Trastuzumab deruxtecan versus trastuzumab emtansine for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: A cost-effectiveness analysis.
DESTINY-Breast03 (NCT03529110) was the first global phase III study to assess the antitumor activity of trastuzumab deruxtecan (T-DXd) compared to trastuzumab emtansine (T-DM1) in 2022. However, the balance between efficacy and cost of T-DXd remains unclear. As a result, the present study's goal is to investigate the cost-effectiveness of T-DXd vs T-DM1 as a second-line treatment for patients with HER2-positive MBC from the US and Chinese payer's perspectives. A Markov model with a 20-year time horizon was developed to evaluate the overall cost of patient treatment, incremental cost-effectiveness ratio (ICER), quality-adjusted life-years (QALYs), and life-years (LYs) in the US and China at WTP levels of 150,000/QALY and 37,653/QALY, respectively (3 times GDP per capita in 2021). Key data were gathered from the US government's official website, the Xiangya Hospital of Central South University, and published literature. To determine the model's stability, a sensitivity analysis was performed. A subgroup analysis was also implemented. Compared with T-DM1, treatment with T-DXd generated an additional 1.672 QALYs (2.796 LYs), resulting in an ICER of $13,342/QALY (US) and $186,017/QALY (China). The cost of drugs is the most influential factor in the American and Chinese models. Subgroup analysis revealed that the T-DXd and T-DM1 regimens were more cost-effective at reducing the risk of death in the US and Chinese HER2-positive MBC patients. T-DXd as second-line treatment could gain more health benefits for HER2-positive MBC patients in comparison with T-DM1, which is considered to be cost-effective in the US but not in China.


Phase II study of perifosine in previously untreated patients with metastatic melanoma.
To assess the response rate and toxicity of the alkylphosphocholine analogue, perifosine, in patients with metastatic or recurrent malignant melanoma. Patients had histologically proven, unidimensionally measurable disease which was incurable by standard therapy. Prior adjuvant immunotherapy was allowed but patients had not received prior chemotherapy. Perisfosine was given orally as a loading dose of 900 mg on day 1 followed by a maintenance dose of 150 mg po on days 2-21 in a 28 day cycle. The loading dose was 300 mg on day 1 of all subsequent cycles. Tumour response was assessed every 2 cycles. 18 patients were accrued over 7 mos. No objective responses occurred in the 14 evaluable patients. Three patients (21%) achieved stable disease after 2 cycles and 11 had progression. Seventeen patients were evaluable for toxicity. Grade 3 or 4 non-hematologic toxicities included: diarrhea (12%), arthralgia (12%), nausea (6%), headache (6%), and fatigue (6%). No grade 3 or 4 hematological or biochemical toxicity were observed. Seventy-seven percent of patients received >or=90% of planned cycle 1 dose intensity and 58% received >or=90% of planned dose for cycle 2+. Four patients required dose reductions; treatment was delayed in 5 patients; and 5 patients missed doses because of toxicity. Perifosine can be safely administered when given as an initial loading dose followed by daily maintenance therapy over 28 days. Gastrointestinal toxicity is common but generally of low grade. Hematological toxicity is minimal. No objective responses were observed. No further development of single-agent perifosine is recommended in malignant melanoma.


Predictors of long-term adverse outcomes after successful chronic total occlusion intervention: physiology or morphology?
Quantitative flow ratio (QFR) and target-vessel SYNTAX score (tvSS) are novel indices used to assess lesion physiology and morphology in percutaneous coronary intervention (PCI). Their prognostic implication after successful recanalization of coronary chronic total occlusion (CTO) is unknown. To investigate the prognostic value of QFR measured immediately after successful CTO-recanalization in predicting vessel-oriented adverse events, and to compare it with the pre-procedural morphological tvSS. QFR was measured offline after successful CTO-PCIs in a single center. We grouped the patients according to a cut-off value of post-PCI QFR (0.91). The primary outcome was target-vessel failure (TVF) at 2 years. Among 470 CTO lesions performed during the study period, 324 were eligible for QFR analysis (258 with QFR ≥ 0.91 and 66 with QFR < 0.91). The mean age of the study population was 68.3 ± 10.7 years. The low QFR group had a lower left ventricular ejection fraction (45.8 ± 13.9% vs. 49.8 ± 12.4%, p = 0.025) and a higher rate of atrial fibrillation (19.7% vs. 11.2%, p = 0.020). The mean tvSS was 12.8 ± 4.8, and it showed no significant difference in both groups (13.6 ± 5.1 vs. 12.6 ± 4.6, p = 0.122). Patients with low post-CTO QFR had a trend to develop more TVF at 2 years (21.2% vs. 12.4%, HR 1.74; 95% CI 0.93-3.25, p = 0.086). Low post-CTO QFR failed to predict 2-year TVF (aHR 1.67; 95% CI 0.85-3.29, p = 0.136), while pre-procedural tvSS was an independent predictor for 2-year TVF (aHR 1.06; 95% CI 1.01-1.13, p = 0.030). We found a limited prognostic value of immediate physiological assessment using QFR after successful CTO intervention. Pre-procedure morphological characteristics of CTO lesions using tvSS can play a role in predicting long-term adverse events.


A retropharyngeal multinodular goiter: A case report and literature review.
Thyroid goiter is a benign chronic enlargement of the thyroid gland, which presents as a painless anterior neck mass with occasional extension to the mediastinum. Retropharyngeal goiter is a rare presentation and hardly reported in the literature. A 70-year-old male presented with a multinodular goiter with a large retropharyngeal component. Physical examination of the head and neck revealed a massive anterior neck mass. Laryngeal endoscopy with a 70-degree rigid endoscope demonstrated a large retropharyngeal mass completely obstructing the view of the larynx. Computed tomography (CT) scan revealed a large multinodular goiter with suprahyoid and retrosternal extension, resulting in displacement of the trachea. The mass was excised completely under general anesthesia and intubation was done under fiberoptic bronchoscopy guidance. The mass was sent for histological analysis, which confirmed the diagnosis of Hashimoto thyroiditis. Eventually, upon follow-up at three months post excision, no evidence of recurrence was detected.


A possible missense mutation detected in the dystrophin gene by Double-Strand Conformation Analysis (DSCA).
A new and simple method for detecting point mutations is presented. The method, based on Double-Strand Conformation Analysis (DSCA) of PCR amplification products in polyacrylamide gel electrophoresis, was applied to 78 unrelated subjects affected with Duchenne or Becker muscular dystrophy and to 9 subjects suspected to be affected with an atypical dystrophinopathy. An A-->G substitution in the nucleotide 2525, which changes the codon for lysine to a codon for glutamic acid was detected in an 8-year-old boy, with normal neurological examination, but showing increased CK level and an abnormal EMG. The muscle biopsy was normal, without features of necrosis or regeneration. Immunoreactions with anti-dystrophin antibodies showed a normal distribution and intensity of the staining. A review of the dystrophin mutations detected so far is included.


[Diagnosis and treatment of cardiospasm].
The treatment by means of bloodless dilatation was carried out upon 82 cases of cardiospasm. Good results were achieved in 80 cases the results were satisfactory. An improved method of cardiodilatation is described.


Enantioselective toxic effects of cyproconazole enantiomers against Chlorella pyrenoidosa.
Enantioselectivity in ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to Chlorella pyrenoidosa was studied. The 96h-EC50 values of rac- and the four enantiomers were 9.005, 6.616, 8.311, 4.290 and 9.410 mg/L, respectively. At the concentrations of 8 mg/L and 14 mg/L, the contents of pigments exposed in rac-, enantiomer-2 and 4 were higher than that exposed in enantiomer-1 and 3. The superoxide dismutase (SOD) and catalase (CAT) activity of algae exposed to enantiomer-1 and 3 was higher than that exposed to the rac-, enantiomer-2 and 4 at three levels. In addition, the malondialdehyde (MDA) concentrations in algae disposed with enantiomer-1 and 3 were increased remarkably at three levels. For the digestion experiment, the half-lives of four enantiomers in algae suspension were 28.06, 19.10, 21.13, 15.17 days, respectively. During the uptake experiment, the order of the concentrations of cyproconazole in algae cells was enantiomer-4, 2, 3 and 1. Based on these data, we concluded that ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to C. pyrenoidosa were enantioselective, and such enantiomeric differences must be taken into consideration when assessing the risk of cyproconazole to environment.


Geographic pathology of uterine cancers in Oregon: risks of double primaries and effects of socioeconomic status.
An intensive statewide study of uterine cancer incidence for the period 1968-1972 revealed that women with one histologic type of uterine cancer were much more susceptible to the simultaneous presence of a second histologic type than were the rest of the residents of the state. Squamous cell carcinoma was the most common uterine cancer; peak number and rate were found in the age group 25-29 years, indicating the need for periodic screening of young adult women and the need for discussion of neoplasia risk in adolescent sex education classes. Risks of squamous cell carcinoma and leiomyosarcoma were excessive among blacks. Socioeconomic status had a strong and consistent inverse relationship with uterine squamous cell carcinoma incidence, implying that its major risk determinant, sexual behavior, could have a similar socioeconomic pattern. Uterine adenocarcinoma incidence had a weaker but consistent direct relationship with socioeconomic status for which the cause is unknown.


Impact of Maintenance Therapy for Patients with Non-small Cell Lung Cancer in a Real-world Setting.
The purpose of this study was to explore the role of maintenance therapy for patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. This was a prospective observational cohort multicenter study. Eligible patients were observed from initiation of first-line platinum-based chemotherapy until final follow-up. Between 2010 and 2011, a total of 864 patients were enrolled in this study. The primary study population was 396 patients who had progressive disease during observation after first-line chemotherapy without maintenance. Of these, 113 patients (29%) did not receive second-line therapy. In contrast, only 18% of patients who had progressive disease during maintenance therapy missed second-line therapy. Overall survival of patients without maintenance who received second-line therapy was similar to that of those who received maintenance, but no second-line therapy. Maintenance therapy for patients with advanced NSCLC might be an appropriate strategy to maximize the chance of receiving more active therapy.


