and heart of foetal goats during gestation. A total of 24 Liuyang black goats (2.0±0.3 yr) with similar body weight (BW, 31.22±8.09 kg) and parity (2) were allocated equally to either a control group (CG) or a restriction group (RG) during both early (from 26 to 65 days) and late (from 96 to 135 days) gestation. All goats were fed a mixed diet and had free access to fresh water. The feed of the RG was 40% less than that of the CG. The early and late gestation goats were weighed, bled and slaughtered on days 65 and 135 of gestation, respectively. In early gestation, the foetal weight, body length, the weight of foetal heart and liver were greater (P < 0.05) in the RG. The CpG methylation of genomic DNA in the foetal heart was less (P = 0.0001) in the RG. The relative abundance of mRNA of methyl-CpG-binding domain protein 2 (MBD2) and methyl-CpG-binding domain protein 3 (MBD3) genes in the foetal liver were greater (P < 0.05) in the RG. During the late gestation, the foetal weight, heart weight and liver weight were less (P < 0.05) in the RG. The relative abundance of mRNA for the MBD2 gene (P = 0.043) in the foetal heart, and the ten-eleven translocation protein 1 (TET1) gene (P < 0.05) in both the foetal heart and liver were greater in the RG. These results indicate feed intake restriction during gestation influenced foetal development and regulated the relative abundance of mRNA for epigenetic transcription-related genes.


Analysis of NOD-like receptor NLRP1 in multiple sclerosis families.
The implementation of exome sequencing technologies has started to unravel the genetic etiology of familial multiple sclerosis (MS). A homozygote p.G587S mutation in NLRP1 has been suggested as potentially causative for the onset of MS in an affected sibling pair, who later developed malignant melanoma. To validate the proposed role of recessive NLRP1 mutations in the pathological mechanisms of MS, we examined exome sequencing data from 326 MS patients from Canada for the identification of NLRP1 missense and nonsense variants. This analysis did not identify the previously described p.G587S mutation; however, three patients with potential NLRP1 compound heterozygote mutations were observed. Haplotype and segregation analyses indicate that the variants observed in these patients were inherited in cis, and do not segregate with disease within families. Thus, the analysis of MS patients from Canada failed to identify potentially pathogenic mutations in NLRP1, including the previously described p.G587S mutation. Further studies are necessary to confirm a role of NLRP1 in the pathophysiology of MS.


Dysphoria and anhedonia as risk factors for disability or death in older persons: implications for the assessment of geriatric depression.
Either dysphoria (sadness) or anhedonia (loss of interest in usually pleasurable activities) is required for a diagnosis of major depression. Although major depression is a known risk factor for disability in older persons, few studies have examined the relationship between the two core symptoms of major depression and disability or mortality. Our objective was to examine the relationship between these two core symptoms and time to disability or death. In a longitudinal cohort study, we used the nationally representative Health and Retirement Study to examine this relationship in 11,353 persons older than 62 years (mean: 73 years) followed for up to 13 years. Dysphoria and anhedonia were assessed with the Short Form Composite International Diagnostic Interview. Our outcome measure was time to either death or increased disability, defined as the new need for help in a basic activity of daily living. We adjusted for a validated disability risk index and other confounders. Compared with subjects without either dysphoria or anhedonia, the risk for disability or death was not elevated in elders with dysphoria without anhedonia (adjusted hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.91-1.36). The risk was elevated in those with anhedonia without dysphoria (HR: 1.30; 95% CI: 1.06-1.60) and those with both anhedonia and dysphoria (HR: 1.28; 95% CI: 1.13-1.46). Our results highlight the need for clinicians to learn whether patients have lost interest in usually pleasurable activities, even if they deny sadness.


Intravenous catheter-assisted scleral fixation of an intraocular lens in eyes without adequate capsular support.
Sutureless scleral fixation is an effective technique for placement of a secondary intraocular lens. The authors propose a modification that may simplify intraoperative technical challenges. Description of surgical technique. Successful placement of stable secondary intraocular lens. This modified technique has the potential to reduce intraoperative complications. Studies including more patients with longer follow-up are needed to test the viability.


Hypolipidemic Effect of Celastrus paniculatus in Experimentally Induced Hypercholesterolemic Wistar Rats.
The objective of the present study was to evaluate hypolipidemic effect of methanolic extract of Celastrus paniculatus in experimentally induced hypercholesterolemic rats. Hypercholesterolemia was induced by feeding the animals with high fat diet. Oral administration of methanolic seed extract (50%) of Celastrus paniculatus at the optimized dose of 65 mg/kg body weight, substantially reduced the plasma total cholesterol, triglycerides and LDL cholesterol in comparison with induced hypercholesterolemic animal group and the results were comparable with the standard hypocholesterolemic drug and almost similar to the control group. Atherogenic index and liver weight of treated animals also showed significant decrease compared to the hypercholesterolemic animals. It substantially increased the HDL cholesterol level as compared to control group. A significant increase in the activities of lipoprotein lipase and plasma LCAT enhanced hepatic bile acid synthesis and thereby, increased degradation of cholesterol to neutral sterols. Furthermore, the activities of HMG-CoA reductase, glucose 6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Histological studies showed less cholesterol deposits in the aorta of animals fed with seed extract of C. paniculatus compared to the induced hypercholesterolemic animals not given C. paniculatus supplement.


