Effects of Systemic Steroid Administration on Recurrence of Pericardial Effusion in Pediatric Patients After Hematopoietic Stem Cell Transplantation.
Although rare in the general pediatric population, the incidence of pericardial effusion is significantly higher in pediatric patients undergoing hematopoietic stem cell transplant (HCT) with a reported incidence of up to 16.9%. The development of pericardial effusion in this setting is associated with higher mortality. Although pericardiocentesis is a relatively safe procedure for treating pericardial effusion, it is invasive, painful, and exposes an immunosuppressed patient to the risks of infection, bleeding, and injury to surrounding structures. Given the procedural risks of pericardiocentesis, systemic steroids are often administered for the treatment of pericardial effusion given their use for pericarditis in the general population. However, the effectiveness of systemic steroids for the treatment of pericardial effusion in the pediatric HCT population has not been confirmed. We studied the role of systemic steroids, administered at the time of initial pericardiocentesis performed for pericardial effusion, in preventing repeat pericardiocentesis. A total of 37 pericardiocenteses after HCT were performed during the study period with 25 patients undergoing first-time pericardiocentesis and 15 of those patients receiving systemic steroids. Eight patients required repeat pericardiocentesis; 5 of 15 (33%) received steroids and 3 of 10 (30%) did not receive steroids. Our data in this small cohort of pediatric HCT patients did not show a significant difference in the need for repeat pericardiocentesis with the use of systemic steroids, initiated within 48 hours of pericardiocentesis.


Description of Eikenella halliae sp. nov. and Eikenella longinqua sp. nov., derived from human clinical materials, emendation of Eikenella exigua Stormo et al. 2019 and emendation of the genus Eikenella to include species which are strict anaerobes.
The Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella (HACEK) group genus Eikenella contained a single species, Eikenella corrodens, for many years. In November 2019, Eikenella exigua was described after recovery from a brain abscess and blood culture in Norway. Coincidentally, characterization of 22 Gram-negative bacteria resembling Eikenella from 17 Canadian patients had been underway. Seven isolates from five patients were conclusively identifiable as E. corrodens. One (NML 120819) was deemed to represent a species of the genus Eikenella most closely related to E. corrodens. Fourteen isolates had 97.6 to 98.8% similarities to E. corrodens by 16S rRNA gene sequencing, forming three distinct groups by genome analyses. The largest contained ten anaerobic isolates from eight patients recovered from blood, brain, bone and other abscesses; upon re-evaluation, this group was found to be most consistent with E. exigua. A second facultatively anaerobic clade consisted of two ocular isolates from one patient and a sinus isolate from a second patient. The third taxon consisted of a single strictly anaerobic blood culture isolate. The novel taxa, like E. corrodens, were poorly reactive biochemically and difficult to discern from each other phenotypically and chemotaxonomically, including by cellular fatty acids. MALDI-TOF (Bruker) and whole-genome sequencing were used to further characterize isolates. Draft genomes for the strains had similar DNA G+C contents (55.38-58.53 mol%) while sizes varied from 1.82 Mb to 2.54 Mb. We propose here emendations of the genus Eikenella and the species Eikenella exigua, as well as describing Eikenella halliae sp. nov. NML 130454T (=LMG 30894T=NCTC 14180T) and Eikenella longinqua sp. nov. NML 02-A-017T (=LMG 30896T=NCTC 14179T), on the basis of these findings.


Methionine restriction inhibits colon carcinogenesis.
Previously, we demonstrated that life-long methionine restriction (MR) in rats increases life span and inhibits aging-related disease processes. The present study examines the effects of MR on the formation of preneoplastic aberrant crypt foci (ACF) in the colon of azoxymethane (AOM)-treated rats. Six-week-old male F344 rats were placed on essential amino acid-defined diets containing either 0.86% Met (control diet) or 0.17% Met (MR diet) and 1 wk later were given AOM (15 mg/kg/wk, s.c.) for 2 consecutive wk. Ten weeks after the final AOM treatment, ACF formation was markedly reduced in rats fed the MR diet with ACF containing > or = 4 crypts/focus being reduced by over 80% compared to controls (P < 0.001). A similar 83% reduction in ACF containing > or = 4 crypts/focus was observed in rats fed the MR diet only during the post-initiation period (after the final dose of AOM; P < 0.001). Five weeks after AOM administration, a 12% reduction in colonic cell proliferation was observed in MR rats compared to controls (P < 0.05). These results show that MR inhibits colonic tumor development in the rat, an effect that occurs primarily during post-initiation phases of carcinogenesis and may be due, in part, to an inhibition of colonic cell proliferation.


Profession differences in family focused practice in the adult mental health system.
There is a large gulf between what psychiatric services should (or could) provide and what they do in practice. This article sought to determine practice differences between the differing professions working in adult mental health services in terms of their family focused work. Three hundred and seven adult mental health professionals completed a cross-sectional survey of family focused practices in adult mental health services. Findings highlight that social workers engaged in more family focused practice compared to psychiatric nurses, who performed consistently the lowest on direct family care, compared to both social workers and psychologists. Clear skill, knowledge, and confidence differences are indicated between the professions. The article concludes by offering direction for future profession education and training in family focused practices.


Negotiating Emotional Support: Sober Gay Latinos and their Families.
This study explores how sober gay Latino men obtain support from their families. Familial ties can be a protective health factor, yet many gay Latinos experience rejection from family members because of their sexuality. There are very few studies that examine the extent and quality of emotional support from kin for this population. Understanding family dynamics within the context of recovery and sexuality can increase our understanding of how to leverage family ties to develop alcohol abuse interventions. The study was conducted semi-structured interviews with 30 sober gay Latinos using a grounded theory approach. Analyses of the qualitative data identified the following themes: Family values shaped the participants' perception of their range of choices and emotional responses; participants reported feeling loved and supported even when sexuality was not discussed with parents; and family support for sobriety is essential. Findings suggest that familial ties shape perceptions of support and importance of disclosing sexual identity. Family support often results from agreements about sexual identity disclosure, and some families can overcome cultural and religious taboos on sexuality. Future studies should investigate families that negotiate acceptance with their gay members, and whether they exhibit heterosexual biases that may influence the psychological stress of gay Latino men who wish to be sober.


Does Immunohistochemistry for Discovered on GIST1 and Minichromosome Maintenance Protein7 Provide Additional Clinicopathological Value in Gastrointestinal Stromal Tumors?
The aim of the study was to investigate the expression of discovered on GIST 1 (DOG1) and minichromosome maintenance protein 7 (MCM7) in addition to the traditional markers, C-KIT and Ki-67, in gastrointestinal stromal tumors (GISTs) to specify the diagnosis and to evaluate their clinicopathological significance in GIST patients. Hematoxylin and eosin sections of 43 GISTs were re-examined to review histopathological criteria and risk stratification of these tumors. Immunohistochemistry for DOG1, C-KIT, MCM7, Ki-67 antibodies was performed. Positive DOG1 and C-KIT expressions were found in 42 (97.7%) and 39 (90.7%) of cases, respectively. DOG1 and C-KIT expression scores were significantly correlated (P < 0.001). Among four C-KIT-negative GISTs, three cases were DOG1-positive. DOG1 was more sensitive and specific than C-KIT in the diagnosis of GISTs. High DOG1 expression scores were significantly associated with tumor size (P = 0.023) and risk (P = 0.037). Significant positive correlation was noted between MCM7 and Ki-67 labeling indices (LIs) (P < 0.001, r = 0.885). MCM7 demonstrated higher proliferation LIs than Ki-67. Significant associations were found between MCM7 and Ki-67 LIs and tumor size (P = 0.001 and 0.003 respectively), mitotic rate (P < 0.001 both) and risk stratification (P < 0.001 both) with a stepwise increase in MCM7 LIs with increasing tumor risk. DOG1 is an important diagnostic tool for GISTs particularly in C-KIT-negative tumors. It may have a role in GISTs tumorogenesis and progression. Despite the established clinicopathological value of Ki-67 in GISTs, detection of MCM7 expression is recommended as a prognostic adjunct, given its better sensitivity for cellular proliferation and stepwise association with tumor risk.


B3GAT3-related linkeropathy and an in-frame homozygous deletion in an adult patient.
Proteoglycans (PGs) are complex macromolecules consisting of a core protein and glycosaminoglycan (GAG) side chains. PGs are important for the constitution and functioning of the connective tissue. The normal composition of the GAG side chains defines the nature of the PGs and a wide range of biological events. Deficiencies of specific enzymes involved in the linkage of GAGs to the core protein to form functional PGs, lead to a heterogeneous disease group called Linkeropathies. This is a group of multisystem conditions characterized by different phenotypes that include skeletal dysplasia and various extra-skeletal features: developmental delay/intellectual disability, ophthalmological abnormalities including blue sclerae, facial characteristics, cardiac defects, abdominal wall defects (hernias), cutis laxa, hypermobility and hypotonia. The conditions show variable severity and often overlapping phenotypes. The enzyme β-1,3-glucuronyltransferase 3, encoded by B3GAT3, is involved in the linkage process to form functional PGs. Biallelic pathogenic variants in B3GAT3 hence lead to Linkeropathy due to loss of function or decreased activity of this enzyme. We describe a 22-year-old female patient, born of consanguineous parents. The disease history includes congenital severe joint malalignment of elbows, hips, knees and feet, hypermobility, severe kyphoscoliosis, osteoporosis with multiple fractures in childhood, congenital diaphragmatic hernia, minor dental anomalies, digital malformations, and characteristic facial features. Whole exome sequencing was performed, and homozygosity for a novel in-frame deletion in B3GAT3, (c.61_63delCTC (p.(Leu21del))) was detected. Both unaffected parents (double second cousins) were shown to be heterozygous carriers. This is the first report to describe homozygosity for this specific in-frame deletion in B3GAT3 (p.(Leu21del)). We present a young adult phenotype and a summary of previous reported patients with other biallelic B3GAT3-variants for comparison. Previously described patients of B3GAT3-deficiency were, however, all children with phenotypes ranging from prenatal manifestation and early lethality to less severe. We suggest that this novel homozygous in-frame deletion in B3GAT3 may be the cause of a recessive form of Linkeropathy.


