How do the physiological traits of a lizard change during its invasion of an oceanic island?
Physiology is crucial for the survival of invasive species in new environments. Yet, new climatic conditions and the limited genetic variation found within many invasive populations may influence physiological responses to new environmental conditions. Here, we studied the case of the delicate skinks (Lampropholis delicata) invading Lord Howe Island (LHI), Australia. On LHI, the climate is different from the mainland source of the skinks, and independent introduction events generated invasive populations with distinct genetic backgrounds. To understand how climate and genetic background may shape physiological responses along biological invasions, we compared the physiological traits of a source and two invasive (single-haplotype and multi-haplotype) populations of the delicate skink. For each population, we quantified physiological traits related to metabolism, sprint speed, and thermal physiology. We found that, for most physiological traits analysed, population history did not influence the ecophysiology of delicate skinks. However, invasive populations showed higher maximum speed than the source population, which indicates that locomotor performance might be a trait under selection during biological invasions. As well, the invasive population with a single haplotype was less cold-tolerant than the multi-haplotype and source populations. Our results suggest that limited genetic variability and climate may influence physiological responses of invasive organisms in novel environments. Incorporating the interplay between genetic and physiological responses into models predicting species invasions can result in more accurate understanding of the potential habitats those species can occupy.


Response mode-dependent differences in neurofunctional networks during response inhibition: an EEG-beamforming study.
Response inhibition processes are one of the most important executive control functions and have been subject to intense research in cognitive neuroscience. However, knowledge on the neurophysiology and functional neuroanatomy on response inhibition is biased because studies usually employ experimental paradigms (e.g., sustained attention to response task, SART) in which behavior is susceptible to impulsive errors. Here, we investigate whether there are differences in neurophysiological mechanisms and networks depending on the response mode that predominates behavior in a response inhibition task. We do so comparing a SART with a traditionally formatted task paradigm. We use EEG-beamforming in two tasks inducing opposite response modes during action selection. We focus on theta frequency modulations, since these are implicated in cognitive control processes. The results show that a response mode that is susceptible to impulsive errors (response mode used in the SART) is associated with stronger theta band activity in the left temporo-parietal junction. The results suggest that the response modes applied during response inhibition differ in the encoding of surprise signals, or related processes of attentional sampling. Response modes during response inhibition seem to differ in processes necessary to update task representations relevant to behavioral control.


Variation in the evaluation of testicular conditions across United States pediatric emergency departments.
To explore the variation in diagnostic testing and management for males diagnosed with three testicular conditions (testicular torsion, appendix testis torsion, epididymitis/orchitis) using a large pediatric health care database. Diagnostic testing is frequently used in evaluation of the acute scrotum; however, there is likely variability in the use of these tests in the emergency department setting. We conducted a cross-sectional study of males with the diagnoses of testicular torsion, appendix testis torsion, and epididymitis/orchitis. We identified emergency department patients in the Pediatric Health Information Systems (PHIS) database from 2010 to 2015 using diagnostic and procedure codes from the International Classification of Diseases Codes 9 and 10. Frequencies of diagnoses by demographic characteristics and of procedures and diagnostic testing (ultrasound, urinalysis, urine culture and sexually transmitted infection testing) by age group were calculated. We analyzed testing trends over time. We identified 17,000 males with the diagnoses of testicular torsion (21.7%), appendix testis torsion (17.9%), and epididymitis/orchitis (60.3%) from 2010 to 2015. There was substantial variation among hospitals in all categories of testing for each of the diagnoses. Overall, ultrasound utilization ranged from 33.1-100% and urinalysis testing ranged from 17.0-84.9% for all conditions. Only urine culture testing decreased over time for all three diagnoses (40.6% in 2010 to 31.5 in 2015). There was wide variation in the use of diagnostic testing across pediatric hospitals for males with common testicular conditions. Development of evaluation guidelines for the acute scrotum could decrease variation in testing.


Detection of injuries in traumatic deaths. The significance of medico-legal autopsy.
A material of 218 medico-legal autopsies on persons with traumatic injuries was analysed. All these persons had been admitted to hospital. In 75 (34%) injuries had been missed in hospital. In 11 (5%) the overlooked injuries were the sole cause of death, while in 51 (23%) they were contributory. The missed injuries were found in all regions: 27% were moderate (AIS 2), 28% serious (AIS 3), 40% severe (AIS 4), and 5% critical (AIS 5). It is concluded that medico-legal autopsies are necessary for an exhaustive evaluation of traumatic deaths. They are of significance not only to legal security, but also to the social need for analysing injury mechanisms and the consequent possibility of preventive efforts.


White and green striate leaves 1, predicted to encode a 16S rRNA processing protein, plays a critical role in the processing of chloroplast ribosomes in maize (Zea mays L.).
Ribosomes play a crucial role in protein biosynthesis and are linked to plant growth and development. The RimM protein has been shown to be involved in the maturation of 30S ribosomal subunits, but its exact function in plants is still unknown. In this study, we discovered a maize mutant with white and green striate leaves (wgsl1) and reduced chlorophyll content. Genetic analysis showed that the wgsl1 mutation was recessive and controlled by a single nuclear gene. Map-based cloning of ZmWGSL1 identified a base substitution (G to A) that generated a missense mutation within the Zm00001d039036 gene in the wgsl1 mutant. Zm00001d039036 encodes a 16S rRNA processing protein containing the RimM motif. Further analysis of transcriptomic data showed that the transcript levels of many ribosomal proteins involved in the small and big ribosomal subunits were dramatically up-regulated in the wgsl1 mutant. Moreover, the level of ribosomal multimers was decreased. This suggests that ZmWGSL1 plays a crucial role in the maturation of the ribosome, leading to abnormal plant growth and development. In addition, subcellular localization results indicate that WGSL1 is localized in chloroplasts. Therefore, we suggest that WGSL1 is a nuclear-encoded protein, is transported to the chloroplast to drive functions, and affects the processing of ribosomes in the chloroplast. The online version contains supplementary material available at 10.1007/s11032-023-01407-y.