[End to side porto-caval shunt in familial type II homozygote hypercholesterolemia (author's transl)].
Two patients with homozygous type II familial hypercholemia have had significant improvement by end to side porta-caval shunt. Follow-up is respectively 1 and 4 years. When all the other treatment have failed in lowering blood cholesterol and L.D.L. levels, a portal diversion may help to prevent cardio-vascular atherosclerotic complications in the pediatric age.


Circadian signaling in the Northern krill Meganyctiphanes norvegica: In silico prediction of the protein components of a putative clock system using a publicly accessible transcriptome.
The Northern krill Meganyctiphanes norvegica is a significant component of the zooplankton community in many regions of the North Atlantic Ocean. In the areas it inhabits, M. norvegica is of great importance ecologically, as it is both a major consumer of phytoplankton/small zooplankton and is a primary food source for higher-level consumers. One behavior of significance for both feeding and predator avoidance in Meganyctiphanes is diel vertical migration (DVM), i.e., a rising from depth at dusk and a return to depth at dawn. In this and other euphausiids, an endogenous circadian pacemaker is thought, at least in part, to control DVM. Currently, there is no information concerning the identity of the genes/proteins that comprise the M. norvegica circadian system. In fact, there is little information concerning the molecular underpinnings of circadian rhythmicity in crustaceans generally. Here, a publicly accessible transcriptome was used to identify the molecular components of a putative Meganyctiphanes circadian system. A complete set of core clock proteins was deduced from the M. norvegica transcriptome (clock, cryptochrome 2, cycle, period and timeless), as was a large suite of proteins that likely function as modulators of the core clock (e.g., doubletime), or serves as inputs to it (cryptochrome 1) or outputs from it (pigment dispersing hormone). This is the first description of a "complete" (core clock through putative output pathway signals) euphausiid clock system, and as such, provides a foundation for initiating molecular investigations of circadian signaling in M. norvegica and other krill species, including how clock systems may regulate DVM and other behaviors.


Association between Glaucoma and At-fault Motor Vehicle Collision Involvement among Older Drivers: A Population-based Study.
To examine the association between glaucoma and motor vehicle collision (MVC) involvement among older drivers, including the role of visual field impairment that may underlie any association found. A retrospective, population-based study. A sample of 2000 licensed drivers aged ≥70 years who reside in north central Alabama. At-fault MVC involvement over the 5 years before enrollment was obtained from state records. Three aspects of visual function were measured: habitual binocular distance visual acuity, binocular contrast sensitivity (CS), and the binocular driving visual field constructed from combining the monocular visual fields of each eye. Poisson regression was used to calculate crude and adjusted rate ratios (RRs) and 95% confidence intervals (CIs). At-fault MVC involvement over the 5 years before enrollment. Drivers with glaucoma (n = 206) had a 1.65 times higher MVC rate (95% CI, 1.20-2.28; P = 0.002) compared with those without glaucoma after adjusting for age, and mental status. Among those with glaucoma, drivers with severe visual field loss had higher MVC rates (RR, 2.11; 95% CI, 1.09-4.09; P = 0.027), whereas no association was found among those with impaired visual acuity and CS. When the visual field was subdivided into 6 regions (upper, lower, left, and right visual fields; horizontal and vertical meridians), we found that impairment in the left, upper, or lower visual field was associated with higher MVC rates, and an impaired left visual field showed the highest RR (3.16; P = 0.001) compared with other regions. However, no association was found in deficits in the right side or along the horizontal or vertical meridian. A population-based study suggests that older drivers with glaucoma are more likely to have a history of at-fault MVC involvement than those without glaucoma. Impairment in the driving visual field in drivers with glaucoma seems to have an independent association with at-fault MVC involvement, whereas visual acuity and CS impairments do not.


Research Progress on the Experimental Animal Model of Gestational Diabetes Mellitus.
Gestational diabetes mellitus (GDM) refers to different degrees of abnormal glucose metabolism during pregnancy, where blood glucose levels do not reach the level of overt diabetes, accounting for 80-90% of pregnancy with hyperglycemia. Hyperglycemia affects the pregnancy process, leading to a series of adverse maternal outcomes that have a profound impact on the future of the offspring. The establishing of an appropriate GDM model will provide theoretical basis for study GDM pathogenesis involves, the choice of resonable drugs and the observation the disease trends and outcomes. At present, there are many methods for establishing experimental GDM animal models and animal choices. This paper examines the different GDM models and their induction methods.


