Peroral administration of 14C-poly(D,L-lactic acid) nanoparticles coated with human serum albumin or polyvinyl alcohol to guinea pigs.
Biodegradable 14C-poly(D,L-lactic acid) (PLA50) nanoparticles coated either with a readily digestible protein albumin or with a non-digestible coating agent, polyvinyl alcohol (PVA), were prepared by the solvent evaporation technique. The nanoparticles were administered perorally to guinea pigs to evaluate the gastro-intestinal degradation of their PLA50 matrix. In the case of PLA50 nanoparticles coated with digestible albumin, substantial gastro-intestinal degradation of the PLA50 matrix occurred, leading to the passage of considerable amount (> or =45%) of water-soluble products across the gastrointestinal barrier. When a non-digestible coating agent like PVA was used, the degradation of the PLA50 matrix in the gastro-intestinal tract was at least two times lower (> or =19%). The results show that it is possible to control the in vivo degradation of PLA50 nanoparticles using appropriate coating agents. The present investigations showed a good correlation between previously observed in vitro results and the in vivo findings.


A rapid experimental protocol to determine the desorption resistant fraction of sediment-sorbed hydrophobic organic contaminants.
Desorption of hydrophobic organic contaminants (HOCs) from sedimentary materials plays a vital role in dictating the fate and transport of HOCs in the environment. Desorption irreversibility is a commonly observed phenomenon in laboratory sorption/desorption studies of HOCs. A desorption-resistant fraction (DRF) typically exists during the desorption process. To correctly evaluate the DRF of HOCs can considerably contribute to the understanding of availability and bioavailability of HOCs. This can substantially benefit contaminant remediation and cleanup operations. Conventional batch method to measure the DRF replies on repetitive washing of the sediments, which is time-consuming and can be impractical. This study presents an experimental protocol to quantify the DRF of the sediment-sorbed organic contaminants in a rapid manner. This protocol utilizes cosolvent to expedite desorption kinetics and adopts an ultrafiltration/centrifugation combined method to achieve a complete separation of sediment and solution phases. This proposed experimental protocol can facilitate the quantification of the DRF of sorbed contaminants to understand and minimize the uncertainties associated with risk-based pollution remediation approach. This protocol has the potential to be widely used in environmental studies to characterize sorption and desorption properties of HOCs with soil and sedimentary materials.


Can animals recall the past and plan for the future?
According to the 'mental time travel hypothesis' animals, unlike humans, cannot mentally travel backwards in time to recollect specific past events (episodic memory) or forwards to anticipate future needs (future planning). Until recently, there was little evidence in animals for either ability. Experiments on memory in food-caching birds, however, question this assumption by showing that western scrub-jays form integrated, flexible, trial-unique memories of what they hid, where and when. Moreover, these birds can adjust their caching behaviour in anticipation of future needs. We suggest that some animals have elements of both episodic-like memory and future planning.


Impact of COVID-19 on emergency service usage in Turkey: interrupted time series analysis.
The aim of this study is to reveal the impact of the COVID-19 pandemic, which constitutes an extraordinary situation, on the habits of emergency health service use. The data of the study consist of emergency service applications of a public hospital in Turkey between the years 2018-2021. The number of applications to the emergency service was examined periodically. The interrupted time series analysis method was used to reveal the impact of the COVID-19 outbreak on emergency service admissions. When the main findings are analyzed in quarterly periods (3 months = 1 quarter); there has been a sharp decrease in emergency service applications since March 2019, when the first case was seen in Turkey. When an evaluation is made between consecutive quarters, it is seen that there are fluctuations up to 80% in the number of applications. When the statistical analysis findings are examined; while the effect of COVID-19 on the number of applications was found to be significant for the first four periods, it was found to be insignificant for the following periods. With the conducted study, it was revealed that COVID-19 has a significant impact on the use of emergency health services. Although there was a statistically significant decrease in the number of applications, especially in the months following the first case, there was an increase in the number of applications over time. Considering the necessity of using emergency health services when necessary, it can be thought that some of the decrease in the number of applications during the COVID-19 period will be related to the use of unnecessary emergency health services.


Surgical treatment of congenital heart disease; the evaluation of diagnostic data.
In the diagnosis of congenital heart disease, the cardiologist was formerly concerned with distinguishing the operable from the inoperable cases. With the development of "open" heart operations under hypothermia and extracorporeal circulation, the majority of congenital heart lesions have become correctable. It is now necessary to make an exact anatomic diagnosis preoperatively. The present discussion reviews the diagnostic methods employed by the cardiac team in investigating a patient with congenital heart disease.


Conversion of an anti-single-stranded DNA active site to an anti-fluorescein active site through heavy chain complementarity determining region transplantation.
Complementarity determining region (CDR) transplant studies were conducted between two monoclonal antibodies of distinctly different specificities (anti-fluorescein monoclonal antibody (mAb) 4-4-20 and anti-single-stranded DNA (ssDNA) mAb 04-01) which possessed nearly identical light chains but dissimilar heavy chains. The variations in binding specificities between the two immunoglobulins suggested that the active-site features of anti-fluorescein antibodies were dictated by characteristics intrinsic to the heavy chain (H-chain). To identify specific regions of the H-chain which influence the structure and function of an anti-fluorescein active site, CDR transplantation was systematically employed to convert the anti-ssDNA 04-01 antibody active site to an active site with anti-fluorescein activity. Each mAb 4-4-20 H-chain CDR (HCDR) was transplanted into the H-chain of a single-chain derivative of the 04-01 molecule. A fluorescence polarization ligand binding assay was utilized to determine the equilibrium dissociation constant, Kd, of hybrid transplant single-chain antibody HCDR1-HCDR2-HCDR3(4-4-20) for fluorescein (3.8 x 10(-7) M, indicating successful conversion of an anti-ssDNA active site to an anti-fluorescein binding site. A similar Kd (6.3 x 10(-7) M) was determined using a fluorescein fluorescence quenching assay. The transplantation results are discussed in terms of the relative contribution of each HCDR to a successful conversion in antibody specificity.


Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.
Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N-glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N-glycans on HN glycoprotein.


Faster or slower decarbonization? Policymaker and stakeholder expectations on the effect of the COVID-19 pandemic on the global energy transition.
The COVID-19 pandemic might have tremendous consequences on decarbonization efforts across the globe. Understanding governments' policy action in the short and medium term is key to assess whether the response to the crisis will crowd out or fast-track decarbonization efforts. We surveyed over 200 policymakers and stakeholders from 55 different countries to collect climate policy expectations in various sectors and regions in the next five years. While support for high-emitting sectors is not expected to dissolve completely, commitment to policies supporting the transition to low-carbon energy and transport sectors is expected to increase substantially. This is true for OECD and Asian countries, representing approximately 90% of global emissions. Our results suggest that expectations that the COVID-19 pandemic will accelerate decarbonization efforts are widely shared.


Outcomes of exertional rhabdomyolysis following high-intensity resistance training.
High-intensity resistance training (HIRT) programmes are increasingly popular amongst personal trainers and those attending gymnasiums. We report the experience of exertional rhabdomyolysis (ER) at two tertiary hospitals in Melbourne, Australia. To compare the clinical outcomes of ER with other causes of rhabdomyolysis. Retrospective cross-sectional study of patients presenting with a serum creatine kinase (CK) of greater than 25 000 units/L from 1 September 2013 to 31 August 2014 at two tertiary referral hospitals in Melbourne, Australia. Records were examined to identify care measures implemented during hospital stay, clinical outcomes during admission and on subsequent follow up. Thirty four cases of rhabdomyolysis with a CK of greater than 25 000 units/L (normal range: 20-180 units/L) were identified during the 12-month study period. Twelve of the 34 cases (35%) had ER with 10 of 12 related to HIRT. No acute kidney injury, intensive care admission or death were seen among those with ER. All cases were managed conservatively, with 11 admitted and 9 receiving intravenous fluids only. In contrast, patients with rhabdomyolysis from other causes experienced significantly higher rates of intensive care admission (64%, P = 0.0002), acute kidney injury (82%, P = 0.0001) and death (27%, P = 0.069). ER resulting from HIRT appears to have a benign course compared with rhabdomyolysis of other aetiologies in patients with a serum CK greater than 25 000 units/L. Conservative management of ER appears to be adequate, although this requires confirmation in future prospective studies.


Dual therapy in IPAH and SSc-PAH. A qualitative systematic review.
Use of endothelin receptor antagonists (ERA), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogues has resulted in improved outcomes in idiopathic pulmonary arterial hypertension (IPAH) and systemic sclerosis-associated PAH (SSc-PAH) patients. However, patients often deteriorate on monotherapy. The objective of this study is to evaluate the effect of dual therapy on outcomes in IPAH and SSc-PAH. A systematic review of MEDLINE (1950-2011), EMBASE (1980-2011) and CINAHL (inception-2011) was conducted to identify studies that evaluated the effect of any dual combination of ERA, PDE-5 inhibitors or prostaglandin analogues on 6-min walk distance (6MWD), functional class (FC), haemodynamics, quality-of-life (QoL) or time-to-clinical-worsening in IPAH or SSc-PAH. A standardized form was used to abstract design, sample size, aetiology, outcome and treatment effect. Twenty-six observational studies and 6 randomized trials were identified. Using combination PDE-5 inhibitor and prostaglandin analogues, 6/7 studies reported improvement in 6MWD, 6/8 studies reported improvement in FC, 6/6 studies reported improvement in haemodynamics and 1 trial demonstrated improvement in QoL and time-to-clinical-worsening. Using combination ERA and prostaglandin analogues, 4/6 studies and 1 trial reported improvement in 6MWD, 3/3 studies and 1 trial reported improvement in FC, 4/5 studies and 1 trial reported improvement in PAP. Using combination ERA and PDE-5 inhibitor, 4/7 studies reported an improvement in 6MWD, and 2/6 report improvement in FC. The evidence suggests a beneficial effect of dual therapy in IPAH and SSc-PAH, particularly those who are deteriorating on monotherapy. Research should focus on subsets of patients to identify the optimal timing and combination of dual therapy.