Silver/silver chloride nanoparticles inhibit the proliferation of human glioblastoma cells.
Glioblastomas (GBM) are aggressive brain tumors with very poor prognosis. While silver nanoparticles represent a potential new strategy for anticancer therapy, the silver/silver chloride nanoparticles (Ag/AgCl-NPs) have microbicidal activity, but had not been tested against tumor cells. Here, we analyzed the effect of biogenically produced Ag/AgCl-NPs (from yeast cultures) on the proliferation of GBM02 glioblastoma cells (and of human astrocytes) by automated, image-based high-content analysis (HCA). We compared the effect of 0.1-5.0 µg mL-1 Ag/AgCl-NPs with that of 9.7-48.5 µg mL-1 temozolomide (TMZ, chemotherapy drug currently used to treat glioblastomas), alone or in combination. At higher concentrations, Ag/AgCl-NPs inhibited GBM02 proliferation more effectively than TMZ (up to 82 and 62% inhibition, respectively), while the opposite occurred at lower concentrations (up to 23 and 53% inhibition, for Ag/AgCl-NPs and TMZ, respectively). The combined treatment (Ag/AgCl-NPs + TMZ) inhibited GBM02 proliferation by 54-83%. Ag/AgCl-NPs had a reduced effect on astrocyte proliferation compared with TMZ, and Ag/AgCl-NPs + TMZ inhibited astrocyte proliferation by 5-42%. The growth rate and population doubling time analyses confirmed that treatment with Ag/AgCl-NPs was more effective against GBM02 cells than TMZ (~ 67-fold), and less aggressive to astrocytes, while Ag/AgCl-NP + TMZ treatment was no more effective against GBM02 cells than Ag/AgCl-NPs monotherapy. Taken together, our data indicate that 2.5 µg mL-1 Ag/AgCl-NPs represents the safest dose tested here, which affects GBM02 proliferation, with limited effect on astrocytes. Our findings show that HCA is a useful approach to evaluate the antiproliferative effect of nanoparticles against tumor cells.


Nine case series with phototoxic dermatitis related to Chenopodium album.
Chenopodium album L. ssp. album is a common plant species worldwide, especially in humid areas. Sun exposure after oral intake of the plant can lead to sunburn-like rashes owing to its furocoumarin content. In this article, we reported nine patients who developed dermatitis with edema, erythema and necrosis on the face and dorsum of the hands. Each was exposed to sunlight after eating selemez (the vernacular name of C. album L. ssp. album). The plant samples analyzed by an expert botanist were described as C. album L. ssp. album belonging to Chenopodiacea family.


Pharmacology of nadolol (SQ 11725), a beta-adrenergic antagonist lacking direct myocardial depression.
SQ 11725 was approximately 1/3 as potent as propranolol in blocking the stimulant effects of isoproterenol in vitro, but was 2-4 times more potent than propranolol in blocking the diastolic blood-pressure and heart-rate responses, respectively, to isoproterenol in vivo. SQ 11725 had no depressant effects on contractile force of isolated guinea pig atrial muscle at the largest bath concentration studied (1000 mug/ml), whereas propranolol caused significant depression at a concentration of 1-10 mug/ml. Propranolol was at least 20-30 times more depressant than SQ 11725 to canine myocardium in vivo. SQ 11725 was more effective then propranolol in inhibiting tachycardic responses to treadmill exercise in unanesthetized dogs. The duration of blockade of the heart-rate response to exercise or to isoproterenol administration in the unanesthetized dog was approximately 5 times greater with SQ 11725 than with propranolol.


Prospective randomized comparison between an open and closed vaginal cuff in abdominal hysterectomy.
To compare an operative and postoperative course of open vaginal cuff hysterectomy and closed vaginal cuff hysterectomy, and to correlate the length of stay, febrile morbidity and the incidence of pelvic fluid collections to the type of surgery. One-hundred women scheduled for hysterectomy were prospectively randomized into two groups that underwent either a closed or an open vaginal cuff technique. The open vaginal cuff technique took on average 19% more time than the closed vaginal cuff operation (P < 0.05, t-test). The incidence and size of pelvic fluid collections was significantly higher after the closed vaginal cuff hysterectomy than after the open technique (P < 0.01, t-test). However, the postoperative length of stay, febrile morbidity and the rate of complications were similar. Both techniques of hysterectomy produced a similar postoperative course despite the fact that the closed vaginal cuff technique resulted in a higher incidence of pelvic fluid collections. Therefore considering a shorter operation time for the closed vaginal cuff hysterectomy, this technique seems slightly preferable.


RNA quality and gene expression analysis of ovarian tumor tissue undergoing repeated thaw-freezing.
Gene expression profiles evaluated by microarray-based quantization of RNA are used in studies of differential diagnosis and prognosis in cancer. RNA of good quality is mandatory for this evaluation. The RNA most often comes from tumor banks with limited amount of tissue, and the tissue often undergoes repeated thawing and freezing. We evaluated the influence of repeated division of tumor samples at room temperature, on RNA quality and quantity, in addition to the gene expression profile. Sixteen ovarian tumor samples were divided in three aliquots each, undergoing respectively one, two, and three thaw-freeze cycles. RNA from each aliquot was extracted on the day of division, and quantity and quality were evaluated. RNA from all three aliquots of four tumor samples underwent microarray analysis on Affymetrix Human Genome U133A 2.0 arrays. Microarray data were evaluated using both unsupervised, and supervised multivariate statistical methods, reliability analysis, as well as verification using published gene lists in ovarian cancer studies. RNA quality and quantity did not change during the division procedure and microarray data showed insignificant difference in gene expression. Tumor samples from tumor banks can be frozen and thawed at least three times without compromising the RNA integrity and genetic expression profile.