Dense deposit disease in children: prognostic value of clinical and pathologic indicators. The Southwest Pediatric Nephrology Study Group.
Clinical and pathological features were examined in 16 children with dense deposit disease. The children ranged in age from 5 to 15 years (mean: 9.3 years). There were nine boys and seven girls. Semiquantitative grading of renal biopsy findings was performed in these patients and compared to clinical features at the time of presentation, and at the time of latest follow-up. Initial clinical features included hypertension and decreased glomerular filtration rate in 50% of patients, nephrotic syndrome in 69%, and gross hematuria in 73%. Serum C3 concentrations were low in nine of nine patients. All but one of the patients subsequently received steroid therapy, the dosage of which varied. Of the 16 patients, six developed progressive renal insufficiency, six have normal renal function after a period of 7 to 12 years, and four have normal renal function but have been followed for less than 6 years. When these different subgroups were compared, clinical and laboratory features were not helpful outcome indicators. By contrast, poor outcome was correlated with the following pathologic features: excessive prominence of glomerular lobules, severe mesangial hypercellularity and sclerosis, severe glomerular loop obliteration, and mesangial electron dense deposit alteration. We conclude that the course of dense deposit disease is variable and that certain pathologic features may be helpful in predicting clinical outcome. Whether alternate-day prednisone therapy may have been of benefit for the patients in this study is uncertain.


Small alkyl amines as ion-pair reagents for the separation of positional isomers of impurities in phosphate diester oligonucleotides.
In an effort to improve separation of impurities in oligonucleotide drugs, alkyl amines of different length and carbon content were evaluated as reagents in ion pair-reversed phase (IP-RP) HPLC with mass spectrometric detection. A range of columns was tested in combination with different buffers, ion-pair modifiers and varying pH adjustments. For phosphorothioate oligonucleotides, larger amines, like tributyl and hexyl amine provided the best chromatography, as small amines tended to broaden peaks due to the separation of diastereoisomers. For phosphate diester oligonucleotides, the best separations were obtained using small alkyl amines, like propyl-, isopropyl- and diethylamine. Conditions optimized for oligonucleotide sequence and type of impurity enabled full separation of the individual components of composite impurities, such as n-1, N3-(2-cyanoethyl)thymine (CNET), deaminated and 3-(2-oxopropyl)imidazopyrimidinone (OPC) impurities. The addition of long-chain alkyl acids like hexanoic acid to the IP buffer resulted in further improvements in peak separation.


The perception of visual emotion: comparing different measures of awareness.
Here, we explore the sensitivity of different awareness scales in revealing conscious reports on visual emotion perception. Participants were exposed to a backward masking task involving fearful faces and asked to rate their conscious awareness in perceiving emotion in facial expression using three different subjective measures: confidence ratings (CRs), with the conventional taxonomy of certainty, the perceptual awareness scale (PAS), through which participants categorize "raw" visual experience, and post-decision wagering (PDW), which involves economic categorization. Our results show that the CR measure was the most exhaustive and the most graded. In contrast, the PAS and PDW measures suggested instead that consciousness of emotional stimuli is dichotomous. Possible explanations of the inconsistency were discussed. Finally, our results also indicate that PDW biases awareness ratings by enhancing first-order accuracy of emotion perception. This effect was possibly a result of higher motivation induced by monetary incentives.


The Symptoms Self-Management Center (SSMC): Methods for developing and implementing technology-enhanced self-management interventions for pain and fatigue.
The National Institutes of Nursing Research provides funding via the P20 grant mechanism for research infrastructure and resources to develop nurse scientists with expertise in symptom self-management. The Medical University of South Carolina College of Nursing was awarded a P20 grant in 2016 to build the Symptoms Self-Management Center for technology-enhanced interventions to address pain and fatigue in individuals with chronic health conditions. Resources were derived from three key subcores: bioinformatics, mHealth and eHealth consultative services, and community engagement. This paper describes methods for deriving specific resources within each subcore, the application of subcore resources in two pilot studies, and lessons learned during the early phases of our Symptoms Self-Management Center implementation.


Genome Editing Inhibits Retinal Angiogenesis in a Mouse Model of Oxygen-Induced Retinopathy.
This protocol describes a novel approach harnessing the technology of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9-based gene editing for treating retinal angiogenesis. In this system, adeno-associated virus (AAV)-mediated CRISPR/Cas9 was employed to edit the genome of vascular endothelial growth factor receptor (VEGFR)2 in retinal vascular endothelial cells in a mouse model of oxygen-induced retinopathy. The results showed that genome editing of VEGFR2 suppressed pathological retinal angiogenesis. This mouse model mimics a critical aspect of abnormal retinal angiogenesis in patients with neovascular diabetic retinopathy and retinopathy of prematurity, indicating genome editing has high potential for treating angiogenesis-associated retinopathies.