Radical-Based C-C Bond-Forming Processes Enabled by the Photoexcitation of 4-Alkyl-1,4-dihydropyridines.
We report herein that 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) can directly reach an electronically excited state upon light absorption and trigger the generation of C(sp3 )-centered radicals without the need for an external photocatalyst. Selective excitation with a violet-light-emitting diode turns alkyl-DHPs into strong reducing agents that can activate reagents through single-electron transfer manifolds while undergoing homolytic cleavage to generate radicals. We used this photochemical dual-reactivity profile to trigger radical-based carbon-carbon bond-forming processes, including nickel-catalyzed cross-coupling reactions.


Elusive but not hypothetical: axillary meristems in Wollemia nobilis.
The branches of Wollemia nobilis are unbranched; however, it has been noted that new branches can form from the distal end of damaged ones, and branches can grow from axillary structures once a terminal strobilus has fallen. Tomlinson and Huggett (2011, Annals of Botany 107: 909-916) have recently investigated the formation of these reiterative branches and stated in the title of their paper that 'Partial shoot reiteration in Wollemia nobilis (Araucariaceae) does not arise from "axillary meristems"'. They go on to state 'Further research may reveal the presence of these elusive, but still only hypothetical, axillary meristems'. In this Viewpoint, I argue that Tomlinson and Huggett do not refer to previously published information that indicates that axillary meristems are present in Wollemia nobilis branch leaf axils, and that their anatomical methods were probably not optimal for locating and examining these minute structures. Thus, whilst I would agree that the axillary meristems in branch leaf axils of Wollemia nobilis are elusive, I contend that they are not hypothetical.


Early attachment networks to multiple caregivers: History, assessment models, and future research recommendations.
Early attachment has been commonly hypothesized to predict children's future developmental outcomes, and robust evidence relying on assessments of single caregiver-child attachment patterns has corroborated this hypothesis. Nevertheless, most often children are raised by multiple caregivers, and they tend to form attachment bonds with more than one of them. In this paper, we briefly describe the conceptual and empirical roots underlying the notion of attachment networks to multiple caregivers. We detail potential reasons for research focusing on a single caregiver (most often mothers, but recently also fathers) and the historical attempts to establish a more ecologically valid assessment of attachment to multiple caregivers. Finally, we describe a recently developed organizational framework that includes testable models on which future research may rely for assessing the predictive power of attachment networks to multiple caregivers on children's developmental outcomes.


The binding orientations of structurally-related ligands can differ; A cautionary note.
Crystal structures can identify ligand-receptor interactions and assist the development of novel therapeutics, but experimental challenges sometimes necessitate the use of homologous proteins. Tropisetron is an orthosteric ligand at both 5-HT3 and α7 nACh receptors and its binding orientation has been determined in the structural homologue AChBP (pdbid: 2WNC). Co-crystallisation with a structurally-related ligand, granisetron, reveals an almost identical orientation (pdbid; 2YME). However, there is a >1000-fold difference in the affinity of tropisetron at 5-HT3 versus α7 nACh receptors, and α7 nACh receptors do not bind granisetron. These striking pharmacological differences prompt questions about which receptor the crystal structures most closely represent and whether the ligand orientations are correct. Here we probe the binding orientation of tropisetron and granisetron at 5-HT3 receptors by in silico modelling and docking, radioligand binding on cysteine-substituted 5-HT3 receptor mutants transiently expressed in HEK 293 cells, and synthetic modification of the ligands. For 15 of the 23 cysteine substitutions, the effects on tropisetron and granisetron were different. Structure-activity relationships on synthesised derivatives of both ligands were also consistent with different orientations, revealing that contrary to the crystallographic evidence from AChBP, the two ligands adopt different orientations in the 5-HT3 receptor binding site. Our results show that even quite structurally similar molecules can adopt different orientations in the same binding site, and that caution may be needed when using homologous proteins to predict ligand binding.


Shotgun mitogenomics across body size classes in a local assemblage of tropical Diptera: Phylogeny, species diversity and mitochondrial abundance spectrum.
Mitochondrial genomes can be assembled readily from shotgun-sequenced DNA mixtures of mass-trapped arthropods ("mitochondrial metagenomics"), speeding up the taxonomic characterization. Bulk sequencing was conducted on some 800 individuals of Diptera obtained by canopy fogging of a single tree in Borneo dominated by small (<1.5 mm) individuals. Specimens were split into five body size classes for DNA extraction, to equalize read numbers across specimens and to study how body size, a key ecological trait, interacts with species and phylogenetic diversity. Genome assembly produced 304 orthologous mitochondrial contigs presumed to each represent a different species. The small-bodied fraction was the by far most species-rich (187 contigs). Identification of contigs was through phylogenetic analysis together with 56 reference mitogenomes, which placed most of the Bornean community into seven clades of small-bodied species, indicating phylogenetic conservation of body size. Mapping of shotgun reads against the mitogenomes showed wide ranges of read abundances within each size class. Ranked read abundance plots were largely log-linear, indicating a uniformly filled abundance spectrum, especially for small-bodied species. Small-bodied species differed greatly from other size classes in neutral metacommunity parameters, exhibiting greater levels of immigration, besides greater total community size. We suggest that the established uses of mitochondrial metagenomics for analysis of species and phylogenetic diversity can be extended to parameterize recent theories of community ecology and biodiversity, and by focusing on the number mitochondria, rather than individuals, a new theoretical framework for analysis of mitochondrial abundance spectra can be developed that incorporates metabolic activity approximated by the count of mitochondria.


The Scylla and Charybdis of glucose control in childhood type 1 diabetes?
Glucose control in childhood type 1 diabetes is difficult and often characterized by significant glucose variability, including periods of prolonged hyperglycemia and intermittent episodes of hypoglycemia that can be severe. The brain of the developing child is thought to be more susceptible to metabolic insults because of its relatively high demand for glucose to fuel neuronal growth and differentiation. In this review we consider the impact of glucose variability, especially when associated with recurrent hypoglycemia, on long-term cognitive function in childhood type 1 diabetes. At present, this indicates a subtle effect of type 1 diabetes per se on a number of cognitive modalities. Within the population of children with type 1 diabetes, a history of severe hypoglycemia also appears to have an additional negative effect on cognitive function. However, interpretation of the literature is difficult in that the human studies draw largely from cross-sectional observational epidemiology while more basic work has used models that do not translate well into human disease. Moreover, it is likely to be many years before we will be able to clearly document the effects of recurrent hypoglycemia or chronic hyperglycemia on cognitive function. In the meantime, it seems appropriate to advocate that minimizing glucose variability when achieving glycemic targets should be the therapeutic goal of clinicians involved in the management of childhood type 1 diabetes.


Percutaneous Endoscopic Gastrostomy with Jejunal Extension Tube for the Delivery of Levodopa Carbidopa Intestinal Gel: Clinical Practice Guidelines of the Romanian Society of Digestive Endoscopy.
Percutaneous endoscopic gastrostomy with jejunal extension (PEG/J) was first described in 1998 and has become the standard technique for fixing the tube in place for levodopa carbidopa intestinal gel (LCIG) infusion. The Romanian Society of Digestive Endoscopy (RSDE) decided to create a consensus paper to meet the needs in medical training and practice. After reviewing the available published data and existing recommendations, a consensus process was carried out involving the leaders of opinion in this field. The resulting text and recommendations were approved, after reaching expert consensus, and reflects the views of the RSDE for the best practice of PEG/J tube placement. The pull through method ("pull technique") is the prevailing PEG-tube placement procedure in Romania. The procedure can be performed with intravenous sedation combined with local anesthesia. Although minor complications are common, serious complications are infrequent, and the tube insertion procedures have a good safety record. Redo procedures are sometimes necessary and clinicians should be aware of these situations.


Template boundary in a yeast telomerase specified by RNA structure.
The telomerase ribonucleoprotein has a phylogenetically divergent RNA subunit, which contains a short template for telomeric DNA synthesis. To understand how telomerase RNA participates in mechanistic aspects of telomere synthesis, we studied a conserved secondary structure adjacent to the template. Disruption of this structure caused DNA synthesis to proceed beyond the normal template boundary, resulting in altered telomere sequences, telomere shortening, and cellular growth defects. Compensatory mutations restored normal telomerase function. Thus, the RNA structure, rather than its sequence, specifies the template boundary. This study reveals a specific function for an RNA structure in the enzymatic action of telomerase.


Structural isomerism in the [(Ni@Sn9)In(Ni@Sn9)]5- Zintl ion.
A new Zintl cluster, [(Ni@Sn9)In(Ni@Sn9)]5-, has been isolated in two distinct isomeric forms, one where both Ni@Sn9 units are coordinated to the bridging In atom in an η3- mode, the other where one is η3- and the other η4-. Density functional theory indicates that the energetic separation between these two structures is minimal, suggesting that crystal packing plays a decisive role in the structural chemistry. A comparison of the electronic structure of [(Ni@Sn9)In(Ni@Sn9)]5- with [(Ni@Ge9)Ni(Ni@Ge9)]4-, which has four fewer valence electrons, sheds some light on possible mechanisms that lead to the fusion of cluster fragments.


Tumor localization of 131-I-labeled antibodies by radionuclide inaging.
Intravenous injections of 131-I-labeled anti-EL4 lymphoma antibodies showed progressive localization of radioactivity in EL4 transplants but not in B16 melanoma in mice carrying both tumors. Normal rabbit globulin labeled with 131-I did not localize in either tumor and cleared more slowly from the internal organs. Metastatic localization of intravenous 131-I-labeled anti-tumor antibodies was also observed in 2 cancer patients.


[Dynamic protein assemblies in biological membranes].
The peculiarities of structural organization and functioning of enzymes in biological membranes are reviewed. Based on experimental data it is suggested that these peculiarities are due to the ability of many proteins to form intramembrane aggregates and assemblies differing in life-time and consisting of related and functionally different enzymes, which determines the structural and functional heterogeneity of biological membranes. The importance of formation of dynamical essembl es for the functioning of multienzyme systems is illustrated by the hormone--receptor--adenylate cyclase and redox carrier chains. The general principles of functioning of these systems (e. g. lateral diffusion of constituent components, formation of protein-protein aggregates with terminal life-time, etc.) are discussed. On the whole the biological membranes appear as microheterogenous dynamical structures, whose functioning strongly depends on aggregation-deaggregation of membrane proteins. These processes are affected (i. e. accelerated or decelerated) by a number of factors, such as, for instance, multienzyme system functioning, which also stabilize the molecular assemblies formed. It is assumed that changes in reciprocal intramembrane arrangement of the enzymes and formation of protein-protein complexes may control the local activity of membrane-dependent processes in the cell.


