Robotic Ureteral Reconstruction in Patients with Radiation-Induced Ureteral Strictures: Experience from the Collaborative of Reconstructive Robotic Ureteral Surgery.
Objectives: Management of radiation-induced ureteral stricture (RIUS) is complex, requiring chronic drainage or morbid definitive open reconstruction. Herein, we report our multi-institutional comprehensive experience with robotic ureteral reconstruction (RUR) in patients with RIUSs. Patients and Methods: In a retrospective review of our multi-institutional RUR database between January 2013 and January 2020, we identified patients with RIUSs. Five major reconstruction techniques were utilized: end-to-end (anastomosing the bladder to the transected ureter) and side-to-side (anastomosing the bladder to an anterior ureterotomy proximal to the stricture without ureteral transection) ureteral reimplantation, buccal or appendiceal mucosa graft ureteroplasty, appendiceal bypass graft, and ileal ureter interposition. When necessary, adjunctive procedures were performed for mobility (i.e., psoas hitch) and improved vascularity (i.e., omental wrap). Outcomes of surgery were determined by the absence of flank pain (clinical success) and absence of obstruction on imaging (radiological success). Results: A total of 32 patients with 35 ureteral units underwent RUR with a median stricture length of 2.5 cm (interquartile range [IQR] 2-5.5). End-to-end and side-to-side reimplantation techniques were performed in 21 (60.0%) and 8 (22.9%) RUR cases, respectively, while 4 (11.4%) underwent an appendiceal procedure. One patient (2.9%) required buccal mucosa graft ureteroplasty, while another needed an ileal ureter interposition. The median operative time was 215 minutes (IQR 177-281), estimated blood loss was 100 mL (IQR 50-150), and length of stay was 2 days (IQR 1-3). One patient required repair of a small bowel leak. Another patient died from a major cardiac event and was excluded from follow-up calculations. At a median follow-up of 13 months (IQR 9-22), 30 ureteral units (88.2%) were clinically and radiologically effective. Conclusion: RUR can be performed in patients with RIUSs with excellent outcomes. Surgeons must be prepared to perform adjunctive procedures for mobility and improved vascularity due to poor tissue quality. Repeat procedures for RIUSs heighten the risk of necrosis and failure.


Nutrition-related practices and attitudes of Kansas skipped-generation(s) caregivers and their grandchildren.
Despite growing numbers, the nutrition practices and attitudes of skipped-generation(s) kinship caregivers regarding feeding the dependent children in their care have not been examined. In this qualitative study, transcriptions of semi-structured interviews with 19 female and four male skipped-generation(s) Kansas caregivers (ages 47 to 80, 92% non-Hispanic whites, 83% female, 78% grandparents and 22% great-aunt or great-grandparent caregivers; caring for a range of one to four children, ages three to 18, for an average of nine years) were content analyzed for how their nutrition-related practices and attitudes had changed since parenting the first time. Sub-themes regarding practices included: being more nutrition and food safety conscious now, and shifting their child feeding style. The children seemed to be adversely affected by an on-the-go lifestyle and the use of more electronics. Caregivers described their sources for child feeding advice as being based mostly on information from their mothers, physicians, and their past parenting experiences. Sub-themes for attitudes included opinions that nutrition and safe food handling are important and that nutritious food is expensive. They preferred printed or video nutrition education materials and wanted to receive information through organizations they trusted. This population could benefit from education on: infant, child, adolescent, and sports nutrition; feeding "picky eaters"; healthful recipes, "fast foods" and packaged foods; quick, inexpensive meals and snacks low in fat, sugar, and salt; limiting sedentary time; family meals; using food thermometers; and intergenerational gardening and cooking.


Joint determination of todralazine and acetazolamide in human serum by differential pulse polarography.
Differential pulse polarography (DPP) is proposed as a direct method for the quantitation of todralazine and acetazolamide in human serum. The method was applied to the determination of these drugs in human serum, after a liquid-liquid extraction process. This extraction process together with the use of the standard additions method is essential for the elimination of the matrix effect. The proposed method enables detection limits of 0.107 microgram ml-1 for acetazolamide and 0.111 microgram ml-1 for todralazine to be achieved at reduction potentials of -0.59 and -0.86 V, respectively, using Britton-Robinson buffer (pH 1.65) as the supporting electrolyte.


Biceps muscle injury associated with non-invasive automatic blood pressure monitoring.
This case describes a young, healthy woman who developed a grade 1 biceps muscle strain after the use of automatic non-invasive blood pressure monitoring during an elective surgical procedure. She was treated conservatively with simple analgesia, physiotherapy and a sling for comfort. Follow-up conducted 1 week later revealed occasional soreness, but she had almost returned to her baseline activity. The patient made a full recovery without any residual symptoms by the end of 6 weeks. This case highlights the importance of careful monitoring to ensure that routine use of blood pressure cuffs does not cause any pressure injuries.


Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer.
Metformin is a well-known AMPK (AMP-activated protein kinase) activator that suppresses cancer stem cells (CSCs) in some cancers. However, the mechanisms of the CSC-suppressing effects of metformin are not yet well understood. In this study, we investigated the CSC-suppressive effect of metformin via the mevalonate (MVA) pathway in colorectal cancer (CRC). Two colorectal cancer cell lines, HT29 and DLD-1 cells, were treated with metformin, mevalonate, or a combination of the two. We measured CSC populations by flow cytometric analysis (CD44+/CD133+) and by tumor spheroid growth. The expression of p-AMPK, mTORC1 (pS6), and key enzymes (HMGCR, FDPS, GGPS1, and SQLE) of the MVA pathway was also analyzed. We investigated the effects of metformin and/or mevalonate in xenograft mice using HT29 cells; immunohistochemical staining for CSC markers and key enzymes of the MVA pathway in tumor xenografts was performed. In both HT29 and DLD-1 cells, the CSC population was significantly decreased following treatment with metformin, AMPK activator (AICAR), HMG-CoA reductase inhibitor (simvastatin), or mTOR inhibitor (rapamycin), and was increased by mevalonate. The CSC-suppressing effect of these drugs was attenuated by mevalonate. The results of tumor spheroid growth matched those of the CSC population experiments. Metformin treatment increased p-AMPK and decreased mTOR (pS6) expression; these effects were reversed by addition of mevalonate. The expression of key MVA pathway enzymes was significantly increased in tumor spheroid culture, and by addition of mevalonate, and decreased upon treatment with metformin, AICAR, or rapamycin. In xenograft experiments, tumor growth and CSC populations were significantly reduced by metformin, and this inhibitory effect of metformin was abrogated by combined treatment with mevalonate. Furthermore, in the MVA pathway, CSC populations were reduced by inhibition of protein prenylation with a farnesyl transferase inhibitor (FTI-277) or a geranylgeranyl transferase inhibitor (GGTI-298), but not by inhibition of cholesterol synthesis with a squalene synthase inhibitor (YM-53601). In conclusion, the CSC-suppressive effect of metformin was associated with AMPK activation and repression of protein prenylation through MVA pathway suppression in colorectal cancer.


Anion channels: master switches of stress responses.
During stress, plant cells activate anion channels and trigger the release of anions across the plasma membrane. Recently, two new gene families have been identified that encode major groups of anion channels. The SLAC/SLAH channels are characterized by slow voltage-dependent activation (S-type), whereas ALMT genes encode rapid-activating channels (R-type). Both S- and R-type channels are stimulated in guard cells by the stress hormone ABA, which leads to stomatal closure. Besides their role in ABA-dependent stomatal movement, anion channels are also activated by biotic stress factors such as microbe-associated molecular patterns (MAMPs). Given that anion channels occur throughout the plant kingdom, they are likely to serve a general function as master switches of stress responses.


Taxonomic and functional structure of macrobenthic invertebrate communities and their response to environmental variables along the subbranches of the Nile River (rayahs), Egypt.
Macrobenthic invertebrate communities serve as markers of anthropogenic stress in freshwater ecosystems. In this study, 17 sampling sites were selected from two Nile river subbranches (El-Rayah El-Behery and El-Rayah El-Nassery) and subjected to different anthropogenic influences to explore the ecological environment and characteristics of macrobenthos communities. Macrobenthos were studied using taxonomic diversity and biological trait analysis to investigate how human activity and variation in water quality affect their structure and function. A total of 37 taxa represented by 43,389 individuals were recognized. The communities are composed chiefly of Oligochaeta and aquatic insects. Multivariate statistical analyses found that the most influential environmental variables in the structural and functional community were sodium, dissolved oxygen, silicate, pH, calcium, and cadmium. At high levels of pollution, notably sewage and industrial pollution in the northern part of El-Rayah El-Behery, characteristics such as larger body size, detritus feeders, burrowers, and high tolerance to pollution predominated, whereas at low levels of pollution, features such as small body sizes, scraper and predator feeders, intolerant and fairly tolerant of pollution, and climber and swimmer mobility are predominant. The results confirm our prediction that the distribution of macroinvertebrate traits varies spatially in response to environmental changes. The diversity-based method distinguished impacted sewage and industrial sites from thermal effluent sites, while the trait-based approach illustrated an apparent variance between the ecological status of contaminated regions. Therefore, the biological features should be employed in addition to structural aspects for assessing the biodiversity of macroinvertebrate communities under environmental stressors.


Port site ischemic necrosis: an unforeseen complication of laparoscopic surgery.
A case of necrosis of the 10-mm umbilical port site after laparoscopic closure of enterocele in a 66-year-old woman is reported. Ischemic necrosis of the superficial tissue with cellulitis of the umbilical wound was seen during debridement. This highlights a hitherto unforeseen complication of laparoscopic surgery.


Evaluating the complete (44-item), short (20-item) and ultra-short (10-item) versions of the Big Five Inventory (BFI) in the Brazilian population.
The Big Five Inventory (BFI) is an instrument designed to assess the personality of individuals aged 18 and above. The original version consists of 44 items divided into five sub-scales representing each of the five personality factors: agreeableness, neuroticism, conscientiousness, openness, and extraversion. The main purpose of this study was to assess the factorial structure of the 44-item BFI and the reliability of two shorter versions with 20 and 10 items. The study also aimed to present normative data for interpreting scores from the short and ultrashort versions of the BFI for the Brazilian population. A total of 3565 individuals with a mean age of 33.3 years (SD = 13.0) from all Brazilian states participated in the study, with 44.2% from the State of Rio Grande do Sul. Participants completed a sociodemographic questionnaire and the BFI. Confirmatory factor analysis showed poor adaptation of the original 44-item model, but the short and ultrashort versions with 20 and 10 items respectively had good adaptation indexes and reliability, with Omega coefficients above 0.70. Normative data for the shorter versions were presented using mean, standard deviation, and percentiles (lower, medium, and higher). The study concluded that the short and ultrashort versions of the BFI have good reliability and can be used in surveys requiring a brief personality assessment.