Predictors of late cardiac events following treatment with Sr-90 beta-irradiation for instent restenosis.
Intracoronary radiation therapy (IRT) with Sr-90 using the Novoste Beta-Cath system has been shown to be an effective therapy for instent restenosis (ISR), but the temporal occurrence of cardiac events and the predictors of late complications require further investigation. We analyzed the demographics, lesion characteristics and clinical outcomes of 138 consecutive patients with ISR treated with IRT from September 1998 to March 2002. Major adverse cardiac events (MACE) were defined as death, myocardial infarction (MI) or target vessel revascularization (TVR). Characteristics of early (< or =8 months) and late (>8 months) failures were analyzed. Thirty-two (23.1%) of 138 patients had MACE on follow-up; 25% (8/32) of failures occurred late after treatment with IRT. A comparison of the clinical and angiographic profile of early and late failures using univariate analysis indicates no correlations to late failure following IRT. Duration to failure after IRT was 14.25+/-3.69 months in the late group compared to 4.63+/-2.86 months in the early group (P<.001). Late MACE after IRT with Sr-90 for ISR occur beyond the traditional period for clinical restenosis in 25% of cases and are difficult to predict. Further study is warranted to identify patients at risk for the development of late complications after IRT.


The Utility of a Novel Definition of Health Care Regions in the United States in the Era of COVID-19: A Validation of the Pittsburgh Atlas Using Pneumonia Admissions.
The COVID-19 pandemic in the United States has underscored the need to understand health care in a regional context. However, there are multiple definitions of health care regions available for conducting geospatial analyses. In this study, we compare the novel Pittsburgh Atlas, which defined regions for emergency care, with the existing definitions of regions, counties, and the Dartmouth Atlas, with respect to nonemergent acute medical conditions using pneumonia admissions. We identified patients hospitalized with a primary diagnosis of pneumonia or a primary admitting diagnosis of sepsis with a secondary diagnosis of pneumonia in the Agency for Healthcare Research and Quality's State Inpatient Databases. We calculated the percentage of region concordant care, the localization index, and market share for 3 definitions of health care regions (the Pittsburgh Atlas, Dartmouth Atlas, and counties). We used logistic regression identified predictors of region concordant care. We identified 1,582,287 patients who met the inclusion criteria. We found that the Pittsburgh Atlas and Dartmouth Atlas definitions of regions performed similarly with respect to both localization index (92.0 [interquartile range 87.9 to 95.7] versus 90.3 [interquartile range 81.4 to 94.5]) and market share (8.5 [interquartile range 5.1 to 13.6] versus 9.4 [interquartile range 6.7 to 14.1]). Both atlases outperformed the localization index (67.5 [interquartile range 49.9 to 83.9]) and market share (20.0% [interquartile range 11.4 to 31.4]) of the counties. Within a given referral region, the demographic factors, including age, sex, race/ethnicity, insurance status, and the level of severity, affected concordance rates between residential and hospital regions. Because the Pittsburgh Atlas also has the benefit of respecting state and county boundaries, the use of this definition may have improved policy applicability without sacrificing accuracy in defining health care regions for acute medical conditions.


Soil radioactivity-depth profiles from regularized inversion of borehole gamma spectrometry data.
An in situ borehole gamma logging method using a LaBr3 gamma detector has been developed to characterize a137Cs contaminated site. The activity-depth distribution of 137Cs was derived by inversion of the in situ measurement data using two different least squares methods, (i) Least squares optimization (LSO) and (ii) Tikhonov regularization. The regularization parameter (λ) of the Tikhonov regularization method was estimated using three different methods i.e. the L-curve, Generalized Cross Validation (GCV) and a prior information based method (PIBM). The considered inversion method variants were first validated for a137Cs contaminated pipe, and in most of the cases, the calculated activity of 137Cs was found to be within the acceptable range. The calculated 137Cs activity-depth profiles from in situ measurements were also in good agreement with the ones obtained from soil sample analysis, with an R2 ranging from 0.76 to 0.82. The GCV method for estimating λ appeared to perform better than the two other methods in terms of R2 and root mean squared error (RMSE). The L-curve method resulted in higher RMSE than the other Tikhonov regularization methods. Instability was observed in the activity concentration depth profile obtained from the LSO method. Therefore, we recommend the Tikhonov regularization with GCV for estimating λ for estimating the activity concentration-depth profile. The site studied showed 137Cs activity concentrations above the exemption limit down to depths of 0.50-0.90 m.