Alkaloids of tobacco and blood coagulation: effect of nicotine on thrombin and fibrinogen.
An alkaloid of tobacco, nicotine, affected the clot-formation property of the enzyme, thrombin, on the substrate, plasma or fibrinogen (thrombin time). Higher concentrations of nicotine retarded the clot-formation property of thrombin. By decreasing the nicotine concentration in the clotting mixture, the clotting time of thrombin was accelerated. Nicotine also modified the clot formation property of plasma or fibrinogen to thrombin, and this effect was dose dependent. From this experimental evidence, it is suggested that nicotine does alter the clot-forming properties of thrombin on fibrinogen.


Stability of three commonly compounded extemporaneous enrofloxacin suspensions for oral administration to exotic animals.
To evaluate the stability of 3 extemporaneous oral suspensions of enrofloxacin mixed with readily available flavoring vehicles when stored at room temperature (approx 22°C). Evaluation study. 3 commonly compounded oral suspensions of enrofloxacin. On day 0, commercially available enrofloxacin tablets were compounded with a mixture of distilled water and corn syrup (formulation A) or cherry syrup (formulation B) flavoring vehicles to create suspensions with a nominal enrofloxacin concentration of 22.95 mg/mL, and 2.27% enrofloxacin injectable solution was compounded with a liquid sweetener (formulation C) to create a suspension with a nominal enrofloxacin concentration of 11.35 mg/mL. Preparations were stored in amber-colored vials at room temperature for 56 days. For each preparation, the enrofloxacin concentration was evaluated with high-performance liquid chromatography at prespecified intervals during the study. The pH, odor, and consistency for all suspensions were recorded at the start and completion of the study. Relative to the nominal enrofloxacin concentration, the enrofloxacin concentration strength ranged from 95.80% to 100.69% for formulation A, 108.44% to 111.06% for formulation B, and 100.99% to 103.28% for formulation C. A mild pH increase was detected in all 3 suspensions during the study. Results indicated that, when stored in amber-colored vials at room temperature for 56 days, the enrofloxacin concentration strength in all 3 formulations was retained within acceptance criteria of 90% to 110%. Subjectively, cherry syrup flavoring was better at masking the smell and taste of enrofloxacin than were the other mixing vehicles.


Oxidation of glutathione and superoxide generation by inorganic and organic selenium compounds.
The carcinostatic activities of selenium (Se) compounds have been shown to be composition and concentration dependent. Several studies have indicated that the ratios between glutathione (GSH) and Se may play an important role in Se catalysis and toxicity. The present study examined the catalytic effect of three selenium compounds on GSH oxidation using lucigenin-dependent chemiluminescence (CL) as an indirect measure of superoxide generation. Various GSH:Se ratios were assayed for the glutathione oxidase activity of selenite, selenocystamine and diselenodipropionic acid. CL emitted from the reaction of selenite with GSH increased more rapidly and was greater than those from the diselenides, but the diselenide CL reactions were sustainable. Both selenite- and diselenide-induced CL were markedly suppressed by superoxide dismutase (SOD). Iodoacetic acid (IAc) effectively inhibited CL generated from selenite-, selenocystamine- and diselenodipropionic acid-catalyzed GSH oxidation. These results suggest that GSH oxidation catalyzed by selenite, and the diselenides selenocystamine and diselenodipropionic acid, generated the superoxide radical in which the CL was inhibited by SOD. Furthermore, CL inhibition by IAc suggests that the catalytic species producing superoxide were the GSSe(-) or RSe(-) anion. This redox chemistry may be responsible for selenite and organoselenium toxicity and apoptosis, making possible the design and synthesis of organoselenium-containing pharmaceuticals.


[Radiation myelopathy and plexopathy].
Radiation myelopathy (RM) is a relatively rare disorder characterized by white matter lesions of the spinal cord resulting from irradiation. It is divided into two forms by the latent periods: transient RM and delayed RM. The delayed RM develops usually non-transverse myelopathy symptoms such as dissociated sensory disturbance, unilateral leg weakness, and gait disturbance with asymmetric steps. Spinal MRI shows initially cord swelling and long T1/T2 intramedullary lesion with enhancement, then exhibits cord atrophy. Histopathological findings of delayed RM are white matter necrosis, demyelination, venous wall thickening and hyalinization. Glial theory and vascular hypothesis have been proposed to explain its pathophysiology. Several therapies such as adrenocorticosteroid, anticoagulation and hyperbaric oxygen have been tried to this disease with variable benefits. Radiation plexopathy is classified into two major types by the location: radiation-induced brachial plexopathy (BP) and radiation-induced lumbosacral plexopathy (LSP). The BP initially emerges as arm and shoulder pain, whereas LSP as leg weakness. Myokymia and fasciculations are observed in both types. Electrophysiological study reveals findings of peripheral neuropathy. It is often difficult to distinguish the radiation plexopathy from cancer invasion to the plexus, but MRI is useful to differentiate between these diseases. Pathological findings are small vessel obstruction, thick fibrosis, axonal degeneration and demyelination. Its pathomechanism is presumed that radiation-induced fibrous tissue compresses the nerve root as well as microvascular obstruction of the nerve. Adrenocorticosteroid and anticoagulation are considered as the strategy for symptomatic relief.


Evodiamine ameliorates liver fibrosis in rats via TGF-β1/Smad signaling pathway.
Liver fibrosis is considered to be a result of chronic liver pathological changes, and hepatic stellate cells (HSCs) play an important role during this process. Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities. This study focused on the effects of evodiamine on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and HSCs in vitro via the TGF-β1/Smad signaling pathway. A liver fibrosis rat model was established by the intraperitoneal injection of CCl4 (3 ml/kg, 30% in olive oil). Evodiamine (15 and 25 mg/kg) was administered orally for 8 weeks. HSCs were treated with different evodiamine concentrations. The results indicated that evodiamine could improve the histopathological abnormalities in liver tissues and decrease the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hydroxyproline, and total bilirubin (TBIL). Concentrations of IL-6, tumor necrosis factor-α (TNF-α), collagen-I (COL-I), and collagen-III (COL-III) were reduced by evodiamine. Western blotting and real-time PCR showed that protein expression of transforming growth factor-β (TGF-β1), p-Smad 2/3 (phosphorylation of Smad 2/3), and smooth muscle alpha-actin (α-SMA) as well as mRNA expression of TGF-β1 and α-SMA in liver tissues were downregulated by evodiamine. The cell proliferation, production of hydroxyproline, and the protein expression of TGF-β1, p-Smad 2/3, and α-SMA in HSCs were dose-dependently reduced by evodiamine. Collectively, evodiamine had an antifibrosis effect in CCl4-induced liver fibrosis, and reduced HSCs proliferation and collagen metabolism in vitro. The major mechanism was downregulation of relative expression of TGF-β1, p-Smad 2/3, and α-SMA.


Application of a web-based cognitive-behavioural therapy programme for the treatment of selective mutism in Singapore: a case series study.
Selective mutism (SM) is characterised by limited or a lack of speech in selected social settings. Recent reviews suggest that cognitive-behavioural therapy (CBT) is an effective and promising treatment approach for SM. However, there is still a lack of studies documenting the applicability of CBT for SM in diverse populations. The goal of the present study was to examine the use of a web-based CBT programme ('Meeky Mouse') among Singaporean children diagnosed with SM. Five children with SM (one boy and four girls aged 6-11 years) participated in the 14-week 'Meeky Mouse' programme, in addition to being prescribed with an unchanged dosage of fluoxetine 10-20 mg daily. The progress made by the children throughout the course of the programme was documented by the therapist. Post treatment, four out of the five children demonstrated improvements in the frequency of speech during therapy sessions at home, in school and at other social situations. Findings from the present study provide support for the use of a web-based CBT programme in improving speech and decreasing the severity of SM among affected children.


Rational Drug and Antibiotic Use Status, E-Health Literacy in Syrian Immigrants and Related Factors: A Cross-Sectional Study.
Rational drug use is a pivotal concept linked with morbidity and mortality. Immigration plays a significant role as a determinant affecting individuals' health-related attitudes, behaviors, and the pursuit of health services. Within this context, the study was initiated to assess the factors influencing health literacy and rational drug use among Syrian immigrants in Istanbul. A cross-sectional study was undertaken on 542 Syrian adults utilizing a three-part questionnaire encompassing sociodemographics, rational drug use, and the e-health literacy scale (eHEALS). With an average age of 39.19 ± 13.10 years, a majority of participants believed medications should solely be doctor-prescribed (97%) and opposed keeping antibiotics at home (93.7%). Yet, 62.5% thought excessive herbal medicine use was harmless. The mean eHEALS score stood at 20.57 ± 7.26, and factors like age, marital status, income, and duration of stay in Turkey influenced e-health literacy. Associations were seen between low e-health literacy and being female, being older, having a lower education level, and regular medication use. Syrian immigrants displayed proper knowledge concerning antibiotics yet exhibited gaps in their understanding of general drug usage, treatment adherence, and herbal medicines. Approximately 80.3% had limited health literacy, pointing to the need for targeted interventions for enhanced health and societal assimilation.


Human laryngeal ganglia contain both sympathetic and parasympathetic cell types.
The presence of ganglia associated with the laryngeal nerves is well documented. In man, these ganglia have been less well studied than in other species and, in particular, the cell types within these ganglia are less well characterized. Using a panel of antibodies to a variety of markers found in the paraganglion cells of other species, we were able to show the existence of at least two populations of cells within human laryngeal paraganglia. One population contained chromogranin and tyrosine hydroxylase representing a neurosecretory population possibly secreting dopamine. A second population of choline acetyltransferase positive cells would appear to have a putative parasympathetic function. Further work is needed to characterize these cell populations more fully before it will be possible to assign functions to these cell types but our results are consistent with the postulated functions of these ganglia as chemoreceptors, neurosecretory cells, and regulators of laryngeal mucus secretion.