The effect of anion transport inhibitors and extracellular Cl- concentration on eosinophil respiratory burst activity.
Furosemide has been shown recently to protect asthmatic patients against certain bronchoconstrictor challenges. We investigated the effect of furosemide on eosinophil function. Since furosemide may be exerting its inhibitory effect on the eosinophil by inhibiting anion transport, we also assessed the effects of the anion transport inhibitors 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Furosemide, NPPB and DIDS inhibited the eosinophil respiratory burst in response to leukotriene B4 (LTB4) and, to a smaller extent, inhibited the response to opsonized zymosan (OZ). To assess whether the anion transport inhibitors were achieving their inhibitory effect by inhibiting an influx of Cl- ions into the eosinophil, the effect of removing extracellular Cl- on eosinophil function was determined. OZ-induced H2O2 production was inhibited by removing extracellular Cl- whereas the LTB4 response was not affected by the concentration of extracellular Cl-.


Late effects arising from volumetric modulated arc therapy to the breast: A systematic review.
Volumetric modulated arc therapy (VMAT) to the breast offers the potential for excellent dose conformity with the possibility of integrating a simultaneous boost within the treatment plan. This technique, however, also delivers a low dose to a large amount of healthy tissue. This systematic review aimed to determine if VMAT offers a clinically significant difference in late effects compared with conformal radiotherapy techniques for breast radiotherapy. A systematic review and quality appraisal of primary studies evaluating VMAT to the breast was performed, adopting the PRISMA checklist. A total of 8 studies were included in the review. These demonstrated variation in prescription, outcome measures and cohort characteristics. Findings supported the value of VMAT for reducing organ at risk (OAR) doses but also confirmed the potential secondary cancer risk arising from the low dose bath. Hybrid techniques combining VMAT with tangential intensity modulated or standard radiotherapy showed promise when tangential plans failed to meet objectives. VMAT alone does not offer any significant benefit to late effects over conventional for breast radiotherapy due to the creation of a low dose bath, despite improving OAR doses. More research into hybrid techniques is warranted to identify the most appropriate treatment for different patient subgroups and tumour locations. VMAT may not be the optimal technique for breast radiotherapy; hybrid plans combining tangential IMRT with VMAT are recommended.


Antimicrobial resistance patterns, virulence gene profiles, and genetic diversity of Salmonella enterica serotype Enteritidis isolated from patients with gastroenteritis in various Iranian cities.
This study aimed to evaluate antibiotic resistance profiles and presence of virulence genes among Salmonella enterica serovar Enteritidis (S. Enteritidis) isolated from patients with gastroenteritis in various regions of Iran. Moreover, genetic relatedness among the strains was assessed by pulsed-field gel electrophoresis (PFGE). From April through September 2017, 59 Salmonella strains were isolated from 2116 stool samples. Of these strains, 27 S. Enteritidis were recovered. These strains were subjected to disk diffusion tests, polymerase chain reaction (PCR) for detection of virulence genes (invA, hilA, pefA, rck, stn, ssrA, ssaR, sefA, spvC, sipA, sipC, sopB, sopE, and sopE2), and PFGE. High prevalence of resistance towards cefuroxime (n = 20, 74.1%) and ciprofloxacin (n = 13, 48.2%) were demonstrated. All tested strains possessed invA, hilA, sefA, sipA, sopB, and sopE. The least prevalent virulence gene was rck (n = 6; 22.2%). Based on combinations of virulence genes, 12 virulotypes were observed. The most common virulotype was VP2 (n = 12; 44.4%), harboring all of the virulence genes except for rck. PFGE typing showed only two distinct fingerprints among tested strains. Each fingerprint had completely different virulotypes. Notably, VP4 (harboring all genes except for rck and spvC) was only presented in pulsotype A, while VP2 was confined to pulsotype B. S. Enteritidis strains were derived from a limited number of clones, suggesting that it is highly homogenous. Future works should consider combinations of other genotyping methods together with larger sample sizes from more diverse sources.


Helicobacter pylori and Gastrointestinal Malignancies.
Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population dependent.


Primary extragastrointestinal stromal tumor arising in the pancreas: report of a case.
Primary extragastrointestinal stromal tumors (EGISTs) arising in the pancreas are extremely rare, with only ten cases documented to our knowledge. We report a further case of EGIST of the pancreas. The patient was a 55-year-old man who presented with postprandial abdominal discomfort. Abdominal computed tomography and magnetic resonance imaging showed a lobulated heterogenous enhancing mass, 11 cm in diameter, in the abdominal cavity. No regional lymphadenopathy, ascites, or metastasis was seen radiologically. There was no obvious lesion in the stomach or small intestine. The initial diagnosis was a solid pseudopapillary tumor or serous cystic neoplasm. The patient underwent distal pancreatectomy with splenectomy. Microscopically, the tumor consisted of spindle cells arranged in short fascicles. Mitotic figures were seen in 7/50 high-power fields. Immunohistochemical examination revealed strongly positive staining for CD117. Based on these findings, the final pathologic diagnosis was a primary EGIST of the pancreas. This case consolidates the possibility that this rare tumor can involve the pancreas as a primary site and should be included in the differential diagnosis of cystic lesions in this site.


Clinical and manometric assessment of anorectal function after Martin's operation.
Anorectal function after Martin's operation for total colonic aganglionosis was assessed in five patients by clinical and manometric studies. One year after operation the frequency of bowel movements decreased to three times a day, and the stools became semi-formed. Anorectal manometry showed decreasing anal resting pressure and anorectal pressure difference one month after the operation. However, these values became gradually normal. Rectal compliance increased as bowel function improved clinically. These results show that increasing rectal compliance and normalisation of stools by adequate absorption of intestinal fluid are important factors in the improvement of faecal continence after Martin's operation.


Binding thermodynamics at the human A(3) adenosine receptor.
The thermodynamic parameters DeltaG , DeltaH and DeltaS of the binding equilibrium of six adenosine receptor agonists and five antagonists at adenosine A(3) receptors were determined by means of affinity measurements at six different temperatures (4, 10, 15, 20, 25 and 30) and van't Hoff plots were constructed. Affinity constants were measured on Chinese hamster ovary (CHO) cells transfected with the human A(3) receptors by inhibition assays of the binding of the selective A(3) antagonist [3H]MRE 3008F20. van't Hoff plots were linear for agonists and antagonists in the temperature range 4-30 degree. Their thermodynamic parameters fall in the ranges 21 < or = DeltaH < or = 67kJmol(-1) and 208 < or = DeltaS < or =410 J(Kmol)(-1) for agonists and -52 < or = DeltaH < or = -9 kJmol(-1) and 16 < or = DeltaS < or =81 J(K/mol)(-1) for antagonists, showing that agonist binding is always totally entropy-driven while antagonist binding is enthalpy- and entropy-driven. The results are discussed with the aim of obtaining new details on the nature of the forces driving the A(3) binding at a molecular level.


Proteomic analyses of the interaction between the plant-growth promoting rhizobacterium Paenibacillus polymyxa E681 and Arabidopsis thaliana.
Plant growth-promoting rhizobacteria (PGPR) facilitate the plant growth and enhance their induced systemic resistance (ISR) against a variety of environmental stresses. In this study, we carried out integrative analyses on the proteome, transcriptome, and metabolome to investigate Arabidopsis root and shoot responses to the well-known PGPR strain Paenibacillus polymyxa (P. polymyxa) E681. Shoot fresh and root dry weights were increased, whereas root length was decreased by treatment with P. polymyxa E681. 2DE approach in conjunction with MALDI-TOF/TOF analysis revealed a total of 41 (17 spots in root, 24 spots in shoot) that were differentially expressed in response to P. polymyxa E681. Biological process- and molecular function-based bioinformatics analysis resulted in their classification into seven different protein groups. Of these, 36 proteins including amino acid metabolism, antioxidant, defense and stress response, photosynthesis, and plant hormone-related proteins were up-regulated, whereas five proteins including three carbohydrate metabolism- and one amino acid metabolism-related, and one unknown protein were down-regulated, respectively. A good correlation was observed between protein and transcript abundances for the 12 differentially expressed proteins during interactions as determined by qPCR analysis. Metabolite analysis using LC-MS/MS revealed highly increased levels of tryptophan, indole-3-acetonitrile (IAN), indole-3-acetic acid (IAA), and camalexin in the treated plants. Arabidopsis plant inoculated P. polymyxa E681 also showed resistance to Botrytis cinerea infection. Taken together these results suggest that P. polymyxa E681 may promote plant growth by induced metabolism and activation of defense-related proteins against fungal pathogen.


Synthesis and reactions of O-acetylated benzyl alpha-glycosides of 6-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-N-acetylmuramoyl-L- alanyl-D-isoglutamine esters: the base-catalysed isoglutamine in equilibrium glutamine rearrangement in peptidoglycan-related structures.
Condensation of benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2- deoxy-3-O-[(R)-1-carboxyethyl]-alpha-D-glucopyranoside (2) and its 4-acetate (4) with L-alanyl-D-isoglutamine benzyl ester via the mixed anhydride method yielded N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D- glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyranosid-3-yl]-(R)-lacto yl)-L- alanyl-D-isoglutamine benzyl ester (5) and its 4-acetate (6), respectively. Condensation by the dicyclohexylcarbodi-imide-N-hydroxysuccinimide method converted 2 into benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl- 2-deoxy-beta-D-glucopyranosyl)-3-O-[(R)-1-carboxyethyl]-2-deoxy-alpha-D- glucopyranoside 1',4-lactone (7). In the presence of activating agents, 7 underwent aminolysis with the dipeptide ester to give 5. Zemplén O-deacetylation of 5 and 6 led to transesterification and alpha----gamma transamidation of the isoglutaminyl residue to give N-(2-O-[benzyl 2-acetamido-6-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyr anosid-3- yl]-(R)-lactoyl)-L-alanyl-D-isoglutamine methyl ester (8) and -glutamine methyl ester (9). Treatment of 6 with MgO-methanol caused deacetylation at the GlcNAc residue to give a mixture of N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-2- deoxy-beta-D-glucopyranosyl)-4-O-acetyl-2,3-dideoxy-alpha-D-glucopyra nosid-3- yl]-(R)-lactoyl)-L-alanyl-D-isoglutamine methyl ester (11) and -glutamine methyl ester (12). Benzyl or methyl ester-protection of peptidoglycan-related structures is not compatible with any of the reactions requiring alkaline media. Condensation of 2 with L-alanyl-D-isoglutamine tert-butyl ester gave N-(2-O-[benzyl 2-acetamido- 6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-2,3-d ideoxy- alpha-D-glucopyranosid-3-yl]-(R)-lactoyl-L-alanyl-D-isoglutamine tert-butyl ester (16), deacetylation of which, under Zemplén conditions, proceeded without side-reactions to afford N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyranosid-3-yl]-(R)-la cotyl)-L- alanyl-D-isoglutamine tert-butyl ester (17).