Simvastatin ameliorates testosterone-induced prostatic hyperplasia in rats via modulating IGF-1/PI3K/AKT/FOXO signaling.
Benign prostatic hyperplasia (BPH) is characterized by non-malignant enlargement of prostate cells causing many lower urinary tract symptoms. BPH pathogenesis includes androgens receptors signaling pathways, oxidative stress, apoptosis, and possibly changes in IGF-1/PI3K/AKT/FOXO pathway. Altogether, modulating IGF-1/PI3K/AKT/FOXO signaling along with regulating oxidative stress and apoptosis might preserve prostatic cells from increased proliferation. Beyond statins' common uses, they also have anti-inflammatory, antioxidant, and anti-tumor effects. This study aims to determine simvastatin's beneficial effect on testosterone-induced BPH. Rats were randomly allocated into four groups, 9 rats each. The control group received olive oil subcutaneously and distilled water orally for 30 consecutive days. The second group received simvastatin (20 mg/kg, p.o.) dissolved in distilled water. The BPH-induced group received testosterone enanthate (3 mg/kg, s.c.) dissolved in olive oil, and the BPH-induced treated group received both simvastatin and testosterone. Testosterone significantly increased prostate index and severity of histopathological alterations in prostate tissues as well as 5-alpha reductase enzyme level in contrast to simvastatin treatment that reversed the testosterone-induced alterations in these parameters. Likewise, testosterone up-regulated IGF-1/PI3K/AKT signaling pathway and down-regulated FOXO transcription factor. It also decreased apoptotic markers level in prostatic tissue BAX, caspase-3, and caspase-9, while it elevated Bcl-2 level. In addition, it alleviated reduced GSH and GPX5 levels and SOD activity. Simvastatin treatment significantly opposed testosterone's effect on all aforementioned parameters. In conclusion, this study demonstrates that simvastatin is a possible treatment for BPH which may be attributed to its effect on IGF-1/PI3K/AKT/FOXO signaling pathway as well as anti-oxidant and apoptotic effects.


Applications of MR angiography in head and neck pathology.
MR angiography is a useful examination in the area of head and neck pathology when correctly applied and tailored to a specific clinical problem. Of the cases presented in this article, the most common application is evaluation of vascular invasion or displacement to aid in surgical planning of tumor resection. Applications to evaluation of vascular thrombosis or dissection, assessment of tumor vascularity, and visualization of variant vascular anatomy and acquired vascular disease were also demonstrated.


Serological and coat protein sequence studies suggest that necrosis disease on sunflower in India is caused by a strain of Tobacco streak ilarvirus.
Serological and coat protein sequence studies were conducted to identify an ilarvirus associated with necrosis disease on sunflower in India. In electroblot immunoassay, sunflower ilarvirus reacted strongly only with antiserum to Tobacco streak virus (TSV). The coat protein gene of sunflower ilarvirus was cloned and sequenced. The sequence analyses also showed that the CP gene was most closely related to TSV, the member of subgroup I of Ilarvirus. The sunflower ilarvirus CP shared 90% amino acid sequence identity with TSV. On the basis of serological relatedness and sequence identity, it is proposed that the sunflower ilarvirus from India should be considered a strain of TSV belonging to subgroup I and designated as TSV-SF. This is the first report of the molecular characterization of TSV on sunflower from the Indian subcontinent.


Application of a joint latent space item response model to clustering stressful life events and the Beck Depression Inventory-II: results from Korean epidemiological survey data.
According to previous findings, stressful life events (SLEs) and their subtypes are associated with depressive symptoms. However, few studies have explored potential models for these events and incidental symptoms of depression. Participants (3,966 men; 5,709 women) were recruited from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort. SLEs were measured using a 47-item Life Experiences Survey (LES) with a standardized protocol. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II). Joint latent space item response models were applied by gender and age group (<50 vs. ≥50 years old). Among the LES items, death or illness of close relatives, legal problems, sexual difficulties, family relationships, and social relationships shared latent positions with major depressive symptoms regardless of gender or age. We also observed a gender-specific domain: occupational and family-related items. By projecting LES and BDI-II data onto the same interaction map for each subgroup, we could specify the associations between specific LES items and depressive symptoms.


Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells.
Histone H3 lysine 9 trimethylation (H3K9Me3) has been associated with transcriptional repression, but recent findings implicate this chromatin modification in transcriptional activation and mRNA elongation by RNA polymerase II. Here, we applied immunoprecipitation (IP) with a custom DNA tiling microarray containing many transcription factors important in development and cancer (for example homeotic genes; N=683 total genes) to explore the relationship between H3K9Me3 and other histone modifications with the differential expression of genes. Cancer cell lines derived from different tissues (2 leukemia, 2 medulloblastoma) were characterized with IP antibodies to H3K9Me3, H3K4 dimethylation (H3K4Me2) and H3K9 acetylation (H3K9Ac). MV4-11 is known to overexpress the HOXA9 and MEIS1 genes, whereas D283 overexpresses the OTX2 homeobox gene. Gene expression was assessed by Affymetrix U133 array. Mapping the number and size of histone markings demonstrated significant colocalization of H3K9Ac and H3K4Me2 with H3K9Me3, indicating a pattern of putative 'activating' and 'repressive' markings. The median site size was 600-821 bp and 72-95% or 53-80% of chromatin signal sites were located within 1 kb or 500 bp of transcription start sites (TSS), respectively. A relatively small number of genes displayed additional H3K9Me3 sites in the 5'-region distant from the TSS. Comparing genes with modification sites to those without sites in their promoters confirmed the positive associations of H3K9Ac and H3K4Me2 with gene expression and revealed that H3K9Me3 is associated with active genes rather than being a repressive marking as previously thought. The positive regulatory effect of all three types of modifications were quantitatively correlated with site size, and applied to absolute gene expression within a single cell line as well as relative expression among pairs of cell lines. Extended patterns of H3K9Me3 upstream of some genes (for example HOXA9 and OTX2) may result from the action of multiple promoter elements. We found an inverse relationship between promoter DNA hypermethylation and H3K9Me3 in three studied genes (HOXA9, TMS1, RASSF1A). The localization of H3K9Me3 downstream of the TSSs of expressed genes and not within promoter regions of hypermethylated and silenced genes is consistent with the proposed coupling of H3K9Me3 with RNA polymerase II. Our results indicate a need for revising aspects of the histone code involving H3 lysine methylation. Awareness of H3K9Me3 as a mark of gene activity, not repression, is especially important for the classification of human cancer using chromatin and histone profiles.


Comprehensive Postoperative Management After Endoscopic Skull Base Surgery.
To maximize outcomes from endoscopic skull base surgery, careful early postoperative management is critically important. Standardized postoperative regimens are lacking. The type of reconstruction and presence and type of cerebrospinal fluid leak dictate management. If a leak is encountered intraoperatively, patients should avoid maneuvers that increase intracranial pressures for at least 1 month. Early postoperative care focuses on minimizing and managing nasal crusting. This article reviews the evidence in the literature on postoperative management, complications, and quality of life after surgery, and outlines our experience in the management of patients after endoscopic skull base surgery.


Ultrastructure of mesodermal mixed tumor of the uterus.
A case of mesodermal mixed tumor arising in the uterus of a 57-year-old woman is presented. The tumor was a mixture of adenocarcinoma with occasional squamous metaplasia, stromal sarcoma, myxosarcoma and chondrosarcoma. Light and electron microscopic examinations of the tumor revealed close transition between stromal sarcomatous component and each of other sarcomatous and carcinomatous component. The histogenesis of mixed mesodermal tumor was discussed and it was concluded that the tumor might be derived from endometrial stromal cell which possessed the pluripotency to differentiate toward various epithelial and mesenchymal tissues including the heterologous mesenchymal tissue.


A current overview of two viroids that infect chrysanthemums: Chrysanthemum stunt viroid and Chrysanthemum chlorotic mottle viroid.
The chrysanthemum (Dendranthema X grandiflorum) belongs to the family Asteraceae and it is one of the most popular flowers in the world. Viroids are the smallest known plant pathogens. They consist of a circular, single-stranded RNA, which does not encode a protein. Chrysanthemums are a common host for two different viroids, the Chrysanthemum stunt viroid (CSVd) and the Chrysanthemum chlorotic mottle viroid (CChMVd). These viroids are quite different from each other in structure and function. Here, we reviewed research associated with CSVd and CChMVd that covered disease symptoms, identification, host range, nucleotide sequences, phylogenetic relationships, structures, replication mechanisms, symptom determinants, detection methods, viroid elimination, and development of viroid resistant chrysanthemums, among other studies. We propose that the chrysanthemum and these two viroids represent convenient genetic resources for host-viroid interaction studies.


Across climates and species, higher vapour pressure deficit is associated with wider vessels for plants of the same height.
While plant height is the main driver of variation in mean vessel diameter at the stem base (VD) across angiosperms, climate, specifically temperature, does play an explanatory role, with vessels being wider with warmer temperature for plants of the same height. Using a comparative approach sampling 537 species of angiosperms across 19 communities, we rejected selection favouring freezing-induced embolism resistance as being able to account for wider vessels for a given height in warmer climates. Instead, we give reason to suspect that higher vapour pressure deficit (VPD) accounts for the positive scaling of height-standardized VD (and potential xylem conductance) with temperature. Selection likely favours conductive systems that are able to meet the higher transpirational demand of warmer climates, which have higher VPD, resulting in wider vessels for a given height. At the same time, wider vessels are likely more vulnerable to dysfunction. With future climates likely to experience ever greater extremes of VPD, future forests could be increasingly vulnerable.


Loss of phospholipid membrane asymmetry and sialylated glycoconjugates from erythrocyte surface in haemoglobin E beta-thalassaemia.
This study aimed to investigate any correlation between the extent of phosphatidylserine (PS) asymmetry and sialylated glycoconjugate levels with the faster clearance of circulating erythrocytes in haemoglobin E (HbE) beta-thalassaemia. Erythrocytes from peripheral blood samples of different HbEbeta-thalassaemia patients showed loss of PS asymmetry measured by annexin V binding using flow cytometry. Maximum PS exposure was found when HbE was 50-60% and HbF was <20% indicating a possible correlation with severity of the disease. Separation of erythrocytes into aged and younger cells showed higher loss of PS asymmetry in the younger erythrocytes of HbEbeta-thalassaemia patients when compared with normal blood, where PS asymmetry was lost only in the older cells. Sialylated glycoconjugate measurement using the lectins wheatgerm agglutinin and pokeweed mitogen showed loss of sialic acid and N-acetyl-D-glucosamine-bearing glycoproteins in the order normal<homozygous E<HbEbeta-thalassaemic upon ageing. A possible correlation was found between the loss of PS asymmetry with HbE level and the reduction of glycophorins from the cell surface, mediated by membrane vesiculation. A more facilitated vesiculation process in HbEbeta-thalassaemic erythrocytes could lead to faster shedding of glycophorin-containing microvesicles, leaving highly PS-exposed erythrocytes accessible to phagocytes.