Validation of the Sarcoidosis Diagnostic Score in a Multicontinental Study.
Rationale: The Sarcoidosis Diagnostic Score (SDS) has been established to quantitate the clinical features consistent with sarcoidosis in a monocentric study. Objectives: We aimed to confirm the diagnostic value of SDS in a large, multicontinental study and to assess the utility of SDS in differentiating sarcoidosis from alternative diagnoses, including infectious and noninfectious granulomatous diseases. Methods: We included patients with biopsy-confirmed sarcoidosis at nine centers across the world. Patients without sarcoidosis seen at the same sites served as control patients. Using a modified World Association of Sarcoidosis and Other Granulomatous Disorders organ assessment instrument, we scored all patients for the presence of granuloma on biopsy, highly probable symptoms, and least probable symptoms for each area. Two sarcoidosis scores were generated: SDS Biopsy (with biopsy) and SDS Clinical (without biopsy). SDS Clinical and Biopsy were calculated for all patients. We calculated and compared the area under the curve (AUC) for SDS Clinical and Biopsy according to different diagnosis scenarios. Results: A total of 1,041 patients with sarcoidosis and 1,035 without sarcoidosis were included. The results for SDS Clinical (AUC, 0.888; 95% confidence interval [CI], 0.874-0.902) and SDS Biopsy (AUC, 0.979; 95% CI, 0.973-0.985) according to AUC were good to excellent for differentiating sarcoidosis from alternative diagnosis. SDS Clinical was less discriminatory in males (P = 0.01) and in high tuberculosis prevalence centers (P < 0.001). However, SDS Clinical (AUC, 0.684; 95% CI, 0.602-0.766) and SDS Biopsy (AUC, 0.754; 95% CI, 0.673-0.835) were not sufficiently discriminative for noninfectious granulomatous diseases, but both SDSs could differentiate sarcoidosis from infectious granulomatous diseases. Algorithms were proposed for the SDS Clinical and SDS Biopsy to assist the clinician in the diagnostic process, and cutoff values were proposed for the SDS Clinical and SDS Biopsy, allowing the diagnosis of sarcoidosis to be safely confirmed or rejected in most cases except for noninfectious granulomatous disease. Conclusions: This multicontinental study confirms that both SDS Clinical and SDS Biopsy have good to excellent performance in discriminating sarcoidosis from alternative diagnoses. Differences in the AUC were seen for high tuberculosis prevalence versus low tuberculosis prevalence centers and for males versus females. Both SDSs had good discriminatory function for infectious granulomatous disease but failed in cases of noninfectious granulomatous disease such as berylliosis.


Dissolution at porous interfaces. IV. Pore effects in natural convection flow.
The dissolution rate of a nicotinic acid tablet surface was measured in a dissolution system where mass transport in the solvent is governed by a combination of natural and forced convection. While such experimental conditions were chosen that natural convection outweighted forced convection, the dissolution rate increasing effect of large pores in the tablet surface was studied. To that end cylindrical pores were drilled into the tablet. The increase in dissolution rate was measured as a function of the number of pores, their depth and diameter and their position with respect to each other and to the centre of the dissolving surface. The results are discussed with regard to the hydrodynamic conditions near the pores. In addition to the regularly arranged cylindrical pores a more irregular configuration of cubic pores was investigated. These pores were created by embedding cubic sodium chloride crystals in the tablet surface during the compression procedure. After the sodium chloride particles had dissolved rapidly a porous surface of much slower dissolving nicotinic acid remained. The dissolution rate of the porous surface was determined and a comparison was made between surfaces with and without pores of several sizes.


Erythrocyte sodium-potassium transport in cystic fibrosis.
Erythrocytes from 15 patients with cystic fibrosis (CF) aged 8 mo to 22 y (mean age 12.8 y) were analyzed for Na+,K(+)-ATPase activity and sodium, potassium, and ATP concentrations. Sodium concentrations and Na(+)-K+ ratio of erythrocytes were statistically significantly lower in the CF patients [6.6 (SD 1.9) versus 9.2 (SD 1.1) mmol/L (p less than 0.01) and 0.070 (SD 0.023) versus 0.104 (SD 0.016) mmol/L (p less than 0.01), respectively]. The Na+,K(+)-ATPase activity was similar compared with that of reference individuals [536 (SD 100) versus 488 (SD 92) nmol inorganic phosphate/mg protein/h]. Intraerythrocyte sodium concentration and Na(+)-K+ ratio were thus lower in relation to the recorded Na+,K(+)-ATPase activities in controls, indicating a change of the passive transmembrane movements of sodium ions in CF. There was a rise of erythrocyte sodium and Na(+)-K+ ratio despite unchanged Na+,K(+)-ATPase activity after regular infusion of a fat emulsion rich in essential fatty acids, inferring that an altered membrane composition by essential fatty acid deficiency could explain the low intracellular sodium concentration in CF.


Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema.
To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes. In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20. The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm) in the Lucentis group. The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.