Induction of protective immunity against Eimeria tenella, Eimeria necatrix, Eimeria maxima and Eimeria acervulina infections using multivalent epitope DNA vaccines.
Avian coccidiosis is mostly caused by mixed infection of several Eimeria species under natural conditions and immunity to avian coccidiosis is largely dependent on T-cell immune response. In this study, 14 T-cell epitope fragments from eight antigens of Eimeria tenella (E. tenella), Eimeria necatrix (E. necatrix), Eimeria maxima (E. maxima) and Eimeria acervulina (E. acervulina) were ligated with pVAX1 producing 14 monovalent DNA vaccines, respectively. Protective immunity of the monovalent DNA vaccines was assessed by in vivo challenge experiments and then four most protective fragments of each species were chosen to construct multivalent epitope DNA vaccines with or without chicken IL-2 as genetic adjuvant. Protective efficacies of the epitope DNA vaccines on chickens against E. tenella, E. necatrix, E. maxima and E. acervulina were evaluated. The results showed that the constructed multivalent epitope DNA vaccines significantly increased body weight gain, alleviated enteric lesions and reduced oocyst output of the infected birds. Especially, the multivalent epitope DNA vaccines of pVAX1-NA4-1-TA4-1-LDH-2-EMCDPK-1 and pVAX1-NA4-1-TA4-1-LDH-2-EMCDPK-1-IL-2 not only significantly increased body weight gain, alleviated enteric lesions and reduced oocyst output of the infected birds, but also resulted in anti-coccidial index (ACI) more than 170 against E. tenella, E. necatrix, E. maxima and E. acervulina, which indicated they could induce protective immunity against E. tenella, E. necatrix, E. maxima and E. acervulina. Our findings suggest the constructed multivalent epitope DNA vaccines are the potential candidate multivalent vaccines against mixed infection of Eimeria.


Reoperative sentinel lymph node biopsy after previous mastectomy.
Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in breast cancer, but many clinical scenarios questioning the validity of SLN biopsy remain. Here we describe our experience with reoperative-SLN (re-SLN) biopsy after previous mastectomy. Review of the SLN database from September 1996 to December 2007 yielded 20 procedures done in the setting of previous mastectomy. SLN biopsy was performed using radioisotope with or without blue dye injection superior to the mastectomy incision, in the skin flap in all patients. In 17 of 20 patients (85%), re-SLN biopsy was performed for local or regional recurrence after mastectomy. Re-SLN biopsy was successful in 13 of 20 patients (65%) after previous mastectomy. Of the 13 patients, 2 had positive re-SLN, and completion axillary dissection was performed, with 1 having additional positive nodes. In the 11 patients with negative re-SLN, 2 patients underwent completion axillary dissection demonstrating additional negative nodes. One patient with a negative re-SLN experienced chest wall recurrence combined with axillary recurrence 11 months after re-SLN biopsy. All others remained free of local or axillary recurrence. Re-SLN biopsy was unsuccessful in 7 of 20 patients (35%). In three of seven patients, axillary dissection was performed, yielding positive nodes in two of the three. The remaining four of seven patients all had previous modified radical mastectomy, so underwent no additional axillary surgery. In this small series, re-SLN was successful after previous mastectomy, and this procedure may play some role when axillary staging is warranted after mastectomy.


Novel insight into cellulose supramolecular structure through ¹³C CP-MAS NMR spectroscopy and paramagnetic relaxation enhancement.
(13)C CP-MAS NMR and paramagnetic relaxation enhancement provide novel insight into the supramolecular structure of solid cellulose I and II. Separable NMR signals associated with crystalline interiors, solvent accessible and inaccessible surfaces, as well as non-crystalline material are assigned and confirmed. For the first time solvent accessibility is evidenced and monitored through (13)C T1 NMR relaxation enhancement in paramagnetic medium. Established NMR signal assignments for cellulose I have been confirmed. Existing cellulose II resonance attributions have been modified and extended. Novel spectral fitting routines for cellulose II allow for the reproducible quantification of separable signal contributions. Results from NMR line shape analyses are straightforwardly introduced into a model for cellulose II supramolecular structure.


From HLA association to function.
A new study refines the association signals for rheumatoid arthritis susceptibility in the major histocompatibility complex (MHC) region to five amino-acid positions encoded in three HLA genes, all within peptide-binding grooves. By adapting statistical methods from genome-wide association studies (GWAS) and using imputation from a large reference panel, they demonstrate the potential for this approach to identify functional variants in associated regions.


Cerebral vasospasm and corticospinal tract injury induced by a modified rat model of subarachnoid hemorrhage.
Double-hemorrhage rat models of subarachnoid hemorrhages (SAH) are most effective at simulating delayed cerebral vasospasms (CVS). The present study modified the models to minimize additional trauma and investigated injury of the corticospinal tract (CST) using diffusion tensor imaging (DTI). On the first day, 0.3ml of autologous arterial blood was collected by puncturing the caudal artery and injected into the cisterna magna via percutaneous puncture; and the operation was repeated on the third day. The diameters of the basilar artery (BA), middle cerebral artery (MCA), and anterior cerebral artery (ACA) were measured by magnetic resonance angiography on days 3, 5, 7, 9, and 11 post-SAH. Meanwhile, on days 3, 7, 11, 15 and 19, DTI was performed to evaluate the injury of the CST at cerebral peduncle (CP) and pyramidal tract (Py) by measuring fractional anisotropy (FA) value. Blood was deposited mainly in the basal cistern. Diameters of BA, MCA, and ACA were significantly reduced. FA value of the CP was lower in the SAH group than in the control group; but FA value of Py wasn't different between the two groups. This is a minimally-invasive and high performance rat model of SAH. Additionally, the occurrence of CVS is firm and the axons in CP are injured.


Changes of some postural reflexes during the first postnatal weeks in the dog.
During the first two postnatal weeks postural reflexes were either absent or abortive. First adult-like patterns of reactions were seen at the end of the 3rd week but they could be regularly elicited only by the 6th-9th week.


Antihypoxic and Neuroprotective Effects of Glial Cell-Derived Neurotrophic Factor (GDNF) in Cultures of Dissociated Hippocampal Cells under Conditions of Experimental Hypoxia.
We analyzed the effect of glial cell derived neurotrophic factor (GDNF) on changes in functional bioelectric and calcium activity in dissociated hippocampal cell cultures under conditions of modeled acute normobaric hypoxia in vitro. GDNF (1 ng/ml) partially neutralized the negative effects of hypoxia on cell survival and parameters of functional network activity. GDNF exhibited a pronounced anti-hypoxic effect.


Interfacial rheology for the assessment of potential health effects of inhaled carbon nanomaterials at variable breathing conditions.
Lung surface is the first line of contact between inhaled carbon nanomaterials, CNMs, and the organism, so this is the place where pulmonary health effects begin. The paper analyzes the influence of several CNMs (single- and multi-walled nanotubes with various surface area: 90-1,280 m2/g and aspect ratio: 8-3,750) on the surface-active properties of the lung surfactant, LS, model (Survanta). Effects of CNM concentration (0.1-1 mg/ml) and surface oscillation rate were determined using the oscillating drop method at simulated breathing conditions (2-10 s per cycle, 37 °C). Based on the values of apparent elasticity and viscosity of the interfacial region, new parameters: Sε and Sμ were proposed to evaluate potential effect of particles on the LS at various breathing rates. Some of tested CNMs (e.g., COOH- functionalized short nanotubes) significantly influenced the surfactant dynamics, while the other had weaker effects even at high particle concentration. Analysis of changes in Sε and Sμ provides a new way to evaluate of a possible disturbance of the basic functions of LS. The results show that the expected pulmonary effects caused by inhaled CNMs at variable breathing rate depend not only on particle concentration (inhaled dose) but also on their size, structure and surface properties.


Multi-dimensional single-cell characterization revealed suppressive immune microenvironment in AFP-positive hepatocellular carcinoma.
Alpha-fetoprotein (AFP)-secreting hepatocellular carcinoma (HCC), which accounts for ~75% of HCCs, is more aggressive with a worse prognosis than those without AFP production. The mechanism through which the interaction between tumors and the microenvironment leads to distinct phenotypes is not yet clear. Therefore, our study aims to identify the characteristic features and potential treatment targets of AFP-negative HCC (ANHC) and AFP-positive HCC (APHC). We utilized single-cell RNA sequencing to analyze 6 ANHC, 6 APHC, and 4 adjacent normal tissues. Integrated multi-omics analysis together with survival analysis were also performed. Further validation was conducted via cytometry time-of-flight on 30 HCCs and multiplex immunohistochemistry on additional 59 HCCs. Our data showed that the genes related to antigen processing and interferon-γ response were abundant in tumor cells of APHC. Meanwhile, APHC was associated with multifaceted immune distortion, including exhaustion of diverse T cell subpopulations, and the accumulation of tumor-associated macrophages (TAMs). Notably, TAM-SPP1+ was highly enriched in APHC, as was its receptor CD44 on T cells and tumor cells. Targeting the Spp1-Cd44 axis restored T cell function in vitro and significantly reduced tumor burden when treated with either anti-Spp1 or anti-Cd44 antibody alone or in combination with anti-Pd-1 antibody in the mouse model. Furthermore, elevated IL6 and TGF-β1 signaling contributed to the enrichment of TAM-SPP1+ in APHC. In conclusion, this study uncovered a highly suppressive microenvironment in APHC and highlighted the role of TAM-SPP1+ in regulating the immune microenvironment, thereby revealing the SPP1-CD44 axis as a promising target for achieving a more favorable immune response in APHC treatment.


Aryl sulfonamides as selective PDE4 inhibitors.
A series of novel selective phosphodiesterase 4 (PDE4) inhibitors has been developed which displays activity both in vitro and in vivo. These compounds possess good selectivity for the catalytic site of PDE4 over the high affinity Rolipram binding site. In vivo studies demonstrate a reduced propensity to display the emetic side effects which are commonly observed with PDE4 inhibitors.