Autoradiographic mapping of neurotransmitter system receptors in mammalian brain.
Regional localization of neurotransmitter system receptors was visualized in the gerbil grain and in the rat brain using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyladenosine (CHA), [3H]muscimol, [3H]MK-801, [3H]SCH 23390, [3H]PN200-110, [3H]spiperone, and [3H]naloxone were label muscarinic receptors, adenosine A1 receptors, GABAA receptors, N-methyl-D-aspartate (NMDA) receptors, dopamine D1 receptors, L-type calcium channels, spirodecanone receptors, and opioid receptors, respectively. Regional localization of [3H]QNB, [3H]muscimol, [3H]MK-801, [3H]SCH 23390, and [3H]PN200-110 binding sites in the gerbil brain was relatively similar to that in the rat brain. In contrast, the autoradiographic distribution of [3H]spiperone and [3H]naloxone binding sites in the gerbil was quite different from that in the rat. This phenomenon was found especially in the hippocampus and the cerebellum. The results suggest that the gerbil differs from the rat with respect to spirodecanone and opioid binding sites in the hippocampus and the cerebellum. This finding may help to further elucidate the species differences and relationships for brain function and behavioral pharmacology.


Lectin histochemistry shows the comparative biosynthesis and cellular biodistribution of alpha L-fucose residues in some tissues of tetrapoda representatives.
Fucose is a monosaccharide that plays several immunological roles. This study investigated the comparative biosynthesis and cellular biodistribution of fucose residues in some tissues of tetrapoda representatives using lectin histochemistry. In this study, the mouse was used as a representative for mammalian, pigeon for avian, lizard for reptilian, and toad for amphibians. The localization of the fucose residues was seen in several cell types of mice ileum, such as villi microfold (M) cells, goblet cells, some of intestinal crypts cells, and lamina propria cells. In other tetrapoda representatives, fucose was only seen in M cells of lizard ileum and some cells of villi lamina propria of pigeon, lizard, and toad. It was also observed in the pancreatic acinar cells of the mouse and some cell aggregations of pancreatic parenchyma of the lizard. Contrarily, it was not seen either in pigeon or in toad pancreases parenchyma. Spleen of all animals showed the fucose residues in some splenic cells in the red pulp only, barring the white pulp. The liver parenchyma of all tetrapoda representatives hadn't fucose residues. The fucose cellular biodistribution in some cells of tetrapoda representatives differed based on the cell type. In the mouse, it was highly seen in the apical cytoplasm of the villi M cells as well as in the cup-like part of goblet cells. In addition, it was seen as "rings" in the granule membranes of the Ulex europeaus agglutinin I (UEAI(+)) cells in the intestinal crypts cells. Furthermore, the UEAI(+) cells in the lamina propria showed fucose granules in their cytoplasm. There is no clear evidence about the relation between the cellular biosynthesis of fucose residues and mucosal immune cells. The role of fucose residues in the pancreatic acinar cells are not well understood and need further investigations. In this study, fucose residues were synthesized in several types of cells in the mouse ileum, spleen and pancreas as compared with other tetrapoda. The data obtained from this study can help us to get more information about the cellular biodistribution and synthesis of fucose residues in several animal species rather than mammalians.


Metastatic pheochromocytoma and paraganglioma: Management of endocrine manifestations, surgery and ablative procedures, and systemic therapies.
Metastatic pheochromocytomas and paragangliomas (MPPGs) are rare neuroendocrine tumors. Most patients present with advanced disease that is associated with manifestations of catecholamine release. Surgical resection of the primary tumor and ablative therapies of metastases-whenever possible-may improve clinical outcomes and, perhaps, lengthen the patient's overall survival. Significant steps in understanding the genetic alterations linked to MPPGs and scientific progress made on cancers that share a similar pathogenesis are leading to the recognition of potential systemic therapeutic options. Data derived from clinical trials evaluating targeted therapies such as tyrosine kinase inhibitors, radiopharmaceuticals, immunotherapy, and combinations of these will likely improve the outcomes of patients with advanced and progressive MPPGs. Exemplary of this success is the recent approval in the United States of the high-specific-activity iodine131 meta-iodine-benzylguanidine (MIBG) for patients with unresectable and progressive MPPGs that express the noradrenaline transporter. This review will discuss the therapeutic approaches for patients with MPPGs.


Monitoring salivary misonidazole in man: a possible alternative to plasma monitoring.
Concentrations of misonidazole and its O-demethylated metabolite Ro 05-9963 in the plasma and saliva of 10 patients with malignant disease have been determined. A good linear correlation was established between plasma and saliva misonidazole concentration, and salivary sampling was found to be suitable for the estimation of a number of pharmacokinetic parameters. Data are also presented for serial tumour cencentrations of misonidazole and Ro 05-9963 in 3 of the 10 patients. Monitoring of salivary misonidazole concentration appears to be a useful alternative to plasma monitoring, particularly for those patients in whom plasma sampling is unsuitable or impossible.


A novel wound dressing consisting of PVA-SA hybrid hydrogel membrane for topical delivery of bacteriophages and antibiotics.
The emergence of antibiotic-resistant pathogens has made the treatment of infected burn wounds even more problematical than the pre-antibiotic era. Phage therapy is now being considered a promising treatment options to fight against antibiotic resistant pathogens. Hence, we introduce a novel PVA-SA hydrogel based wound dressing system for topical delivery of bacteriophages and antibiotic to treat infected burn injuries. Hydrogel membrane provides wound healing environment while surface absorbed bacteriophages/antibiotic takes care of the local infection. Different blends of PVA and SA were crosslinked by boric acid and calcium ions to form the hydrogel membrane and assessed for ideal wound dressing properties. 1:2 blended PVA: SA membrane displayed highest swelling index, gel fraction, protein adsorption, hemocompatibility and best mechanical properties among the 3 blends studied in this study. The selected membrane was further characterised by FTIR, FESEM and TGA. Overall, self-adherent, antibacterial and biocompatible membrane was obtained as revealed by the in-vitro antibacterial assays, elution assays and cell cytotoxicity assays. The in-vivo potential was evaluated using MRSA-infected murine burn wound model revealing significant bacterial reduction, wound contraction and reduced inflammation in membrane treated groups in comparison to control group. The dual coated hydrogel membrane delivering both MR10 phage and minocycline proved to be better treatment strategy to treat the resistant burn wound infection rather than phage and antibiotic alone.


Fertility signals in the bumblebee Bombus terrestris (Hymenoptera: Apidae).
In eusocial Hymenoptera, queen control over workers is probably inseparable from the mechanism of queen recognition. In primitively eusocial bumblebees (Bombus), worker reproduction is controlled not only by the presence or absence of a dominant queen but also by other dominant workers. Furthermore, it was shown that the queen dominance is maintained by pheromonal cues. We investigated whether there is a similar odor signal released by egg-laying queens and workers that may have a function as a fertility signal. We collected cuticular surface extracts from nest-searching and breeding Bombus terrestris queens and workers that were characterized by their ovarian stages. In chemical analyses, we identified 61 compounds consisting of aldehydes, alkanes, alkenes, and fatty acid esters. Nest-searching queens and all groups of breeding females differed significantly in their odor bouquets. Furthermore, workers before the competition point (time point of colony development where workers start to develop ovaries and lay eggs) differed largely from queens and all other groups of workers. Breeding queens showed a unique bouquet of chemical compounds and certain queen-specific compounds, and the differences toward workers decrease with an increasing development of the workers' ovaries, hinting the presence of a reliable fertility signal. Among the worker groups, the smallest differences were found after the competition point. Egg-laying females contained higher total amounts of chemical compounds and of relative proportions of wax-type esters and aldehydes than nest-searching queens and workers before the competition point. Therefore, these compounds may have a function as a fertility signal present in queens and workers.


Comparison of transconjunctival versus subciliary approaches for orbital fractures: a review of 60 cases.
The increasing emphasis on open reduction in the management of orbital fractures has led to an extensive debate as to which approach provides adequate exposure for these fractures. This retrospective study compares the exposure provided and the rate of complications between transconjunctival and subciliary incisions for orbital rim and floor fractures. The charts of 55 patients with orbital fractures, treated with open reduction and internal fixation, were reviewed. A total of 30 subciliary and 30 transconjunctival incisions had been performed, and the adequacy of exposure as well as intraoperative and postoperative complication rates were compared. The authors found a higher rate of complications with the subciliary approach and, therefore, advocate the use of a transconjunctival incision for the management of orbital fractures.


Classification of the vasculitides: are they clinically useful?
Several classification systems for the vasculitides have been developed over the second half of the past century. These classifications systems have been modified according to the advances made in the differentiation of these syndromes, particularly their histopathologic features (the vessel size involved) and their clinical features. Although these classifications have been widely used in the clinical setting for the diagnosis of these disorders, they were developed for research purposes. Given the common clinical and, sometimes, histopathologic features of the different vasculitides, a classification system that facilitates a diagnosis and the formulation of a therapeutic plan is still needed. The development and utilization of novel serum markers and new imaging modalities coupled with advances in the understanding of these disorders, may allow the development of a classification system for the vasculitides that will be of greater value in the clinical setting.


Ultrastructural localization of complex carbohydrates present in the sublingual gland of rabbits.
Stainings with dialized iron (DI), high-iron diamine-thiocarbohydrazide-silver proteinate HID-TCH-SP), tannic acid-uranylacetate (TA-U), tannic acid-ferric chloride (TA-F), and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) were applied to samples of sublingual glands of rabbits. Comparing the results obtained with what had been previously demonstrated biochemically, it is possible to assert that the faintly electron-opaque, granules of the cells of the preterminal tracts contain sulphated glycoconjugates because of the presence of sulphated hexosamines and hexoses, acid glycoconjugates because of the presence of sialic acid and uronic acids, and neutral glycoconjugates because of the presence of hexoses.