Medicare's Stewardship Role to Improve Care Delivery: Opportunities for the Biden Administration.
Medicare initiatives have been instrumental in improving care delivery and payment as exemplified by its role in broadly expanding the use of telehealth during the COVID-19 pandemic. Medicare innovations have been adopted or adapted in Medicaid and by private payers, while Medicare Advantage plans successfully compete with traditional Medicare only because their payment rates are tied by regulation to those in the traditional Medicare program. However, Medicare has not succeeded in implementing new, value-based payment approaches that also would serve as models for other payers, nor has Medicare succeeded in improving quality by relying on public reporting of measured performance. It is increasingly clear that burdensome attention to measurement and reporting distracts from what could be successful efforts to actually improve care through quality improvement programs, with Medicare leading in partnership with providers, other payers, and patients. Although Congress is unlikely to adopt President Biden's proposals to decrease the eligibility age for Medicare or to adopt a public option based on Medicare prices and payment methods in the marketplaces, the Biden administration has an opportunity to provide overdue, strategic direction to the pursuit of value-based payments and to replace failed pay-for-performance with provider-managed projects to improve quality and reduce health disparities.


Amblyopia and strabismus.
Strabismus and amblyopia, two of the most common problems in children's vision, can be prevented only by early recognition, diagnosis, and treatment. Strabismus, a misalignment of the eyes that causes one eye to deviate from its normal position, is the most common cause of amblyopia. Amblyopia is impaired vision in one eye caused by disuse. The author describes diagnostic tests, common causes, and frequently used treatment for both conditions.


The relationship of vascular endothelial growth factor and osteopontin expression with 3-year progression-free survival of locally advanced nasopharyngeal cancer patients treated with platinum-based chemoradiation.
The incidence of nasopharyngeal cancer (NPC) is high, with new cases accounting for 5.2% of all malignancies in Indonesia. Most cases are detected at an advanced stage, and recurrences are common. Vascular endothelial growth factor (VEGF) and osteopontin (OPN) are important markers in tumorigenesis that serve as prognostic predictors. This study aims to determine the correlation of VEGF and OPN expression with 3-year progression-free survival (PFS). This retrospective cohort study analyzed 155 patients with locally advanced NPC. Data were obtained from medical records between 2015 and 2017. The locally advanced sample of this disease that met the inclusion criteria was stained with H&E before being prepared in a paraffin block. Furthermore, the immunohistochemistry staining results for VEGF and OPN were observed with ImageJ 1.50i and calculated semi-quantitatively using the histoscore. The 3-year PFS obtained was 39%, with a median of 23 months. Vascular endothelial growth factor expression was detected in 113 of 155 samples (72.9%), while positive OPN expression was discovered in 99 of 155 samples (63.8%). There was a correlation between VEGF (p = 0.747) and OPN expression (p = 0.584) and 3-year PFS. Positive VEGF and OPN expression in the subgroup of patients with stage IVB and N3 tumors was related to improved 3-year PFS (p < 0.05). This was similar to the positive VEGF expression in the subgroup of patients receiving neoadjuvant chemotherapy (p < 0.05). Vascular endothelial growth factor and OPN remained potential prognostic predictors in NPC. Patients with positive VEGF and OPN expression in N3, IVB, and neoadjuvant treatment had significantly improved 3-year PFS.


Chokeberry (Aronia melanocarpa (Michx.) Elliot) concentrate inhibits NF-κB and synergizes with selenium to inhibit the release of pro-inflammatory mediators in macrophages.
Black chokeberry has been known to play a protective role in human health due to its high polyphenolic content including anthocyanins and caffeic acid derivatives. In the present study, we first characterized the polyphenolic content of a commercial chokeberry concentrate and investigated its effect on LPS-induced NF-κB activation and release of pro-inflammatory mediators in macrophages in the presence or the absence of sodium selenite. Examination of the phytochemical profile of the juice concentrate revealed high content of polyphenols (3.3%), including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids. Among them, cyanidin-3-O-galactoside and caffeoylquinic acids were identified as the major compounds. Data indicated that chokeberry concentrate inhibited both the release of TNFα, IL-6 and IL-8 in human peripheral monocytes and the activation of the NF-κB pathway in RAW 264.7 macrophage cells. Furthermore, chokeberry synergizes with sodium selenite to inhibit NF-κB activation, cytokine release and PGE2 synthesis. These findings suggest that selenium added to chokeberry juice enhances significantly its anti-inflammatory activity, thus revealing a sound approach in order to tune the use of traditional herbals by combining them with micronutrients.


Diagnostic Performance of Cerebroplacental Ratio Thresholds at Term for Prediction of Low Birthweight and Adverse Intrapartum and Neonatal Outcomes in a Term, Low-Risk Population.
To investigate the screening performance and best threshold centile (5th vs. 10th) of the cerebroplacental ratio (CPR) in low-risk, term pregnancies to predict low birthweight and adverse intrapartum and neonatal outcomes in a term, low-risk population. This was a blinded, prospective, cross-sectional study of low-risk singleton pregnancies at term. Women attended fortnightly from 36 weeks for CPR and estimated fetal weight assessment. Intrapartum and neonatal outcomes were recorded. Primary outcomes assessed were low birthweight, cesarean section for intrapartum fetal compromise, and composite adverse neonatal outcome. A total of 483 women participated in the study. The CPR 10th centile (1.48) threshold resulted in the best screening performance. Sensitivities for low birthweight, cesarean section for intrapartum fetal compromise, and composite adverse neonatal outcome of 41.9, 61.1, and 38.3% were achieved for false-positive rates of 17.7, 17.7, and 15.2%, respectively. The corresponding areas under the receiver operating characteristic curves were 0.62, 0.72, and 0.62. The CPR 10th centile resulted in the best screening performance, although this would be considered fair at best. The CPR 10th centile may be useful as part of a risk stratification tool for prediction of low birthweight and adverse intrapartum and neonatal outcomes.


Monotonicity of effect sizes: Questioning kappa-squared as mediation effect size measure.
Mediation analysis is important for research in psychology and other social and behavioral sciences. Great progress has been made in testing mediation effects and in constructing their confidence intervals. Mediation effect sizes have also been considered. Preacher and Kelley (2011) proposed and recommended κ² as an effect size measure for a mediation effect. In this article, we argue that κ² is not an appropriate effect size measure for mediation models, because of its lack of the property of rank preservation (e.g., the magnitude of κ² may decrease when the mediation effect that κ² represents increases). Furthermore, κ² can lead to paradoxical results in multiple mediation models. We show that the problem of κ² is due to (a) the improper calculation of the maximum possible value of the indirect effect, and (b) mathematically, the maximum possible indirect effect is infinity, implying that the definition of κ² is mathematically incorrect. At this time, it appears that the traditional mediation effect size measure PM (the ratio of the indirect effect to the total effect), together with some other statistical information, should be preferred for basic mediation models. But for inconsistent mediation models where the indirect effect and the direct effect have opposite signs, the situation is less clear. Other considerations and suggestions for future research are also discussed.


Early or late appearance of "dropped head syndrome" in amyotrophic lateral sclerosis.
"Dropped head syndrome" caused by neck extensor weakness has been reported in a variety of neuromuscular disorders. Previously published reports include isolated cases with amyotrophic lateral sclerosis (ALS). In this report, nine patients with ALS and dropped head syndrome seen during a 20 year period are described. PATIENTS AND INVESTIGATIONS: Between 1981 and 2000, 683 patients with ALS were diagnosed, based on El Escorial criteria. Nine of these had profound neck extensor weakness observed as an early feature, or developing during the later stages of the disease. The protocol for evaluation included detailed clinical history, neurological examination, electromyography, and nerve conduction studies. Investigations were undertaken to exclude malignancy, lymphoproliferative disorders, thyroid dysfunction, and collagen vascular disease. The incidence of dropped head syndrome was 1.3%. The mean (SD) age of the affected patients was 53.3 (10.3) years (range 33 to 65), with an equal distribution of cases in the fourth to seventh decades. In six patients, head drop was an early feature (mean interval from onset of illness 11.6 months (range 3 to 24)); in three it was late (between three and eight years after onset). In five patients, mild neck flexor weakness was present in addition to severe extensor weakness. In all nine patients there were diffuse upper and lower motor neurone signs. None of the patients had difficulty in breathing but all had difficulty in swallowing and social embarrassment, both of which could be corrected by simple measures. Dropped head syndrome is an important clinical sign and usually occurs as an early feature within the first one to two years after the onset of ALS. The cause of dropped head syndrome in these nine cases could be easily established as ALS by the presence of generalised signs.


Baboon vaginal microbiota: an overlooked aspect of primate physiology.
The bacterial population of the primate vaginal canal is an infant primate's first exposure to the microbial population inhabiting the outside world. Yet, little is known about this population and the effect it might have on the development and survival of the infant primate. As a first step toward characterizing the vaginal microbiota of a nonhuman primate, we used denaturing gradient gel electrophoresis to evaluate variations in the vaginal microbiota of a group of 35 baboons (Papio hamadryas), which were housed in a facility where they shared the same diet and the same environmental conditions. We found that, despite the uniform environment, there were appreciable differences in the composition of the microbiota from one individual to another. Our results also indicate that a simple swab test is sufficient for sampling the vaginal microbiota in the field, a finding that should help make more detailed characterization of the microbiota of wild primates feasible in the future.


Maternal and Perinatal Outcome in Women with Systemic Lupus Erythematosus: A Retrospective Bicenter Cohort Study.
To investigate disease activity around and during pregnancy and pregnancy outcome in women with systemic lupus erythematosus (SLE) considering antiphospholipid antibody status. Moreover, differences between first and consecutive pregnancies were examined. Pregnancies > 16 weeks gestation of SLE patients receiving joint care from rheumatologists and gynecologists in two tertiary centers in the Netherlands between 2000 and 2015 were included. Disease activity, flare rate, and pregnancy outcomes and complications were assessed. Ninety-six women (84% Caucasian) with 144 pregnancies were included. The median SLE(P)DAI score was 2 before, during, and after pregnancy. Flare rates were 6.3%, 20.1%, and 15.3%, respectively. Severe hypertensive disorder of pregnancy, intrauterine fetal death, preterm birth, and small-for-gestational age infants occurred in 18.1%, 4.1%, 32.7%, and 14.8%, respectively. Complication rates were similar in the first and consecutive pregnancies. Half of the women did not experience any pregnancy complication whereas 42.7% developed a complication during all pregnancies. Mean number of pregnancies was 2.4 and live births 1.7. In this SLE population with low disease activity, pregnancy complications were present irrespective of antiphospholipid antibody status. Furthermore, there were no differences in complication rates between the first and consecutive pregnancies as seen in healthy mothers. This information is useful for patient counseling.