Development of Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae) in different pig tissues.
Chrysomya albiceps (Wiedemann) has been encountered breeding in animal carcasses and human bodies in many geographical regions. This species is considered an important postmortem indicator for Medical Legal Forensic Entomology. Studies have also demonstrated its capacity to develop in various natural and semi-synthetic substrates. The present study was undertaken to examine the development of immature C. albiceps in four different pig tissues. Eggs of this fly were deposited in flasks containing liver, abdominal fat, meat, and brain tissues. The flasks were maintained in an incubator at 25 ± 1°C, 70 ± 10% humidity, and 12-h/12-h photoperiod until emergence of the imagoes. Samples of the larvae were taken from different tissues/substrates to be weighed and measured. Their respective rates of development were accompanied. Comparisons among data from the different tissues indicated differences in the size and rate of development of larvae of the same age. Males emerged, on average, 1 day before females. Considerations as to the differences encountered for the estimate of postmortem interval were elaborated and consequences for the accuracy of the inferences discussed. The results indicate that such inferences should consider the disparities in the development of larvae presented by this species in different tissues.


In vivo tumor formation from primate embryonic stem cells.
To achieve human embryonic stem (ES) cell-based transplantation therapies, allogeneic transplantation models of nonhuman primates would be particularly useful. In this chapter, we describe an example of this model. We prepared cynomolgus ES cells genetically marked with the green fluorescent protein. The cells were transplanted into the allogeneic fetus because the fetus is immunologically premature and does not induce immune responses to transplanted cells. In addition, fetal tissue compartments are rapidly expanding, presumably providing space for engraftment. At 3 mo posttransplantation, a fluorescent teratoma, obviously derived from transplanted ES cells, was found in the fetus. However, transplanted cell progeny were also detected (approx 1%) in multiple fetal tissues. The cells were solitary and indistinguishable from surrounding host cells as assessed by in situ polymerase chain reaction. Transplanted cynomolgus ES cells can engraft in allogeneic fetuses. The cells will, however, form a tumor if they "leak" into an improper space, such as the thoracic cavity.


Lysinibacillus macroides-mediated control of cellulose-producing morphotype of Salmonella.
Soil-dwelling human pathogens like Salmonella are transmitted by fresh produce such as tomato, spinach, onion and cabbage. With >2600 serovars, it is difficult to classify the good plant colonizers from the non-colonizers. Generally, soil microbiota are classified as autochthonous or zymogenous organisms, based on their ability to survive in soil. However, such information for soil-dwelling human pathogens is not available Thus there is a need to classify these organisms for designing a strategy to prevent their outbreak. Moreover, soil harbours a plethora of microbes, which can be screened for competitive organisms to control such human pathogens. In this study, we examined whether the morphotype based on the attachment factors (e.g., cellulose and curli fimbri) of Salmonella was important for its colonization of roots. Secondly, we tracked the location of the bacteria in the plant cell. Interestingly, most of the epidermal cells occupied by Salmonella showed propidium iodide-positive nuclei. As an extension of the study, a screening of competitive rhizospheric bacteria was performed. One isolate, identified as Lysinibacillus macroides, was able to inhibit the biofilm of Salmonella and subsequently reduced its colonization on roots. Based on this study, we classified the Rdar (red, dry and rough) morphotypes as good plant colonists. The ability to colonize and subsequent kill the live plant cell throws light on the zymogenous life cycle of soil-dwelling Salmonella. Additionally, Lysinibacillus macroides served as a biocontrol agent by reducing the burden of Salmonella in various vegetables. Such organisms can further be explored to prevent contamination of the food chain. © 2022 Society of Chemical Industry.


Leveraging the timing and frequency of patient decision aids in longitudinal shared decision-making: A narrative review and applied model.
Shared decision-making (SDM) is intended to increase patient-centredness of medical decision-making for patients with acute and chronic conditions. Concurrently, patient decision aids (PtDAs) can supplement SDM by providing information to guide communication between patients and healthcare providers. Because of the prevalence of chronic conditions, where decisions may be extended or recurring, we sought to explore how effectively these tools have been leveraged in this context. We conducted a narrative review of the literature on both SDM and PtDAs, searching PubMed and Boston University's library database search tool for English-language articles published from January 2005 until March 2021. Additional search terms focused on temporality. Drawing from our findings, we developed a combined framework to highlight areas for future research using the discussion of end-of-life decisions as an exemplar to illustrate its relevance to chronic care contexts. After screening 57 articles, we identified 25 articles that fulfilled the inclusion criteria on SDM, PtDA use and temporality for chronic care. The literature on SDM highlighted time outside of the medical visit and opportunity to include outside decision partners as important elements of the process. PtDAs were commonly evaluated for process-related and proximal outcomes, but less often for distal outcomes. Early evidence points to the value of comparative outcome evaluation based on the timing of PtDA distribution. Our review of the literature on SDM and PtDAs reveals less attention to the timing of PtDAs relative to that of SDM. We highlight the need for further study of timing in PtDA use to improve longitudinal SDM for chronic care. The model that we propose in our discussion provides a starting point for future research on PtDA efficacy. Five patient consultants provided input and feedback on the development and utility of our model.


Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds.
Naturally occurring methylxanthines were the first inhibitors of cyclic nucleotide (cN) phosphodiesterases (PDEs) to be discovered. To improve potency and specificity for inhibition of various PDEs in research and for treatment of diseases, thousands of compounds with related structures have now been synthesized. All known PDE inhibitors contain one or more rings that mimic the purine in the cN substrate and directly compete with cN for access to the catalytic site; this review focuses on inhibitors that contain a nucleus that is closely related to the xanthine ring of theophylline and caffeine and the purine ring of cNs. The specificity and potency of these compounds for blocking PDE action have been improved by appending groups at positions on the rings as well as by modification of the number and distribution of nitrogens and carbons in those rings. Several of these inhibitors are highly selective for particular PDEs; potent and largely selective PDE5 inhibitors are used clinically for treatment of erectile dysfunction [sildenafil (Viagra™), tadalafil (Cialis™) and vardenafil (Levitra™)] and pulmonary hypertension [sildenafil (Revatio™) and tadalafil (Adenocirca)]. Related compounds target other PDEs and show therapeutic promise for a number of maladies.


Coexistence of Type-1 Diabetes Mellitus and Papillary Thyroid Carcinoma.
İntroduction: Type 1 diabetes mellitus (DM) is characterized by selective autoimmune destruction of pancreatic b-cells, resulting in insulin deficiency and associated autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and gastritis, which can coexist in patients with type 1 DM. These disorders are characterized by the presence of antibodies against tissue transglutaminase, thyroglobulin, and thyroid peroxidase (TPO), as well as against gastric parietal cells. Cross-sectional studies have reported that the risk of autoimmune thyroid diseases in patients with type-1 DM is two- to threefold higher than in the general population. However, there are a few studies in the literature that investigated the relationship between malignancy and type-1 DM, and it has been shown that type-1 DM does not increase thyroid cancer. Furthermore, there is a lot of controversy regarding the role of thyroid autoimmunity in the pathogenesis of thyroid cancer. Here, a type-1 DM patient diagnosed with papillary thyroid cancer is presented. Case Report: Herein, it was aimed to present a 20-year-old female patient diagnosed with type-1 DM and subsequently with papillary thyroid carcinoma (PTC). Thyroid ultrasound revealed a 10×12×18 mm hypoechoic irregular edges nodule with macrocalcification and microcalcification foci in the left lobe and pathological lymph nodes without echogenic hilus were detected at the fourth level of the left cervical chain. Fine needle aspiration biopsy of the nodule was consistent with papillary thyroid carcinoma. Total thyroidectomy, bilateral central lymph node dissection, and left neck dissection (level II to IV) were performed. Pathological examination revealed a 1.4× 0.9 cm diameter papillary carcinoma located in the left lobe of the thyroid gland with 13 lymph node metastases. Conclusion: Patients with type 1 DM should be examined for thyroid diseases, and patients with suspected thyroid disease should be evaluated with a thyroid ultrasound. Type 1 DM and PTC can coexist, albeit very rare. It should be known that type 1 diabetes can be observed together with thyroid cancer.


botXminer: mining biomedical literature with a new web-based application.
This paper outlines botXminer, a publicly available application to search XML-formatted MEDLINE data in a complete, object-relational schema implemented in Oracle XML DB. An advantage offered by botXminer is that it can generate quantitative results with certain queries that are not feasible through the Entrez-PubMed interface. After retrieving citations associated with user-supplied search terms, MEDLINE fields (title, abstract, journal, MeSH and chemical) and terms (MeSH qualifiers and descriptors, keywords, author, gene symbol and chemical), these citations are grouped and displayed as tabulated or graphic results. This work represents an extension of previous research for integrating these citations with relational systems. botXminer has a user-friendly, intuitive interface that can be freely accessed at http://botdb.abcc.ncifcrf.gov.