Effect of omental transposition on to the brain on the cortical content of norepinephrine, dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in experimental cerebral ischaemia.
Local cerebral ischaemia causes a significant decrease in norepinephrine, dopamine, 5-hydroxytryptamine in the cortical brain tissue of rabbits, associated with an increase in 5-hydroxyindoleacetic acid. Previous transposition of the omentum on to the brain surface maintains, to a large extent, physiological levels of these metabolites. This study stresses the role of the transposed omentum in reducing the effects of experimental occlusion of a major cerebral artery.


Airway complications of infant botulism: ten-year experience with 60 cases.
The study goal was to understand the incidence, etiology, and management of airway complications in infant botulism. We conducted a retrospective review of the period from January 1, 1987, to December 31, 1997. Urban tertiary care children's hospital. Of 60 children with infant botulism, 37 (61.7%) required endotracheal intubation for a mean of 21 days. No patient required a tracheostomy. Airway complications (stridor, subglottic stenosis, granuloma formation) occurred in 5 (13.5%) of 37 patients, with 3 requiring surgical bronchoscopy. Of the 37 children, 14 (37.8%), including 4 with airway complications, had endotracheal tube leak pressures recorded. In 3 (50%) of 6 patients with measured leak pressures of greater than 40 cm H2O, airway complications developed. Complications did not develop in patients with leak pressures of less than 20 cm H2O. No correlation between length of intubation and complications could be established. Airway complications in infant botulism may be accompanied by high leak pressures and can be managed with endoscopic techniques. The study data suggest that leak pressures should be measured on a regular basis and maintained at less than 20 to 25 cm H2O. A prospective trial to study this issue is warranted. Tracheotomy is not routinely necessary. A high index of suspicion, early diagnosis, and prompt intervention are required for the optimal management of airway complications in infant botulism.


P2 and behavioral effects of stroke count in Chinese characters: Evidence for an analytic and attentional view.
The inconsistent stroke-count effect in Chinese character recognition has resulted in an intense debate between the analytic and holistic views of character processing. The length effects of English words on behavioral responses and event-related potentials (ERPs) are similarly inconclusive. In this study, we identified any behavioral and ERP stroke-count effects when orthographic neighborhood sizes are balanced across three stroke counts. A delayed character-matching task was conducted while ERPs were recorded. The behavioral data indicated that both response latency and error rate increased with increasing stroke count. The ERP data showed higher P2 but lower N2 amplitudes in the large count than in the median count condition. A higher P2 can reflect increased attentional load and reduced attentional resource for processing each stroke because of the additional strokes in the large count condition. The behavioral and ERP effects of stroke count provide evidence for the analytic view of character processing but also provide evidence against the holistic view.


Calorie restriction in mice does not affect LDL reverse cholesterol transport in vivo.
Calorie restriction (CR) prolongs life in animals, but may reduce plasma HDL, important in reverse cholesterol transport (RCT). The effect of CR, 60% of an ad libitum (AL) diet, on cholesterol removal from rectus femoris muscle injected with cationized LDL, was studied in C57BL male mice. RCT in vivo, on CR and AL diet, and cholesterol efflux from macrophages exposed to CR or AL sera, was similar, despite a 22% reduction in plasma HDL-cholesterol (HDL-C). In CR fed mice total cholesterol (TC) and phospholipid (T-PL) decreased by 32% and 38%, while HDL-C and HDL-PL decreased by 22% and 16% only, resulting in increased HDL-PL/T-PL ratio, which enhanced RCT. Partial re-feeding (CR-RF, 70% of AL) induced normalization of plasma lipids (excluding triglycerides), while HDL-PL/T-PL remained elevated. Thus, as CR did not interfere with RCT in vivo, it could possibly be beneficial to patients at risk for coronary heart disease.


[Study on effect of berberine on modulating lipid and CPT I A gene expression].
To investigate the modulating effect on lipid and gene expressions of CPT I A caused by berberine (Ber) in experimental hyperlipidemia rats. Male SD rats were randomly divided into 5 groups according to the blood lipid values: normal group, hyperlipidemia group, 300 mg x kg(-1) x d(-1) Ber-treated group, 60 mg x kg(-1) x d(-1) Ber-treated group, and 7.2 mg x kg(-1) x d(-1) lovastatin-treated group. Normal group were fed with base diet and other groups were fed with high fat and cholesterol diet. 12 weeks after drugs were given the TC, TG, LDL-C, and HDL-C from rat blood samples were tested by automatic biochemistry analyzer. Gene expressions of CPT I A and PPARalpha were evaluated by RT-PCR and Western blot, respectively. It was shown that Ber significantly decreased TC and LDL-C, but increased HDL-C in dose-dependent manner, elevated expressions of CPT I A mRNA and protein without influence on PPARalpha expression. Similar effects from lovastatin on lipidemia were observed except the Ber effect on CPT I A gene expression. Ber has modulating effect on the lipid metabolism, the mechanism of which may be by promoting the CPT I A gene expression.


Heat, pH, and salt: synthesis strategies to favor formation of near-infrared emissive DNA-stabilized silver nanoclusters.
We present chemical synthesis strategies for DNA-stabilized silver nanoclusters (AgN-DNAs) with near-infrared (NIR) emission in the biological tissue transparency windows. Elevated temperatures can significantly increase chemical yield of near-infrared nanoclusters. In most cases, basic pH favors near-infrared nanoclusters while micromolar amounts of NaCl inhibit their formation.


Neuronavigational neuroendoscopy--to be or not to be? An international pilot questionnaire-based study.
The almost age-old neuroendoscopy (NE) and neuronavigation (NN) in its twenties independently and indisputably have proved their high value as neurosurgical armamentarium and became even indispensable in some pathologies. However, nowadays the effectiveness of their simultaneous and combined application still is a matter of debate. The purpose of our pilot international, questionnaire-based survey was to assess the position of the opinion leaders in the field of neuroendoscopy worldwide toward the neuronavigational neuroendoscopy (NNNE). Within 3 months, a questionnaire with 17 questions was emailed repeatedly to 55 leading academic neuroendoscopic neurosurgeons from 50 institutions in 24 countries. The questionnaire covered aspects of personal and institutional experience in NE, NN, and NNNE, the most frequently treated pathologies by NNNE as well as inquiring the neurosurgeons' opinion for the importance and future of NNNE. Forty-one questionnaires were returned (response rate = 74.6%). Six questionnaires were excluded because of incomplete or incorrect answers, leaving in the survey 35 respondents from 35 institutions in 18 countries. The less experienced neurosurgeons rely in higher degree on NNNE. Most frequently, NNNE is performed for hydrocephalus (procedures other than third ventriculostomy), transsphenoidal surgery, tumor biopsy, and cyst fenestration. Regardless their neurosurgical and NE experience, more than 75% of the respondents state that NNNE extends the range of neuroendoscopic procedures in their neurosurgical departments. NNNE represents a valuable operative technique with excellent future prospects. NNNE extends the range of neuroendoscopic procedures, transforming some number of patients from "nonoperable" neuroendoscopically to suitable for neuroendoscopy.


A custom-made mandibular repositioning device for obstructive sleep apnoea-hypopnoea syndrome: the ORCADES study.
Mandibular repositioning devices (MRDs) are usually recommended as the first therapy option in patients with mild-to-moderate obstructive sleep apnoea (OSA). However, data on the long-term efficacy of MRDs are limited, not only in OSA patients who are noncompliant with continuous positive airway pressure (CPAP) but also in those with more severe OSA. The ORCADES study aimed to prospectively determine the long-term efficacy and tolerability of two custom-made Narval(™) MRDs for obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients. The interim 3- to 6-month data are reported. Eligible patients had OSAHS and had refused or were noncompliant with prescribed CPAP. Outcome measurements after gradual mandibular advancement titration included: apnoea-hypopnoea index (AHI), oxygen saturation, sleepiness, symptoms, quality of life, side effects and compliance. A total of 369 patients were included. Overall, MRD treatment was successful (≥50% decrease in AHI) in 76.2% of the participants; complete response (AHI <10/h) was achieved in 63.5%. Severe OSAHS was effectively treated (AHI <15/h) in about 60% of the participants; 38% had complete symptom resolution. Mandibular repositioning devices significantly decreased subjective sleepiness, eliminated symptoms and improved quality of life. They were well tolerated and compliance was excellent. Only 8% of the participants stopped MRD treatment due to side effects. Custom-made Narval(™) MRDs are effective for mild to severe OSA in patients who refuse or are noncompliant with CPAP. They are well tolerated and have excellent compliance.


Linking Numbers in Three-Manifolds.
Let M be a connected, closed, oriented three-manifold and K, L two rationally null-homologous oriented simple closed curves in M. We give an explicit algorithm for computing the linking number between K and L in terms of a presentation of M as an irregular dihedral three-fold cover of S 3 branched along a knot α ⊂ S 3 . Since every closed, oriented three-manifold admits such a presentation, our results apply to all (well-defined) linking numbers in all three-manifolds. Furthermore, ribbon obstructions for a knot α can be derived from dihedral covers of α . The linking numbers we compute are necessary for evaluating one such obstruction. This work is a step toward testing potential counter-examples to the Slice-Ribbon Conjecture, among other applications.


Cystatin C and creatinine in an HIV cohort: the nutrition for healthy living study.
Human immunodeficiency virus (HIV)-infected persons have an increased risk of chronic kidney disease (CKD). Serum creatinine level may underestimate the prevalence of CKD in subjects with decreased lean body mass or liver disease. Level of serum cystatin C, an alternative kidney function marker, is independent of lean body mass. Cross-sectional. 250 HIV-infected subjects on highly active antiretroviral therapy in the Nutrition for Healthy Living (NFHL) cohort; 2,628 National Health and Nutrition Examination Survey (NHANES) 2001-2002 subjects. Comparison of serum creatinine levels in NFHL to those in NHANES subjects; comparison of CKD in NFHL subjects ascertained using serum creatinine versus cystatin C levels. Standardized serum creatinine, serum cystatin C, glomerular filtration rate (GFR) estimated from serum creatinine and cystatin C levels. Creatinine levels were lower in NFHL than NHANES subjects despite greater rates of hepatitis, diabetes, and drug use (mean difference, -0.18 mg/dL; P < 0.001 adjusted for age, sex, and race). Of NFHL subjects, only 2.4% had a creatinine-based estimated GFR less than 60 mL/min/1.73 m(2), but 15.2% had a cystatin-based estimated GFR less than 60 mL/min/1.73 m(2). GFR was estimated rather than measured. Other factors in addition to GFR may affect creatinine and cystatin C levels. Measurements of proteinuria were not available. Serum creatinine levels may overestimate GFRs in HIV-infected subjects. Kidney disease prevalence may be greater than previously appreciated.