Glucose Appearance Rate Rather than the Blood Glucose Concentrations Explains Differences in Postprandial Insulin Responses between Wholemeal Rye and Refined Wheat Breads-Results from A Cross-Over Meal Study.
Ingestion of rye bread leads to lower postprandial plasma insulin concentrations than wheat bread ingestion, but most often not too different glucose profiles. The mechanism behind this discrepancy is still largely unknown. This study investigates whether glucose kinetics may explain the observed discrepancy. Nine healthy men participated in a crossover study, eating 50 g of available carbohydrates as either refined wheat (WB) or traditional wholemeal rye bread (WMR) during d-[6,6-2 H2 ]glucose infusion. Labeled glucose enrichment is measured by an HPLC-TOF-MS method. The calculated rate of glucose appearance (RaE) is significantly lower after ingestion of WMR during the initial 15 min postprandial period. Additionally, the 0-90 min RaE area under the curve (AUC) is significantly lower after ingestion of WMR, as is plasma gastric inhibitory polypeptide (GIP) at 60 and 90 min. Postprandial glycemic responses do not differ between the breads. Postprandial insulin is lower after ingestion of WMR at 45 and 60 min, as is the 0-90 min AUC. Ingestion of WMR elicits a lower rate of glucose appearance into the bloodstream compared with WB. This may explain the lower insulin response observed after rye bread ingestion, commonly known as the rye factor.


An agglutinin with mitogenic and antiproliferative activities from the mushroom Flammulina velutipes.
A hemagglutinin with a molecular mass of 12 kDa was isolated from the fruiting bodies of the mushroom Flammulina velutipes. Its molecular mass is similar to that of the fungal immunomodulatory protein isolated from F. velutipes (FIP-fve) with ice-cold 5% acetic acid and 50 mM 2-mercaptoethanol as extraction medium and to that of the larger 12 kDa subunit of F. velutipes lectin isolated with phosphate buffer as extraction medium. Its hemagglutinating activity cannot be inhibited by a variety of carbohydrates tested. The activity is stable between pH 4 and pH 11. Loss in activity occurred when the temperature is raised to 60 C and 70 C. Activity is indiscernible at and above 80 C. Its N-terminal sequence shows differences from that of FIP-fve. F. velutipes hemagglutinin stimulates [3H-methyl] thymidine uptake by mouse splenocytes. It inhibits proliferation of leukemia L1210 cells with an IC50 of 13 microM.


Water and electrolyte in plasma, skin and skeletal muscles of young and growing guinea pigs.
Studies on the alterations of water and electrolytes in young and growing guinea pigs have shown that in the skin there was reduction of water, sodium and potassium contents with age while the chloride content was increased. In the skeletal muscle the same tendency was observed in reduction of water, sodium and potassium content but the chloride content was reduced with age. The decrease in sodium content of skin and that of potassium in the skeletal muscle were observed particularly in the oldest group of the present study. Plasma electrolytes were not altered.


Impurity-induced bound states and proximity effect in a bilayer exciton condensate.
The effect of impurities which induce local interlayer tunneling in bilayer exciton condensates is discussed. We show that a localized single-fermion bound state emerges inside the gap for any strength of impurity scattering and calculate the dependence of the impurity state energy and wave function on the potential strength. We show that such an impurity-induced single-fermion state enhances the interlayer coherence around it, and is similar to the superconducting proximity effect. As a direct consequence of these single-impurity states, we predict that a finite concentration of such impurities will increase the critical temperature for exciton condensation.


Total Breast-Feeding Duration and Dental Caries in Healthy Urban Children.
To determine if there is an association between longer breast-feeding duration and dental caries in healthy urban children. We conducted a cross-sectional study of urban children aged 1 to 6 years recruited through The Applied Research Group for Kids (TARGet Kids!) practice-based research network between September 2011 and August 2013. The main outcome measure was parental report of dental caries. The adjusted predicted probability of dental caries was 7%, 8%, 11%, and 16% with total duration of breast-feeding duration of 12, 18, 24, and 36 months, respectively. In the adjusted logistic regression analyses, relative to breast-feeding 0 to 5 months, the odds of dental caries with total breast-feeding duration >24 months was 2.75 (95% confidence interval 1.61-4.72). Among healthy urban children, longer breast-feeding duration was associated with higher odds of dental caries. These findings support heightened awareness and enhanced anticipatory guidance for preventive dental care, particularly among children who breast-feed beyond 2 years of age.


Oxylipin signaling in salt-stressed soybean is modulated by ligand-dependent interaction of Class II acyl-CoA-binding proteins with lipoxygenase.
Plant lipoxygenases (LOXs) oxygenate linoleic and linolenic acids, creating hydroperoxy derivatives, and from these, jasmonates and other oxylipins are derived. Despite the importance of oxylipin signaling, its activation mechanism remains largely unknown. Here, we show that soybean ACYL-COA-BINDING PROTEIN3 (ACBP3) and ACBP4, two Class II acyl-CoA-binding proteins, suppressed activity of the vegetative LOX homolog VLXB by sequestering it at the endoplasmic reticulum. The ACBP4-VLXB interaction was facilitated by linoleoyl-CoA and linolenoyl-CoA, which competed with phosphatidic acid (PA) for ACBP4 binding. In salt-stressed roots, alternative splicing produced ACBP variants incapable of VLXB interaction. Overexpression of the variants enhanced LOX activity and salt tolerance in Arabidopsis and soybean hairy roots, whereas overexpressors of the native forms exhibited reciprocal phenotypes. Consistently, the differential alternative splicing pattern in two soybean genotypes coincided with their difference in salt-induced lipid peroxidation. Salt-treated soybean roots were enriched in C32:0-PA species that showed high affinity to Class II ACBPs. We conclude that PA signaling and alternative splicing suppress ligand-dependent interaction of Class II ACBPs with VLXB, thereby triggering lipid peroxidation during salt stress. Hence, our findings unveil a dual mechanism that initiates the onset of oxylipin signaling in the salinity response.


Plasma fluoride and bromide concentrations during occupational exposure to enflurane or halothane.
The plasma fluoride and bromide concentrations were studied in operating theatre personnel. When enflurane was used, the increase in plasma fluoride concentration could not be distinguished from normal individual variations, but the plasma bromide concentration increased significantly when halothane was used. Seven patients were exposed to enflurane in a concentration of 200 parts per million for 4 h. A significant increase in the plasma concentration of fluoride was observed. The peak concentrations of fluoride occurred during exposure and the increase lasted less than 12 h. The increase in fluoride concentration was larger at this trace concentration than reported after anaesthetic concentrations. Cerebrospinal fluid (CSF) fluoride concentration was also studied; a smaller and delayed increase was found in CSF compared to plasma.


Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management.
The Adult Treatment Panel III report reemphasized the importance of reducing elevated levels of low-density lipoprotein cholesterol as the most efficacious treatment target to reducing coronary heart disease morbidity and mortality, which is the leading cause of disability and death in the United States. Although the etiologic role of elevated levels of low-density lipoprotein cholesterol in atherosclerosis is well established, treatment with statins still leaves a large proportion of patients vulnerable to cardiovascular events. The role of high-density lipoprotein cholesterol in atherosclerosis is increasingly recognized because of its strong inverse association with coronary heart disease in epidemiologic studies, and the observed high prevalence of low high-density lipoprotein cholesterol that occurs in populations with coronary heart disease, with or without elevated low-density lipoprotein cholesterol, especially among patients with diabetes and metabolic syndrome. This report highlights some of the therapeutic implications of the Adult Treatment Panel III report and various therapeutic approaches to both lowering elevated low-density lipoprotein cholesterol and triglycerides as well as increasing low levels of high-density lipoprotein cholesterol to optimize clinical event rate reduction in patients with coronary heart disease. Among available dyslipidemic therapies, although statins remain the mainstay for lowering low-density lipoprotein cholesterol and clinical events, niacin is currently the most effective agent for increasing low high-density lipoprotein cholesterol levels. The importance of combination dyslipidemic therapy, such as a statin plus niacin, in treating more optimally the entire lipid profile has been demonstrated not only to decrease progression and increase regression of atherosclerotic lesions, but to enhance event-free survival compared with statin monotherapy. Combination dyslipidemic therapy affords the most efficacious approach to controlling the multiple lipid abnormalities associated with atherosclerotic cardiovascular disease and optimizing cardiovascular event rate reduction in patients with coronary heart disease.


[Dialogues with neural networks about the present and future of medical professions: risks and prospects].
The article examines the risks to social perception of health professions in the context of the growing popularity of generative textual and visual neural networks. The article is consistent with the growing body of research that tends to see more risks of this technology, including for healthcare. The second focus of the article - the stereotypes about health professions - is critical, as they have been associated with negative outcomes for the healthcare system. The study primarily focuses on the perception of nursing professionals as most stereotyped by the public. Using uploads from the chatGPT, Kandinsky, and Shedevrum networks, the author has investigated the neural network's embedded perceptions of the nursing profession. Reproduction of certain stereotypes has been identified in all neural networks; the appearance stereotypes (gender, age, race, uniform) are more often shared by visual neural networks, while the function stereotypes (lack of autonomy, dependence on colleagues) - by text networks. Actually, we can assume the risks of a vicious circle, when the network is trained on the largely stereotypical data, and products based on its output increase the scale of stereotypical representations during subsequent training of the neural network. Developers' efforts to avoid reproducing stereotypes are acknowledged, however, the uploads show that they are not fully successful. To prevent the spread of perceptual distortions in neural networks, it is recommended to promote their sociohumanistic evaluation. A «prompt-experiment» is proposed as a mechanism for identifying such risks.