Intracellular zinc increase inhibits p53(-/-) pancreatic adenocarcinoma cell growth by ROS/AIF-mediated apoptosis.
We show that treatment with non-toxic doses of zinc in association to the ionophore compound pyrrolidine dithiocarbamate (PDTC) inhibits p53(-/-) pancreatic cancer cell growth much more efficiently than gemcitabine, the gold standard chemotherapeutic agent for pancreatic cancer. Both the metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine and the radical scavenger N-acetyl-l-cysteine are able to recover cell growth inhibition by Zn/PDTC, demonstrating that this effect depends on the increased levels of intracellular zinc and of reactive oxygen species (ROS). Zn/PDTC treatment induces a strong apoptotic cell death that is associated to ROS-dependent nuclear translocation of the mitochondrial factor AIF, but not to the regulation of apoptotic genes and caspase activation. Primary fibroblasts are more resistant than pancreatic cancer cells to Zn/PDTC treatment and exhibit a lower basal and Zn/PDTC-induced enhancement of intracellular zinc. We show that Zn/PDTC induces p53 proteasomal degradation and that the proteasome inhibitor MG132 further increases fibroblast growth inhibition by Zn/PDTC, suggesting that p53 degradation plays an important role in fibroblast resistance to Zn/PDTC.


Benzodiazepine use in patients hospitalized in a department of internal medicine: frequency and clinical correlates.
Misuse and overuse of benzodiazepines (BZD) are common. Several studies have shown that benzodiazepines are frequently used in hospitalized patients, but fewer studies have been conducted to investigate whether BZD use increases during the hospital stay or whether patients have already taken BZD before admission. To assess the prevalence of benzodiazepine use in hospitalized patients and to determine characteristics associated with this use. Prospective study over a 4-month period based on all admissions to a department of internal medicine. The main outcome was the prevalence of benzodiazepine use at admission, during hospital stay and at discharge. Of 444 patients admitted, 147 (33%) used at least one benzodiazepine which was in 75% of the cases, short-elimination half-life BZD used as hypnotic. Of 105 (23.6%) patients using BZD at admission, 23 (5.2%) stopped BZD during hospital stay or when leaving hospital. The in-hospital prevalence of BZD use was 30% (133 patients). In 28 (6.3%) patients without BZD at baseline, BZD was introduced during the hospital stay then stopped at discharge in 18 (4%) patients. The prevalence of BZD use at discharge was 23.9% (106 patients). In multivariate analyses, BZD use was significantly associated with number of drugs taken during hospitalization (OR: 1.13; 95% CI: 1.03-1.24), and current neuropsychiatric diseases (OR: 2.12; 95% CI: 0.86-5.23), but not with gender, age or length of stay. Prevalence of BZD use appeared to be fairly high among hospitalized patients. There were very few new BZD users during hospital stay, most of whom were stopped at discharge. Most treatments were started before hospital, and continued during and after hospital stay without clear reevaluation.


Next generation sequencing-aided comprehensive geographic coverage sheds light on the status of rare and extinct populations of Aporia butterflies (Lepidoptera: Pieridae).
The Black-veined White Aporia crataegi (Linnaeus, 1758), a common and widespread butterfly ranging from northwestern Africa to Europe and Asia, has been extinct in Britain since the 1920s and is on a steady decline in several other parts of its range. In order to investigate genetic diversity within A. crataegi and its correspondence with current subspecies-level taxonomy, we barcoded 173 specimens from across its range including, for the first time, extinct populations from Britain and Korea. Using next generation sequencing we also obtained a sequence for Aporia joubini, a peculiar taxon from China known only by its type specimen collected in the early twentieth century. Our phylogenetic analysis placed A. joubini sister to A. oberthuri, although further taxon sampling may reveal a different scheme. Within A. crataegi, we observed a shallow and weak mitogenomic structure with only a few distinct lineages in North Africa, Sicily, Iran, and Japan. Eurasian populations, including those extinct in Britain and Korea, clustered into a large set of closely allied lineages, consistent with a recent expansion during the Late Pleistocene glacial period. This study highlights the importance of museum collections and the unique opportunities they provide in documenting species diversity and helping conservation efforts.


The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. I. The tryptic peptides from the maleylated protein.
Six tryptic peptides ranging in size from 3 to 126 residues were isolated from maleylated Fragment A of diphtheria toxin after tryptic hydrolysis. These peptides accounted for all 193 residues found by amino acid analysis. After demaleylation, the six peptides were purified by chromatography on Sephadex G-50, coupled with paper chromatography and electrophoresis, and were analyzed by various methods. The compositions and properties of the peptides are reported. Almost 70% of the residues were positioned within these peptides.


In Vitro Priming and Hyper-Activation of Brain Microglia: an Assessment of Phenotypes.
Microglia are the resident immune cells of the central nervous system that mediate the life and death of nervous tissue. During normal function, they exhibit a surveying phenotype and maintain vital functions in nervous tissue. In the event of injury or disease, chronic inflammation can result, wherein microglia develop a hyper-activated phenotype, shed their regenerative function, actively kill contiguous cells, and can partition injured tissue by initiating scar formation. With recoverable injury, microglia can develop a primed phenotype, where they appear to recover from an inflammatory event, but are limited in their support functions and show inappropriate responses to future injury often associated with neurodegenerative disorders. These microglial phenotypes were acutely recreated in vitro with potent pro- and anti-inflammatory treatments. Primary cultured microglia or mixed glia (microglia, astrocytes, and oligodendrocytes) were treated for 6 h with lipopolysaccharide (LPS). Recovery from an inflammatory state was modeled with 18-h treatment of the anti-inflammatory steroid dexamethasone. The cells were then treated for 24 h with interferon gamma (IFNγ) to detect inflammatory memory after recovery. Surveying was best represented in the untreated vehicle (Veh) cases and was characterized by negligible secretion of pro-inflammatory factors, limited expression of immune proteins such as induced nitric oxide synthase (iNOS), major histocompatibility complex class II (MHCII), relatively high expression of brain-derived and glial-derived neurotrophic factors (BDNF and GDNF), and thinly branched smaller microglia. Activation was noted in the LPS- and IFNγ-treated microglia with increased cytokines, NO, NGF, iNOS, proliferation, phagocytosis, reduced BDNF, and flattened round amoeboid-shaped microglia. Priming was observed to be an incomplete surveying restoration using dexamethasone from an activation comparison of LPS, IFNγ, and LPS/IFNγ. Dexamethasone treatments resulted in the most profound dysregulation of expression of NO, TNF, IL-1β, NGF, CD68, and MHCII as well as ramified morphology and uptake of myelin. These findings suggest microglial priming and hyper-activation may be effectively modeled in vitro to allow mechanistic investigations into these key cellular phenotypes.


Management of patients with statin intolerance.
Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality, and statins have become a cornerstone in its treatment and prevention. Despite the well-documented benefits of statins, many patients stop taking them, with adverse muscle symptoms being a commonly cited reason. Although some statin-associated adverse muscle effects are real, some can be attributed to the nocebo effect, which is the patient's perception of harm. The purpose of this article is to review the literature on statin safety, particularly that related to muscle, to analyze adverse effects, and to propose various treatment strategies for the statin intolerant patient.


Malignant lymphoma of plasmablastic identity. A neoplasm with both "immunoblastic" and plasma cellular features.
A solitary extramedullary lymphoid neoplasm had characteristics of plasma cell precursors or plasmablasts. Conventional microscopic study classified this tumor as a diffuse large cell lymphoma of "immunoblastic sarcoma" type. Immunologic cell surface markers could not be detected, but cytoplasmic immunoglobulin G (IgG)-kappa was demonstrated by immunoperoxidase technic, and IgG was present in the supernatant of the tumor tissue culture. The distinction between lymphoid and plasma cellular neoplasms is made.


Intraoperative visualization of morphological patterns of the thoracic duct by subcutaneous inguinal injection of indocyanine green in esophagectomy for esophageal cancer.
To prevent chylothorax after esophageal cancer surgery, it is important to recognize morphological patterns of the thoracic duct intraoperatively. The present study aimed to evaluate the safety and usefulness of near-infrared (NIR) fluorescence imaging with subcutaneous inguinal injection of indocyanine green (SII-ICG) to detect the thoracic duct during thoracoscopic esophagectomy for esophageal cancer. Patients (n = 16) who underwent thoracoscopic esophagectomy in the prone position with SII-ICG at Shinshu University Hospital between June 2020 and January 2022 were enrolled in the present study and retrospectively reviewed. Immediately prior to thoracoscopic esophagectomy, we injected 0.2-0.5 mg/kg ICG into the subcutaneous tissue in the bilateral inguinal region. The identification rate of the thoracic duct was 93.8% (n = 15), and the success rate of fluorescence using SII-ICG was 87.5% (n = 14). The visible thoracic ducts had four patterns: a typical pattern in 50% (n = 8), duplication pattern in 18.8% (n = 3), branching pattern in 12.5% (n = 2), and plexiform pattern in 12.5% (n = 2). In all cases, ICG fluorescence did not disappear and was visible during the thoracic surgery. No SII-ICG-related complications were observed. Intraoperative NIR fluorescence imaging of the thoracic duct using SII-ICG is a simple and safe method with very high detection sensitivity. This method can be a powerful tool for avoiding thoracic duct injuries during esophageal cancer surgery.


Weight-management interventions for pregnant or postpartum women.
A review of randomized controlled trials of weight-management interventions for pregnant or postpartum women was conducted to assess whether effective weight-management interventions exist for this population. The MEDLINE, EMBASE, PsycINFO, Sociological Abstracts, and CINAHL databases were searched, as well as the reference lists of relevant publications. English-language articles published between January 1985 and August 2007 that used a randomized controlled trial study design and incorporated a weight-related outcome measure were reviewed. All potentially relevant articles were reviewed separately, and final selections were based on consensus reached through discussion. Three studies met the inclusion criteria, one conducted among pregnant women and two among postpartum women. The interventions addressed modifications in diet and exercise and included individual or group-counseling sessions combined with written and telephone correspondence or food and exercise diaries. In two studies, the weight-related outcome was significantly better in the intervention group than in the control group. The third study found a significant interaction between weight category and intervention group. In all studies, the refusal or attrition rates were high. While these studies indicate that interventions can help pregnant and postpartum women manage their weight, many questions remain unanswered. Several research gaps for weight-management interventions in this important population have been identified.