Launching continuous kangaroo mother care through participatory action research in Iran.
This study describes the launching of a unit for continuous kangaroo mother care (KMC) in a teaching hospital (Taleghani) in Iran. We used a participatory three-stage action research approach to establish a unit for continuous KMC: design (needs identification and planning for change); implementation (and reflection); and evaluation (and institutionalization). As part of the design and implementation stages, individual and focus group interviews were conducted with mothers, physicians, nurses, other healthcare personnel and policy makers. The evaluation was done by means of a standardized tool specifically developed for monitoring progress with the implementation of KMC. Four themes relating to potential barriers to implementation emerged from the analysis of the staff interviews, namely barriers associated with the mother, the father, the physician and the health system. Mothers' experiences of barriers were grouped into five themes: personal discomfort, fear, healthcare provider attitudes and actions, infrastructure constraints and family matters. An implementation progress score of 27.05 out of 30 was achieved, indicating that the continuous KMC unit was on the path to institutionalization. Some of the gaps identified related to policies on resource allocation, the discharge and follow-up system, and the transportation of infants in the KMC position. The study findings indicated that participatory action research is a suitable method for studying the establishment of a continuous KMC unit. When action research is practiced, there is a prospect of turning knowledge into action in the real world.


Inbred strains of zebrafish exhibit variation in growth performance and myostatin expression following fasting.
Although the zebrafish (Danio rerio) has been widely utilized as a model organism for several decades, there is little information available on physiological variation underlying genetic variation among the most commonly used inbred strains. This study evaluated growth performance using physiological and molecular markers of growth in response to fasting in six commonly used zebrafish strains [AB, TU, TL, SJA, WIK, and petstore (PET) zebrafish]. Fasting resulted in a standard decrease in whole blood glucose levels, a typical vertebrate glucose metabolism pattern, in AB, PET, TL, and TU zebrafish strains. Alternatively, fasting did not affect glucose levels in SJA and WIK zebrafish strains. Similarly, fasting had no effect on myostatin mRNA levels in AB, PET, TU, and WIK zebrafish strains, but decreased myostatin-1 and -2 mRNA levels in SJA zebrafish. Consistent with previous work, fasting increased myostatin-2 mRNA levels in TL zebrafish. These data demonstrate that variation is present in growth performance between commonly used inbred strains of zebrafish. These data can help future research endeavors by highlighting the attributes of each strain with regard to growth performance so that the most fitting strain may be utilized.


Cost-Benefit Analysis of the Implementation of an Enhanced Recovery Program in Liver Surgery.
Enhanced recovery after surgery (ERAS) programs have been shown to ease the postoperative recovery and improve clinical outcomes for various surgery types. ERAS cost-effectiveness was demonstrated for colorectal surgery but not for liver surgery. The present study aim was to analyze the implementation costs and benefits of a specific ERAS program in liver surgery. A dedicated ERAS protocol for liver surgery was implemented in our department in July 2013. The subsequent year all consecutive patients undergoing liver surgery were treated according to this protocol (ERAS group). They were compared in terms of real in-hospital costs with a patient series before ERAS implementation (pre-ERAS group). Mean costs per patient were compared with a bootstrap T test. A cost-minimization analysis was performed. Seventy-four ERAS patients were compared with 100 pre-ERAS patients. There were no significant pre- and intraoperative differences between the two groups, except for the laparoscopy number (n = 18 ERAS, n = 9 pre-ERAS, p = 0.010). Overall postoperative complications were observed in 36 (49 %) and 64 patients (64 %) in the ERAS and pre-ERAS groups, respectively (p = 0.046). The median length of stay was significantly shorter for the ERAS group (8 vs. 10 days, p = 0.006). The total mean costs per patient were €38,726 and €42,356 for ERAS and pre-ERAS (p = 0.467). The cost-minimization analysis showed a total mean cost reduction of €3080 per patient after ERAS implementation. ERAS implementation for liver surgery induced a non-significant decrease in cost compared to standard care. Significant decreased complication rate and hospital stay were observed in the ERAS group.


NMR studies and GC analysis of the antibacterial agent taurolidine.
The NMR spectrum of taurolidine in deuterium oxide was compared with spectra obtained from model experiments with amines and formaldehyde. Head-space analysis combined with capillary GC showed that there was less than 0.004% free formaldehyde present in 2% solutions of taurolidine. This value is comparable to the concentration of formaldehyde found when the taurolidine solutions were injected directly onto GC columns.


Investigation of novel cyclic structure in glycoconjugate using a simple model system.
Bacterial capsular polysaccharide protein conjugates are a major class of vaccines for preventing severe bacterial infections. The conjugation of a polysaccharide to a carrier protein is critical for inducing adaptive immune response in healthy humans. Due to the high molecular mass and extensive structural heterogeneity of the glycoconjugate, the underlying sugar linkages and polypeptide site selectivity of the conjugation reaction are not well characterized and understood. Here, we report a model conjugation study using a monosaccharide and a synthetic peptide to investigate the fundamental reductive amination chemistry, which is one of the most commonly utilized conjugation strategies for glycoconjugate vaccines. We identified a cyclic tertiary amine linkage as the primary conjugation linkage for monosaccharides containing dialdehydes. Such linkage is previously not well-recognized by the glycoconjugate vaccine field. Our study has provided insights into this commonly used, yet complex conjugation chemistry and will benefit the design of future protein-polysaccharide-based vaccines.


Thoracolumbar paravertebral giant ganglioneuroma and scoliosis: a case report and literature review.
Paravertebral ganglioneuroma and scoliosis is a rare clinical benign disease. The case we reported is about a 12-year-old girl who was hospitalized due to neoplasm with spinal deformity in the right abdomen for 1 month. Based on a careful preoperative evaluation and found no obvious surgery contraindications, the patient was treated with surgical resection of the tumor and correction of the deformity by surgery. Postoperative pathologic examination confirmed it was a ganglioneuroma. After the operation, the patient recovered well. Her spinal deformity was corrected, and she was 5 cm taller. Complete resection of ganglioneuroma following with a low recurrence rate and a good prognosis, patient does not need further chemotherapy, radiation therapy, or other treatments. All follow-up radiographic studies demonstrated no relapse of the tumor in the following 18 months. Combining this case with similar cases at home and aboard and reviewing related literature, we formed conclusions based on the manifestations, diagnosis, treatment, and prognosis of this disease and provided treatments for similar cases.


Structural deficits in the emotion circuit and cerebellum are associated with depression, anxiety and cognitive dysfunction in methadone maintenance patients: a voxel-based morphometric study.
Heroin users on methadone maintenance treatment (MMT) have elevated rates of co-morbid depression and are associated with have higher relapse rates for substance abuse. Structural abnormalities in MMT patients have been reported, but their impact on clinical performance is unknown. We investigated differences in gray matter volume (GMV) between 27 MMT patients and 23 healthy controls with voxel-based morphometry, and we correlated findings in the patients with Beck Depression Inventory scores, Beck Anxiety Inventory scores, and diminished cognitive functioning. MMT patients exhibited higher emotional deficits than healthy subjects. There was significantly smaller GMV in multiple cortices, especially in the left inferior frontal gyrus and left cerebellar vermis in the MMT group. The smaller GMV in the pre-frontal cortices, left sub-callosal cingulate gyrus, left post-central gyrus, left insula, and right cerebellar declive correlated with higher depression scores. The smaller GMV in the pre-frontal cortices, left sub-callosal cingulate gyrus, and left postcentral gyrus also correlated with higher anxiety scores, while smaller GMV in the cerebellum and bilateral insula was associated with impaired performance on tests of executive function. These results reveal that MMT patients have low GMV in brain regions that are hypothesized to influence cognition and emotion, and the GMV findings might be involved comorbid disorders in the MMT group.


Differentiating brucella spondylitis from tuberculous spondylitis by the conventional MRI and MR T2 mapping: a prospective study.
Brucella spondylitis (BS) and tuberculous spondylitis (TS), caused initially by bacteremia, are the two leading types of granulomatous spinal infections. BS is easy to miss or may be misdiagnosed as TS. Our purpose aims to differentiate BS from TS in conventional MR imaging and MR T2 mapping. We performed on 26 BS and 27 TS patients conventional MR imaging and MR T2 mapping. We analyzed the features in conventional MR imaging and measured T2 values of the lesion vertebrae (LV) and unaffected adjacent vertebrae (UAV) in BS and TS patients, respectively. There were no significant differences in sex, age, national between BS and TS. There was significantly lower severity of vertebral destruction, vertebral posterior convex deformity, dead bone, and abscess scope in BS when compared to TS (p < 0.001, p = 0.048, p < 0.001, p < 0.001, respectively). The vertebral hyperplasia was significantly higher in BS when compared to TS (p < 0.001). The T2 value of the LV with BS was markedly higher than that in the UAV with BS and that in the LV and UAV with TS (p < 0.001, p < 0.037, p < 0.001, respectively). The T2 value of the LV with TS was significantly higher than that of the UAV in TS and BS (p < 0.001, p < 0.001, respectively). There were no significant differences in the T2 value of the UAV between BS and TS (p = 0.568). The qualitative and quantitative evaluation may differentiate BS from TS. The conventional MR imaging helps to distinguish BS from TS by several distinctive features. MR T2 mapping has the additional potential to provide quantitative information between BS and TS.


Transurethral bladder eversion concurrent with uterovaginal prolapse.
Transurethral bladder eversion is rare. A case of transurethral bladder eversion with concurrent uterovaginal prolapse is presented. The patient was postmenopausal, had a long history of uterovaginal prolapse, and developed bladder eversion. Examination under anesthesia revealed full-thickness transurethral bladder eversion and complete uterine procidentia. Temporary reduction of the prolapse was done initially because of her unstable medical condition. After medical stabilization, definitive surgical reconstruction was completed by a vaginal approach. Full-thickness, transurethral bladder eversion can be surgically treated by a vaginal approach.