An investigation into the onset, pattern, and effects of pain relief on lumbar extensor electromyography in people with acute and chronic low back pain.
The aim of this study was to use an experimental pain relief model to determine the effect of pain relief on lumbar muscle function in people with low back pain. A test-retest design was used with all data collection being completed within a therapy setting. Twenty people with acute and 20 with chronic low back pain were recruited from general practitioner and therapist referrals. Participants completed spinal movements and lifting. Electromyography (EMG) was used to measure the pattern of muscle activity, onset of muscle activation, and peak activation of bilateral lumbar multifidus and iliocostalis. Movements were investigated before and after pain relief, through the self-administration of oral analgesia. Electromyography profiles and peak values were reliable across 3 trials, and EMG profiles correlated well with kinematic profiles. Specific EMG profiles were commonly associated with specific kinematic values, and on the whole, the EMG profiles were unaffected by pain relief. Muscle onset times and peak muscle amplitudes were not affected by pain relief in either acute or chronic low back pain. This study showed that the EMG activities from the lumbar region, including lumbar multifidus and iliocostalis, are reliable, and specific EMG profiles are identifiable. Pain relief as achieved in this study did not affect the pattern of EMG activity, onset of muscle activation, or peak activation values.


bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses.
We recently developed a user-friendly web-based application called bc-GenExMiner (http://bcgenex.centregauducheau.fr), which offered the possibility to evaluate prognostic informativity of genes in breast cancer by means of a 'prognostic module'. In this study, we develop a new module called 'correlation module', which includes three kinds of gene expression correlation analyses. The first one computes correlation coefficient between 2 or more (up to 10) chosen genes. The second one produces two lists of genes that are most correlated (positively and negatively) to a 'tested' gene. A gene ontology (GO) mining function is also proposed to explore GO 'biological process', 'molecular function' and 'cellular component' terms enrichment for the output lists of most correlated genes. The third one explores gene expression correlation between the 15 telomeric and 15 centromeric genes surrounding a 'tested' gene. These correlation analyses can be performed in different groups of patients: all patients (without any subtyping), in molecular subtypes (basal-like, HER2+, luminal A and luminal B) and according to oestrogen receptor status. Validation tests based on published data showed that these automatized analyses lead to results consistent with studies' conclusions. In brief, this new module has been developed to help basic researchers explore molecular mechanisms of breast cancer. DATABASE URL: http://bcgenex.centregauducheau.fr


[Computed tomography in patients with chronic stable angina : Fractional flow reserve measurement].
Coronary computed tomography angiography (cCTA) has been established for the non-invasive diagnosis of coronary artery disease (CAD). Previous studies demonstrated the high diagnostic accuracy of cCTA, particularly for ruling out CAD. As a known limitation of cCTA a large number of visually significant coronary stenoses are found to be hemodynamically not relevant by invasive fractional flow reserve (FFR). CT-based FFR (CT-FFR) builds on recent advances in computational fluid dynamics and image simulation techniques. Along with CT myocardial perfusion imaging, CT-FFR is a promising approach towards a more accurate estimation of the hemodynamic relevance of coronary artery stenoses. CT-FFR is derived from regular CT datasets without additional image acquisitions, contrast material, or medication. Two CT-FFR techniques can be differentiated. The initial method requires external use of supercomputers and has gained approval for clinical use in the USA. Furthermore, a prototype-software has been introduced which is less computationally demanding via integration of reduced-order models for on-site calculation of CT-FFR. The present article reviews these methods in the context of available study results and meta-analyses. Furthermore, limitations and future concepts of CT-FFR are discussed.


Tuberculous epididymo-orchitis.
In the clinical course of epididymitis in a forty-four-year-old male patient, enlargement of ipsilateral testis developed which was difficult to distinguish clinically from testicular tumor. High inguinal orchiectomy was performed. Microscopic sections revealed many granulomas with caseous necrosis and giant cells. Tuberculous bacilli also were demonstrated in the histologic examination.


Enprostil, a prostaglandin E2 analogue, in the treatment of gastric ulcer--a multicentre comparison with pirenzepine.
In a double-blind, multicentre study 77 patients with benign gastric ulcer were randomly allocated to treatment with either enprostil 35 micrograms bd or pirenzepine 50 mg bd. After four weeks of treatment 13/26 (50 per cent) of evaluable enprostil-treated patients and 9/30 (30 per cent) of evaluable pirenzepine-treated patients were healed. Corresponding healing figures after eight weeks were 20/25 (80 per cent) and 25/31 (81 per cent). Both drugs rapidly reduced the severity of ulcer pain and the need for antacid use. No statistically significant differences were detected between the treatments with respect to healing rate or symptom control. Adverse events were reported by eight patients taking enprostil and by 17 patients taking pirenzepine. Two patients withdrew from each treatment group because of adverse events. None of these was serious. In conclusion, enprostil and pirenzepine were equally effective in healing gastric ulcers and no statistically significant differences in safety and efficacy were detected. There was a tendency for earlier healing and fewer side effects in the enprostil-treated patients.


Fluorocarbon-enhanced mutagenesis of polyaromatic hydrocarbons.
The widely used fluorocarbon refrigerant and cleaning solvent 1,1,2-trichloro-1,2,2-trifluoroethane (Freon TF), though generally considered biologically inert, enhances the metabolic activation of chemical carcinogens. Liver microsomal extracts from mice given single intraperitoneal injections of this fluorocarbon showed significant increases in their ability to activate carcinogenic polyaromatic hydrocarbons to form mutagens, compared to control mice injected with saline. Polyaromatic hydrocarbons aminofluorene and acetylaminofluorene were activated in this way. Mutagenicity was measured by a microbial assay. Both commercial grade and redistilled fluorocarbons gave similar results, that is, more highly active liver extracts after administration of the fluorocarbon preparation to mice. Neither industrial grade nor redistilled preparation was itself mutagenic. A combined liver microsomal extract from mice breathing Freon TF at 20,000 ppm in air for 8 hr also had enhanced ability to activate aminofluorene as a mutagen. Exposing mice to Freon TF by inhalation more closely matches the normal route of human exposure to fluorocarbons. The results of this study imply that low-molecular-weight fluorocarbons may pose a carcinogenic risk by acting as cocarcinogenic enhancers of carcinogen activation. The possibility that fluorocarbons are cocarcinogens in this way has apparently not been heretofore considered.