Pathogenic postzygotic mosaicism in the tyrosine receptor kinase pathway: potential unidentified human disease hidden away in a few cells.
Mutations occurring during embryonic development affect only a subset of cells resulting in two or more distinct cell populations that are present at different levels, also known as postzygotic mosaicism (PZM). Although PZM is a common biological phenomenon, it is often overlooked as a source of disease due to the challenges associated with its detection and characterization, especially for very low-frequency variants. Moreover, PZM can cause a different phenotype compared to constitutional mutations. Especially, lethal mutations in receptor tyrosine kinase (RTK) pathway genes, which exist only in a mosaic state, can have completely new clinical manifestations and can look very different from the associated monogenic disorder. However, some key questions are still not addressed, such as the level of mosaicism resulting in a pathogenic phenotype and how the clinical outcome changes with the development and age. Addressing these questions is not trivial as we require methods with the sensitivity to capture some of these variants hidden away in very few cells. Recent ultra-accurate deep-sequencing approaches can now identify these low-level mosaics and will be central to understand systemic and local effects of mosaicism in the RTK pathway. The main focus of this review is to highlight the importance of low-level mosaics and the need to include their detection in studies of genomic variation associated with disease.


Endovascular Embolization of a Large High-Flow Splenic Arteriovenous Fistula and Aneurysm Using the Amplatzer Vascular Plug II.
We describe the use of an Amplatzer Vascular Plug (AVP) II for embolizing a large high-flow splenic arteriovenous fistula and an aneurysm in a young patient. This patient presented to our center with persistent mild abdominal discomfort, 5 years after open splenectomy. Contrast-enhanced computed tomography angiography showed the presence of a fistula between the splenic arterial and splenic venous remnants and a resultant fusiform aneurysmal dilatation of the residual splenic vein. We decide to embolize the splenic artery with a 12-mm diameter AVP II with an oversizing by 70% of the vessel diameter. Celiac angiography performed 5 min postembolization revealed complete obliteration of the splenic artery and closure of the arteriovenous fistula. The overall procedure time was 40 min, and overall radiation exposure was 32 Gy cm(2) (dose-area product).


Ca2+-dependent conformational changes in bovine GCAP-2.
GCAP-2, a mammalian photoreceptor-specific protein, is a Ca2+-dependent regulator of the retinal membrane guanylyl cyclases (Ret-GCs). Sensing the fall in intracellular free Ca2+ after photo-excitation, GCAP-2 stimulates the activity of Ret-GC leading to cGMP production. Like other members of the recoverin superfamily, GCAP-2 is a small N-myristoylated protein containing four EF-hand consensus motifs. In this study, we demonstrate that like recoverin and neurocalcin, GCAP-2 alters its conformation in response to Ca2+-binding as measured by a Ca2+-dependent change in its far UV CD spectrum. Differences in the conformation of the Ca2+-bound and Ca2+-free forms of GCAP-2 were also observed by examining their relative susceptibility to V8 protease. In contrast to recoverin, we do not observe proteolytic cleavage of the myristoylated N-terminus of Ca2+-bound GCAP-2. NMR spectra also show that, in contrast to recoverin, the chemical environment of the N-terminus of GCAP-2 is not dramatically altered by Ca2+ binding. Despite the similarity of GCAP-2 and recoverin, the structural consequences of Ca2+-binding for these two proteins are significantly dissimilar.


First febrile convulsions: inquiry about the knowledge, attitudes and concerns of the patients' mothers.
In comparison with other diseases, febrile convulsion, despite its excellent prognosis, is a cause of high anxiety among mothers. The objective of our study was to evaluate the knowledge, concerns, attitudes and practices of the mothers of children with first febrile convulsion. A prospective questionnaire-based study was carried out at the Mofid Children's Hospital. One hundred and twenty-six mothers of consecutive children presenting with febrile convulsion were enrolled. Only 58 (46%) mothers recognised the convulsion. Forty-nine (39%) of them interpreted the seizure as death. Others interpreted it as other causes. Eighty-five (68%) parents did not carry out any intervention prior to getting the child to the hospital. The most common cause of concern among parents was the state of their child's health in the future (n=120, 95%), followed by the fear of recurrence (n=83, 66%), mental retardation (n=60, 48%), paralysis (n=39, 31%), physical disability (n=37, 30%) and learning dysfunction (n=28, 22%). In 41 (33%) mothers, there were other causes of concerns, including fear of visual defect, hearing loss, memory loss, brain defect, delay in walking, drug adverse effects, coma and death. Sixty-eight percent of mothers had acceptable information about the measures that should be taken to prevent recurrence. Awareness of preventive measures was higher in mothers with high educational level (P<0.01). Seventy-six percent of mothers did not know anything about the necessary measures in case of recurrence. From this study, we conclude that parental fear of febrile convulsion is a major problem, with serious negative consequences affecting daily familial life.


Lack of alpha 2-antiplasmin promotes re-endothelialization via over-release of VEGF after vascular injury in mice.
We here report that the arterial blood flow after endothelial injury in mice deficient in alpha 2-antiplasmin (alpha 2-AP-/- mice) was well maintained compared with that of wild-type mice. Moreover, the development of neointima 4 weeks after injury in alpha 2-AP-/- mice was significantly decreased. Histologic observations showed a prompt recovery of endothelial cells with a much higher proliferating index in repaired endothelium in alpha 2-AP-/- mice. The amount of secreted vascular endothelial growth factor (VEGF) by explanted vascular smooth muscle cells (SMCs) from alpha 2-AP-/- mice was significantly increased. In separate experiments using a human endothelial cell (EC) line, we could demonstrate that plasminogen binds to ECs and that this binding can be prevented by alpha 2-AP. Finally, an injection of either an anti-VEGF receptor-1 antibody or alpha 2-AP reduced the prompt endothelial healing. alpha 2-AP is the main inactivator of plasmin, which cleaves extracellular matrix-bound VEGF to release a diffusible proteolytic fragment. Lack of alpha 2-AP, therefore, could lead to a local over-release of VEGF by the continuously active plasmin in the injured area, which could result in a prompt re-endothelialization after vascular injury. Our results provide new insight into the role of alpha 2-AP and VEGF in the pathogenesis of re-endothelialization following vascular injury.


Interventional computed tomography and MR imaging in the head and neck.
Many modern surgical techniques have been developed to provide exposure or visualization of the surgical field to perform definitive treatment. The actual therapeutic part of surgery is often a small fraction of the procedure. In obtaining exposure, however, morbidity can ensue. This has led to newer techniques that use minimally invasive treatments, thus substantially decreasing overall morbidity and patient costs. By providing physicians with visualization alternatives, MR imaging and computed tomography, when combined with a therapeutic procedure, can reduce the morbidity of surgery.


[Short-term effects of air pollutants on pulmonary function in adolescent with a history of asthma or allergies].
Transboundary pollution including airborne fine particulate matter (PM(2.5)) has been attracting attention in recent years and its health effects are concerned. We evaluated the short-term effects of air pollutants on pulmonary function among young students. Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were examined every morning for 1 month in 37 students who attend a school in a remote island of the Seto Inland Sea. The concentrations of fine and coarse particles (PM(2.5) and PM(10-2.5)), optical black carbon (OBC) and nitrogen dioxide (NO₂) were measured on the rooftop of the school. The change in PEF was significantly associated with an increase in the prior 24-h average concentration of PM(2.5) among subjects with a history of asthma (-42.5 L/min [95% confidence interval (CI): -77.0, -8.1], for an interquartile rage increase of 17.6 μg/m³). Negative associations between pulmonary function and the concentrations of NO₂and OBC were observed as well. On the other hand, among the subjects with a history of allergy other than asthma and those without such history, negative association between air pollutants and pulmonary function was not observed. Subjects with a history of asthma are considered to be more affected by short-term exposure to air pollutants.


[Development of biochemical and histopathological parameters in paracetamol overdose in experimental cholestasis].
The aim of the present paper is to determine the effect of Paracetamol (P) acute intoxication in cholestatic rats. Four groups of animals were considered: controls, controls intoxicated with P, rats intoxicated with P and cholestatic rats. Hepatic biochemical tests and liver histology were performed in every group. It is concluded that cholestatic rats intoxicated with P showed less Liver damage than in control groups.


Divergent variant patterns among 19 patients with Rubinstein-Taybi syndrome uncovered by comprehensive genetic analysis including whole genome sequencing.
Rubinstein-Taybi syndrome (RSTS) is characterized by dysmorphic facial features, broad thumbs, and intellectual disability. CREB-binding protein (CREBBP) or E1A-binding protein P300 (EP300) are causative genes. To elucidate the underlying genetic and genomic architecture related to the RSTS phenotype, we performed comprehensive genetic analysis targeting CREBBP and/or EP300 in 22 clinically diagnosed patients. During the 11-year study period, we used several analysis methods including high-resolution melting, array-based comparative genomic hybridization, panel-based exome sequencing, whole exome sequencing, and whole genome sequencing (WGS). We identified the causative variants in 19 patients (86.3%), but they were variable and complex, so we must combine multiple analysis methods. Notably, we found genetic alterations in the non-coding regions of two patients (10.5%, 2/19): scattered deletions including a partial 5'-untranslated region of CREBBP in one patient (all coding exons were intact), and a deep 229-bp intronic deletion in another patient, resulting in a splicing error. Furthermore, we identified rare clinical findings: two patients with an EP300 variant showed abnormal development of the neural tube, and one patient with a CREBBP variant had anorectal atresia with a cloaca. Our findings expand the allelic heterogeneity of RSTS, underscore the utility of comprehensive genetic analysis, and suggest that WGS may be a practical diagnostic strategy.


Micronutrient status and fertilizer use scenario in India.
India was dependent on external food supplies in the early 1960s. To meet the growing demand for food, fiber and fuel, high yielding cultivars were introduced. These high yielding crop cultivars were highly responsive to fertilizers. Thus, slowly the soils were exhausted of their nutrients. Application of major nutrients (nitrogen, phosphorus, potassium) became common, therefore the crops started responding to micronutrient fertilizers. Concerted efforts have been made through the All India Coordinated Research Project on Micronutrients to delineate the soils of India regarding the deficiency of micronutrients. At present about 48.1% of Indian soils are deficient in diethylene-triaminepentaacetate (DTPA) extractable zinc, 11.2% in iron, 7% in copper and 5.1% in manganese. Apart from the deficiency of these micronutrients, deficiencies of boron and molybdenum have also been reported in some areas. Areas with multi-micronutrient deficiencies are limited, thus simple fertilizers are sufficient to exploit the potential of crops and cropping systems. Based on the extent of deficiency, cultivated area, and crop removal, the micronutrient fertilizer demand in 2025 is projected using sufficiency and maintenance approaches.