Advances in the application of robotic surgical systems to gastric cancer: A narrative review.
Gastric cancer is one of the common malignant tumors in the gastrointestinal tract, and surgery is currently an important treatment for progressive gastric cancer. With the development of technology, the simultaneous maturation of artificial intelligence (AI), fifth-generation (5G) telecommunication networks and the internet of things (IOT) has brought significant efficacy and new opportunities for the surgical treatment of gastric malignancies. The combination of 5G network and remote surgical robotic system is the future trend of radical gastric cancer surgery, and the "unmanned" treatment mode of fully automated robotic gastric cancer radical surgery will be realized soon.


Protocol to image and quantify nucleocytoplasmic transport in cultured cells using fluorescent in situ hybridization and a dual reporter system.
Nucleocytoplasmic transport (NCT) plays critical roles in maintaining cellular homeostasis. Here, we present a protocol to measure NCT for both transcript and protein cargos in cultured cells. We first describe the fluorescent in situ hybridization (FISH) assay to measure the nuclear mRNA export. We then detail a dual reporter system to measure the protein NCT. This protocol also includes image analysis and data output using CellProfiler™. The combined approach can be used to unbiasedly analyze NCT activities in cultured cells. For complete details on the use and execution of this protocol, please refer to Ding et al. (2020, 2021).


β-Hydroxybutyrate Boosts Mitochondrial and Neuronal Metabolism but is not Preferred Over Glucose Under Activated Conditions.
The ketone body, β-hydroxybutyrate (βOHB), is metabolised by the brain alongside the mandatory brain fuel glucose. To examine the extent and circumstances by which βOHB can supplement glucose metabolism, we studied guinea pig cortical brain slices using increasing concentrations of [U-13C]D-βOHB in conjunction with [1-13C]D-glucose under conditions of normo- and hypoglycaemia, as well as under high potassium (40 mmol/L K+) depolarization in normo- and hypoglycaemic conditions. The contribution of βOHB to synthesis of GABA was also probed by inhibiting the synthesis of glutamine, a GABA precursor, with methionine sulfoximine (MSO). [U-13C]D-βOHB at lower concentrations (0.25 and 1.25 mmol/L) stimulated mitochondrial metabolism, producing greater total incorporation of label into glutamate and GABA but did not have a similar effect in the cytosolic compartment where labelling of glutamine was reduced at 1.25 mmol/L [U-13C]D-βOHB. At higher concentrations (2.5 mmol/L) [U-13C]D-βOHB inhibited metabolism of [1-13C]D-glucose, and reduced total label incorporation and total metabolite pools. When glucose levels were reduced, βOHB was able to partially restore the loss of glutamate and GABA caused by hypoglycaemia, but was not able to supplement levels of lactate, glutamine or alanine or to prevent the increase in aspartate. Under depolarizing conditions glucose was the preferred substrate over βOHB, even in hypoglycaemic conditions where comparatively less βOHB was incorporated except into aspartate isotopomers. Inhibition of glutamine synthesis with MSO had no significant effect on incorporation of label from [U-13C]D-βOHB into GABA C2,1 indicating that the majority of this GABA was synthesized in GABAergic neurons from [U-13C]D-βOHB rather than from Gln C4,5 imported from astrocytes.


Suppression of atrial tachyarrhythmias by pacing.
Treatment of atrial tachyarrhythmias (ATs) remains difficult in many patients. Accordingly, new therapeutic approaches for AT suppression are evaluated. Atrial pacing may prevent ATs by modifying the electrophysiologic conditions required for sustained ATs. New pacing algorithms for prevention of AT are aimed at permanent overdrive suppression of arrhythmic activity, reduction of dispersion of atrial refractoriness produced by short-long cycles, more aggressive overdrive pacing after spontaneous sinus conversion to prevent early reinitiation of ATs, and prevention of inadequate rate decay in patients with vagally induced ATs. AT prevention may be achieved by dedicated atrial pacing sites, e.g., pacing at the insertion of Bachmann's bundle or biatrial pacing, which compensates for interatrial conduction delay. Preexciting regions of critical conduction delay, pacing at the triangle of Koch or coronary sinus os, and dual-site right atrial pacing have shown antiarrhythmic effects. Atrial preventive pacing and pharmacologic treatment may work synergistically in the concept of hybrid therapy. To prevent atrial electrical remodeling, early termination of AT seems desirable. This may be achieved by implanted devices that automatically detect ATs and provide atrial antitachycardia pacing for organized ATs. Initial studies showed that regular AT can automatically be terminated in approximately 50% of treated episodes. Pacing for prevention of AT and termination of organized AT episodes may become important steps within the concept of hybrid therapy of AT. However, their clinical efficacy and optimal patient selection remain to be evaluated in prospective, well-designed clinical trials.