The effect of IL4 +33C/T polymorphism on risk of Japanese sporadic Alzheimer's disease.
Interleukin-4 (IL4) is an anti-inflammatory cytokine that may play a role in the inflammation pathology observed surrounding senile plaques, and may also associate with Alzheimer's disease (AD) pathogenesis. Recently, it has been reported that a single nucleotide polymorphism in the IL4 gene promoter region, IL4 +33C/T polymorphism, associates with its phenotype. It was thought that the IL4 +33C/T polymorphism causing high IL4 production may reduce the risk for AD. In the present study, therefore, we investigated this mutation in 108 healthy controls and in 178 sporadic AD cases by the polymerase chain reaction restriction fragment length polymorphism method in a Japanese AD population. Allelic frequencies with +33C/T polymorphism in the gene were 35.6 and 32.6% in the control and AD groups, respectively. Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD. We also tested whether the IL4 functional variants were regulated by this polymorphism in a portion of the subjects (16 AD cases and 13 control cases). We could not find any relationship between the IL4 +33C/T polymorphism and plasma IL4 concentration.


Assessment of long-range transboundary aerosols in Seoul, South Korea from Geostationary Ocean Color Imager (GOCI) and ground-based observations.
To better understand air quality issues in South Korea, it is essential to identify the main contributors of air pollution and to quantify the effects of transboundary transport. In this study, geostationary satellite measurements were used to assess the effects of aerosol transport on air quality in South Korea. This study proposes a method to define the long-range transport (LRT) of aerosols into the Korean Peninsula using remote sensing obervations and back-trajectories and estimates the LRT effects on air quality in Seoul using in-situ particulate matter (PM) measurements. Aerosol optical depths (AODs) are obtained from the Geostationary Ocean Color Imager (GOCI), and the back-trajectories are from the National Ocean and Atmospheric Administration (NOAA) HYbrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model. For LRT events, satellite observations showed high AOD plumes over the Yellow Sea, a pathway between Eastern China and South Korea, and the movements of aerosol plumes transported to South Korea were also detected. PM2.5 concentrations, PM10 concentrations, and AOD during LRT increased by 52%, 49%, and 81%, respectively, relative to their average values for 2015-2018. To quantitatively characterize the LRT of aerosols, the effects of LRT on PM2.5 concentrations were estimated for each PM concentration category. The contribution of LRT to PM2.5 concentrations was estimated to be 33% during 2015-2018. When high concentrations of PM2.5 were observed in Seoul, they were likely to be associated with LRT events.


Antigenic Drift of A/H3N2/Virus and Circulation of Influenza-Like Viruses During the 2014/2015 Influenza Season in Poland.
Morbidity rates of influenza could be greatly reduced due to vaccination. However, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. Their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. In Poland, the 2014/2015 influenza epidemic started in week 5 (January/February) of 2015 and continued until week 17 (April) of 2015. The influenza activity was moderate with the highest incidence of influence-like illness at week 10/2015 (March). During that season, antigenic drift of influenza virus A/H3N2/ occurred causing higher rates of A/H3N2/ infections. Among the 2416 tested specimens, 22.6 % of influenza cases were positive for A/H3N2/, while A/H1N1/pdm09 constituted 14.6 % cases. Influenza A viruses were detected in co-circulation with influenza B viruses; the latter amounted to 34.1 % of all influenza detections. Other detected causes of influenza-like illness consisted of respiratory syncytial virus (RSV), being predominant, and, sporadically, human coronavirus, parainfluenza 1-3, rhinovirus, and adenovirus. Despite low vaccine effectiveness of solely one component, A/H3N2/, the vaccine could mitigate or shorten the length of influenza infection and reduce the number of severe outcomes and mortality. Thus, vaccination against influenza remains the most effective way to prevent illness and possibly fatal outcomes.


Chemoselective Synthesis of Sulfenylated Spiroindolenines from Indolyl-ynones via Organosulfenyl Chloride-Mediated Dearomatizing Spirocyclization.
A metal-free sulfenylation/spirocyclization of indolyl-ynones realized by organosulfenyl chloride, generated in situ from the reaction of disulfides and PhICl2, is presented. This cascade one-pot process enables a chemoselective synthesis of diverse sulfenylated spiroindolenines depending on the substituent pattern at the two-position of indolyl-ynones.


Molecular Diagnosis of Dengue.
Several protocols for genomic amplification using reverse transcription followed by polymerase chain reaction (RT-PCR), important in the identification of the infecting serotype, have been used in the rapid diagnosis of Dengue Virus (DENV) infections. The qualitative protocol described by Lanciotti et al. (J Clin Microbiol 30: 545-551, 1992) suggested by WHO detects the four DENV serotypes simultaneously in one procedure "semi-nested," generating amplified products with specific sizes in base pairs for each serotype and it has been the most used in the past two decades. However, advances in molecular diagnosis have enabled the development of RT-PCR in real time (qRT-PCR) based on the use of dyes and probes (SYBR green and TaqMan), which is performed in a single step and is capable of providing quantitative data. In addition to quantification, the advantages of qRT-PCR over conventional RT-PCR include speed, greater sensitivity and specificity, and low rate of false positives. Several protocols for the diagnosis and/or quantification of DENV have already been described. Non-PCR-based methods such as reverse transcription loop-mediated isothermal amplification have shown high sensitivities and specificities. RT-PCR and qRT-PCR techniques can be performed using serum, plasma, infected cells, mosquitoes, fresh, and paraffin-embedded tissues. However, despite fast and accurate, they are limited to samples collected during the acute phase of infection (up to 7 days after the onset of symptoms) and require specialized equipment and trained staff.


A comparison of the cerebral protective effects of isoflurane and barbiturates during temporary focal ischemia in primates.
Isoflurane has protective properties during experimental global brain ischemia or hypoxia. However, this has not been evaluated in the more common case of focal ischemia, e.g., as caused by middle cerebral artery occlusion (MCAO). The authors therefore compared the effects of isoflurane, thiopental, and N2O/fentanyl anesthesia on neurologic and neuropathologic outcome in baboons subjected to 6 h of transorbital left MCAO. Prior to MCAO, animals were assigned to one of three groups: Group 1 (n = 7) received isoflurane (in O2/air) in concentrations sufficient to maintain deep burst suppression on the EEG (2.0% +/- 0.5% inspired, mean +/- SD); group 2 (n = 6) received thiopental (O2/air) in doses adequate to maintain similar EEG suppression (3.6 +/- 0.7 g total); and group 3 (n = 6) received 60% N2O/40% O2 and fentanyl (25 micrograms/kg load, 3 micrograms X kg-1 X h-1 infusion). Efforts were made to keep mean arterial pressure (MABP) between approximately 80 and 100 mmHg, using nitroprusside/hydralazine or phenylephrine/metaraminol, with PaCO2 at approximately 30 mmHg. The selected anesthetic was established 45 min before MCAO, was maintained until 1 h after clip removal, and in decreasing concentrations for 5 h. Neurologic status was scored for 7 days and formalin-fixed brains were later sectioned for determination of infarction volume. Six of seven group 1 (isoflurane) animals were hemiplegic, and 7/7 had verified infarctions. By contrast, 4 of 6 group 2 (thiopental) animals were normal, with 2/6 having infarctions. Outcome in group 3 (N2O/fentanyl) was intermediate between groups 1 and 2 (3/6 hemiplegic, 4/6 with infarctions). Differences in the infarction rates between groups 1 and 2 was significant (P less than 0.05), while a similar comparison of neurologic outcome scores achieved a P value of 0.055. Infarctions in group 1 were more hemorrhagic in character than in group 3 (groups 1 and 2 could not be meaningfully compared). These results must be considered in light of differences in MABP during the occlusion period; MABP in group 1 was approximately 80 mm Hg in spite of vasopressor use, while that in group 2 was approximately 100 mmHg (in spite of vasodilators). Nevertheless, they fail to demonstrate any protective value of isoflurane anesthesia, at least when compared with thiopental.


Cytopathological features of cell suffering and death: Role of plasma membrane and cytoskeleton.
Morphological and ultrastructural modifications related to the cell injury and leading to cell death have been investigated by using different compounds. Data obtained by treating various cultured cells with a quinone (menadione), a polar solvent (NMF) and a bacterial protein toxin (toxin B fromClostridium difficile) are here reported Differences seem to exist between such injuries, but changes in plasma membrane structure, called surface blebbing phenomenon, represent a common feature which can be in any case detected. Our results also allow to hypothesize an important role of cytoskeleton in such a process.


Chimeric antigen receptor T cell therapies for multiple myeloma.
Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable despite the advent of numerous new drugs such as proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. There is an unmet need to develop novel therapies for refractory/relapsed MM. In the past few years, chimeric antigen receptor (CAR)-modified T cell therapy for MM has shown promising efficacy in preclinical and clinical studies. Furthermore, the toxicities of CAR-T cell therapy are manageable. This article summarizes recent developments of CAR-T therapy in MM, focusing on promising targets, new technologies, and new research areas. Additionally, a comprehensive overview of antigen selection is presented along with preliminary results and future directions of CAR-T therapy development.


Cervical dilatation and preparation prior to outpatient hysteroscopy: a systematic review and meta-analysis.
There are uncertainties about the benefit of routine cervical preparation and/or cervical dilatation before outpatient hysteroscopy. To determine if cervical preparation and/or routine mechanical dilatation reduces pain during outpatient hysteroscopy. MEDLINE, EMBASE, CINAHL and CENTRAL were searched on 19 October 2020, using keywords 'hysteroscopy', 'cervical preparation', 'cervical ripening', 'cervical dilatation', 'outpatient', 'office' and/or 'ambulatory' and associated medical subject headings. Randomised controlled trials investigating the benefit of cervical preparation and/or cervical dilatation on pain in women undergoing outpatient hysteroscopy were included. Two independent reviewers selected eligible trials and extracted data on pain, feasibility, adverse events and satisfaction/acceptability for meta-analysis. The literature search yielded 807 records, of which 24 were included for review and 19 provided data for meta-analysis. No trials investigated the role of routine mechanical cervical dilatation. Cervical preparation significantly reduced pain during outpatient hysteroscopy; standard mean difference (SMD) -0.67, 95% confidence interval (CI) -1.05 to -0.29. Feasibility also improved as priming provided significantly easier hysteroscopic entry (SMD 0.89, 95% CI 0.32-1.46), greater cervical dilatation (SMD 0.81, 95% CI 0.08-1.53) and shorter procedural times (SMD -0.51, 95% CI -0.88 to -0.13). Cervical preparation, however, incurred significantly more adverse effects, mainly comprising genital tract bleeding, abdominal pain and gastrointestinal symptoms (odds ratio 2.94, 95% CI 1.58-5.47). There were limited data regarding satisfaction, acceptability and complications. Cervical preparation reduces pain and improves feasibility associated with outpatient hysteroscopy but increases the risk of adverse effects. Cervical preparation before outpatient hysteroscopy reduces pain, enhances feasibility but increases adverse effects.