Fracture of the glenoid fossa and dislocation of the mandibular condyle into the middle cranial fossa.
Reported cases of dislocation of the mandibular condyle into the middle cranial fossa have been rare, and treatment modalities have varied. The case presented represents an instance of successful closed reduction. Numerous factors should be considered when determining the technique of reduction. Primary goals in selecting the method of treatment are stabilization of the neurologic status, control of the bone fragments in the brain, reduction of the occlusion, maintenance of ramus height for facial symmetry, preservation of growth potential, and assurance of satisfactory long-term function of the mandible.


Formation of unusual iridabenzene and metallanaphthalene containing electron-withdrawing substituents.
A new route to irida-aromatic derivatives which consists of the oxidation of bicyclic compounds has been disclosed. The iridanaphthalene 3 experiences hydrolytic cleavage of the Ir-carboxylate moiety regenerating the bicyclic structure 5, whereas treatment of 5 with ClC(O)CO2Me yields back the metalla-aromatic 3.


Comparison of live Newcastle disease vaccines in a simple vaccination and challenge experiment.
Groups of day-old chicks with haemagglutination inhibiting antibodies (HIA) were exposed by the spray method to equal doses of three different live Newcastle disease (ND) commercial vaccines and allantoic preparations of them. After three weeks the HIA response was measured and the chicks were challenged with a pathogenic strain of Newcastle disease virus (NDV). The degree of protection of each bird was compared with its HIA response. The commercial vaccines all provided good protection at identical levels, but significant differences were detected between the allantoic fluid preparations. Two of the commercial vaccines produced significantly better protection than the allantoic fluid preparations. In addition to the protection conferred by HIA antibody, other mechanisms of protection apparently played a part.


Stability and activity of an Enterobacter aerogenes-specific bacteriophage under simulated gastro-intestinal conditions.
A bacteriophage, designated UZ1 and showing lytic activity against a clinically important strain (BE1) of Enterobacter aerogenes was isolated from hospital sewage. The stability and lytic activity against this strain under simulated gastro-intestinal conditions was evaluated. After addition of bacteriophage UZ1 to a liquid feed at gastric pH 2, the phage was immediately inactivated and could not be recovered. However, by use of an antacid to neutralize stomach acidity, no significant changes in phage titer were observed after 2 h incubation at 37 degrees C. After supplementing pancreatic juice and further incubation for 4 h, the phage titer remained stable. The persistence of UZ1 in a mixed microbial ecosystem that was representative for the large intestine was monitored using an in vitro simulation of the human intestinal microbial ecosystem. A pulse administration of bacteriophage UZ1 at a concentration of 10(5) plaque-forming units (PFU)/ml to reactor 3 (which simulates the ascending colon) showed that, in the absence of the host, bacteriophage UZ1 persisted for 13 days in the simulated colon, while the theoretical washout was calculated at 16 days. To assess its lytic activity in an intestinal microbial ecosystem, a green fluorescent protein (gfp)-labeled E. aerogenes BE1 strain was constructed and gfp-specific primers were designed in order to quantify the host strain using real-time PCR. It was observed that bacteriophage UZ1 was able to replicate and showed lytic activity against E. aerogenes BE1/ gfp in an intestinal microbial ecosystem. Indeed, after 17 h a 2 log unit reduction of E. aerogenes BE1/ gfp was measured as compared with the assay without bacteriophage UZ1, while the phage titer increased by 2 log units at an initial multiplicity of infection of 0.07 PFU/colony-forming unit. This is the first report of an in vitro model to study bacteriophage activity in the complex intestinal microbial community.


Enlarging head size as the only presentation of Salmonella Typhimurium brain abscess in an infant: a short report.
The authors describe a 5-month-old male harbouring a giant Salmonella Typhimurium cerebral abscess who presented with progressively enlarging head size, without any features of septicemia. The report details the radiological findings, differential diagnoses and management problems regarding the index case.


Assessing drug exposure in rodent toxicity studies without satellite animals.
Five major objectives for pharmacokinetic investigations in support of toxicity studies are identified as follows: Assess whether animals exhibited measurable blood concentrations in a dose-dependent manner; estimate average area under the concentration-time curve (AUC) and maximal concentration (Cmax) for each treatment group; elucidate general patterns in the concentration-time (CxT) profile, and summarize relationships between CxT and treatment group; determine CxT dependence on day into study; and judge interanimal variability and identify any animals with unusual concentration response. Such objectives are generally addressed in rodent toxicity studies by including "satellite" animals in the study. Satellite animals are extra animals dosed as per protocol but not subjected to toxicological and pathological observations and tests. Instead, they are used exclusively for the evaluation of pharmacokinetic characteristics of the test compound. In this paper, methods are described for achieving the five listed pharmacokinetic objectives in rodent toxicity studies without the use of satellite animals. A rat toxicity study is presented as an example.


Epidemiology of Mixed Connective Tissue Disease, 1985-2014: A Population-Based Study.
To characterize the epidemiology of mixed connective tissue disease (MCTD) from 1983 to 2014. An inception cohort of patients with incident MCTD in 1985-2014 in Olmsted County, Minnesota was identified based on comprehensive individual medical record review. Diagnosis of MCTD required fulfillment of at least 1 of the 4 widely accepted diagnostic criteria without fulfillment of classification criteria for other connective tissue diseases. Data were collected on demographic characteristics, clinical presentation, laboratory investigations, and mortality. A total of 50 incident cases of MCTD were identified (mean age 48.1 years and 84% were female). The annual incidence of MCTD was 1.9 per 100,000 population. Raynaud's phenomenon was the most common initial symptoms (50%), followed by arthralgia (30%) and swollen hands (16%). The diagnosis was frequently delayed with the median time from first symptom to fulfillment of criteria of 3.6 years. At fulfillment of criteria, arthralgia was the most prevalent manifestation (86%), followed by Raynaud's phenomenon (80%), swollen hands (64%), leukopenia/lymphopenia (44%), and heartburn (38%). Evolution to other connective tissue occurred infrequently with a 10-year rate of evolution of 8.5% and 6.3% for systemic lupus erythematosus and systemic sclerosis, respectively. The overall mortality was not different from the general population with a standardized mortality ratio of 1.1 (95% confidence interval 0.4-2.6). This study was the first population-based study of MCTD to provide a complete picture of epidemiology and clinical characteristics of MCTD. MCTD occurred in about 2 persons per 100,000 per year. Evolution to other connective diseases occurred infrequently and the mortality was not affected.


Vertebral hemangiomas: diagnosis, management, natural history and clinicopathological correlates in 86 patients.
Vertebral hemangiomas are characterized by diverse clinical histories, radiological features, and results of surgical treatment. It still remains unclear how these differences in clinical behavior relate to pathological type. A retrospective diagnostic, surgical, and histopathological study of 86 consecutive patients with various pathological types of vertebral hemangioma was performed to establish clinicopathological correlates. The study confirmed that differences exist in clinical course, appearance on imaging, and outcomes in pathological types of hemangiomas. Based on these findings the authors attempted to identify signs characterizing each group. Differences in clinical history and radiological features exist among pathological types of vertebral hemangiomas. These differences cannot precisely predict the type pathology before histologic examination, but do help us to understand the natural history of such lesions more fully.


Effect of fluoride incorporation into human dental enamel on its demineralization in vitro.
Coronal surfaces of extracted human teeth were ground to a depth of about 1 mm and then cut in half labiolingually. One half was used as a control; the other half was exposed, for 3 days, to a fluoride-enriching buffer (0.1 mol/l lactic acid, 19.7 mmol/l CaCl2, 10.8 mmol/l KH2PO4, 3 mmol/l NaN3; pH adjusted to 4.68 with KOH) having fluoride concentrations from 0.0002 to 2.2 parts/10(6). This exposure resulted in an uptake of fluoride by the enamel to a depth of 2 microns without any apparent demineralization. The fluoride uptake was proportional to the F concentration of the enriching solution, reaching concentrations of about 8000 parts/10(6) within the first micrometre of enamel exposed to the highest F concentration; the controls had uniform F concentrations not exceeding 50 parts/10(6) along the 2.5 microns of enamel depth sampled. Thin sections (140-160 microns) were cut perpendicularly to the lingual surface, coated with protective resin except for a window about 1 mm long on the ground lingual surface, and exposed to a demineralizing buffer. The mineral losses of the sections were followed over 5 days by microradiography and image analysis. Fluoride enrichment resulted in reduced demineralization and the reduction was inversely related to the enamel fluoride content. The controls displayed a uniform erosion of the surface enamel whereas all the treatments below 1.5 parts/10(6) in the enriching solutions developed typical subsurface 'lesions'. The mineral content of the surface layer increased with increasing time of exposure to the demineralizing buffer.(ABSTRACT TRUNCATED AT 250 WORDS)


The binding of DNA intercalating and non-intercalating compounds to A-form and protonated form of poly(rC).poly(rG): spectroscopic and viscometric study.
Polymorphic RNA conformations may serve as potential targets for structure specific antiviral agents. As an initial step in the development of such drugs, the interaction of a wide variety of compounds which are characterized to bind to DNA through classical or partial intercalation or by mechanism of groove binding, with the A-form and the protonated form of poly(rC).poly(rG), been evaluated by multifaceted spectroscopic and viscometric techniques. Results of this study suggest that (i) ethidium intercalates to the A-form of RNA, but does not intercalate to the protonated form, (ii) methylene blue intercalates to the protonated form of the RNA but does not intercalate to the A-form, (iii) actinomycin D does not bind to either conformations of the RNA, and (iv) berberine binds to the protonated form by partial intercalation process, while its binding to the A-form is very weak. The DNA groove binder distamycin A has much higher affinity to the protonated form of the RNA compared to the A-form and binds to both structures by non-intercalative mechanism. We conclude that the binding affinity characteristics of these DNA binding molecules to the RNA conformations are vastly different and may serve as data for the development of RNA based antiviral drugs.