Meditation in the Workplace: Does Mindfulness Reduce Bias and Increase Organisational Citizenship Behaviours?
Mindfulness is becoming increasingly popular in the workplace. This likely relates to a growing body of research linking mindfulness to a range of psychological outcomes such as reduced anxiety, depression and increased subjective wellbeing. However, while mindfulness has received a great deal of attention in clinical research, the evidence for workplace relevant benefits is less established. Additionally, outside of clinical research, mindfulness studies have rarely been replicated. Recent evidence suggests that the cognitive skills cultivated during meditation may be instrumental in reducing biased thinking and increasing prosocial behaviour, but these findings have not been previously tested in a workplace setting. Specifically, mindfulness has been linked to reductions in implicit age bias, sunk-cost decision-making bias and increases in organisational citizenship behaviours (OCB). In two experiments using a workplace and laboratory sample, the present investigation aimed to test the reliability and generalisability of previous findings that a brief mindfulness meditation can reduce age and sunk-cost decision-making biases. To more directly test the potential positive benefits of mindfulness in a workplace setting, this study also investigated the impact of a mindfulness intervention on intention to perform OCB. While meditation significantly increased OCB intent, predictions relating to bias were not supported. Considerations for the degree to which empirical evidence aligns with claims in popular culture, along with implications for the practical uses of mindfulness in the workplace are explored.


Repopulation ability and proliferation stimulus in the hematopoietic system of mice following gamma-irradiation.
The repopulation ability of bone marrow was measured following whole body gamma irradiation of mice. Immediately after irradiation (100--500 rad) bone marrow suspensions were transfused into lethally irradiated syngeneic recipients. At various time intervals after transfusion (1 hour--20 days) DNA synthetic activity in femur and spleen was measured by incorporation of 125iodo-deoxyuridine (125IUdR). The cellularity of femoral bone marrow and the spleen weight was determined. A dose dependent retardation of repopulation was found to be correlated with an increasing duration of an elevated proliferation index (125IUdR-incorporation per unit bone marrow cells of per unit spleen weight, resp.). This suggests that the organism exerted a stimulus on the hematopoietic system to promote regeneration. This proliferation stimulus was kept at a high level unit a certain degree of hematopoietic function was restored either by regeneration of the bone marrow or, by compensating proliferation, in the spleen. The repopulation ability apparently was not only impared by the loss of stem cells but also by the induction of genetic damage in stem cells whose survival and partial functioning may have been enabled by the elevated proliferation pressure.


Self-harm in the emergency setting: understanding and responding.
Nurses are the people most consistently and intensely involved in the care of people who present to emergency departments because of self-harm, yet most have received no training or support to provide strategic care. This paper will explore unique features of the emergency context for care and provide practical instruction on how nurses working in the area can respond effectively. As this paper argues there is much that the emergency nurse can provide for the client who self-harms and it describes important steps toward recovery--a respectful human encounter, understanding, support for the person's efforts in coping, optimism and hope that pain will lessen and recovery will take place.


False-negative responses in glaucoma perimetry: indicators of patient performance or test reliability?
To study whether false-negative answers in computerized glaucoma perimetry indicate the patient's ability to perform perimetry or test result reliability. A retrospective evaluation was performed of visual field test results obtained with a perimetry program (Humphrey 30-2 Sita Standard; Humphrey Instruments, San Leandro, CA) in 70 consecutive patients with unilateral glaucomatous field loss. Frequencies of false-negative answers were compared between the two eyes of each patient and related to amount of visual field damage in the glaucomatous eyes using linear regression analysis. Frequencies of false-negative answers were higher in eyes with field loss. The intrapatient intereye difference was 6.6% on average (P < 0.0001). In seven subjects with false-negative frequency of 5% or more in both eyes, the mean difference was 12.7% between eyes. The differences in false-negative answers depended significantly on the amount of field loss in the glaucomatous eyes (P = 0.0003). Larger differences were seen in patients with advanced field loss in the affected eye. The increased frequencies of false-negative answers in eyes with field loss were strongly associated with field status. The higher false-negative frequencies in eyes with glaucomatous field loss compared with unaffected eyes may be explained by the increased variability in threshold values typically found in such eyes. False-negative answers in patients with glaucoma therefore represent eye rather than patient status.


Estimation via corrected scores in general semiparametric regression models with error-prone covariates.
This paper considers the problem of estimation in a general semiparametric regression model when error-prone covariates are modeled parametrically while covariates measured without error are modeled nonparametrically. To account for the effects of measurement error, we apply a correction to a criterion function. The specific form of the correction proposed allows Monte Carlo simulations in problems for which the direct calculation of a corrected criterion is difficult. Therefore, in contrast to methods that require solving integral equations of possibly multiple dimensions, as in the case of multiple error-prone covariates, we propose methodology which offers a simple implementation. The resulting methods are functional, they make no assumptions about the distribution of the mismeasured covariates. We utilize profile kernel and backfitting estimation methods and derive the asymptotic distribution of the resulting estimators. Through numerical studies we demonstrate the applicability of proposed methods to Poisson, logistic and multivariate Gaussian partially linear models. We show that the performance of our methods is similar to a computationally demanding alternative. Finally, we demonstrate the practical value of our methods when applied to Nevada Test Site (NTS) Thyroid Disease Study data.


Identification of nine novel DHCR7 missense mutations in patients with Smith-Lemli-Opitz syndrome (SLOS).
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome caused by deficiency of 7-dehydrocholesterol reductase (DHCR7), which catalyzes the last step of endogenous cholesterol synthesis. Surveys of SLOS patients have identified more than one hundred point mutations of the DHCR7 gene, most of which are missense mutations. Here, we report the identification of nine novel missense mutations of the DHCR7 gene.


A longitudinal study of emotional adjustment, quality of life and adaptive function in attenuated MPS II.
The behavioral, adaptive and quality of life characteristics of attenuated mucopolysaccharidosis type II (MPS II) have not been well studied. Understanding changes over time in the attenuated phenotype may assist in helping achieve better outcomes in long-term function. This longitudinal study investigates these outcomes in relation to age, somatic disease burden, and IQ. Specifically, somatic disease burden is a major challenge for these patients, even with treatment with enzyme replacement therapy. 15 patients, 10 between ages 6 and < 12 and 5 between ages ≥ 12 and 18, were selected who had at least 2 yearly visits. The occurrence of physical signs, the Physical Symptom Score, and IQ in these two groups was studied as well as the longitudinal association of age with standardized measures of quality of life, adaptive function, and behavioral symptoms as rated by parents and the child's self-report. Slopes by age across and within patients were calculated for these measures. All but one child had hearing loss, most had joint contractures and short stature. Somatic disease burden increased with age. IQ, although normal for most, also improved with age in those under 12 years of age. Physical quality of life decreased while psychosocial quality of life increased with age. Although other adaptive skills were in the broad average range, daily living skills were low at baseline relative to normative data and decreased over time. Behavior ratings indicated improvement in attention and hyperactivity over time. No patient had severe psychopathology, but older children reported an increasing sense of inadequacy and low self-esteem on self-report, presumably due to increasing awareness of differences from peers over time. Attenuated MPS II patients have increasing somatic disease burden and poor physical quality of life as they develop as well as decreasing self-esteem and sense of adequacy. Psychosocial quality of life, adaptive skills, and attention improve. Recognition of and intervention around these issues will be beneficial to MPS II attenuated patients who have the resources to use such assistance to improve their long-term outcomes.


High-speed evaluation of track-structure Monte Carlo electron transport simulations.
There are many instances where Monte Carlo simulation using the track-structure method for electron transport is necessary for the accurate analytical computation and estimation of dose and other tally data. Because of the large electron interaction cross-sections and highly anisotropic scattering behavior, the track-structure method requires an enormous amount of computation time. For microdosimetry, radiation biology and other applications involving small site and tally sizes, low electron energies or high-Z/low-Z material interfaces where the track-structure method is preferred, a computational device called a field-programmable gate array (FPGA) is capable of executing track-structure Monte Carlo electron-transport simulations as fast as or faster than a standard computer can complete an identical simulation using the condensed history (CH) technique. In this paper, data from FPGA-based track-structure electron-transport computations are presented for five test cases, from simple slab-style geometries to radiation biology applications involving electrons incident on endosteal bone surface cells. For the most complex test case presented, an FPGA is capable of evaluating track-structure electron-transport problems more than 500 times faster than a standard computer can perform the same track-structure simulation and with comparable accuracy.


Optimization of Proprioceptive Stimulation Frequency and Movement Range for fMRI.
For vision, audition and tactile sense, the optimal stimulus frequency for fMRI is somewhat known. For proprioception, i.e., the "movement sense", however, the optimal frequency is unknown. We studied the effect of passive-finger-movement frequency on proprioceptive fMRI responses using a novel pneumatic-movement actuator. Eleven healthy right-handed volunteers participated in the study. The movement actuator passively moved the participant's right index finger at frequencies of 0.3, 1, 3, 6, 9, or 12 Hz in a blocked design. A functional localizer was used to define regions-of-interest in SI and SII cortices. In addition, effect of movement range on the fMRI responses was tested in a separate session with 1, 3, 5, and 7 mm movement ranges at a fixed 2 Hz frequency. In primary somatosensory (SI) cortex, the responses were stronger at 3 Hz than at 0.3 Hz (p < 0.001) or 1 Hz (p < 0.05), and at ≥6 Hz than 0.3 Hz (p < 0.001 for frequencies ≥ 6 Hz). In secondary somatosensory (SII) cortex, all movements, except at 0.3 Hz, elicited significant responses of similar strength. In addition, 6, 9, and 12-Hz movements elicited a significant offset response in both SI and SII cortices (p < 0.001-0.05). SI cortex required a total stimulation duration of 4 min to elicit significant activations at the group-level whereas for SII cortex 1 min 20 s was sufficient. Increase in the movement range led to stronger responses in SI cortex, but not in SII cortex. Movements above 3 Hz elicited the strongest SI cortex responses, and increase in the movement range enhanced the response strength. We thus recommend that movements at 3-6 Hz with a movement range of 5 mm or higher to be used in future studies of proprioception. Our results are in-line with previous fMRI and PET studies using tactile or median nerve stimulation at different stimulation frequencies.