Nutritionally induced adipose hypertrophy in young pigs is transient and independent of changes in the expression of the obese and peroxisome proliferator activated receptor genes.
Previous studies have shown that piglets weaned to a liquid milk replacer (MR), rather than a typical dry diet (DD) regimen, have improved growth rates and deposit more energy as body fat. In the present study, we used this model to determine whether changes in the expression of genes linked to the regulation of adiposity were related to the accelerated fat accretion. We also determined whether the increase in body fat was sustained throughout a substantial proportion of the growth curve. At weaning (19 plus minus 2 days of age), 96 piglets were placed in 12 replicate pens per diet (4 pigs per pen, 2 barrows and 2 gilts), and fed a liquid MR or conventional DD regimen for 5 weeks. Thereafter, 6 barrows and 6 gilts pigs from each diet were killed for determination of whole body chemical composition (less gastrointestinal contents). The remaining pigs were assigned randomly to weight target groups (60, 85, and 110 kg), placed in individual pens, and fed a conventional dietary regimen until killed at their respective weight targets for tissue sampling and determination of whole body chemical composition. Over the 5-week period in which the MR was fed, the growth rate of the pigs consuming the MR exceeded that of the pigs fed the DD by 36% (P <.05). Fat gain in these pigs was increased to 1.8 times that of the pigs fed the DD, and percentage body fat was 45% greater (P <.05). Acetyl Co-A carboxylase (ACC) activity (per mg of adipose extract protein) was not different between the two diet groups at the conclusion of the 5-week period, or at 110 kg body weight. During the MR period, actual protein gain was increased (P <.05) 22% in the pigs fed the MR as well. By 110 kg of body weight, body fat was reduced (P <.05) by 7.7% (total fat mass) and 8.3% (percentage of body weight basis) in the pigs fed MR vs. the DD group. The expression of the peroxisome proliferator activated receptors (PPAR) alpha and gamma was not influenced by diet or by body weight. Expression of the obese gene was independent of diet, but was greater (P <.09) in pigs at 110 kg body weight than at 60 kg. These data provide additional evidence that piglets weaned to liquid diets have greater rates of growth and deposit more body fat, but that this difference subsides quickly when a typical dry dietary regimen is imposed. Furthermore, the biochemical changes responsible for the increased adiposity are independent of changes in the expression of the obese or PPAR genes, at least at the mRNA level.


Differential hormonal and gene expression dynamics in two inbred sunflower lines with contrasting dormancy level.
Seed germination and dormancy are tightly regulated by hormone metabolism and signaling pathway. We investigated the endogenous content of abscisic acid (ABA), its catabolites, and gibberellins (GAs), as well as the expression level of certain ABA and GAs metabolic and signaling genes in embryo of dry and imbibed cypselas of inbred sunflower (Helianthus annuus L., Asteraceae) lines: B123 (dormant) and B91 (non-dormant). Under our experimental conditions, the expression of RGL2 gene might be related to the ABA peak in B123 line at 3 h of imbibition. Indeed, RGL2 transcripts are absent in dry and early embedded cypselas of the non-dormant line B91. ABA increase was accompanied by a significant ABA-Glucosyl ester (ABA-GE) and phaseic acid (PA) (two ABA catabolites) decrease in B123 line (3 h) which indicates that ABA metabolism seems to be more active in this line, and that it would be involved in the imposition and maintenance of sunflower seed dormancy, as it has been reported for many species. Finally, an increase of bioactive GAs (GA1 and GA3) occurs at 12 h of imbibition in both lines after a decrease in ABA content. This study shows the first report about the RGL2 tissue-specific gene expression in sunflower inbred lines with contrasting dormancy level. Furthermore, our results provide evidence that ABA and GAs content and differential expression of metabolism and signaling genes would be interacting in seed dormancy regulation through a mechanism of action related to embryo itself.


Effects of trabecular bone on marrow relaxation in the tibia.
The effects of bone on marrow relaxation in the trabecular volume of the most proximal 3 cm in the left tibia were studied with a RF-spoiled gradient echo MRI protocol on a 1.0 T MR unit. The MR measurements were performed on six healthy volunteers, and repeated within one month in order to assess the precision of the method. In the same subjects, the area bone mineral density (BMD, g/cm2) was measured at the left proximal femur using dual-energy X-ray absorptiometry. The calcaneus of the same side was examined with quantitative ultrasound. The marrow T2* relaxation deviated from a mono-exponential decay, and resembled the decay of subcutaneous fat. The shape of the relaxation curve reflected the presence of several spectral components in bone marrow, and was further influenced by the amount and structure of the surrounding trabecular bone. The bone marrow decays showed substantially reduced inter-subject variability after normalisation of the marrow data fit parameters to corresponding values for s.c. fat. This suggests the use of an internal adipose tissue reference in order to correct for diet-related variations of marrow T2* estimates. The mean relative precision of the MR measurements was between 5% and 10% depending on the data fit model. Moderate-to-strong correlations between DXA BMD indices in the proximal femur and MR parameters were found (r(max)=-0.96; p < 0.01), while ultrasound-derived measures of bone strength measured on the calcaneus demonstrated significantly weaker correlations to the MR parameters (r(max)=-0.78; p > 0.05). The method employed in this study showed reasonable precision and a moderate to good correlation compared to other bone parameters derived at the same extremity, and is a promising tool for the use on patients.


[Influences of food browning on nutrition. I. Effects of alcohol extract of egg plant on growth and plasma lipid composition in the rat (author's transl)].
Browning substances are produced on incubation of minced or finely crushed egg plant in alcohol for various periods (from 3 to 12 months). Effects of chronic ingestion of the browning substances were studied on growth rate, general nutrition, and plasma lipids, especially on cholesterol and fatty acid composition in five groups of rats. Control rats (the sixth group) were fed standard diet and water ad libitum. 1. The browning substances reduced the growth rate and nutritional efficiency in the rat. 2. This inhibitory effect was more marked when rats were fed the diet containing advanced browning substances on the longest incubation of 12 months. 3. Ingestion of the browning substances of long incubation caused an elevation of the serum cholesterol level as compared with controls. 4. Analysis of serum fatty acid composition showed in general a reduction in unsaturated fatty acid and an increase in saturated fatty acid, especially in palmitic acid after ingestion of browning substances. 5. Ingestion of lyophilized powder of fresh egg plants also caused inhibition of growth rate and nutritional efficiency.


Neoadjuvant imatinib treatment and laparoscopic anus-preserving surgery for a large gastrointestinal stromal tumor of the rectum.
Resection of a gastrointestinal stromal tumor (GIST) of the rectum can be difficult because of the particular location in the pelvis, and a large rectal GIST often requires abdominoperineal resection. Recent reports demonstrate that neoadjuvant imatinib treatment improves surgical outcomes in patients with a rectal GIST, and there are only a few reports of the effectiveness of laparoscopic surgery for a rectal GIST. A 46-year-old man was found to have a rectal GIST that measured 80 mm and was located on the anterior wall of the lower rectum. After 6 months treatment with imatinib, the tumor decreased in size to 37 mm, and laparoscopic low anterior resection was performed. The patient is currently alive without any evidence of recurrence 37 months after surgery. Neoadjuvant imatinib should be a treatment of choice for a large rectal GIST. When marked tumor shrinkage is achieved, laparoscopic surgery may be the preferred procedure.


Visual outcome after removal of silicone oil in patients undergoing retinectomy for complex retinal detachment.
To evaluate the functional outcome after removal of silicone oil (ROSO) in patients undergoing retinectomy for complex retinal detachment. We performed a retrospective case note review of patients who underwent ROSO after retinectomy for complex retinal detachment. Patients with less than 6mo follow up and recurrent retinal detachment following ROSO were excluded. Thirty-six patients were included. The mean best corrected visual acuity (BCVA) pre-ROSO was 1.13 logMAR (SD 0.5). The mean BCVA 3mo following ROSO was 1.16 logMAR (SD 0.53), 6mo following ROSO 1.13 (SD 0.63), and 12mo following ROSO 1.18 (SD 0.69). At 12mo after ROSO, the BCVA improved in 38.9% of patients, remained unchanged in 25%, and deteriorated in 36.1%, although there was no statistical significant difference in BCVA after ROSO at 3, 6 and 12mo (P=0.93). The size of retinectomy ranged from 15° to 270° (SD 53) and did not influence the visual outcome (P=0.11). There was no statistically significanT difference in BCVA between pre- and post- ROSO following retinectomy for complex retinal detachment. There was no statistical difference in visual outcome related to the size of the retinectomy.


VEGF and bFGF gene polymorphisms in Polish patients with B-CLL.
Among a variety of angiogenic factors involved in the B cell chronic lymphocytic leukemia (B-CLL), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were identified. Their levels have been regarded as prognostic markers of the progression of disease. The objective of the present study was to assess whether polymorphisms located within the genes coding for these key angiogenic activators contribute to disease susceptibility and/or progression in patients with B-CLL. For this purpose, 180 individuals were investigated, including 68 B-CLL patients and 112 healthy controls. All individuals were typed for the VEGF (936 C > T) and bFGF (-921 C > G) alleles using PCR-RFLP technique. Only a slight prevalence of the VEGF T variant was observed among patients as compared to healthy individuals (p = 0.095) with a significant difference when high risk (stage III/IV) patients were considered (OR = 3.81, p = 0.045). No other significant association was observed between the VEGF polymorphism and progression of the disease. The VEGF alleles and genotypes segregated similarly in patients with different stage of the disease according to Rai classification. No significant relationships were also observed for the bFGF polymorphism with either susceptibility to B-CLL (when compared to control group) or progression of the disease. These results suggest the possible association of the VEGF polymorphism with high risk B-CLL.


Determination of deoxynivalenol (DON) in blood, bile, urine and excrement samples from swine using immunoaffinity chromatography and LC-UV-detection.
A work up procedure is described by which DON concentrations in blood, bile, urine and excrements from swine can be quantified by HPLC and UV- detection at λ = 220 nm. The central step thereby is the purification and concentration of DON by means of an immunoaffinity column. While, in our experiments, the quantification of DON in blood and urine was straightforward an additional purification step by a preparative HPLC run prior to immunoaffinity chromatography was needed when bile and excrements were investigated.However, when low DON concentrations in blood and urine are expected, a preparative HPLC run prior to immunoaffinity chromatography is recommended as well, because larger amounts of sample materials should be analyzed and more impurities interfere with the column proteins.In our study, using spiked samples, recoveries ranged from 75-90% and limits of detection were 0.01 to 0.02 μg/ml.


Calorimetric studies on the interaction of gangliosides with phospholipids and myelin basic protein.
Differential scanning calorimetry was employed to investigate the interaction of GM1 gangliosides with phospholipids (phosphatidylethanolamine, phosphatidylserine or phosphatidylcholine). It was found that GM1 is completely miscible with phosphatidylethanolamine; however, the interaction with phosphatidylserine is minimal. Addition of excess Ca2+ to the interaction products of GM1 with phosphatidylcholine or phosphatidylethanolamine did not induce phase separation. The influence of myelin basic protein on the thermotropic behaviour of GM1 was also studied. It was found that basic protein has a very strong perturbing effect on GM1 micelles.