Prevalence and persistence of coagulase-negative Staphylococcus species in three dairy research herds.
Coagulase-negative Staphylococcus species (CNS) were isolated from 11.3% (1407 of 12,412) of mammary quarter milk samples obtained from cows in three dairy research herds in 2005. Approximately 27% (383/1407) of CNS was identified to the species level. The species distribution among those CNS identified from all herds was Staphylococcus chromogenes (48%), Staphylococcus hyicus (26%), Staphylococcus epidermidis (10%), Staphylococcus simulans (7%), Staphylococcus warneri (2%), Staphylococcus hominis (2%), Staphylococcus saprophyticus (1%), Staphylococcus xylosus (1%), Staphylococcus haemolyticus (<1%), Staphylococcus sciuri (<1%), and Staphylococcus intermedius (<1%). Staphylococcuschromogenes was the predominant CNS isolated from all three herds; however, differences were seen in the prevalence of other CNS species. A total of 158 CNS (S. chromogenesn=66, S. hyicusn=38, S. epidermidisn=37, S. simulans n=10, and S. warneri n=7) were analyzed by pulsed-field gel electrophoresis (PFGE). The majority (33/41) of CNS isolated from the same mammary quarter on more than one occasion had the same PFGE pattern indicating persistence of the same infection over time. When all PFGE patterns for each CNS were analyzed, no common pulsotype was seen among the three herds indicating that CNS are quite diverse. Composite milk somatic cell count (SCC) data were obtained +/-14d of when CNS were isolated. Average milk SCC (5.32 log(10)/ml) for cows in which CNS was the only bacteria isolated was significantly higher than the average milk SCC (4.90 log(10)/ml) from cows with quarter milk samples that were bacteriologically negative.


Direct syncytial assay for the quantitation of bovine leukemia virus.
A direct in vitro tissue culture method is described for the quantitation of bovine leukemia virus, utlizing a feline S+L-- cell line.


Petrosal ganglion responses to acetylcholine and ATP are enhanced by chronic normobaric hypoxia in the rabbit.
In mammals, adaptation to chronic hypoxia requires the integrity of the arterial chemoreceptors, specially the carotid body (CB). Chronic hypoxia increases the sensibility of the CB by acting on the receptor cells, but there is limited information on the effects of chronic hypoxia on the sensory neurons that innervate the CB. Therefore, we studied the responses evoked by ACh and ATP, the main transmitters that generate the chemoafferent activity, on the petrosal ganglion (PG) of rabbits exposed to chronic normobaric hypoxia (CNH) during fourteen days. ATP and ACh increased the activity of PG neurons in a dose-dependent manner, in a similar way than in rabbits not exposed to hypoxia (naïve). However, the duration of the responses were significantly increased by CNH, with the mean maximal responses to ACh and ATP increased by a factor of two and four, respectively. Our results suggest that CNH increases duration of the responses by modifying the expression and/or content of ACh and ATP receptors.


Is suicidal behaviour increasing among Australian youth?
The rate of suicide of 15- to 19-year-old Australian boys appears to have doubled since 1965. Some of this rise might be due to a trend by coroners to reach a verdict of suicide more frequently than previously. One in seven deaths of teenage boys is now termed suicide. Hospital admissions of boys and girls in Western Australia for attempted suicide doubled in the past decade. These figures indicate that suicidal behaviour among the young constitutes a serious problem for health and welfare services.


The in-hospital costs of treating high-risk patients with fenestrated and branched endografts.
This study determined the 30-day morbidity and mortality and in-hospital costs of elective fenestrated (fEVAR) and branched (bEVAR) endovascular aneurysm repairs at a single academic institution and determined factors that influence them. All elective fEVAR or bEVAR patients treated between November 2007 and March 2014 in a Canadian academic hospital were included. Procedural details, 30-day morbidity and mortality rates, and cost of hospitalization were analyzed. Nonparametric bootstrap analysis was used to compare means between groups and calculate confidence intervals (CIs). There were 84 consecutive fEVAR (n = 61) and bEVAR (n = 23) procedures. The 30-day mortality was 3.3% for fEVAR and 4.3% for bEVAR. Mean hospital stay was 7.2 ± 0.8 days for fEVAR and 12.6 ± 2.2 days for bEVAR. The mean cost of the index hospitalization was $57,000 for fEVAR and $91,000 for bEVAR. Device-related costs accounted for 55% of the total costs. The occurrence of intraoperative or postoperative events were used to further divide each of the fEVAR and bEVAR groups into "complicated hospitalization" (fEVAR, n = 10; bEVAR, n = 13) and "uncomplicated hospitalization" (fEVAR, n = 51; bEVAR, n = 10) groups. Device-related costs were not significantly different between the complicated and uncomplicated hospitalization groups (mean difference [95% CI] fEVAR: $3383 [-$3405 to $9809], P = .3; and bEVAR: $1930 [-$7892 to $11,288], P = .68). However, there were significant differences between the complicated and uncomplicated hospitalization groups in hospital length of stay (mean difference [95% CI] fEVAR: 8.1 [3.0-13.2] days, P = .001; and bEVAR: 10.8 [5.9-19.9] days, P = .002) and nondevice-related costs (mean difference [95% CI,] fEVAR: $25,843 [$11,689-$43,247], P = .001; and bEVAR; $20,326 [$9362-$36,615], P = .002). bEVAR and fEVAR are expensive interventions. Intraoperative adverse events and postoperative systemic complications dramatically increase costs and length of stay. Measures to minimize complications will reduce hospitalization costs and improve patient outcomes.