Preliminary report: the role of short-leg, tone-reducing casts as an adjunct to physical therapy of patients with cerebral palsy.
In the past two years, we have used specially constructed, short-leg casts as an adjunct to the therapy program for 99 patients with cerebral palsy. The casts provide tone reduction and increased stability, while allowing mobility, and have been useful in initiating weight-bearing activities and improvement of gait pattern.


Axonal transport of opiate receptors in capsaicin-sensitive neurones.
Opiate receptors measured in vitro or in vivo with [3H]lofentanil in the rat vagus nerve were found to accumulate on both sides of a ligature, thus indicating a bidirectional axoplasmic transport of these receptors. When rats were treated with capsaicin, the accumulation of opiate receptors was tremendously reduced in the vagus whereas muscarinic receptors in ligated sciatic nerves were unaffected. Since capsaicin is known to affect sensory neurones, mostly those containing substance P, the present results support the idea that the opiate receptors in the vagus are associated with substance P neurones.


Sensory and physical properties of peanut brittle prepared in different types of cookware and with different levels of sodium bicarbonate.
Two studies to evaluate peanut brittle containing either raw or roasted peanuts were conducted. In the first study, brittles were prepared in iron, aluminum, stainless steel and nonstick stainless steel pans. In the second study, brittles containing 0, 2 or 4 g of sodium bicarbonate prepared in either stainless steel or nonstick stainless steel pans were evaluated. All brittles were evaluated for color, shear strength and sensory properties at 0, 30 and 60 days. Products prepared in a nonstick stainless steel pan and those with added sodium bicarbonate were lighter, more yellow and slightly greener than other products. Pan type did not affect shear force but increasing sodium bicarbonate was associated with decreasing force needed to shear brittles. Peanut and caramel aromas were not affected by pan type or sodium bicarbonate level but were greater (p < 0.05) in products containing roasted peanuts. Burned flavors were more prevalent in products prepared in iron or stainless steel pans with roasted peanuts. More intense sweet and buttery flavors were detected as level of sodium bicarbonate increased.


Dynamic regulation of alpha-dystroglycan in mouse placenta.
Alpha dystroglycan (alpha-DG) is a peripheral membrane protein important in cellular interaction with other cells and the extracellular matrix. Recent data suggests that the Dag1 gene, which encodes alpha-DG, is important for implantation. In addition to its importance in cellular function, alpha-DG also serves as a cellular receptor for members of the arenaviridae family of viruses, which can cause placental infection. Because of its apparent dual role in implantation and its role as a viral receptor, we sought to determine placental and uterine alpha-DG expression during mouse pregnancy. Dag1 is expressed throughout gestation in the placenta and to a lesser extent in the uterus, with the highest levels in early gestation. By Western blot analysis, the glycosylated protein is also expressed and the pattern of glycosylation changes to favor the most highly glycosylated forms at mid gestation. These data support the idea that alpha-DG may be a target for evolutionary host-pathogen interactions at the maternal-fetal interface.


Retracted: The Effect of Synthetic Osteoconductive Bone Graft Material for Augmentation of Internally Fixed Unstable Trochanteric Fractures.
[This retracts the article DOI: 10.1155/2019/5879089.].


Revealing unbound β-diketiminate anions: structural dynamics from caesium complexes.
This study reports the first structural elucidation of β-diketiminate anions (BDI-), known for strong coordination, in their unbound form within caesium complexes. β-Diketiminate caesium salts (BDICs) were synthesised, and upon the addition of Lewis donor ligands, free BDI- anions and donor-solvated Cs+ cations were observed. Notably, the liberated BDI- anions exhibited an unprecedented dynamic cisoid-transoid exchange in solution.


A method to predict the percutaneous permeability of various compounds: shed snake skin as a model membrane.
Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and the more lipophilic the compound, the greater the permeability. Equations have been developed to predict the permeability from the molecular weight and the distribution coefficient of a compound. Further, the lipophilicity of shed snake skin is similar to that of human skin and the response of shed snake skin to the molecular size of a permeant is more similar to human skin than to hairless mouse skin. Considering the similarities between shed snake skin and human stratum corneum in terms of structure, composition, and permeability characteristics, the same considerations may apply to permeability through human stratum corneum.


Glutathione S-transferase activity in patients with cancer of the digestive tract.
Glutathione S-transferase (GST) and carcinoembryonic antigen were measured in the plasma of 95 patients with neoplasm of digestive tract, in 40 patients suffering from non-neoplastic diseases and in 40 healthy subjects. The mean value of the GST activity was significantly (P < 0.001) elevated in patients with gastric, liver and colorectal cancer (10.4 U/l, 14.1 U/l and 12.3 U/l respectively) as compared with the reference population (3.2 U/l). GST elevations above normal were observed in 26 (90%) patients with gastric cancer, in 18 (100%) with liver cancer and in 25 (89%) with colorectal cancer. Carcinoembryonic antigen appeared less sensitive. In 15 patients the postoperative levels of serum GST were increased after surgery then gradually declined and after 1 month showed a normalization in 10 patients. Our data suggest that GST measurement may be useful as a tumour marker in gastric, liver and colorectal cancer. Moreover the combined determination of GST and other markers increase the sensitivity for cancer detection.