Pilot study on the effect of grape seed proanthocyanidin extract on inferior vene cava blood flow in patients with chronic venous insufficiency using 4D flow MRI.
Four-dimensional (4D) flow magnetic resonance imaging (MRI) was used to objectively assess changes in blood flow velocity in patients with chronic venous insufficiency (CVI) who underwent stocking treatment alone and stocking combined with Grape seed proanthocyanidin extract (GSPE) treatment. Patients diagnosed with CVI were recruited from August 31, 2018 to December 31, 2020. A total of 23 participants were selected, with 10 and 13 patients in the stocking treatment and stocking + GSPE treatment groups, respectively. The blood flow velocity (Th-plane peak and average velocities) was calculated using 4D flow MRI. A paired t test was used to evaluate the differences in blood flow velocity before and after treatment. In the stocking treatment group, The Th-Plane peak velocity increased by 2.48 ± 5.05 cm/s after treatment (P = .16). In the stocking + GSPE treatment group, the Th-Plane peak velocity increased by 4.85 ± 5.57 cm/s after treatment (P < .001). The blood flow velocity on 4D flow MRI was significantly increased in participants who underwent GSPE, highlighting the potential of GSPE for CVI treatment.


Transport to the bloodstream of amylase following retrograde infusion of amylase into the parotid glands in the rat.
Amylase secretion into parotid saliva was increased more by isoprenaline whereas the secretion rate of parotid saliva was increased more by pilocarpine. Retrograde infusion of parotid-amylase solution into excretory ducts of the parotid gland elevated the activity of the enzyme in the serum. Direct evidence that retrogradely-infused amylase reaches the blood from the parotid gland was obtained using amylase prepared from Bacillus subtilis. Pretreatment with pilocarpine accelerated the release of amylase into the blood. The elevation of intraductal pressure may be the primary mechanism for the release of amylase into the blood from the parotid glands.


Storage and release of acetylcholine in the isolated superior cervical ganglion of the rat.
The storage and release of acetylcholine and choline were studied in the isolated superior cervical ganglion of the rat by a radioenzymic method. The acetylcholine and choline contents were 202.2 +/- 5.1 and 624.7 +/- 20.2 pmole/ganglion, respectively. The transmitter tissue store was unaffected during 1 h of superfusion in choline--Krebs solution, while a 20% decrease was exhibited after 2 h and then remained approximately stable. Conversely, choline content declined to 50% within 1 h and further to 37% of the original level by 4 h. About 24% of the choline assayed in the intact preparation is located in the connective sheath. Preganglionic nerve stimulation at 10--20/sec or potassium stimulation (40 mM KCl) invariably decreased the transmitter tissue stores by 25--45%; such a depletion is independent of the presence or absence of external choline. By contrast, the presence of choline proved to be a prerequisite for the efficient release of acetylcholine from eserinized ganglia during continuous 10/sex stimulation. A drastic depression in the acetylcholine release is described which is related to the time of preincubation of the ganglia with eserine prior to stimulation. Indeed, a 30 min exposure to eserine, compared with a 5 min period, resulted in a 4-fold decrease in the steady output rate. Under optimal conditions, the initial volley output at 10/sec was 1.3 X 10(-4) of the releasable transmitter pool and 1.9 X 10(-4) during the steady-state output. These results are discussed in the light of the electrophysiological knowledge of the quantal release process at the ganglionic synapse.


Antiparasitic compounds that target DNA.
Designed, synthetic heterocyclic diamidines have excellent activity against eukaryotic parasites that cause diseases such as sleeping sickness and leishmania and adversely affect millions of people each year. The most active compounds bind specifically and strongly in the DNA minor groove at AT sequences. The compounds enter parasite cells rapidly and appear first in the kinetoplast that contains the mitochondrial DNA of the parasite. With time the compounds are also generally seen in the cell nucleus but are not significantly observed in the cytoplasm. The kinetoplast decays over time and disappears from the mitochondria of treated cells. At this point the compounds begin to be observed in other regions of the cell, such as the acidocalcisomes. The cells typically die in 24-48h after treatment. Active compounds appear to selectively target extended AT sequences and induce changes in kinetoplast DNA minicircles that cause a synergistic destruction of the catenated kinetoplast DNA network and cell death.


Syndrome resembling Kawasaki disease in COVID-19 asymptomatic children.
The current knowledge about the COVID-19 (Coronavirus Disease-2019) pandemic is still limited and is unravelling with the passing days, especially clinical data, and research in pediatric age group. Recently, there is a new and crucial development reported recently among the COVID-19 asymptomatic children, a novel syndrome affecting asymptomatic COVID-19 children, presenting as a hyperinflammatory syndrome which is like Kawasaki disease shock syndrome. The purpose of this correspondence is to discuss some important findings of the syndrome for the better understanding of the disease.


Phenotype MicroArray™ system in the study of fungal functional diversity and catabolic versatility.
Fungi cover a range of important ecological functions associated with nutrient and carbon cycling in leaf litter and soil. As a result, research on existing relationships between fungal functional diversity, decomposition rates and competition is of key interest. Indeed, availability of nutrients in soil is largely the consequence of organic matter degradation dynamics. The Biolog® Phenotype MicroArrays™ (PM) system allows for the testing of fungi against many different carbon sources at any one time. The use and potential of the PM system as a tool for studying niche overlap and catabolic versatility of saprotrophic fungi is discussed here, and examples of its application are provided.


Emotional processing in bullying: an event-related potential study.
Bullying is a subtype of violence that leads to maladaptive behaviors and emotional responses, with implications for social competence, emotions, and empathy. The present study compared the time course of emotional processing in children who were involved in the dynamics of bullying (i.e., as victims, bullies, and observers) by evaluating event-related potentials [early posterior negativity and late positive potential (LPP)] in different brain regions during a passive visualization task that involved positive, neutral, and negative social pictures. High-density electroencephalograms were recorded in 45 children, 8-12 years old (M = 9.5 years, SD = 1.3), while they observed emotional and neutral social pictures that we selected from the International Affective Picture System. Late positive potential had higher amplitudes in the victim group, especially in posterior and anterior regions. In the central region, LPP was greater toward neutral social pictures in bullying victims. The greater amplitude of LPP in victims was observed during and after the stimulus. The results showed a consistent response with a higher intensity in response to emotional stimuli in the victim group, suggesting a tendency toward hypervigilance that could interfere with emotional regulation.


Computer techniques for the processing of evoked potentials.
A computer technique is described for the systematic characterization of brain evoked potentials. Preprocessing of the data by a causal digital filter is followed by a peak search and identification procedure. A latency histogram of the peaks found is constructed to determine the ranges or clusters of peaks within the single evoked potential. Peaks found within the clusters are then corrected to the mean latency of the cluster and a latency corrected average version of the evoked potential constructed.


Palladium/GF-Phos-catalyzed asymmetric carbenylative amination to access chiral pyrrolidines and piperidines.
The cross-coupling of N-tosylhydrazones has emerged as a powerful method for the construction of structurally diverse molecules, but the development of catalytic enantioselective versions still poses considerable challenges and only very limited examples have been reported. We herein report an asymmetric palladium/GF-Phos-catalyzed carbenylative amination reaction of N-tosylhydrazones and (E)-vinyl iodides pendent with amine, which allows facile access to a range of chiral pyrrolidines and piperidines in good yields (45-93%) with up to 96.5 : 3.5 er. Moreover, mild conditions, general substrate scope, scaled-up preparation, as well as the efficient synthesis of natural product (-)-norruspoline are practical features of this method.


Acid-treated pomegranate peel; An efficient biosorbent for the excision of hexavalent chromium from wastewater.
We studied the sequestration of hexavalent chromium Cr(VI) from an aqueous solution using chemically modified pomegranate peel (CPP) as an efficient bio-adsorbent. The synthesized material was characterized by X-ray diffraction spectroscopy (XRD), Fourier-transform infrared spectroscopy (FTIR), energy dispersive spectroscopy (EDS), and scanning electron microscopy (SEM). The impacts of parameters like solution pH, Cr(VI) concentration, contact time, and adsorbent dosage were investigated. Experimental results of the isotherm studies and adsorption kinetics were found agreeing to the Langmuir isotherm model and pseudo-second-order kinetics, respectively. The CPP showed appreciable Cr(VI) remediation capacity with a maximal loading capacity of 82.99 mg/g at pH 2.0, which was obtained in 180 min at room temperature. Thermodynamic studies revealed the biosorption process as spontaneous, feasible, and thermodynamically favorable. The spent adsorbent was eventually regenerated and reused, and the safe disposal of Cr(VI) was ensured. The study revealed that the CPP can be effectively employed as an affordable sorbent for the excision of Cr(VI) from water.


Capitated groups track claims, reduce costs using MD Hawkeye.
The "MD Hawkeye" software program from Doctor-Driven Systems helps capitated groups manage costs, reduce utilization, and improve quality measurements. See how one capitated group saved more than $100,000 on one project.


Transcriptome profiling and proteomic validation reveals targets of the androgen receptor signaling in the BT-474 breast cancer cell line.
Accumulating evidence suggests that the androgen receptor (AR) and its endogenous ligands influence disease progression in breast cancer (BCa). However, AR-mediated changes in BCa differ among the various BCa subtypes according to their hormone receptor profile [i.e., presence/absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2, (HER2)]. Thus, we explored the androgen-regulated transcriptomic changes in the ER+PR+HER2+ BCa cell line, BT-474, and compared them with PR-mediated changes. We performed RNA sequencing analysis in treated BT-474 cells with dihydrotestosterone (DHT) and progesterone. Validation of the top ten differentially androgen-regulated genes and a number of other genes found in enriched signaling pathways was performed by qRT-PCR in BT-474 and other BCa cell lines. In addition, a parallel reaction monitoring targeted proteomic approach was developed to verify selected transcripts at the protein level. In total 19,450 transcripts were detected, of which 224 were differentially regulated after DHT treatment. The increased expression of two well-known androgen-regulated genes, KLK2 (p < 0.05) and KLK3 (p < 0.001), confirmed the successful androgen stimulation in BT-474 cells. The transcription factor, ZBTB16, was the most highly upregulated gene, with ~ 1000-fold change (p < 0.001). Pathway enrichment analysis revealed downregulation of the DNA replication processes (p < 0.05) and upregulation of the androgen signaling and fatty acid metabolism pathways (p < 0.05). Changes related to progesterone treatment showed opposite effects in gene expression than DHT treatment. Similar expression profiles were observed among other BCa cell lines expressing high levels of AR (ZR75.1 and MBA-MB-453). The parallel reaction monitoring targeted proteomic analysis further confirmed that altered protein expression (KLK3, ALOX15B) in the supernatant and cell lysate of DHT-treated BT-474 cells, compared to control cells. Our findings suggest that AR modulates the metabolism of BT-474 cells by affecting the expression of a large number of genes and proteins. Based on further pathway analysis, we suggest that androgen receptor acts as a tumor suppressor in the BT-474 cells.