The drug use index: a measure of the extent of polydrug usage.
A drug use index (DUI) is constructed from actual usage data of 1,121 respondents (517 males and 604 females). It is proposed that this index represents a quantitative measure of the degree of involvement in polydrug use. Correlations between the DUI and use of 19 drugs or drug classes are reported. Furthermore, some applications of the DUI are demonstrated with specific reference to four psycho-personality tests.


Allostatic load and health status of African Americans and whites.
To compare health risks in 84 healthy African American and 45 white men and women after calculating allostatic load (AL) from biologic, psychosocial, and behavioral measures. Participants (18-45 years) ranging in weight from normal to obese and without hypertension or diabetes. Fitness, body fat, CRP, mood, social support, blood pressure, sleep and exercise habits, coping, and insulin responses were dichotomized as low/high risk and summed for AL. African Americans (3.4±1.9) had significantly higher AL than that of whites (2.4±1.9; P<0.05). Significantly more African Americans had AL≥3 (67.9%) than did whites (48.9%). Identifying cumulative AL may help identify and address the underpinnings of health disparities in African Americans.


Nebulin and titin expression in Duchenne muscular dystrophy appears normal.
Monoclonal antibodies which recognize different epitopes on either titin or nebulin show normal staining patterns on frozen sections of three muscle biopsies of Duchenne muscular dystrophy (DMD). Gel electrophoresis and immunoblotting performed on two of these muscle biopsies show the normal pattern of titin and nebulin polypeptides. Since the donor of one of these biopsies has a large deletion of the 5'-region of the DMD gene, our results argue against the recent proposal that nebulin is the gene mutated in DMD.


Tumour necrosis factor (TNF) and interleukin-1 (IL-1) induce muscle proteolysis through different mechanisms.
The purpose of this study was to test the hypothesis that muscle proteolysis induced by TNF or IL-1 is mediated by glucocorticoids. Rats were treated with 300 mug kg(-1) of recombinant human preparations of IL-1alpha (rIL-1alpha) or TNFalpha (rTNFalpha) divided into three equal intraperitoneal doses given over 16 h. Two hours before each cytokine injection, rats were given 5 mg kg(-1) of the glucocorticoid receptor blocker mifepristone RU 38486, by gavage or were gavaged with the vehicle. Eighteen hours after the first cytokine injection, total and myofibrillar protein breakdown rates were determined in incubated extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine, respectively. Total and myofibrillar proteolytic rates were increased following injection of rIL-1alpha or rTNFalpha. Proteolysis induced by rIL-1alpha was not altered by treatment with RU 38486. In contrast, the glucocorticoid receptor blocker inhibited the proteolytic effect of rTNFalpha. The results suggest that the proteolytic effect of TNF is mediated by glucocorticoids and that IL-1 induces muscle proteolysis through a glucocorticoid independent pathway.


Re-circulation of lymphocytes mediated by sphingosine-1-phosphate receptor-1 contributes to resistance against experimental infection with the protozoan parasite Trypanosoma cruzi.
T-cell mediated immune responses are critical for acquired immunity against infection by the intracellular protozoan parasite Trypanosoma cruzi. Despite its importance, it is currently unknown where protective T cells are primed and whether they need to re-circulate in order to exert their anti-parasitic effector functions. Here, we show that after subcutaneous challenge, CD11c(+)-dependent specific CD8(+) T-cell immune response to immunodominant parasite epitopes arises almost simultaneously in the draining lymph node (LN) and the spleen. However, until day 10 after infection, we observed a clear upregulation of activation markers only on the surface of CD11C(+)PDCA1(+) cells present in the LN and not in the spleen. Therefore, we hypothesized that CD8(+) T cells re-circulated rapidly from the LN to the spleen. We investigated this phenomenon by administering FTY720 to T. cruzi-infected mice to prevent egress of T cells from the LN by interfering specifically with signalling through sphingosine-1-phosphate receptor-1. In T. cruzi-infected mice receiving FTY720, CD8 T-cell immune responses were higher in the draining LN and significantly reduced in their spleen. Most importantly, FTY720 increased susceptibility to infection, as indicated by elevated parasitemia and accelerated mortality. Similarly, administration of FTY720 to mice genetically vaccinated with an immunodominant parasite antigen significantly reduced their protective immunity, as observed by the parasitemia and survival of vaccinated mice. We concluded that re-circulation of lymphocytes mediated by sphingosine-1-phosphate receptor-1 greatly contributes to acquired and vaccine-induced protective immunity against experimental infection with a human protozoan parasite.