Medulloblastomas, CNS embryonal tumors, and cerebellar mutism syndrome: advances in care and future directions.
Central nervous system (CNS) embryonal tumors, commonly found in pediatric patients, represent a heterogeneous mix of lesions with an overall poor (though improving) prognosis. Medulloblastomas are by far the most frequently encountered and most widely studied subtype, though others include atypical teratoid/rhabdoid tumors (AT/RTs), embryonal tumor with multilayered rosettes (ETMRs), and CNS neuroblastomas, FOX-R2 activated. The classification, diagnosis, and treatment of these lesions have evolved drastically over the years as their molecular underpinnings have been elucidated. We describe the most recent 2021 WHO Classification system, discuss current understanding of the genetic basis, and demonstrate current thinking in treatment for these highly complex tumors. Since surgical resection continues to remain a mainstay of treatment, preventing and managing surgical complications, especially cerebellar mutism syndrome (CMS), is paramount. We describe the current theories for the etiology of CMS and two centers' experience in mitigating its risks. As our surgical toolbox continues to evolve along with our understanding of these tumors, we hope future patients can benefit from both improved overall survival and quality of life.


Chronic suppurative otitis media: a review.
Chronic suppurative otitis media (CSOM) remains one of the most common childhood chronic infectious diseases worldwide. Although microbial, immunological, and genetically determined factors, as well as Eustachian tube characteristics, are supposed to be involved in the pathogenesis of CSOM, many aspects of the pathogenesis of CSOM still need to be clarified. Optimal treatment strategy has not been established yet. The objective of this review is to present and evaluate the current state of knowledge of CSOM. Systematic narrative review. A PubMed search (1966-January 2005) was performed for studies on epidemiology, pathogenesis, clinical management, and complications of CSOM. All included articles were categorized according to level of evidence. Five hundred and fifty papers were identified, of which 79 were found to be relevant for this review. The definition of CSOM was found to vary. CSOM is a multifactorial disease. Regarding management of CSOM, there is no consensus as to what the optimal management strategy should entail. No convincing evidence is available for most medical and surgical therapies. Topical quinolones have proven effective, but need further monitoring regarding adverse effects. Important goals in research of CSOM should be achieving consensus about the definition of CSOM and gaining more in-depth knowledge of the pathogenesis of CSOM, especially the role of innate and adaptive immunity. There is also a need for further well-designed studies on the effectiveness of various management strategies for CSOM.


Stereotactic Radiotherapy and Short-course Pembrolizumab for Oligometastatic Renal Cell Carcinoma-The RAPPORT Trial.
Stereotactic ablative body radiotherapy (SABR) is an option for oligometastatic clear cell renal cell carcinoma (ccRCC) but is limited by a lack of prospective clinical trial data. The RAPPORT trial evaluated the safety and efficacy of total metastatic irradiation followed by short-course anti-programmed death receptor-1 immunotherapy in patients with oligometastatic ccRCC. RAPPORT was a single-arm multi-institutional phase I/II trial (NCT02855203). Patients with two or fewer lines of prior systemic therapy and one to five oligometastases from ccRCC were eligible. A single fraction of 20 Gy SABR (or if not feasible, ten fractions of 3 Gy) was given to all metastatic sites, followed by pembrolizumab 200 mg administered Q3W for eight cycles. The endpoints were adverse events (AEs), disease control rate (DCR) for at least 6 mo, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The Kaplan-Meier method was used for time-to-event endpoints. Freedom from local progression (FFLP) was assessed per lesion adding patient as a cluster effect. Thirty evaluable patients, with a median age of 62 yr, were enrolled. The median follow-up was 28 mo. There were 44% of patients with intermediate-risk and 56% with favorable-risk disease. Eighty-three oligometastases were irradiated (median three per patient): eight adrenal, 11 bone, 43 lung, 12 lymph node, and nine soft tissue. Four patients (13%) had grade 3 treatment-related AEs: pneumonitis (n = 2), dyspnea (n = 1), and elevated alkaline phosphatase/alanine transaminase (n = 1). There were no grade 4 or 5 AEs. FFLP at 2 yr was 92%. ORR was 63% and DCR was 83%. Estimated 1- and 2-yr OS was 90% and 74%, respectively, and PFS was 60% and 45%, respectively. Limitations include a single-arm design and selected patient population. SABR and short-course pembrolizumab in oligometastatic ccRCC is well tolerated, with excellent local control. Durable responses and encouraging PFS were observed, warranting further investigation. The RAPPORT trial investigated the combination of high-dose precision radiotherapy and a short course of immunotherapy in patients with low-volume metastatic kidney cancer. We found that this treatment regimen was well tolerated, with excellent cancer control in sites of known disease. A proportion of patients were free from cancer relapse in the longer term, and these encouraging findings warrant further investigation.


Evaluating the impact of hemodynamic support measures on head and neck free tissue transfer outcomes: A population-based analysis.
This study sought to analyze the effects of perioperative blood transfusions and vasopressors on 30-day surgical complications and 1-year mortality after reconstructive surgery in head and neck free tissue transfer (FTT) and to identify predictors of administration of perioperative blood transfusions or vasopressors. TriNetX (TriNetX LLC, Cambridge, USA), an international population-level electronic health record database, was queried to identify subjects that underwent FTT requiring perioperative (intraoperative to postoperative day 7) vasopressors or blood transfusions. Primary dependent variables were 30-day surgical complications and 1-year mortality. Propensity score matching was used to control for population differences, and covariate analysis was used to identify preoperative comorbidities associated with perioperative vasopressor or transfusion requirements. 7,631 patients met inclusion criteria. Preoperative malnutrition was associated with increased odds of perioperative transfusion (p = 0.002) and vasopressor requirement (p < 0.001). Perioperative blood transfusion (n = 941) was associated with increased odds of any surgical complication (p = 0.041) within 30 days postoperatively and specifically increased odds of wound dehiscence (p = 0.008) and FTT failure (p = 0.002), respectively. Perioperative vasopressor was (n = 197) was not associated with 30-day surgical complications. Vasopressor requirement was associated with increased hazards-ratio of mortality at 1-year (p = 0.0031). Perioperative blood transfusion in FTT is associated with increased odds for surgical complications. Judicious use as a hemodynamic support measure should be considered. Perioperative vasopressor use was associated with an increased risk of one-year mortality. Malnutrition is a modifiable risk factor for perioperative transfusion and vasopressor requirement. These data warrant further investigation to assess causation and potential opportunity for practice improvement.