Reduction of desipramine cardiotoxicity and prolongation of survival in rats with the use of polyclonal drug-specific antibody Fab fragments.
Tricyclic antidepressants (TCAs) are a leading cause of death from intentional drug overdose. Available therapies are often unsatisfactory. In this study we evaluated the use of a high-affinity drug-specific polyclonal Fab fragment (TFab) as an antidote to desipramine toxicity. We gave anaesthetized rats under mechanical ventilation IV desipramine so that we might study the effect of TFab on survival or IP desipramine to facilitate study of the interaction of TFab and hypertonic sodium bicarbonate (NaHCO3), the standard clinical treatment for TCA overdose. For the study of the effects of TFab and NaHCO3 on survival, each rat was given a constant IV infusion of desipramine until it died, together with TFab 2 g/kg, bovine serum albumin, or .9% NaCl starting 5 minutes after the desipramine infusion. In the study of the interaction of TFab and NaHCO3, each rat received 30 mg/kg IP desipramine followed by TFab (molar TFab:desipramine ratio, .11), NaHCO3, TFab+NaHCO3, or NaCl at the time of maximal toxicity (15 minutes). In the survival protocol, QRS-interval duration, systolic blood pressure, and heart rate were significantly improved by TFab, and survival was prolonged by 58% compared with that in the albumin and NaCl groups (P < .001). The molar ratio of TFab to administered desipramine was .21. The unbound fraction of desipramine in serum at the time of death was reduced by TFab, but the unbound desipramine concentration was not, suggesting that TFab prolonged survival by delaying the increase in the unbound serum desipramine concentration. In the interaction protocol, neither TFab nor NaHCO3 was effective alone, but the combination significantly reduced QRS-interval prolongation (P = .001). These data demonstrate the efficacy of TFab in reducing desipramine-induced cardiovascular toxicity and prolonging survival. The pharmacokinetic effects of TFab in rats with severe desipramine toxicity were similar to those observed in sublethal desipramine toxicity. Therapeutic benefit is enhanced by the concurrent use of NaHCO3 and may be achieved despite binding only a fraction of the desipramine dose.


Fatty acids in formulae for term infants: compliance of present recommendations with the actual human milk fatty acid composition of geographically different populations.
Recommendations for formula fatty acids (FA) are largely based on the mature human milk FA composition. This study aimed to investigate whether current recommendations for formula FA for term infants comply with the actual breast-milk FA composition of geographically distinct populations and to provide more realistic grounds for future recommendations. 455 mature breast-milk samples were collected in different countries over 25 y. Recommendations of different organizations were projected on their FA data. FA interrelationships were calculated with Spearman's rank tests. FA compositions of 30 formulae were compared with those of breast milk. Many samples from non-Western communities did not meet the recommendations for formula 12:0, 14:0 and 18:2omega6, since these are mainly based on breast milk of mothers living in Western countries. Recommendations for 18:3omega3, 18:2omega6/18:3omega3, 20:4omega6 and 22:6omega3 were not met by many milk samples, which may point to the poorly developed recommendations for long-chain polyunsaturated FA. Most of the investigated breast-milk FA (12:0, 14:0, 16:0, 18:0, 18:3omega3, 22:6omega3, 18:2omega6, 20:4omega6, 18:1omega9) were either positively or negatively interrelated. Many formulae had FA compositions that were not consistent with the physiological interrelationships of FA in breast milk. Future recommendations, if based on human milk, should derive from its FA balance, as indicated by the FA interrelationships. A "humanized" formula FA composition would in this sense be any composition that cannot be distinguished from that of breast milk by techniques such as principal component analysis.


Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review.
Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. Narrative review based on a literature search through PubMed and Cochrane using the following keywords: "multi-drug resistant (MDR)", "extensively drug resistant (XDR)", "pan-drug-resistant (PDR)", "difficult-to-treat (DTR) Gram-negative infection," "antibiotic duration therapy", "antibiotic combination therapy" "antibiotic monotherapy" "Gram-negative bacteremia", "Gram-negative pneumonia", and "Gram-negative intra-abdominal infection". Current literature data suggest adopting longer (≥10-14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45-50%), MDR (35%), XDR (15-20%), PDR (5.9-6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5-20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5-7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.


Volumes Learned: It Takes More Than Size to "Size Up" Pulmonary Lesions.
This study aimed to review the current understanding and capabilities regarding use of imaging for noninvasive lesion characterization and its relationship to lung cancer screening and treatment. Our review of the state of the art was broken down into questions about the different lung cancer image phenotypes being characterized, the role of imaging and requirements for increasing its value with respect to increasing diagnostic confidence and quantitative assessment, and a review of the current capabilities with respect to those needs. The preponderance of the literature has so far been focused on the measurement of lesion size, with increasing contributions being made to determine the formal performance of scanners, measurement tools, and human operators in terms of bias and variability. Concurrently, an increasing number of investigators are reporting utility and predictive value of measures other than size, and sensitivity and specificity is being reported. Relatively little has been documented on quantitative measurement of non-size features with corresponding estimation of measurement performance and reproducibility. The weight of the evidence suggests characterization of pulmonary lesions built on quantitative measures adds value to the screening for, and treatment of, lung cancer. Advanced image analysis techniques may identify patterns or biomarkers not readily assessed by eye and may also facilitate management of multidimensional imaging data in such a way as to efficiently integrate it into the clinical workflow.


Clinical and economic impact of influenza vaccination on healthy children aged 2-5 years.
This paper reports the data concerning the net economic cost savings attributable to influenza vaccination in healthy children aged 2-5 years, and may be useful when deciding the best recommendations for the use of influenza vaccine in pediatrics. A total of 303 previously unprimed healthy children aged 2-5 years (163 males; mean age+/-S.D.: 3.22+/-2.43 years) were prospectively, blindly randomised in a 2:1 ratio to receive two doses of an inactivated, trivalent, virosome-formulated subunit influenza vaccine (Inflexal V, Berna Biotech, Berne, Switzerland) or no vaccination. The results show that influenza vaccination of healthy children aged 2-5 years substantially reduces influenza-like illnesses and related costs in the children themselves and their families. However, larger and longer running study spanning multiple seasons may be warranted before suggesting the universal vaccination of this group of subjects.


The impact of a multi-hospital network on the inequality in odds of receiving resection or ablation for synchronous colorectal liver metastases.
This study investigates whether inequalities in the utilization of resection and/or ablation for synchronous colorectal liver metastases (SCLM) between patients diagnosed in expert and non-expert hospitals changed since a multi-hospital network started. Patients diagnosed with SCLM between 2009 and 2020 were included. The likelihood of receiving ablation and/or resection was analyzed in the prenetwork (2009-2012), startup (2013-2016), and matured-network (2017-2020) periods. Nationwide, 13.981patients were diagnosed between 2009 and 2020, of whom 1.624 were diagnosed in the network. Of patients diagnosed in the network's expert hospitals, 36.7% received ablation and/or resection versus 28.3% in nonexpert hospitals (p < 0.01). The odds ratio (OR) of receiving ablation and/or resection for patients diagnosed in expert versus nonexpert hospitals increased from 1.38 (p = 0.581, pre-network), to 1.66 (p = 0.108, startup), to 2.48 (p = 0.090, matured-network). Nationwide, the same trend occurred (respectively OR 1.41, p = 0.011; OR 2.23, p < 0.001; OR 3.20, p < 0.001). Patients diagnosed in expert hospitals were more likely to receive ablation and/or resection for SCLM than patients diagnosed in non-expert hospitals. This difference increased over time despite the startup of a multi-hospital network. Establishing a multi-hospital network did not have an effect on reducing the existing unequal odds of receiving specialized treatment. Specialized oncology treatments are increasingly provided through multi-hospital networks. However, scant empirical evidence on the effectiveness of these networks exists. This study analyzes whether a regional multi-hospital network was able to improve equal access to specialized oncology treatments.


[Prognostic significance of the morphological signs of the malignancy of a pheochromocytoma].
The authors have studied the prognostic value of such convincing morphological signs of tumor malignancy as cellular and nuclear polymorphism, the mitotic activity, the invasion of tumor cells into the vascular lumen, the presence of metastases in 28 operated patients with a hormone-active tumor of chromaffin tissue. The results of late-term observations within the period from 2 to 17 years indicated that all the patients subjected to radical surgery are alive. Detecting in a histological assay of pheochromocytoma of the aforementioned signs of malignancy except metastases is not an obligatory prognostically unfavourable factor. Such tumor cannot be called pheochromoblastoma, but it should be defined as pheochromocytoma with the morphological signs of malignancy.


[Detection rates of chemosensory evoked Potenzials with healthy and anosmic subjects].
The detection rate of olfactory chemosensory event-related EEG Potentials (oCSERP) and trigeminal chemosensory event-related EEG Potentials (tCSERP) is also dependent on the stimulants and the evaluator of the averaged EEG curves. In 45 subjects with age-appropriate normal olfactory capacity (NP) and 20 anosmics (AN), oCSERP (stimulation by hydrogen sulphide, H2S 6 ppm and phenylethyl alcohol, PEA 30 % v/v,) and tCSERP (irritation with CO2 20-60 % v/v, intensity standardized) were derived by default. Two investigators categorized the averaged EEG curves in: CSERP recognizable, no CSERP recognizable and artefact. Investigator 1 knew whether the subject was a NP or an AN, and which stimulants was used, whereas investigator 2 lacked this information. AN needed higher trigeminal stimulus concentrations but showed same intensity ratings compared to NP. The attention (tracking game) did not deteriorate in the course of test. The detection rate of H2S-CSERP was higher than that of PEA-CSERP. The match of H2S-CSERP detection rates between the two investigators was higher than that of PEA-CSERP and CO2-CSERP. For the standard derivation of oCSERP, stimulation with H2S is usually sufficient. Stimulation with PEA and CO2 as well as a blinded investigator is not necessary.