PEGylated Amphiphilic Gd-DOTA Backboned-Bound Branched Polymers as Magnetic Resonance Imaging Contrast Agents.
MRI contrast agents with high kinetic stability and relaxivity are the key objectives in the field. We previously reported that Gd-DOTA backboned-bound branched polymers possess high kinetic stability and significantly increased T1 relaxivity than traditional branched polymer contrast agents. In this work, non-PEGylated and PEGylated amphiphilic Gd-DOTA backboned-bound branched polymers [P(GdDOTA-C6), P(GdDOTA-C10), mPEG-P(GdDOTA-C6), and mPEG-P(GdDOTA-C10)] were obtained by sequential introduction of rigid carbon chains (1,6-hexamethylenediamine or 1,10-diaminodecane) and mPEG into the structure of Gd-DOTA backboned-bound branched polymers. It is found that the introduction of both rigid carbon chains, especially the longer one, and mPEG can increase the kinetic stability and T1 relaxivity of Gd-DOTA backboned-bound branched polymers. Among them, mPEG-P(GdDOTA-C10) possesses the highest kinetic stability (significantly higher than those of linear Gd-DTPA and cyclic Gd-DOTA-butrol) and T1 relaxivity (42.9 mM-1 s-1, 1.5 T), 11 times that of Gd-DOTA and 1.4 times that of previously reported Gd-DOTA backboned-bound branched polymers. In addition, mPEG-P(GdDOTA-C10) showed excellent MRA effect in cardiovascular and hepatic vessels at a dose (0.025 or 0.05 mmol Gd/kg BW) far below the clinical range (0.1-0.3 mmol Gd/kg BW). Overall, effective branched-polymer-based contrast agents can be obtained by a strategy in which rigid carbon chains and PEG were introduced into the structure of Gd-DOTA backbone-bound branched polymers, resulting in excellent kinetic stability and enhanced T1 relaxivity.


A High-Quality Biobank Supports Breast Cancer Research in Harbin, China.
We established a standard breast cancer biobank at Harbin Medical University Cancer Hospital (HMUCH) in 2009. More than 100,000 biospecimens, including high-quality human breast cancer samples, matched blood samples, and adjacent normal tissues, were collected from patients and healthy donors in HMUCH and were then deposited in the repository. We reported the establishment of a biobank in our hospital and its crucial role in translational medicine research. We stored, processed, and distributed qualified biological specimens in accordance with international standard operating procedures. We also summarized the utilization of this biobank and its influence on research projects over the years since its establishment. Therefore, we can verify specific biomarkers that may aid in the development of targeted breast cancer therapies by using high-quality, well-annotated tissue samples provided by the biobank.


Clinical and Psychosocial Factors Considered When Deciding Whether to Offer Deep Brain Stimulation for Childhood Dystonia.
Childhood dystonia is often nonresponsive to medications, and refractory cases are increasingly being treated with deep brain stimulation (DBS). However, many have noted that there is little consensus about when DBS should be offered, and there has been little examination of clinicians' decision-making process when determining whether to offer DBS for childhood dystonia. This study aimed to identify and examine the factors considered by pediatric movement disorder specialists before offering DBS. Semistructured interviews (N = 29) with pediatric dystonia clinicians were conducted, transcribed, and coded. Using thematic content analysis, nine central themes were identified when clinicians were asked about key factors, clinical factors, and psychosocial factors considered before offering pediatric DBS. Clinicians identified nine main factors. Five of these were classified primarily as clinical factors: early intervention and younger age (raised by 86% of respondents), disease progression and symptom severity (83%), etiology and genetic status (79%), clinicians' perceived risks and benefits of DBS for the patient (79%), and exhaustion of other treatment options (55%). The remaining four were classified primarily as psychosocial factors: social and family support (raised by 97% of respondents), patient and caregiver expectations about outcomes and understanding of DBS treatment (90%), impact of dystonia on quality of life (69%), and financial resources and access to care (31%). Candidacy determinations, in this context, are complicated by an interrelation of clinical and psychosocial factors that contribute to the decision. There is potential for bias when considering family support and quality of life. Uncertainty of outcomes related to the etiology of dystonia makes candidacy judgments challenging. More systematic examination of the characteristics and criteria used to identify pediatric patients with dystonia who can significantly benefit from DBS is necessary to develop clear guidelines and promote the well-being of these children.


Boric acid inhibits embryonic histone deacetylases: a suggested mechanism to explain boric acid-related teratogenicity.
Histone deacetylases (HDAC) control gene expression by changing histonic as well as non histonic protein conformation. HDAC inhibitors (HDACi) are considered to be among the most promising drugs for epigenetic treatment for cancer. Recently a strict relationship between histone hyperacetylation in specific tissues of mouse embryos exposed to two HDACi (valproic acid and trichostatin A) and specific axial skeleton malformations has been demonstrated. The aim of this study is to verify if boric acid (BA), that induces in rodents malformations similar to those valproic acid and trichostatin A-related, acts through similar mechanisms: HDAC inhibition and histone hyperacetylation. Pregnant mice were treated intraperitoneally with a teratogenic dose of BA (1000 mg/kg, day 8 of gestation). Western blot analysis and immunostaining were performed with anti hyperacetylated histone 4 (H4) antibody on embryos explanted 1, 3 or 4 h after treatment and revealed H4 hyperacetylation at the level of somites. HDAC enzyme assay was performed on embryonic nuclear extracts. A significant HDAC inhibition activity (compatible with a mixed type partial inhibition mechanism) was evident with BA. Kinetic analyses indicate that BA modifies substrate affinity by a factor alpha=0.51 and maximum velocity by a factor beta=0.70. This work provides the first evidence for HDAC inhibition by BA and suggests such a molecular mechanism for the induction of BA-related malformations.


Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis.
The tissue inhibitor of metalloproteinases-2 (TIMP-2) has at least two independent functions, i.e., regulation of matrix metalloproteinases and growth promoting activity. We investigated the effects of TIMP-2 overexpression, induced by retroviral mediated gene transfer, on the in vivo development of mammary tumors in syngeneic mice inoculated with EF43.fgf-4 cells. The EF43.fgf-4 cells established by stably infecting the normal mouse mammary EF43 cells with a retroviral expression vector for the fgf-4 oncogene, are highly tumorigenic and overproduce vascular endothelial growth factor (VEGF). Despite a promotion of the in vitro growth rate of EF43.fgf-4 cells overexpressing timp-2, the in vivo tumor growth was delayed. At day 17 post-cell injection, the volume of tumor derived from TIMP-2-overexpressing cells was reduced by 80% as compared with that obtained with control cells. Overexpression of TIMP-2 was associated with a down-regulation of VEGF expression in vitro and in vivo, a reduction of vessel size, density, and blood supply in the induced tumors. In addition, TIMP-2 completely inhibited the angiogenic activity of EF43.fgf-4 cell-conditioned medium in vitro using a rat aortic ring model. Our findings suggest that overexpression of TIMP-2 delays growth and angiogenesis of mammary carcinoma in vivo and that down-regulation of VEGF expression may play an important role in this TIMP-2-mediated antitumoral and antiangiogenic effects. Finally the in vivo delivery of TIMP-2, as assessed by i.v. injection of recombinant adenoviruses vectors, significantly reduced the growth of the EF43.fgf-4-induced tumors. This effect of TIMP-2 was shown to be equally comparable with that of angiostatin, a known potent inhibitor of angiogenesis.


Heterobifunctional Cross-Linker with Dinitroimidazole and N-Hydroxysuccinimide Ester Motifs for Protein Functionalization and Cysteine-Lysine Peptide Stapling.
A heterobifunctional cross-linker with one sulfhydryl-reactive dinitroimidazole end and another amine-reactive N-hydroxysuccinimide (NHS) ester end was designed and synthesized. The two motifs of this cross-linker, dinitroimidazole and NHS ester, proved to react with thiol and amine, respectively, in an orthogonal way. The cross-linker was further applied to construct stapled peptides of different sizes and mono- and dual functionalization (including biotinylation, PEGylation, and fluorescence labeling) of protein.


Do horses suffer from irritable bowel syndrome?
Irritable bowel syndrome (IBS) in man is not a single entity but has several causes. One of the most common forms has similarities with colic and laminitis in horses. Undigested food residues may pass from the small intestine into the colon where bacterial fermentation produces chemicals that lead to disease. In horses the consequences may be disastrous, but in healthy humans such malabsorption may not be harmful. After events such as bacterial gastroenteritis or antibiotic treatment, an imbalance of the colonic microflora with overgrowth of facultative anaerobes may arise, leading to malfermentation and IBS. It is not known whether such subtle changes may likewise be present in the microflora of horses who are susceptible to colic and laminitis. Metabolomic studies of urine and faeces may provide a suitable way forward to identify such changes in the horse's gut and thus help to identify more accurately those at risk and to provide opportunities for the development of improved treatment.


Allometric versus consensus guideline dosing in achieving target vancomycin trough concentrations.
Results of a study comparing the performance of allometric versus consensus guideline-recommended vancomycin dosing in achieving initial trough concentrations within the desired range are reported. A retrospective study was conducted to compare selected outcomes with 2 vancomycin dosing methods: (1) dosing by total body weight, as recommended in current consensus guidelines, and (2) a new empirical vancomycin dosing strategy grounded in allometry (the study of the relationship between body size and physiology). The primary outcome was attainment of an initial vancomycin trough concentration within the target range (10-20 mg/L). Rates of nephrotoxicity associated with the 2 dosing methods were compared. Allometric dosing resulted in 77% of the evaluated patient sample (n = 81) achieving vancomycin trough concentration targets at the initial measurement, as compared with a target attainment rate of 57% (n = 81) with guideline-recommended dosing (p = 0.0121); the rate of target attainment in obese patients was also improved with allometric dosing (73% versus 46%, p = 0.0327). Nephrotoxicity rates did not differ significantly between the 2 groups, but a lower rate was observed with allometric versus guideline-based dosing (1.2% versus 7.4%, p = 0.0584). In hospitalized adults, allometric vancomycin dosing achieved a higher frequency of initial vancomycin trough concentrations within the target range of 10-20 mg/L, compared with dosing as recommended by consensus guidelines. The difference between methods in the percentage of troughs within the target range was most pronounced in obese patients.


How many founders, how large a population?
The number of population founders and the size of the population are two important variables in determining how much gene diversity can be retained in a population. A model is developed to determine the most cost-effective balance of those two variables, based on comparing the marginal costs of increasing the number of founders vs. increasing the population size. Marginal costs, in this case, are the costs of increasing the number of founders or the population size by one animal. For a goal of retaining 90% gene diversity for 10-15 generations (approximately 100 years), the current recommendation of 20 effective founders is very close to the least-cost solution when the ratio of the marginal costs is equal to one. However, when the ratio is greater or less than one that number can change considerably.