Antithrombotic Therapy Increases the Risk of Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matched Analysis.
Whether antithrombotic agent (ATA) usage increases the risk of gastric post-endoscopic submucosal dissection (ESD) bleeding remains controversial. The aim of this study was to elucidate the effects of usage, type, and cessation timing of ATA on post-ESD bleeding. A total of 4775 early gastric cancer patients undergoing ESD were analyzed; 1:3 propensity score matching between ATA and non-ATA groups resulted in 318 and 767 matched patients in each group, respectively. Outcomes were compared between the two groups using a generalized estimating equation method. After matching, post-ESD bleeding rates in ATA users and non-users were 9.1% and 4.2%, respectively (p = 0.001). In multivariable analysis, ATA usage was independently associated with an increased risk of post-ESD bleeding (adjusted odds ratio: 2.28, 95% confidence interval: 1.34-3.86). Both the continued or insufficient cessation groups and the sufficient cessation group had an increased incidence of post-ESD bleeding compared to their matched controls (12.5% versus 5.2%, p = 0.048; 8.1% versus 3.9%, p = 0.014). Post-ESD bleeding rates in antiplatelet agent users were significantly higher than those of their matched controls (8.3% versus 4.2%, p = 0.010). ATA usage increased the risk of post-ESD bleeding even after its sufficient cessation. Careful observation after ESD is required regardless of the cessation status of ATA.


BX795, a TBK1 inhibitor, exhibits antitumor activity in human oral squamous cell carcinoma through apoptosis induction and mitotic phase arrest.
TANK-binding kinase 1 (TBK1), a member of IκB Kinase (IKK)-related kinases, plays a role in regulating innate immunity, inflammation and oncogenic signaling. This study aims to investigate the role of BX795, an inhibitor of TBK1, in a panel of oral squamous cell carcinoma (OSCC) cell lines. The antitumor effects and mechanisms of BX795 were assessed by MTT assays, flow cytometry, Western blotting, and confocal microscopy. BX795 exhibited a dose-responsive antiproliferative effect on OSCC cells with relative sparing of normal human oral keratinocytes. The compound caused apoptosis as evidenced by PARP cleavage, the presence of pyknotic nuclei in the TUNEL assay, and fragmented DNA tails in the Comet assay. BX795 inhibits Akt and NF-κB signaling, arrests cells in the mitotic phase, and increases generation of autophagy in oral cancer cells. Interestingly, the antiproliferative activity of BX795 does not correlate with TBK1 protein expression level in OSCC cells. We propose that the TBK1-independet effect is related to mitotic phase arrest. Pleiotropic anticancer activity with relative sparing of normal oral keratinocytes underscores the potential value of BX795 and warrants its further study in oral squamous cell carcinoma therapy.


New interpretable deep learning model to monitor real-time PM2.5 concentrations from satellite data.
Particulate matter with a mass concentration of particles with a diameter less than 2.5 μm (PM2.5) is a key air quality parameter. A real-time knowledge of PM2.5 is highly valuable for lowering the risk of detrimental impacts on human health. To achieve this goal, we developed a new deep learning model-EntityDenseNet to retrieve ground-level PM2.5 concentrations from Himawari-8, a geostationary satellite providing high temporal resolution data. In contrast to the traditional machine learning model, the new model has the capability to automatically extract PM2.5 spatio-temporal characteristics. Validation across mainland China demonstrates that hourly, daily and monthly PM2.5 retrievals contain the root-mean-square errors of 26.85, 25.3, and 15.34 μg/m3, respectively. In addition to a higher accuracy achievement when compared with various machine learning inversion methods (backpropagation neural network, extreme gradient boosting, light gradient boosting machine, and random forest), EntityDenseNet can "peek inside the black box" to extract the spatio-temporal features of PM2.5. This model can show, for example, that PM2.5 levels in the coastal city of Tianjin were more influenced by air from Hebei than Beijing. Further, EntityDenseNet can still extract the seasonal characteristics that demonstrate that PM2.5 is more closely related within three month groups over mainland China: (1) December, January and February, (2) March, April and May, (3) July, August and September, even without meteorological information. EntityDenseNet has the ability to obtain high temporal resolution satellite-based PM2.5 data over China in real-time. This could act as an important tool to improve our understanding of PM2.5 spatio-temporal features.


2D vs. 3D imaging in laparoscopic surgery-results of a prospective randomized trial.
3D imaging is an upcoming technology in laparoscopic surgery, and recent studies have shown that the modern 3D technique is superior in an experimental setting. However, the first randomized controlled clinical trial in this context dates back to 1998 and showed no significant difference between 2D and 3D visualization using the first 3D generation technique, which is now more than 15 years old. Positive results measured in an experimental setting considering 3D imaging on surgical performance led us to initiate a randomized controlled pragmatic clinical trial to validate our findings in daily clinical routine. Standard laparoscopic operations (cholecystectomy, appendectomy) were preoperatively randomized to a 2D or 3D imaging system. We used a surgical comfort scale (Likert scale) and the Raw NASA Workload TLX for the subjective assessment of 2D and 3D imaging; the duration of surgery was also measured. The results of 3D imaging were statistically significant better than 2D imaging concerning the parameters "own felt safety" and "task efficiency"; the difficulty level of the procedures in the 2D and 3D groups did not differ. Overall, the Raw NASA Workload TLX showed no significance between the groups. 3D imaging could be a possible advantage in laparoscopic surgery. The results of our clinical trial show increased personal felt safety and efficiency of the surgeon using a 3D imaging system. Overall of the procedures, the findings assessed using Likert scales in terms of own felt safety and task efficiency were statistically significant for 3D imaging. The individually perceived workload assessed with the Raw NASA TLX shows no difference. Although these findings are subjective impressions of the performing surgeons without a clear benefit for 3D technology in clinical outcome, we think that these results show the capability that 3D laparoscopy can have a positive impact while performing laparoscopic procedures.