Research and orthodontics: About scientific progress in biomechanics.
This article describes the importance of biomechanics in orthodontics through the development of the segmented arch technique and the research performed in this field. Clinicians are encouraged to develop specific goals of treatment based on a precise diagnosis and to design appliances that will deliver the desired force system. In this article we emphasize the importance of a thorough analysis of the force system needed to achieve the desired orthodontic tooth movement and avoid any of the undesired side effects of treatment mechanics. We show that a well-thought out and planned treatment will lead to better clinical outcomes that will benefit our patients.


Relationship between neurological features and intrathecal synthesis of IgG antibodies to Treponema pallidum in untreated and treated human neurosyphilis.
In syphilitic patients with or without CNS involvement the correlation of Treponema-specific IgG titre per milligram total IgG in CSF and serum (ITPA index) is a dependable source of information on the synthesis of treponemal IgG antibodies in the CNS. This index also provides a more reliable definition of asymptomatic neurosyphilis. Further, a discrimination between Treponema-specific and Treponema-non-specific IgG synthesis in the CNS is possible. Of 261 patients with clinical symptoms of neurosyphilis, 82% had a local production of treponemal IgG antibodies as shown by an elevated ITPA index. In patients with neurosyphilis and intrathecal synthesis of Treponema-specific IgG antibodies, 94% had oligoclonal IgG in the CSF. Comparison of different CSF protein alteration groups in untreated and treated neurosyphilitic patients showed that early diagnosis (and early treatment) led to improvement of the impairment of the blood-CSF barrier and reduction of the immune reaction in the CNS. However, synthesis of treponemal IgG antibodies in the CNS could persist as a 'scar syndrome' even after adequately cured infection.


High rate of de novo esophagitis 5 years after sleeve gastrectomy: a prospective multicenter study in Spain.
Major concerns years after the sleeve gastrectomy (SG) include weight regain, development of hiatal hernia (HH) and gastroesophageal reflux disease, with esophagitis and Barrett's esophagus (BE). Both problems could be related, and the incidence of asymptomatic patients is troubling. To study the incidence of reflux symptoms, esophagitis, BE, HH, and asymptomatic pathology and their relationship with weight regain in patients 5 years after undergoing SG at different bariatric centers in Spain. Public and private hospitals with bariatric surgery units. Prospective, multicenter, nonrandomized study involving 13 Spanish hospitals with a cumulative experience of 4,500 patients having undergone the SG procedure and patients who had been subjected to the procedure at least 5 years previously along with preoperative gastroscopy. The clinical history, preoperative gastroscopy, and technical details of the SG were recorded. A specific clinical questionnaire was given that recorded the intake volume, perception of satiety, and gastroesophageal reflux (GER) symptoms. Gastroscopy, pH-metry, and manometry studies were carried out, and the data were analyzed statistically. The study has been authorized by the official Spanish ethics committee CEI/CEIm Hospital Universitario Gran Canaria Dr Negrín (code 2019-216-1). One hundred and five patients who underwent SG and who had with at least 5 years of follow-up were included. All procedures were performed laparoscopically. The mean age of patients was 51.1 years, and 70.5% were women. The mean characteristics of the SG procedure were a 37.2F probe, at 4.6 cm from the pylorus, and a crura closure was performed in 5 cases. There were no major complications (Clavien-Dindo grade >3) or deaths. The average preoperative body mass index was 46.3 kg/m2, the minimum reached was 20.6 kg/m2, whereas the average after 5 years was of 34.5 kg/m2. GER, HH, and esophagitis symptoms went from 17.1%, 28.6%, and 5.7%, respectively, before the SG to 76%, 30.5%, and 31.4%, respectively, 5 years after the procedure. Symptoms persisted over the years in 37.1% of cases and presented de novo in 52.8% of cases. Fifty-three percent of manometries (n = 27, total 51) and 64% of pH-metries (n = 32, total 53; DeMeester average score was 65) were pathologic 5 years after the procedure. Concerning gastroscopies, 5 years after the procedure, HH was found in 33 patients (30.5% of total) and esophagitis in 32 patients (31.4% of total). Eighty patients (76%) had GER symptoms, and 25 patients (24%) were asymptomatic. Only 1 patient (.9%) developed BE. Our study has confirmed a high rate of both persistent and de novo esophagitis and hiatal hernia, many of which were asymptomatic, 5 years after SG had been performed. Weight regain and a striking increase in gastric capacity are risk factors indicative of esophagitis, even when patients are asymptomatic. We consider a control gastroscopy and the preventive use of proton pump inhibitors necessary in these cases regardless of symptoms. We recommend that a control gastroscopy should be performed in all cases regardless of symptoms 5 years after SG. Further studies are needed to validate these recommendations.


Aconitase, a two-faced protein: enzyme and iron regulatory factor.
In this brief survey, the path of development of our knowledge of the iron-sulfur enzyme aconitase [citrate(isocitrate)hydrolyase EC22.214.171.124.] is traced from its discovery in 1937. Particular emphasis is on developments in the past decade, when EPR, Mössbauer and electron nuclear double resonance spectroscopies, X-ray crystallography, and mutational analysis were applied to the problem. More recently discovered was the significant amino acid sequence identity between mitochondrial aconitase and the iron regulatory factor or iron-responsive element binding protein (IRE-BP). This has led to the realization that IRE-BP is an alternative form of cytosolic (not of mitochondrial) aconitase that is devoid of its cubane Fe-S cluster.


Degradation of acharan sulfate and heparin by Bacteroides stercoris HJ-15, a human intestinal bacterium.
When glycosaminoglycan (GAG)-degrading enzymes were measured in normal human stool suspensions, all 5 tested different stools degraded titrable heparin and acharan sulfate. GAG-degrading bacteria were screened from the isolates of human stools. Among them, HJ-15 had the most potent activities of heparinases (GAGs-degrading enzymes). However, HJ-15 produced the enzyme even if in the media without heparin. Acharan sulfate lyase was induced by acharan sulfate and heparin. Heparinase production was also induced by these GAGs. These enzymes, acharan sulfate lyase and heparinase, were produced in exponential and stationary phase of HJ-15 growth, respectively. Optimal pHs of the acharan sulfate lyase and heparinase activities were 7.2 and 7.5, respectively. The biochemical properties of HJ-15 was similar to those of B. stercoris. However, difference from B. stercoris was utilization of raffinose. This HJ-15 also degraded chondroitin sulfates A and C.


Humid tropical vertebrates are at lower risk of extinction and population decline in forests with higher structural integrity.
Reducing deforestation underpins global biodiversity conservation efforts. However, this focus on retaining forest cover overlooks the multitude of anthropogenic pressures that can degrade forest quality and imperil biodiversity. We use remotely sensed indices of tropical rainforest structural condition and associated human pressures to quantify the relative importance of forest cover, structural condition and integrity (the cumulative effect of condition and pressures) on vertebrate species extinction risk and population trends across the global humid tropics. We found that tropical rainforests of high integrity (structurally intact and under low pressures) were associated with lower likelihood of species being threatened and having declining populations, compared with forest cover alone (without consideration of condition and pressures). Further, species were more likely to be threatened or have declining populations if their geographic ranges contained high proportions of degraded forest than if their ranges contained lower proportions of forest cover but of high quality. Our work suggests that biodiversity conservation policies to preserve forest integrity are now urgently required alongside ongoing efforts to halt deforestation in the hyperdiverse humid tropics.


Social Risk Factors are Associated with Risk for Hospitalization in Home Health Care: A Natural Language Processing Study.
This study aimed to develop a natural language processing (NLP) system that identified social risk factors in home health care (HHC) clinical notes and to examine the association between social risk factors and hospitalization or an emergency department (ED) visit. Retrospective cohort study. We used standardized assessments and clinical notes from one HHC agency located in the northeastern United States. This included 86,866 episodes of care for 65,593 unique patients. Patients received HHC services between 2015 and 2017. Guided by HHC experts, we created a vocabulary of social risk factors that influence hospitalization or ED visit risk in the HHC setting. We then developed an NLP system to automatically identify social risk factors documented in clinical notes. We used an adjusted logistic regression model to examine the association between the NLP-based social risk factors and hospitalization or an ED visit. On the basis of expert consensus, the following social risk factors emerged: Social Environment, Physical Environment, Education and Literacy, Food Insecurity, Access to Care, and Housing and Economic Circumstances. Our NLP system performed "very good" with an F score of 0.91. Approximately 4% of clinical notes (33% episodes of care) documented a social risk factor. The most frequently documented social risk factors were Physical Environment and Social Environment. Except for Housing and Economic Circumstances, all NLP-based social risk factors were associated with higher odds of hospitalization and ED visits. HHC clinicians assess and document social risk factors associated with hospitalizations and ED visits in their clinical notes. Future studies can explore the social risk factors documented in HHC to improve communication across the health care system and to predict patients at risk for being hospitalized or visiting the ED.


Rapid preparation of expanded graphite by microwave irradiation for the extraction of triazine herbicides in milk samples.
In this study, we proposed a rapid and efficient method for the preparation of the expanded graphite (EG). The exfoliation process was accelerated by microwave irradiation, and the preparation time was greatly shortened. The obtained EG was worm-like in shape and exhibits well exfoliated structure. It was successfully applied as solid-phase extraction (SPE) adsorbent to extract and clean up the triazine herbicides in milk, followed by liquid chromatography tandem mass spectrometry (LC-MS) analysis. The parameters affecting the performance of extraction and LC-MS analysis were evaluated. Under the optimal conditions, the detection limits of triazines are in the range of 0.03-0.12 ng mL(-1). At the spiked level (0.4 ng mL(-1)), the recoveries of triazines are in the range of 82.5±2.5% to 97.5±7.5%. The proposed method was successfully applied to determine six triazines in six milk samples.