H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes.
H-2RIIBP (RXR beta) is a member of the nuclear hormone receptor superfamily that activates transcription of MHC class I genes in response to retinoic acid (RA). Using chemical cross-linking, co-immunoprecipitation, gel mobility shift and streptavidin-biotin DNA precipitation assays, we show that H-2RIIBP formed heterodimers with thyroid hormone (T3) and RA receptors (T3R alpha and RAR alpha). H-2RIIBP heterodimer formation required a conserved sub-domain of its C-terminal region, occurred independently of target DNA and was much more efficient than either T3R alpha/RAR alpha heterodimer or H-2RIIBP homodimer formation. Heterodimers displayed enhanced binding to target DNA elements and contacted DNA in a manner distinct from that of homodimers. A functional role for heterodimers in vivo was demonstrated by synergistic enhancement of MHC class I transcription following co-transfection of H-2RIIBP with T3R alpha or RAR alpha. We provide biochemical evidence that H-2RIIBP formed heterodimers with several naturally occurring nuclear proteins. The results suggest that H-2RIIBP, by virtue of its ability to heterodimerize, enhances combinatorial diversity and versatility in gene regulation mediated by nuclear hormone receptors.


A method for determining the origin of crude drugs derived from animals using MinION, a compact next-generation sequencer.
We evaluated whether MinION, an inexpensive portable sequencer, can be used to identify the origin of crude drugs derived from animals. Standard and nonstandard crude drugs with different species of origin were examined. In addition, standards mixed with nonstandard samples were used. As a target gene, cytochrome c oxidase I was amplified and sequenced. The fast mode results had a slightly lower match ratio than high-accuracy mode, but the animals of origin were correctly determined by BLAST for all samples. For antler velvet derived from Rangifer tarandus, even when the sequences were aligned based on Cervus elaphus, the animal of origin was determined correctly. Minor contents could be detected from mixtures of two animals, if the mixtures contained at least 19:1 mtDNA when the coverage allele-fraction threshold was 0.05. By contrast, in fast mode, two sequences could not be separated due to the low accuracy of the base-calling for each read. For fieldwork, the species of origin of crude drugs could be identified with only simple DNA extraction and library preparation. Therefore, MinION appears to be a convenient tool for identifying the origins of crude drugs derived from animals.


Accelerometry-based assessment of physical activity and sedentary behavior in adult survivors of childhood acute lymphoblastic leukemia and their healthy peers.
Adult survivors of childhood acute lymphoblastic leukemia (ASALL) compose a specific group that faces an increased risk of experiencing late effects of their earlier treatment. Physical activity (PA) may be one of the appropriate means for preventing or minimizing the late effects of treatment. The main purpose of this study is to characterize device-measured PA and sedentary behavior (SB) among ASALL. The specific objective was to compare the movement behavior with a group recruited from the healthy population and to determine the degree of compliance with health recommendations for PA in the adult population. Twenty ASALL and 21 healthy control group (CG) members participated in the study. Participants were between 18 and 30 years old. Movement behavior was assessed for seven days using an Axivity AX3 accelerometer and a 24-h wearing protocol. Movement behavior was characterized by the amount of time spent in SB, light PA (LPA), moderate PA (MPA), and vigorous PA (VPA). There were no significant differences in movement behavior or compliance with PA recommendations between the ASALL and CG. During the week, the ASALL accumulated 711 min per day of SB vs. 636 min per day in the CG (p = 0.26); the ASALL had 186 min per day of LPA vs. 201 min per day in the CG (p = 0.47); the ASALL had 132 min per day of MPA vs. 147 min per day in the CG (p = 0.25); and the ASALL had 5 min per day of VPA vs. 4 min per day in the CG (p = 0.48). All research participants (ASALL and CG) met the PA recommendations of > 150 min per week for moderate PA. The results of our study suggest that ASALL, even after suffering from that disease in childhood, display comparable levels of PA and SB to their healthy peers. Both groups met the health recommendations for PA. The device-based monitoring of PA and SB should be an integral part of monitoring the late effects of treatment.


The relevance of stroke care for living well with post-stroke aphasia: a qualitative interview study with working-aged adults.
This study aimed to explore the perspectives of working-aged adults with post-stroke aphasia (PWA) towards what has or would help them in living well with aphasia (LWA). This paper reports the findings in relation to stroke care and its relevance for LWA. This qualitative study was designed with input from a Public and Patient Involvement advisory group. We conducted in-depth, semi-structured interviews with 14 PWA. Data were analysed following principles of reflexive thematic analysis. Support services and LWA spanned five themes: Inpatient care; Support in the community; Speech therapy; Mental health; and Aphasia education and training. Per the findings, all aspects of stroke care were affected and challenged by aphasia. Access to services and information was variable. PWA of working-age, their families and children need access to person-centred stroke care and information responsive to their changing needs at all stages of recovery. Healthcare workers must be equipped with aphasia competency. The results highlight a need for equitable, transparent, responsive access to services, information and stroke liaison support. The findings extend knowledge of the importance of stroke care for supporting working-aged adults and their families to live well in the context of aphasia.Implications for rehabilitationThere is a need for equitable, transparent access to a responsive integrated pathway of stroke care to support living well with aphasia.People with aphasia post-stroke and their families need access to person-centred stroke care and information responsive to their changing needs at all stages of recovery.This includes flexible access to mental healthcare and speech and language therapy.In order to access relevant care, people with post-stroke aphasia need access to information and stroke liaison support.Training to improve aphasia competency is imperative for healthcare workers.


Impact of passive smoke and/or atopy on adenoid immunoglobulin production in children.
The adenoids are exposed to a wide number and variety of microbes, environmental pollutants, and food antigens. Atopy and passive smoke may significantly affect immune responses, mainly in children. The aim of the present study was to investigate whether passive exposure to tobacco smoke and/or atopy could affect immunoglobulin production by adenoidal lymphocytes in a cohort of children presenting with adenoid hypertrophy. A total of 277 children (151 males and 126 females; median age 5.5 years), with adenoidal hypertrophy requiring adenoidectomy and or adeno-tonsillectomy, were consecutively enrolled in the study. Adenoid mononuclear cells were in vitro stimulated with LPS or CpG. When considering both the presence of smoke exposure and atopy, we observed that the CpG-induced decrease in IgA and IgM production was significantly associated with this combination of risk factors. In the T-independent immunoglobulin production assay we found a positive association between the two risk factors and IgA and IgM production. In particular, the presence of both risk factors, showed a significant increase in IgA and IgM production after stimulation. In conclusion, this is the first study that investigated the in vitro adenoidal B cell response after different stimuli in children, also evaluating possible exposure to passive smoke and/or an atopic condition.


[Heart rhythm disorder in congestive cardiomyopathy (data from ECG at rest and from daily ECG monitoring)].
In 55 patients with congestive cardiomyopathy, types of arrhythmias were studied according to the 12 lead data of the ECG at rest and daily monitoring observation. Arrhythmias have ascertained to be one of the constant signs of this disease. Interventricular conduction disturbances (72.7%), atrioventricular block of low degree (56.1%), ventricular extrasystole (40%), and atrial fibrillation (20%) are most frequently recorded on the ECG at rest. While recording the ECG for a day with a Holter monitor, polytopic ventricular extrasystole was revealed in 100% of the patients studied. Ventricular and supraventricular tachycardia paroxysms were found in 54.5% of the cases. This observation is of prognostic significance as it indicates a risk of sudden death.


Detection of EBV DNA in post-nasal space biopsy tissue from asymptomatic EBV-seropositive individuals.
The association between EBV and nasopharyngeal carcinoma (NPC) has been well documented although the precise role of the virus in the genesis of the tumour is not understood. We undertook this study to examine the prevalence of EBV infection in nasopharyngeal tissue obtained from 33 healthy individuals not considered to be at risk of developing NPC. Using polymerase chain amplification (PCR) and in situ hybridization we have identified EBV DNA in 70% (23/33) of the tissues examined. Our data demonstrate that EBV is present at the site of tumour development in the low-risk population and by inference that the virus is also present before the onset of disease in the high-risk group. This survey supports the concept of NPC pathogenesis as a multifactorial process.


Anti-inflammatory and antioxidant efficacy of lavender oil in experimentally induced thrombosis.
Lavender oil (LO) possesses anti-inflammatory, antioxidant, antifungal, antibacterial, sedative, cardio-protective, and antinociceptive properties. Thrombosis and inflammation are interplayed processes that interact and influence one another. Our research compared three routes of administration to assess the efficacy of pretreatment with LO on carrageenan-induced thrombosis in rat tail. Wistar-Bratislava white rats were randomly divided into five groups of ten rats each and pretreated 3 consecutive days prior the inducement of thrombosis to with one dose of LO (150 mg/kg body weight (b.w.)): per os by gavage (TLOPO group), intraperitoneal (TIPLO group) and subcutaneous (TSCLO group). We also have a control (C, received saline solution 0.9% and DMSO (vehicle) 1 ml intraperitoneal (i.p.)) group and a group with thrombosis (T group, received saline solution 0.9% plus vehicle 1 ml i.p.). Histopathological examinations were conducted together with measurements of the circulating levels of three oxidative stress markers, antioxidant effect (TAC and THIOL), and three proinflammatory cytokines (TNF- α, RANTES, and MCP-1). When administered intraperitoneally, lavender oil has the best efficacy on circulating levels of oxidative stress parameters (MDA, NOx, TOS), one oxidative stress marker (THIOL), and all studied proinflammatory cytokines (p-values < 0.02). Moreover, TIPLO displayed the closest values for bleeding and clotting time to the C group, as well as the lowest length of the thrombus than the T, TPOLO, and TSCLO groups (p-values < 0.001). The TIPLO group has histological appearance comparable to the C group, with the exception of the presence of oedema. Lavender oil pretreatment with intraperitoneal administration as three days, one-dose per day, showed anti-inflammatory and antioxidant efficacy in experimentally induced thrombosis.