Effects of surgical or chemical delaying procedures on the survival of proximal predicled venous island flaps: an experimental study in rats.
To increase the survival of proximally pedicled venous island flaps, which are known to be safe only when small, we used surgical and chemical delaying procedures both individually and in combination for 7, 14, and 21 days. Survival was 1% in those flaps designated as controls, in which there was neither surgical nor chemical delay. However, it was 3%, 31%, and 68% at 7, 14, and 21 days, respectively, when surgical delay was used and 16%, 56%, and 86%, at 7, 14, and 21 days, respectively, when chemical delay was used. Survival was 32%, 84%, and 87%, at 7, 14, and 21 days when both chemical and surgical delays were used. We conclude that chemical delay is more effective than surgical delay in increasing survival of proximally pedicled venous island flaps, but the use of combined chemical and surgical delay may reduce the time required for delay.


Surface acoustic wave sensors in the bioanalytical field: recent trends and challenges.
This is a comparison of the latest developments in the emerging field of surface acoustic wave (SAW) sensors. Progress has been made particularly with regard to (sub-) microstructure technology and material sciences. Improvements are displayed based on the impact on a new generation of SAW sensors working efficiently in liquid media, from modeling to the fabrication steps of the individual components. It is explained, which obstacles have to be overcome for applications to the bioanalytical field. SAW sensors are shown to be extremely useful for the analysis of both small and large molecules as well as whole cells interacting with an immobilized binding partner. The output signal gives information about the pure mass loading, intrinsic properties of bound materials, or viscoelastic effects like structural rearrangements. Different setups are shown that minimize the influence of physical bulk effects on the sensor signal, e.g. salt content and viscosity. The choice of materials which can be used for sensible surfaces are presented, enabling the development of completely new coupling chemistries. Finally, the advantages compared to other biosensor technologies are pointed out.


[Which investigations should be selected for the preoperative assessment before the decision for treatment of abdominal aortic aneurysm by endoprosthesis: arteriography, tomodensitometry or magnetic resonance imaging?].
To determine the best imaging technique to obtain all the necessary information before the placement of an aortic endoprosthesis. Each technique is assessed from a review of the literature and the AA's own experience (21 endoprostheses); the advantages and disadvantages of each technique are discussed. 1) Arteriography (with a calibrated catheter), always considered at the investigation of choice to determine the feasibility of the technique, gives no information on the aortic wall; 2) spiral CT scanning is superior to basic scanning in giving a 3-dimensional picture. Many authors have concluded that spiral CT-scanning has replaced aortography, but its limitation, at the moment, is in the quality of the assessment of the renal arteries (number, stenosis); 3) magnetic resonance imaging has not been studied to any extent in terms of assessment for endoprosthetic treatment. Early results are promising and will be described. At the present time, the best compromise is spiral-CT scanning in thin sections with 3-dimensional reconstruction. The AA combine this with arteriography to visualise the renal arteries in particular, and the distal bed.


An adaptation-induced pop-out in visual search.
The present study demonstrates that an object embedded in an array of identical objects can pop-out. Dependent on the stimuli preceding the search display, local (chromatic) adaptation causes an identical object to pop-out because it appears to have a colour (Expt 1) or brightness (Expt 2) that is slightly different from the colour and brightness of the other objects in the display. Experiment 3 shows that this pop-out even occurs when the stimulus preceding the search display is presented for only 100 msec.


Clinical rhabdomyolysis.
Although rhabdomyolysis is an uncommon disorder, especially in children, it can present as a severe, life-threatening event. Paediatricians need to be aware of this important, probably underdiagnosed disorder in order to implement appropriate early treatment. In this report, seven children with rhabdomyolysis of both forms, endogenous and exogenous, are presented. Despite comprehensive 'up-to-date' investigations being performed on paediatric patients with endogenous (often recurrent) rhabdomyolysis, the majority of these patients' underlying disorders will remain undiagnosed. Overall, these patients usually have a very good prognosis even if repeated, severe life-threatening episodes occur. It is recommended that a regimen of early therapy with fluids and sodium bicarbonate be instituted in all patients with rhabdomyolysis.


Practice patterns and real-life outcomes for patients with acute promyelocytic leukemia in the United States.
Acute promyelocytic leukemia (APL) is associated with a favorable long-term prognosis if appropriate treatment is initiated promptly. Outcomes in clinical trials and population-based registries vary; potential explanations include a delay in treatment and lower adherence to guideline-recommended therapy in real-world practice. We used the Vizient Clinical Data Base to describe demographic characteristics, baseline clinical characteristics, and treatment patterns in patients newly diagnosed with APL during the study period of April 2017 to March 2020. Baseline white blood cell count was used to assign risk status and assess treatment concordance with National Comprehensive Cancer Network guidelines. Logistic regression models examined adjusted associations between patient, hospital, disease characteristics, and adverse outcomes (in-hospital death or discharge to hospice). Among 1464 patients with APL, 205 (14.0%) experienced an adverse outcome. A substantial subset (20.6%) of patients did not receive guideline-concordant regimens. Odds of adverse outcomes increased with failure to receive guideline-concordant treatment (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.43-3.75; P = .001), high-risk disease (OR, 2.48; 95% CI, 1.53-4.00; P < .001), and increasing age (≥60 years: OR, 11.13; 95% CI, 4.55-27.22; P < .001). Higher hospital acute myeloid leukemia (AML) patient volume was associated with lower odds of adverse outcome (OR, 0.44; 95% CI, 0.20-0.99 [for ≤50 vs >200 AML patients per year]; P = .046). In conclusion, in this large database analysis, 14.0% of patients newly diagnosed with APL died or were discharged to hospice. A substantial proportion of patients did not receive guideline-concordant therapy, potentially contributing to adverse outcomes.


Hospital-built care homes too expensive, say experts.
ENCOURAGING HOSPITALS to build care homes will not prevent delays in hospital discharge, experts say.


Lack of pharmacokinetic and pharmacodynamic interactions between a smoking cessation therapy, varenicline, and warfarin: an in vivo and in vitro study.
This study investigated the effect of varenicline on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in 24 adult smokers and compared these findings with data generated using human in vitro systems. Subjects were randomized to receive varenicline 1 mg twice a day or placebo for 13 days and then switched to the alternative treatment after a 1-week washout period. A single dose of warfarin 25 mg was given on day 8 of each treatment period, and serial blood samples were collected over 144 hours postdose. Pharmacokinetic parameters for both (R)- and (S)-warfarin and international normalized ratio (INR) values were determined. Varenicline was assessed as an inhibitor and inducer of human cytochrome P450 activities using liver microsomes and hepatocytes, respectively. Consistent with the in vitro data, no alteration in human pharmacokinetics of warfarin enantiomers was observed with varenicline treatment. The 90% confidence intervals for the ratios of area under the concentration-time curve from zero hours to infinity and peak plasma concentrations were completely contained within 80% to 125%. Warfarin pharmacodynamic parameters, maximum INR, and the area under the prothrombin (INR)-time curve, were also unaffected by steady-state varenicline. Concomitant administration of varenicline and warfarin was well tolerated. Consequently, warfarin can be safely administered with varenicline without the need for dose adjustment.


Indole decreases the virulence of the bivalve model pathogens Vibrio tasmaniensis LGP32 and Vibrio crassostreae J2-9.
Indole signaling plays an important role in bacterial pathogenesis. In this study, the impact of indole on biofilm formation, swimming and swarming motility were explored in Vibrio tasmaniensis LGP32 and Vibrio crassostreae J2-9, two model pathogens of bivalves. The results showed that indole decreased swimming and swarming motility in both strains, and decreased biofilm formation in V. crassostreae J2-9. Furthermore, indole affected a large number of genes at RNA level, including genes related to metabolism, ABC transporters, flagellar assembly, chemotaxis, and response regulators. Finally, the bacterial virulence towards mussel larvae was decreased by pretreatment with indole in both V. tasmaniensis LGP32 and V. crassostreae J2-9. After 5 days, the survival rate of mussel larvae increased 2.4-fold and 2.8-fold in mussel larvae challenged with V. tasmaniensis LGP32 pretreated with 200 µM and 500 µM indole, respectively. The survival rate of mussel larvae increased 1.5-fold and 1.9-fold in mussel larvae challenged with V. crassostreae J2-9 pretreated with 200 µM and 500 µM indole, respectively. These data indicate that indole has a significant impact on the virulence of V. tasmaniensis LGP32 and V. crassostreae J2-9, and indole signaling could be a promising target for antivirulence therapy.


Chronic graft-versus-host disease presenting as acute polymyositis: A case series and systematic review.
Chronic graft-versus-host disease (cGvHD) remains a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Commonly targeted organs are skin, eyes, mouth, gastrointestinal tract, and liver. Muscular involvement and presentation as acute polymyositis (APM) remain a rare manifestation of cGvHD. We present a case series of three patients who presented with APM as a sole presentation of cGvHD and were treated successfully with corticosteroids and ruxolitinib. We also conducted a systematic review including 72 patients to summarize current literature regarding APM associated with cGvHD after allo-HSCT. The estimated incidence of cGvHD-associated APM is up to 3.4%, with a median time to onset of 1.6 years post-allo-HSCT. Most cases (85%) presented with myalgia and progressive bilateral proximal muscle weakness with elevated creatine kinase and/or aldolase. Over half of the patients had a prior history of acute GvHD. Isolated APM presenting without other clinical manifestations of cGvHD was rare. Biopsy of affected muscles usually shows characteristic myonecrosis, which remains the gold standard for diagnosis. Most cases respond to systemic steroids and immunosuppressive therapy. However, refractory cases remain challenging to treat and can cause significant morbidity and mortality. Ruxolitinib appears to be an effective therapy in this setting.