Electroconvulsive therapy in patients taking theophylline.
Initiating a course of electroconvulsive therapy (ECT) in patients taking theophylline has been associated with status epilepticus and consequent brain damage or even death. However, some patients with severe pulmonary conditions may both require theophylline and be seriously depressed enough to warrant ECT. Deciding whether to use ECT in such patients is a fairly common clinical problem. The records of seven patients taking theophylline during nine courses of ECT were reviewed to ascertain whether inordinately long seizures occurred. In 77 documented seizures, there was one 190-second seizure as measured by EEG. All others were shorter than 100 seconds, and mean motor and EEG seizure lengths were comparable with those reported in the literature. Theophylline coadministration is a risk factor for prolonged seizures in patients starting a course of ECT. However, in most severely depressed, medication-refractory patients, a course of ECT can be undertaken with safety. Precautions that can decrease the risk of prolonged seizures are discussed.


Functional magnetic resonance imaging of macaque monkeys performing visually guided saccade tasks: comparison of cortical eye fields with humans.
The frontal and parietal eye fields serve as functional landmarks of the primate brain, although their correspondences between humans and macaque monkeys remain unclear. We conducted fMRI at 4.7 T in monkeys performing visually-guided saccade tasks and compared brain activations with those in humans using identical paradigms. Among multiple parietal activations, the dorsal lateral intraparietal area in monkeys and an area in the posterior superior parietal lobule in humans exhibited the highest selectivity to saccade directions. In the frontal cortex, the selectivity was highest at the junction of the precentral and superior frontal sulci in humans and in the frontal eye field (FEF) in monkeys. BOLD activation peaks were also found in premotor areas (BA6) in monkeys, which suggests that the apparent discrepancy in location between putative human FEF (BA6, suggested by imaging studies) and monkey FEF (BA8, identified by microstimulation studies) partly arose from methodological differences.


Mitosis-specific phosphorylation and subcellular redistribution of the RIIalpha regulatory subunit of cAMP-dependent protein kinase.
Phosphorylation of the RII regulatory subunits of cyclic AMP-dependent protein kinases (PKAs) was examined during the HeLa cell cycle. Three RIIalpha isoforms of 51, 54, and 57 kDa were identified by RIIalpha immunodetection and labeling with 8-azido[32P]cAMP in different cell cycle phases. These isoforms were characterized as different phosphorylation states by the use of selective PKA and cyclin-directed kinase inhibitors. Whereas RIIalpha autophosphorylation by PKA caused RIIalpha to shift from 51 to 54 kDa, phosphorylation of RIIalpha by one other or a combination of several kinases activated during mitosis caused RIIalpha to shift from 51 to 57 kDa. In vivo incorporation of [32P]orthophosphate into mitotic cells and RIIalpha immunoprecipitation demonstrated that RIIalpha was hyperphosphorylated on a different site than the one phosphorylated by PKA. Deletion and mutation analysis demonstrated that the cyclin B-p34(cdc2) kinase (CDK1) phosphorylated human recombinant RIIalpha in vitro on Thr54. Whereas RIIalpha was associated with the Golgi-centrosomal region during interphase, it was dissociated from its centrosomal localization at metaphase-anaphase transition. Furthermore, particulate RIIalpha from HeLa cell extracts was solubilized following incubation with CDK1 in vitro. Our results suggest that at the onset of mitosis, CDK1 phosphorylates RIIalpha, and this may alter its subcellular localization.


Raman signatures of inversion symmetry breaking and structural phase transition in type-II Weyl semimetal MoTe2.
Transition metal dichalcogenide MoTe2 is an important candidate for realizing the newly predicted type-II Weyl fermions, for which the breaking of the inversion symmetry is a prerequisite. Here we present direct spectroscopic evidence for the inversion symmetry breaking in the low-temperature phase of MoTe2 by systematic Raman experiments and first-principles calculations. We identify five lattice vibrational modes that are Raman-active only in the low-temperature noncentrosymmetric structure. A hysteresis is also observed in the peak intensity of inversion symmetry-activated Raman modes, confirming a temperature-induced structural phase transition with a concomitant change in the inversion symmetry. Our results provide definitive evidence for the low-temperature noncentrosymmetric Td phase from vibrational spectroscopy, and suggest MoTe2 as an ideal candidate for investigating the temperature-induced topological phase transition.


Morphological and genetic analysis of three new species of Ceratomyxa Thélohan, 1892 (Myxozoa: Myxosporea) from carcharhinid sharks off Australia.
Three new species of Ceratomyxa Thélohan, 1892 are described from the gall-bladders of two species of carcharhinid sharks collected off Heron and Lizard Islands on the Great Barrier Reef, Australia. Ceratomyxa carcharhini n. sp. and C. melanopteri n. sp. are described from Carcharhinus melanopterus (Quoy & Gaimard), and Ceratomyxa negaprioni n. sp. is described from Negaprion acutidens (Rüppell). These species are the first ceratomyxids reported from Australian elasmobranchs, and this is the first paper to formally characterise a novel Ceratomyxa species from an elasmobranch using both morphology and small subunit ribosomal DNA sequence data. Maximum parsimony and Bayesian inference analyses of the SSU rDNA dataset revealed that ceratomyxids from elasmobranchs form a sister clade to that of species infecting marine teleosts and Palliatus indecorus Schulman, Kovaleva & Dubina, 1979. Furthermore, the only sequenced freshwater ceratomyxid, Ceratomyxa shasta Noble, 1950, fell outside the overall marine ceratomyxid clade. These data show that Ceratomyxa, as currently recognised, is polyphyletic and ignites discussion on whether Ceratomyxa should be split. However, further taxon sampling, particularly in freshwater systems, is required to establish relevant biological divisions within the genus.


System-wide rewiring underlies behavioral differences in predatory and bacterial-feeding nematodes.
The relationship between neural circuit function and patterns of synaptic connectivity is poorly understood, in part due to a lack of comparative data for larger complete systems. We compare system-wide maps of synaptic connectivity generated from serial transmission electron microscopy for the pharyngeal nervous systems of two nematodes with divergent feeding behavior: the microbivore Caenorhabditis elegans and the predatory nematode Pristionchus pacificus. We uncover a massive rewiring in a complex system of identified neurons, all of which are homologous based on neurite anatomy and cell body position. Comparative graph theoretical analysis reveals a striking pattern of neuronal wiring with increased connectional complexity in the anterior pharynx correlating with tooth-like denticles, a morphological feature in the mouth of P. pacificus. We apply focused centrality methods to identify neurons I1 and I2 as candidates for regulating predatory feeding and predict substantial divergence in the function of pharyngeal glands.


Plate fixation using parallelogram prism iliac bone grafts for clavicle oblique nonunion with shortening deformity: a case report.
Plate fixation using a tricortical iliac bone graft can provide a high ratio of bone union and restore clavicle length in cases of atrophic nonunion. However, the surgical treatment of clavicle oblique nonunions with marked shortening deformity remains challenging and unresolved. Here, we describe a case of clavicle oblique nonunion with shortening that was treated using plate fixation with parallelogram prism iliac bone grafts. A 46-year-old man presented to our hospital with severe medial scapular pain. He had been diagnosed with a right clavicle mid-shaft fracture in a motorcycle accident 9 months earlier. He underwent conservative treatment, but radiographs and computed tomography showed clavicle oblique nonunion with marked shortening. Physical examination revealed no pain at the nonunion site; however, tenderness was noted on the medial side of the right scapula and protrusion of the inferior scapular angle was prominent. His symptoms interfered with daily life and required surgery. After release of the nonunion, we harvested the parallelogram prism bone grafts from the iliac crest. We inserted these bone grafts into the fracture ends and fixed them with lag screws, after which we performed plate fixation. Immediately after surgery, right medial scapular pain and scapula winging subsided. Bone union was achieved, and the length of the clavicle was restored at 9 months postoperatively. This case report provides new information on the surgical treatment of clavicle oblique nonunion with shortening deformity. The presence of medial scapular pain and winging scapula can be clinically problematic in cases of clavicle nonunion with marked shortening. Our case revealed that reliable bone union and clavicle length recovery can be achieved with plate fixation and iliac bone grafts.


High radiosensitivity of induction in contrast to radioresistance of expression of cells mediating delayed-type hypersensitivity during response to sheep red blood cells in mice.
The delayed-type hypersensitivity DTH) reaction observed in mice primed i.v. with low doses of sheep red blood cells was greatly decreased when mice were irradiated with 300 rad before priming. An estimation of the radiosensitivity of DTH-mediating cells (DTH-C) was performed using a titration assay after local adoptive transfer of these cells mixed with antigen into the footpad of unprimed mice. A high radiosensitivity of the induction of DTH-C was observed with a D37 of approximately 50 rad. In contrast, the expression of DTH-C appeared radioresistant, as the D37 was approximately 2000 rad.


Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity.
We describe a genomic clone encoding the human 5-HT1B receptor. This apparently intronless gene encodes a 390 amino acid polypeptide homologous to the rat 5-HT1B serotonin receptor, with which it shares 93% amino acid sequence identity. Remarkably, [3H]5-hydroxytryptamine binding studies with transfected HeLa cells show that the human 5-HT1B receptor has a pharmacological profile that is markedly different from that of the corresponding rat receptor. Instead, human 5-HT1B drug specificity is highly similar to that of the human 5-HT1D receptor, with which it shares 59% amino acid sequence identity. The human 5-HT1B receptor, like the 5-HT1D receptor, can couple to Gi proteins. The presence of the threonine355 in the human receptor rather than an asparagine, as found in the corresponding rat gene product, may explain much of the marked pharmacological difference between the human and rat 5-HT1B receptors.


Effects of alkaline on horny layer cellularity.
The microscopical changes of plantar Str. corneum after immersion in alkaline were investigated. For this purpose a test system was used in which unexcised skin of guinea pig hind feet was exposed and subsequently analysed by the FITC-staining method. The effect of KOH on the Str. corneum consisted in an immediate swelling of the outer cell layers which was followed by a further increase in cell volume. Cells became separated layer by layer after maximal swelling. There is a high and constant rate of cell loss, when treated superficial cells are repeatedly removed as compared to permanent immersion. Thus, the buffering capacity of the treated outer cell layers has a rate limiting effect upon alkaline-induced cell loss in the Str. corneum.