The interaction of spermine with the ryanodine receptor from skeletal muscle.
The effect of polyamines on ryanodine binding activity of junctional sarcoplasmic reticulum membranes is described. Spermine stimulated the binding of ryanodine to its receptor up to 5-fold, with half-maximal stimulation obtained with 3.5 mM. Spermidine and putrescine also stimulated ryanodine binding, but they were about 12-fold less potent. The degree of stimulation is dependent on the NaCl concentration present in the assay medium. Spermine has no effect on the Ca(2+)-dependency of ryanodine binding but it increases the ryanodine binding affinity (Kd) by about 5.6-fold. Both the rate of ryanodine association with, and dissociation from, its binding site were affected by spermine. Spermine also stimulates the photoaffinity labelling by 3-O-(4-benzoyl)benzoyl[alpha-32P]ATP ([alpha-32P]BzATP) of the ryanodine receptor, increasing the BzATP binding affinity. We suggest that the stimulatory effect of spermine on ryanodine binding is due to its specific interaction with the ryanodine receptor. This spermine interaction enabled us to develop a new, one-step, fast and with high yield method for the purification of ryanodine receptor (Shoshan-Barmatz, V. and Zarka, A. (1992) Biochem. J. 284, in press).


Natural Wood-Derived Macroporous Cellulose for Highly Efficient and Ultrafast Elimination of Double-Stranded RNA from In Vitro-Transcribed mRNA.
Double-stranded RNA (dsRNA) is a major impurity that can induce innate immune responses and cause adverse drug reactions. Removing dsRNA is an essential and non-trivial process in manufacturing mRNA. Current methods for dsRNA elimination use either high-performance liquid chromatography or microcrystalline cellulose, rendering the process complex, expensive, toxic, and/or time-consuming. This study introduces a highly efficient and ultrafast method for dsRNA elimination using natural wood-derived macroporous cellulose (WMC). With a naturally formed large total pore area and low tortuosity, WMC removes up to 98% dsRNA within 5 min. This significantly shortens the time for mRNA purification and improves purification efficiency. WMC can also be filled into chromatographic columns of different sizes and integrates with fast-protein liquid chromatography for large-scale mRNA purification to meet the requirements of mRNA manufacture. This study further shows that WMC purification improves the enhanced green fluorescent protein mRNA expression efficiency by over 28% and significantly reduces cytokine secretion and innate immune responses in the cells. Successfully applying WMC provides an ultrafast and efficient platform for mRNA purification, enabling large-scale production with significant cost reduction.


Clinical evaluation of a resin-modified glass-ionomer adhesive system.
One hundred cervical caries-free, nonundercut lesions were restored in 13 patients of mean age 60.5 years, using Silux Plus or Estio LC resin composite bonded with Fuji Bond LC. Patients were recalled at 6 months and 1 year. A 1-year cumulative retention rate of 98% was recorded, while marginal staining was absent.


A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors.
This integrated analysis of a phase 1/2 study (NCT03046992) evaluated the efficacy and safety of lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive NSCLC after previous EGFR TKI therapy. Adults with EGFR mutation-positive NSCLC that progressed after prior EGFR-directed TKIs received once daily oral lazertinib 240 mg continuously until disease progression. Prior TKIs to treat T790M-positive NSCLC were prohibited. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included progression-free survival, overall survival, and intracranial ORR. A total of 78 patients received lazertinib 240 mg at 17 centers in South Korea. Among patients with T790M-positive tumors at baseline (N = 76), one (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% confidence interval [CI]: 44.1-66.4). Median progression-free survival was 11.1 months (95% CI: 5.5-16.4). Median overall survival was not reached (median follow-up = 22.0 mo). In patients with measurable intracranial lesions (n = 7), one (14.3%) had a complete intracranial response and five (71.4%) had partial responses, giving an intracranial ORR of 85.7% (95% CI: 59.8%-100.0%). The most common treatment-emergent adverse events were rash (37.2%), pruritus (34.6%), and paresthesia (33.3%); most were mild to moderate in severity. Serious drug-related adverse events occurred in three patients (gastritis, pneumonia, pneumonitis). The major mechanism of resistance was EGFR T790M loss. Lazertinib 240 mg/d has a manageable safety profile with durable antitumor efficacy, including brain metastases, in patients with advanced T790M-positive NSCLC after previous EGFR TKI therapy.


Association of Physical Performance, Muscle Strength and Body Composition with Self-Assessed Quality of Life in Hemodialyzed Patients: A Cross-Sectional Study.
(1) Patients on chronic hemodialysis (HD) experience impaired quality of life (QoL). We analyzed HD's relationship with physical performance, body composition, and muscle strength; (2) QoL was assessed with the Short Form-36, composed of physical (PCS) and mental (MCS) health dimensions. Physical performance was assessed with the Short Physical Performance Battery (SPPB), body composition (lean tissue mass% (LTM%), fat tissue mass% (FTM%), and skeletal muscle mass% (SMM%)) was assessed with bioelectrical impedance, and lower extremity strength was assessed with a handheld dynamometer; and (3) we enrolled 76 patients (27 F, 49 M), age 62.26 ± 12.81 years, HD vintage 28.45 (8.65−77.49) months. Their QoL score was 53.57 (41.07−70.64); their PCS and MCS scores were 52.14 (38.69−65.95) and 63.39 (44.64−76.79) and strongly correlated (p < 0.0001, R = 0.738). QoL correlated positively with SPPB (R = 0.35, p ≤ 0.001), muscle strength (R from 0.21 to 0.41, p < 0.05), and LTM% (R = 0.38, p < 0.001) and negatively with FTM% (R = −0.32, p = 0.006). PCS correlated positively with SPPB (R = 0.42 p < 0.001), muscle strength (R 0.25−0.44, p < 0.05), and LTM% (R = 0.32, p = 0.006) and negatively with FTM% (R = −0.25, p = 0.031). MCS correlated positively with SPPB (R = 0.23, p = 0.047), SMM% (R = 0.25; p = 0.003), and LTM% (R = 0.39, p < 0.001) and negatively with FTM% (R = −0.34; p = 0.003). QoL was unrelated to sex (p = 0.213), age (p = 0.157), HD vintage (p = 0.156), and BMI (p = 0.202); (4) Better physical performance, leaner body composition, and higher muscle strength are associated with better mental and physical QoL in HD.


Intraoperative, two-dimensional echocardiography-guided removal of retained intracardiac air.
The removal of intracardiac air after cardiotomy may be simplified with the use of two-dimensional echocardiography. This technique can be used to readily identify retained pockets of air and can function as a guide to needle aspiration of the ventricular chambers. With a valve prosthesis in place, de-airing can be accomplished with minimal displacement of the heart. The technique is easy to use and the images are simple to interpret.


Posterior bone block distraction arthrodesis of the subtalar joint: a review of 22 cases.
Twenty-two patients underwent a posterior bone block distraction arthrodesis of the subtalar joint between 1999 and 2006. The indication for surgery was loss of heel height, subtalar joint arthrosis, decreased talar declination with associated tibiotalar impingement, insufficient Achilles tendon function, malalignment of the rear foot, and pain with ambulation. There were 11 male and 11 female patients with a mean age of 46.7 years (range 20 to 71). The mean follow-up period was 27.3 months (range 12 to 63.9 months). Radiographic analysis revealed a mean increase in heel height of 6.09 mm (P= .0001), 5.83 degrees (P= .12) of lateral talocalcaneal angle, 5.5 degrees (P= .06) of talar declination, and 5.23 degrees (P= .07) of calcaneal inclination. The talo-first metatarsal angle increased an average of 4.5 degrees (P= .18). There was a 95.5% union rate. Postoperative complications included nonunion in 1 patient, subsidence of graft (collapse) in 1 patient, wound dehiscence in 3 patients, painful hardware in 7 patients, sural neuritis in 1 patient, superior cluneal nerve dysfunction in 1 patient and one mild varus malunion. Posterior bone block distraction arthrodesis can be successfully used to restore heel height, realign the foot, and decrease the morbidity associated with late complications of calcaneal fractures, as well as, nonunion and/or malunion following subtalar joint arthrodesis, Charcot neuroarthropathy, and avascular necrosis of the talus. 4.


GET73 modulates rat hippocampal glutamate transmission: evidence for a functional interaction with mGluR5.
In the present study, the effects of the γ-hydroxybutyrate (GHB) analog GET73 on hippocampal glutamate transmission have been evaluated by an approach combining in vivo microdialysis with the in vitro evaluation of tissue slices. The microdialysis results indicated that local perfusion (60 min) with 10 nM - 1mM GET73 increased extracellular glutamate levels in the CA1 region of the hippocampus of freely moving rats in a concentration dependent manner. In tissue slices from the rat hippocampus, GET73 (1 μM - 10 μM) did not affect L-[(3)H]glutamate uptake, whereas treatment with 1 μM GET73 significantly increased K(+)-evoked, but not spontaneous, glutamate efflux. The GHB analog did not affect the increase in glutamate efflux induced by 100 μM and 300 μM NMDA. In contrast, 500 nM GET73, a concentration at which it is ineffective alone, partially but significantly counteracted the increase in K(+)-evoked glutamate efflux induced by 100 μM CHPG, an mGluR5 agonist. When 500 nM GET73 was coperfused with 100 μM MPEP, it amplified the decrease in K(+)-evoked glutamate efflux induced by the mGluR5 antagonist. Interestingly, the increase in K(+)-evoked glutamate efflux induced by 1 μM GET73 was counteracted by coperfusion with a low (10 μM) concentration of MPEP, which by itself is ineffective. Finally, 500 nM GET73 did not affect the reduction of K(+)-evoked glutamate efflux induced by the mGluR2/3 agonist LY379268. These findings demonstrate that the GHB analog GET73 significantly affects glutamate transmission in the hippocampus, and its profile of action differs from that of its parent compound.