Real-time UV imaging of piroxicam diffusion and distribution from oil solutions into gels mimicking the subcutaneous matrix.
A novel real-time UV imaging approach for non-intrusive investigation of the diffusion and partitioning phenomena occurring during piroxicam release from medium chain triglyceride (MCT) solution into two hydrogel matrices is described. Two binary polymer/buffer gel matrices, 0.5% (w/v) agarose and 25% (w/v) Pluronic F127, were applied as simple models mimicking the subcutaneous tissue. The evolution of the absorbance maps as a function of time provided detailed information on the piroxicam release processes upon the exposure of the gel matrices to MCT. Using calibration curves, the concentration maps of piroxicam in the UV imaging area were determined. Regression of the longitudinal concentration-distance profiles, which were obtained using expressions derived from Fick's second law, provided the diffusivity and the distribution coefficients of piroxicam penetrated into the gels. The obtained MCT-agarose (pH 7.4) distribution coefficient of 1.4 was identical to the MCT-aqueous (pH 7.4) distribution coefficient determined by the shake-flask method whereas that of the MCT-Pluronic F127 system was four times less. The experimental data show that UV imaging may have considerable potential for investigating the transport properties of drug formulations intended for the subcutaneous administration.


Outcomes of surgery in lung cancer patients with schizophrenia.
There are very few reports regarding the outcome of lung cancer surgery in patients with schizophrenia, and the clinical features of such patients are still unclear. From 2004 to 2012, 11 lung cancer patients (six male, five female; mean age, 62.7 years) with schizophrenia underwent lung resections at our institutions. All patients had been institutionalized because they were unable to live independently at home. We retrospectively evaluated their postoperative clinical outcomes and long-term results. Ten of the 11 patients had comorbidities, such as diabetes mellitus and chronic obstructive pulmonary disease. Preoperatively, two patients had a history of treatment for other primary cancers in other organs, and one was on hemodialysis. A lobectomy was performed in nine patients, a segmentectomy in one, and a partial resection in one. There were no hospital deaths. The postoperative morbidity included two cases of pneumonia, one of atelectasis, and one of prolonged air leakage lasting more than 7 days. Wandering was postoperatively observed in two patients; one of these fell and fractured the left femur. At the time of our investigation, two patients were deceased, and the overall 5-year survival rate was 74.1 %. The postoperative morbidity and long-term results of schizophrenic patients with lung cancer were acceptable. Therefore, even in patients with schizophrenia, surgical treatment for lung cancer should be recommended when deemed to be necessary.


Effects of Hyaluronic Acid on Stability of Bleomycin Foam.
Bleomycin (BLM) foam sclerotherapy is effective in the treatment of venous malformations (VMs). Foam stability is influenced by factors such as sclerosant concentration, viscosity, and liquid-gas ratio. To investigate whether hyaluronic acid (HA) could increase the stability of BLM foam and to evaluate the safety and efficacy of HA-BLM foam. Experiment: BLM 6.0 IU + human serum albumin (HSA, 2, 1.95, 1.90, and 1.85 mL, respectively) + 1% HA (0, 0.05, 0.10, and 0.15 mL, respectively) + air 6 mL to create foam using the Tessari method. The foam half-life (FHL) was used to evaluate foam stability. Clinical study: Twenty-eight patients with head and neck VMs were enrolled between June 2018 and August 2019 treated by HA-BLM foam to evaluate the safety and efficacy. The FHL of the BLM foam was 8.46, 8.95, 10.45, and 14.51 minutes, respectively. All patients achieved significant efficacy, and no obvious side effects were observed. Addition of HA could improve the stability of BLM foam.


The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination.
The microbiota is now recognized as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress toward therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination-the regeneration of myelin sheaths-also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics impair oligodendrocyte progenitor cell responses during remyelination and further our understanding of how mammalian regeneration relates to the microbiota.


Synthesis of the new mannosidase inhibitors, diversity-oriented 5-substituted swainsonine analogues, via stereoselective Mannich reaction.
5alpha-substituted swainsonine analogues were synthesized by Mannich reaction of an in situ generated (-)-swainsonine iminium ion intermediate. 5alpha-substituted swainsonine analogues were epimerized to their 5beta-isomers in protic solvent. [reaction: see text]