Vasopressin stimulation of Ca2+ mobilization, two bivalent cation entry pathways and Ca2+ efflux in A7r5 rat smooth muscle cells.
1. Arg8-vasopressin (AVP)-regulated Ca2+ transport were investigated in fura-2-loaded A7r5 cells using both single cell and population measurements. 2. AVP evokes an initial concentration-dependent rise in cytosolic free Ca2+ concentration ([Ca2+ ]i) to a peak which is independent of extracellular Ca2+, and a sustained Ca2+ signal that results from a balance between stimulation of Ca2+ entry and efflux. 3. Depletion of intracellular Ca2+ stores with thapsigargin, ionomycin, or prior treatment with AVP in Ca2(+)-free medium activates 'capacitative' entry of Ca2+, Ba2+ or Mn2+. Capacitative Mn2+ entry is inhibited by refilling stores with Ca2+; neither Sr2+ nor Ba2+ substitute for Ca2+ to give this effect. 4. In cells with empty stores, AVP stimulates further bivalent cation entry, and the effect persists when extracellular Na+ is replaced by N-methyl-D-glucamine or under depolarizing condition (extracellular KCl concentration ([KCl]o), 135 mM). This effect of AVP is not therefore merely a consequence of AVP causing membrane hyperpolarization or stimulation of Na(+)-Ca2+ exchange, but results from opening of a bivalent cation influx pathway. 5. Several lines of evidence indicate that AVP-stimulated bivalent cation entry is not a consequence of more complete emptying of the intracellular stores and consequent further activation of the capacitative pathway. AVP stimulates Ba2+ entry when the intracellular Ca2+ stores have been both emptied by ionomycin and prevented from refilling by thapsigargin. Mn2+ permeates the capacitative pathway, but AVP does not further increase Mn2+ entry, confirming that AVP does not further activate the capacitative pathway and that the two pathways differ in their permeability to Mn2+. When the extracellular [Sr2+] is low, empty stores do not stimulate detectable Sr2+ entry, but addition of AVP causes substantial Sr2+ entry. 6. A decrease in [Ca2+]i occurs when 50 nM AVP is added during a sustained elevation of [Ca2+]i evoked by thapsigargin. Since AVP does not inhibit the capacitative pathway, this result suggests that AVP stimulates Ca2+ extrusion. 7. We conclude that stimulation of Ca2+ mobilization, two modes of bivalent cation entry, and Ca2+ efflux all contribute to the complex concentration-dependent effects of AVP in A7r5 smooth muscle cells.


Impact of the rs73598374 polymorphism of the adenosine deaminase gene on platelet reactivity and long-term outcomes among patients with acute coronary syndrome treated with ticagrelor.
The positive interaction of ticagrelor with the metabolism of adenosine has been claimed for the large antithrombotic and antiischemic benefits of this antiplatelet agent in acute coronary syndromes (ACS). Adenosine catabolism is regulated by the activity of the adenosine deaminase enzyme (ADA), for which several polymorphisms have been identified. Therefore, the aim of our study was to explore the impact of the rs73598374 polymorphism of ADA gene on platelet reactivity in ACS patients treated with ticagrelor. We included consecutive patients receiving ASA and ticagrelor after an ACS and coronary intervention. Platelet reactivity was evaluated by impedance aggregometry at 30-90 days post-discharge. The genetic analysis was carried out by PCR and RFLP. Clinical endpoints were mortality, cardiovascular death, recurrent myocardial infarction or coronary revascularization at the maximum available follow-up. Our population is represented by 464 patients, of whom 33.4% were A-heterozygotes and 6 homozygotes. A-allele carriers showed a greater prevalence of renal failure (p = 0.02) and a lower rate of previous coronary artery bypass graft (p = 0.03) and statin treatment (p = 0.02). No differences in the mean values of platelet reactivity or HRPR on ticagrelor were found according to the ADA genotype (11.3%vs13.9%, p = 0.45; adjusted OR[95% CI] = 1.17[0.64-2.14], p = 0.61). At follow up, patients carrying the A-allele showed a non-significantly lower incidence of ACS and repeated unplanned revascularization, although with no effect on mortality. In the present study the rs73598374 polymorphism of the ADA gene did not affect platelet reactivity or the long-term prognosis in patients with ACS receiving dual antiplatelet therapy with ASA and ticagrelor.


Electrocardiography Interpretation Proficiency Among Medical Doctors of Different Grades in the United Kingdom.
Electrocardiography interpretation is a core clinical skill for all doctors participating in emergency medical services. Given the majority of ECGs initially performed in hospital on admission are reviewed by junior doctors, and the need for life-threatening pathology to be diagnosed or excluded, further understanding of the level of competency in interpretation and factors associated with this are needed. This was a cross-sectional, descriptive, analytical study. The data were collected using a structured questionnaire. This was comprised of two sections; the first section contained questions related to confidence, previous ECG learning and factors thought to be associated with ECG interpretation competence. The second section was an ECG quiz of 10 12-lead ECGs of varying complexity for interpretation assessment. Descriptive and inferential statistics were utilized for data analysis. Sixty-two doctors from foundation year 1 to registrar level working in acute medicine across three hospitals participated. The mean overall percentage score for the ECG quiz was 45%. No association was found between junior doctor training grade and overall score on the ECG assessment. Undergraduate and postgraduate teaching strategies also did not impact competence. Only 9.7% reported themselves as "confident" interpreting ECGs. There was a trend towards higher levels of competency among those who felt they had undergone sufficient ECG teaching and those who sought regular feedback from other clinicians. This study demonstrated low overall levels of ECG interpretation competency among junior doctors in a large acute teaching NHS trust regardless of grade. Factors associated with competency remain unclear.


Sorption of lead, copper, and cadmium by calcium alginate. Metal binding stoichiometry and the pH effect.
Binding of heavy metal ions by calcium alginate has been described in the literature with many different models. In the present study, two most basic models were used to systematically compare their simultaneous description of metal uptake dependence on pH and metal ion concentration in the bulk solution. The experimental datasets corresponding to the binary sorption systems containing protons and heavy metal ion (cadmium, lead, or copper) were taken from the literature. The applicability and limitations of both models are discussed. Neither of the models gave a completely satisfactory description of all data. The two-site occupancy model yielded better results compared to the one-site occupancy model when considering the coherence of the parameters (e.g., affinity constants) but the quality of the obtained fits is similar in both cases.


Studies on ticks of veterinary importance in Nigeria. XII. Oviposition and eclosion in five species of ixodid ticks in contrasting habitats.
The preoviposition and oviposition periods, the eclosion periods and numbers of eggs laid by adult ticks of five species, namely Amblyomma variegatum, Boophilus decoloratus, B. geigyi, Hyalomma rufipes and H. truncatum, maintained in a natural habitat were compared with those maintained in semi-natural and artificial habitats. Within the natural habitats, "open" and "shady" sites were distinguished. Maximum oviposition occurred during the peak of the rains in engorged A. variegatum and B. decoloratus, and the numbers of eggs laid by those kept in the natural and semi-natural habitats were significantly lower in the dry season than in the rainy season. Maximum oviposition in engorged H. rufipes kept in the natural habitat occurred during the early rains while minimum oviposition took place during the peak of the rains. Oviposition in engorged H. truncatum was poor among those kept in the natural habitat during the peak and end of the rains. Engorged A. variegatum and B. decoloratus kept in shady sites of the natural habitat laid significantly more eggs than in all other habitats at all seasons, while for H. truncatum and H. rufipes, numbers of eggs laid in the open site were significantly higher than those laid in other habitats at all seasons. In all species investigated, success in oviposition was aided by moisture provided by light to moderate rainfall, while excessive moisture in terms of heavy rainfall adversely affected oviposition.


Sleep during the perimenopause: a SWAN story.
Is there evidence for a perimenopausal sleep disorder? We address this question in our presentation of the Study of Women's Health Across the Nation (SWAN) "sleep story," in which we summarize and discuss data addressing sleep quality, objective measures of sleep patterns, and sleep disorders that have been published to date by the SWAN and the ancillary SWAN Sleep Study. We describe what has been learned about sleep during the perimenopause. Analyses exploring racial/ethnic diversity and the role of hot flashes and mood disturbance in sleep-perimenopause associations are described. Implications for clinical practice are considered.


Magnitude of Myocutaneous Flaps and Factors Associated With Loss of Volume in Oral Cancer Reconstructive Surgery.
Myocutaneous flaps are often used to repair oral and maxillofacial defects after surgery for oral cancer; however, their volume decreases during the postoperative period. To facilitate treatment planning, the authors measured the extent of such postoperative flap volume loss and identified associated factors in patients who underwent oral reconstruction with myocutaneous flaps. The authors designed and performed a retrospective observational study of patients who underwent reconstructive procedures involving rectus abdominal myocutaneous (RAM) or pectoralis major myocutaneous (PMMC) flaps at Tokai University Hospital, Kobe University Hospital, or Nagasaki University Hospital from April 2009 through March 2013. Flap type and other clinical variables were examined as potential predictors of flap loss. The primary outcome was flap loss at 6 months postoperatively. Correlations between each potential predictor and the primary outcome were examined using multiple regression analysis. The subjects were 75 patients whose oral defects were reconstructed with RAM flaps (n = 57) or PMMC flaps (n = 18). RAM flaps exhibited a mean volume shrinkage of 22% at 6 months postoperatively, which was less than the 27.5% displayed by the PMMC flaps, but the difference was not important. Renal failure, previous surgery of the oral region, postoperative radiotherapy, and postoperative serum albumin level were found to be meaningful risk factors for postoperative flap volume loss. The results of this study suggest that larger flaps should be used in patients who possess these risk factors or are scheduled to undergo postoperative radiotherapy. Future studies should examine the utility of postoperative nutritional management for preventing flap volume loss.


Significance of intravascular and intracardiac movement of the cardiac catheter in ventriculo-atrial shunts (review of 655 cases).
Proper placement of ventriculo-atrial shunts can be complicated by three phenomena: 1. Movement of the cardiac catheter intravascularly into the internal jugular vein as noted on chest X-ray. 2. Movement of the cardiac catheter during intraoperative X-ray leading to blurring and hence problems in accurate localization. 3. No sign on X-ray of the catheter tip or even of the catheter itself despite previous X-ray visualization and good function, a problem to be obviated by better radiopaque markings.


Unusual myoid, perivascular, and postradiation lesions, with emphasis on atypical vascular lesion, postradiation cutaneous angiosarcoma, myoepithelial tumors, myopericytoma, and perivascular epithelioid cell tumor.
In recent years, a number of new soft tissue tumor entities have been described that occur in the skin only, or that also occur in other sites but form clinically and pathologically distinct subsets when arising in the skin and subcutaneous tissue. These include a variety of mesenchymal lineages and have variable malignant potential, although superficial malignant soft tissue tumors generally have a more favorable outcome than their more deeply located counterparts. This article reviews the clinical and pathologic features and differential diagnoses of atypical vascular lesion, postradiation cutaneous angiosarcoma, myoepithelioma, myopericytoma, and perivascular epithelioid cell tumor.