A simple, efficient and economical method for isolating and culturing human umbilical cord blood‑derived mesenchymal stromal cells.
Mesenchymal stromal cells (MSCs) hold broad therapeutic potential in various diseases, however, it is difficult to produce sufficient numbers of MSCs for clinical application, therefore, improved culture systems are required. The present study aimed to develop a novel method for isolating and culturing human umbilical cord blood‑derived mesenchymal stromal cells (hUCB‑MSCs). A sequential culture method was developed that uses two types of culture media to optimize the isolation and culture of hUCB‑MSCs. First, DMEM supplemented with mesenchymal stem cell growth supplement was used to improve the colony formation and primary culture success rates of hUCB‑MSCs. Then, after removing the heterogeneous cell population, ordinary DMEM was used from the fourth passage. This method obtained hUCB‑MSCs with high culture efficiency and at a greatly reduced cost. The optimal culture conditions were determined and the hUCB‑MSCs were phenotypically characterized after passaging. Taken together, this simple, efficient and economical method can produce a large number of high‑quality hUCB‑MSCs in <1 month, therefore facilitating the future clinical applications of hUCB‑MSCs.


Flavonoid Naringenin Alleviates Short-Term Osmotic and Salinity Stresses Through Regulating Photosynthetic Machinery and Chloroplastic Antioxidant Metabolism in Phaseolus vulgaris.
The current study was conducted to demonstrate the possible roles of exogenously applied flavonoid naringenin (Nar) on the efficiency of PSII photochemistry and the responses of chloroplastic antioxidant of salt and osmotic-stressed Phaseolus vulgaris (cv. Yunus90). For this aim, plants were grown in a hydroponic culture and were treated with Nar (0.1 mM and 0.4 mM) alone or in a combination with salt (100 mM NaCl) and/or osmotic (10% Polyethylene glycol, -0.54 MPa). Both caused a reduction in water content (RWC), osmotic potential (ΨΠ), chlorophyll fluorescence (Fv/Fm), and potential photochemical efficiency (Fv/Fo). Nar reversed the changes on these parameters. The phenomenological fluxes (TRo/CS and ETo/CS) altered by stress were induced by Nar and Nar led to a notable increase in the performance index (PIABS) and the capacity of light reaction [ΦPo/(1-ΦPo)]. Besides, Nar-applied plants exhibited higher specific fluxes values [ABS/RC, ETo/RC, and ΨEo/(1-ΨEo)] and decreasing controlled dissipation of energy (DIo/CSo and DIo/RC). The transcripts levels of psbA and psbD were lowered in stress-treated bean but upregulated in Nar-treated plants after stress exposure. Nar also alleviated the changes on gas exchange parameters [carbon assimilation rate (A), stomatal conductance (gs), intercellular CO2 concentrations (Ci), transpiration rate (E), and stomatal limitation (Ls)]. By regulating the antioxidant metabolism of the isolated chloroplasts, Nar was able to control the toxic levels of hydrogen peroxide (H2O2) and TBARS (lipid peroxidation) produced by stresses. Chloroplastic superoxide dismutase (SOD) activity reduced by stresses was increased by Nar. In response to NaCl, Nar increased the activities of ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR), as well as peroxidase (POX). Nar protected the bean chloroplasts by minimizing disturbances caused by NaCl exposure via the ascorbate (AsA) and glutathione (GSH) redox-based systems. Under Nar plus PEG, Nar maintained the AsA regeneration by the induction of MDHAR and DHAR, but not GSH recycling by virtue of no induction in GR activity and the reduction in GSH/GSSG and GSH redox state. Based on these advances, Nar protected in bean chloroplasts by minimizing disturbances caused by NaCl or PEG exposure via the AsA or GSH redox-based systems and POX activity.


Foreign body reactions, marginal bone loss and allergies in relation to titanium implants.
To describe general observations of immunological reactions to foreign materials and to realize that CP titanium gives rise to a foreign body reaction with subsequent bone embedment when placed as oral implants. To analyse the possibility of titanium allergy. The present paper is of a narrative review type. Hand and Medline searches were performed to evaluate marginal bone loss of oral implants and the potential of titanium allergy. Immunological reactions to foreign substances include Type I hypersensitivity reactions such as allergy, Type II hypersensitivity reactions characterised by IgM or IgG antibodies that may react with blood group antigens at transfusion, and Type III hypersensitivity caused by antigen-antibody immune complexes exemplified by acute serum sickness. There is also Type IV hypersensitivity, or delayed hypersensitivity, which is typically found in drug and foreign body reactions. It proved very difficult to find a universally acceptable definition of reasons for marginal bone loss around oral implants, which lead to most varying figures of so-called peri-implantitis being 1% to 2% in some 10-year follow-up papers to between 28% and 56% of all placed implants in other papers. It was recognised that bone resorption to oral as well as orthopaedic implants may be due to immunological reactions. Today, osseointegration is seen as an immune-modulated inflammatory process where the immune system is locally either up- or downregulated. Titanium implant allergy is a rare condition, if it exists. The authors found only two papers presenting strong evidence of allergy to CP titanium, but with the lack of universally accepted and tested patch tests, the precise diagnosis is difficult. CP titanium acts as a foreign body when placed in live tissues. There may be immunological reasons behind marginal bone loss. Titanium allergy may exist in rare cases, but there is a lack of properly designed and analysed patch tests at present.


Pronounced benefit of coronary stenting and adjunctive platelet glycoprotein IIb/IIIa inhibition in complex atherosclerotic lesions.
Previous trials testing stents compared with balloon angioplasty excluded patients with complex lesions and did not assess the effect of adjunctive platelet IIb/IIIa inhibition. This analysis sought to assess the effect of stenting and abciximab specifically for patients with complex lesions. Patients with complex lesions (long, tandem, severely calcified, restenotic, thrombotic, or ostial; total occlusions; bifurcations; saphenous vein grafts; and multivessel interventions) from the Evaluation of PTCA to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials were included in the analysis. The 1-year combined death or myocardial infarction rates in the 4 treatment groups were as follows: balloon angioplasty/placebo, 14.2%; stent/placebo, 15.8%; balloon angioplasty/abciximab, 7.6%; and stent/abciximab, 8.0% (P<0.001). Death rates were 3.2%, 3.1%, 2.1%, and 0.5%, respectively (P=0.03). The incidence of target vessel revascularization at 1 year was 30.5%, 18.0%, 24.4%, and 19.7% in the 4 groups, respectively (P<0.001). After adjustment for baseline differences, multivariate analysis demonstrated that the rate of death or myocardial infarction was independently reduced by balloon angioplasty/abciximab (hazard ratio, 0.51; P<0.001) and stent/abciximab (hazard ratio, 0.60; P=0.02) but was not affected by the use of stents alone. Conversely, target vessel revascularization was reduced by stent/placebo (hazard ratio, 0.53; P<0.001), stent/abciximab (hazard ratio, 0.58; P<0.001), and balloon angioplasty/abciximab (hazard ratio, 0.74; P=0.006) compared with balloon angioplasty/placebo, respectively. The combination of stenting and abciximab during percutaneous coronary interventions for patients with angiographically complex lesions confers additive long-term benefit with respect to death, myocardial infarction, and target vessel revascularization.


Robot Assisted Surgery of the Vena Cava: Perioperative Outcomes, Technique, and Lessons Learned at The Mayo Clinic.
Introduction: This study aims to describe robot assisted surgery of the inferior vena cava (IVC) by assessing techniques utilized, perioperative outcomes, complications, and long-term patency of the IVC. Methods: A retrospective review was performed on all robotic surgeries involving dissection and repair of the IVC at our institution. Patient characteristics, operative reports, and follow-up visits were analyzed. Preoperative and postoperative imaging was independently reviewed by a single radiologist to determine changes in IVC diameter. Complications were analyzed according to early (<30 days) vs late (>30 days). Results: Thirty-four patients underwent robot assisted surgery of the vena cava from 2008 to 2018. Twenty-six cases were performed for urologic malignancy, four were performed for IVC filter explantation, and four renal vein transpositions were performed for nutcracker syndrome. Twenty-four of the 26 patients with urologic malignancy underwent radical nephrectomy with IVC tumor thrombectomy. Three cases were converted to open. Median length of stay was two nights, and mean estimated blood loss (EBL) was 375 mL. There were five complications, ranging from Clavien-Dindo grade II-IIIa, four of which were early complications. No patients required return to the operating room, and there were no perioperative mortalities. IVC diameter was reduced by 41% on axial diameter, with no patients experiencing compromised venous return. Conclusion: Robot assisted surgery offers the advantage of minimally invasive surgery with the ability to apply open surgical principles. In our series, an experienced multidisciplinary team approach yielded low EBL, short length of stay, and low complication rates.


her11 is involved in the somitogenesis clock in zebrafish.
Somitogenesis requires an intricate process of pre-patterning, which is driven by an oscillator mechanism consisting of the Delta-Notch pathway and hairy- (h) and Enhancer of split- [E(spl)] related genes. With the aim of unravelling the complex mechanism of somite pre-patterning, we have conducted an extensive search for h/E(spl)-related genes in the third release of the Danio rerio genomic sequence. We identified 14 new h/E(spl) genes and analysed them by in situ hybridisation for their potential role in the somitogenesis process. We describe here the functional analysis of one of these genes, which we have named her11. her11 is a paralogue of her1 and, similar to her1, is arranged in a head to head fashion with another her gene, namely the previously described her5. It shares an expression in the midbrain-hindbrain boundary with her5, but is in addition cyclically expressed in patterns overlapping those of her1 and her7 and complementary to those of hey1. Furthermore it is expressed in the anterior half of the most caudally formed somites. We show that Delta-Notch pathway genes and fused somites ( fss) are necessary for the control of her11 expression. However, some aspects of the her11 regulation suggest that at least one additional as yet unknown gene of the Delta-Notch cascade is required to explain its expression. Morpholino-oligonucleotide-mediated knockdown of her11 shows that it is involved in the zebrafish somitogenesis clock via an interaction with her1 and her7. We have also studied the role of hey1 by morpholino injection, but could not find a direct function for this gene, suggesting that it reflects the output of the clock rather than being a core component of the mechanism.