IL-2 triggers specific signaling pathways in human NKT cells leading to the production of pro- and anti-inflammatory cytokines.
NKT cells belong to a conserved T lymphocyte subgroup that has been implicated in the regulation of various immune responses, including responses to viruses, bacteria, and parasites. They express a semi-invariant TCR that recognizes glycolipids presented by the nonpolymorphic MHC class I-like molecule CD1d, and upon activation, they produce various pro- and anti-inflammatory cytokines. Recent studies have shed light on the nature of glycolipids and the environmental signals that may influence the production of cytokines by NKT cells and thus, modulate the immune response. To better understand the regulation mechanisms of NKT cells, we explored their behavior following activation by IL-2 and investigated the signaling pathways and biological responses triggered. We demonstrated that IL-2 activates not only STAT3 and -5 and the PI-3K and ERK-2 pathways as in all IL-2 responder cells but also STAT4 as in NK cells and the p38 MAPK pathway as in alphabeta T cells. We also showed that STAT6 is activated by IL-2 in NKT cells. Moreover, IL-2 induces the production of IFN-gamma and IL-4. The ability of IL-2 to induce pro- and anti-inflammatory cytokine production, in addition to proliferation, could open new therapeutic approaches for use in combination with molecules that activate NKT cells through TCR activation.


Sacral nerve stimulation reduces corticoanal excitability in patients with faecal incontinence.
Sacral nerve stimulation (SNS) can produce symptomatic relief in patients with faecal incontinence. Moreover, peripheral nerve stimulation has been shown to affect brain function. The aim of this study was to determine whether SNS might produce important changes in cortical activity linked to improved continence. In an experimental study, ten women with intractable faecal incontinence (mean age 51.3 years) were serially mapped with transcranial magnetic stimulation before and immediately after 14 days of temporary SNS (15 Hz, pulse width 210 micros), and then 2 weeks later. Anal sphincter electromyographic responses were recorded to cortical stimulation of multiple points over a scalp grid covering the bilateral medial cortex. Continence scores, anorectal manometry and rectal sensitivity data were also collected. SNS improved global symptom scores in the majority of patients; mean(s.e.m.) continence scores fell from 16.9(1.6) to 10.6(1.8) (P = 0.042). Cortical mapping showed a consistent decrease in corticoanal representation and overall excitability immediately after SNS compared with baseline (mean(s.e.m.) 38,083(13,669) versus 42,507(13,297) microV s; P = 0.017), which was reversed 2 weeks after SNS wire removal. SNS produces symptom benefit in patients with faecal incontinence that is associated with a reversible reduction in corticoanal excitability. SNS therefore drives dynamic brain changes that may play a functional role in influencing anal continence.


Remission of fibrosis: rage to the rescue.
Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and permanent decline of lung function that eventually leads to expiry. A study published in 2017 performed by Kumar et al. revealed that the disease may not be as irreversible as was once believed. The research discovered a novel role for the receptor for advanced glycation end-products (RAGE) in which it acts as a master regulator for DNA double-strand break repair. In doing so, Kumar et al. may have made a breakthrough that could redefine the translational approaches of IPF.


Unchanged electrophoretic mobility in human cryopreserved lymphocytes.
Cell surface charge, assessed by the analytical electrophoresis of fresh and cryopreserved human peripheral blood lymphoctes, is changed in any perceivable manner by freezing and thawing. This was confirmed by different membrane markers (E, EA and EAC rosettes).


Catalytic asymmetric addition to cyclic N-acyl-iminium: access to sulfone-bearing contiguous quaternary stereocenters.
Herein, we report the first chiral phosphoric acid (CPA)-catalyzed asymmetric addition of α-fluoro(phenylsulfonyl)methane (FSM) derivatives to in situ generated cyclic N-acyliminium. This process enables metal-free expeditious access to sulfone and fluorine incorporating contiguous all substituted quaternary stereocenters ingrained in biorelevant isoindolinones in excellent stereoselectivities (up to 99% ee and up to 50 : 1 dr).


IgH enhancer deregulated expression of L-myc: abnormal T lymphocyte development and T cell lymphomagenesis.
Transgenic constructs containing the murine L-myc gene under the control of the immunoglobulin transcriptional enhancer element (Emu) are expressed at unexpectedly high levels in thymocytes and proliferating T cells compared with cells from bone marrow and proliferating B cells. In contrast, double transgenic animals bearing constructs containing the L- and N-myc genes similarly linked to the Emu element maintain preferential L-myc expression in T cells but express the N-myc transgene preferentially in B cells. These results indicate that the L-myc gene contains elements that act in concert with the Emu element to allow preferential expression in T lineage cells. In correspondence to the expression pattern, Emu-L-myc transgenic mice show expanded thymic cortices and irregularly formed splenic follicles with expanded T cell areas. Moreover, the percentage of thymocytes positive for the surface marker 1C11, which defines thymic progenitor cells, activated T cells and preleukemic T cells, is dramatically raised in transgenic mice compared with normal littermates. Emu-L-myc transgenic animals are predisposed to clonal lymphoid tumors, most of which are T cell lymphomas. The relative incidence, latency period, and degree of malignancy of Emu-L-myc tumors compared with Emu-N- or c-myc tumors is consistent with a lower oncogenic potential of the L-myc gene. However, the Emu-L-myc tumors do not express detectable levels of endogenous myc family genes indicating that the L-myc protein can substitute for c- or N-myc in the generation and growth of lymphoid neoplasms.


Abnormal frontal and parietal activity during working memory updating in post-traumatic stress disorder.
This study used event-related potentials (ERPs) to investigate the timing and scalp topography of working memory in post-traumatic stress disorder (PTSD). This study was designed to investigate ERPs associated with a specific working memory updating process. ERPs were recorded from 10 patients and 10 controls during two visual tasks where (a) targets were a specific word or (b) targets were consecutive matching words. In the first task, nontarget words are not retained in working memory. In the second task, as in delay-match-to-sample tasks, a non-target word defines a new target identity, so these words are retained in working memory. This working memory updating process was related to large positive ERPs over frontal and parietal areas at 400-800 ms, which were smaller in PTSD. Estimation of cortical source activity indicated abnormal patterns of frontal and parietal activity in PTSD, which were also observed in regional cerebral blood flow [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M., Marcina, J., Tochon-Danguy, H., Egan, G., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481]. Frontal and parietal cortex are known to be involved in distributed networks for working memory processes, interacting with medial temporal areas during episodic memory processes. Abnormal function in these brain networks helps to explain everyday concentration and memory difficulties in PTSD.


Non-additivity of maximal pilocarpine and cytochalasin effects on outflow facility.
Living cynomolgus monkeys received intracameral infusions of pilocarpine HCI (P)1 mg ml-1, followed by P + cytochalasin B (CB) 50 microgram ml-1; total outflow facility, measured by two-level constant pressure perfusion, tripled after P alone and then remained stable when CB was added. Other eyes received CB 25 micrograms ml-1 or 50 micrograms ml-1, followed by CB + P1 mg ml-1; facility quadrupled to sextupled after CB, but tended to decrease from those levels, although it remained above baseline, after P was added. The facility decrease accompanying the addition of P after CB might have related to the longer CB exposure, rather than to a specific P effect. These data indicate that despite different mechanisms of action and primary attack points on the outflow apparatus, near- or supramaximal P and CB doses are not additive, and are indeed mutually pre-emptive, in their facility increasing effect. These findings have implications in terms of trabecular-meshwork biophysics, fluid mechanics, and their pharmacological manipulation.


YAP/TAZ as therapeutic targets in cancer.
The biology and regulation of YAP and TAZ, two closely related transcriptional regulators, are receiving increasing attention owing to their fundamental roles in organ growth, tissue repair and cancer. In particular, the widespread activation of YAP/TAZ in carcinomas, and the crucial role of YAP/TAZ activation for many 'hallmarks' of cancer are indicating YAP/TAZ as prime targets for designing anti-cancer drugs. Here, we start from the known modalities to regulate YAP/TAZ to highlight possible routes of therapeutic intervention.


Respiratory metabolism of the soft tick, Ornithodoros turicata (Dugès).
The rate of oxygen consumption was investigated in fed larval, nymphal and adult Ornithodoros turicata ticks and in starved nymphal and adult ticks. Oxygen consumption rate of fed adult ticks increased with increasing temperature. The metabolic rate of adult ticks was affected by starvation whereby starved adult ticks showed a significantly lower oxygen consumption than their fed counterparts. The oxygen consumption rate of fed female ticks was significantly higher than that of fed males but, there was no significant difference between the oxygen consumption rates of starved female versus starved male ticks. Oxygen consumption of fed larvae was significantly greater than those of fed first through third instar nymphs. Fed and starved nymphal ticks as well as fed adult ticks ventilated continuously. In contrast, starved adults ventilated discontinuously. The ability to reduce metabolic rate, plus the capability to ventilate discontinuously allow O. turicata adults to cope with prolonged starvation.


Endoscopic excision of forehead lipomas.
Endoscopic surgery is a significant addition in the maxillofacial surgeon's armamentarium. Authors' experience of endoscopically assisted removal of forehead lipomas has been presented. The endoscopic technique permits to hide minimal scars in the hair. The magnification allows a good identification of anatomical structures and thus decreases the risk of numbness. The main disadvantages of this technique are the more expensive equipment and the steep learning curve. But with the expansion of endoscopic techniques, prices should decline and the duration of operations always lessens with experience. This technique might possibly appear to offer a new standard procedure for removal of forehead lipomas, notably in patients with keloid history or high aesthetic concerns.


Deciding to terminate treatment: a practical guide for physicians.
Providing house officers and practicing physicians with annotated, concise, practical guidelines for decisions to terminate treatment is the objective of this report. The study selection and data extraction focused on statutes, regulations, court decisions, medicolegal analyses, clinical studies, and position papers addressing termination-of-treatment issues. To foster a systematic approach, we developed a laminated, pocket-sized card containing a series of questions to be asked by any physician confronted with termination-of-treatment decisions. Systematic identification and deliberate assessment of (1) brain death; (2) the nature, extent, cause, prognosis, and reversibility of impairment; (3) the type of treatment to be withheld or withdrawn; (4) the futility of any proposed intervention; (5) the capacity of the patient for health care decision-making; (6) the evidence of patient's wishes; (7) the proper roles of family members, surrogate decision makers, and other health professionals (eg, ethics committees); and (8) applicable policies, ethics, laws, and potential conflicts of interest will enhance efficiency and add value to the decision-making process at the end of life.


[Multi-shift work and work under conditions of jet lag. Questionnaire studies].
The authors discuss the disturbances in the biorhythm - sleep - waking in the workers who are on duty at the posts of command and in communication ouration pilots surpassing the time zones. The questionnaire method was used. The resultant desynchronization of the biological rhythm is exhibited mainly through the subjective feeling of fatigue and sleepiness. Adaptation and readaptation to changing working conditions occurs.