Positive resection margin and/or pathologic T3 adenocarcinoma of prostate with undetectable postoperative prostate-specific antigen after radical prostatectomy: to irradiate or not?
To evaluate the efficacy of postoperative adjuvant radiotherapy (RT) for positive resection margin and/or pathologic T3 (pT3) adenocarcinoma of the prostate with undetectable postoperative prostate-specific antigen (PSA) levels. We retrospectively analyzed 125 patients with a positive resection margin and/or pT3 adenocarcinoma of the prostate who had undetectable postoperative serum PSA levels after radical prostatectomy. Seventy-three patients received postoperative adjuvant RT and 52 did not. Follow-up ranged from 1.5 to 12.0 years (median 4.2 for the irradiated group and 4.9 for the nonirradiated group). PSA outcome was available for all patients. Freedom from failure was defined as the maintenance of a serum PSA level of < or =0.2 ng/mL, as well as the absence of clinical local recurrence and distant metastasis. No difference was found in the 5-year actuarial overall survival between the irradiated and nonirradiated group (94% vs. 95%). However, patients receiving adjuvant RT had a statistically superior 5-year actuarial relapse-free rate, including freedom from PSA failure, compared with those treated with surgery alone (88% vs. 65%, p = 0.0013). In the irradiated group, 8 patients had relapse with PSA failure alone. None had local or distant recurrence. In the nonirradiated group, 15, 1, and 2 had PSA failure, local recurrence, and distant metastasis, respectively. On Cox regression analysis, pre-radical prostatectomy PSA level and adjuvant RT were statistically significant predictive factors for relapse, and Gleason score, extracapsular invasion, and resection margin status were not. There was a suggestion that seminal vesicle invasion was associated with an increased risk of relapse. The morbidity of postoperative adjuvant RT was acceptable, with only 2 patients developing Radiation Therapy Oncology Group Grade 3 genitourinary complications. Adjuvant RT had a minimal adverse effect on urinary continence and did not cause serious gastrointestinal toxicity. Postoperative adjuvant RT was associated with a lower risk of relapse, including freedom from PSA failure, compared with observation alone for pT3 and/or margin-positive disease with undetectable postoperative PSA levels. This was accomplished with a minimal risk of serious RT morbidity.


EpidemiXs: Harnessing digital technology in the fight against COVID-19 and the associated infodemic.
EpidemiXs is an innovative ecosystem of digital tools centralizing official and validated information on COVID-19 for healthcare workers and the general public in a single hub. The vision of EpidemiXs is to foster collaboration between researchers, institutions and individuals to promote "open data" in order to enrich the scientific community and further accelerate science in the fight against COVID-19. Through its set of solutions, EpidemiXs Info, EpidemiXs TV and EpidemiXs Studies, this innovative ecosystem contributes to advancing collaborations, data collection and analysis, and helps find funders. EpidemiXs was launched in March 2020 in Spain with 30 healthcare institutions and rapidly reached close to 1 million users and 2 million views. EpidemiXs gained international recognition when it was awarded the Barcelona Health Hub Awards (BHHAwards) 2020 of the category "Best Startup Initiative to help tackle COVID-19". EpidemiXs has proven the efficiency of the rapid deployment of digital tools in times of COVID-19.


Immunoglobulin-specific T-B cell interaction. III. B cell activation by immunoglobulin-recognizing T cell clones.
Immunoglobulin (Ig)-specific T-B cell interactions were studied in the model of T cell recognition of Ig kappa chain Ig kappa-1b allotype in Ig kappa-1-congenic rats. Using Ig kappa-1b-recognizing major histocompatibility complex (MHC)-restricted T helper clones from August rats we have shown that Ig kappa-1b+ B cells from congenic August.1b rats presented Ig kappa-1b epitope of the processed self-synthesized Ig to T clones. This interaction was found to be a bidirectional regulatory event inducing specific MHC-dependent proliferation of both interacting T cell and B cell as well as Ig(Ig kappa-1b) synthesis. Small Ig kappa-1b+ B cells were capable of inducing T clone proliferation and becoming activated in response to the same T clone. Limiting dilution analysis suggested that every tenth cell in Ig kappa-1b+ B cell population is involved in this interaction. The bystander activation of Ig kappa-1a+ B cells by T clones in the presence of irradiated Ig kappa-1b+ spleen cells, if observed, was less than the level of specific Ig kappa-1b+ B cell proliferation. In contrast to a 20-fold increase of Ig(Ig kappa-1b) levels upon stimulation of Ig kappa-1b+/1a+ B cell population from heterozygous (August x August.1b)F1 rats by T clones, a "nonspecific" increase of Ig(Ig kappa-1a) was not observed. This result demonstrates the requirement for direct T-B contact for B cell activation to occur. The data suggest a great functional potency of T-B interactions mediated by T cell recognition of Ig-derived peptide/MHC class II complexes on the B cell surface. The implication of the data for idiotypic regulation enables us to propose the existence of putative idiopeptidic network T-B cell interactions.


Structural characterization and immunomodulatory activity of a novel acid polysaccharide isolated from the pulp of Rosa laevigata Michx fruit.
A novel acid polysaccharide (PPRLMF-2) with the Mw of 137,123 Da and a triple-helix conformation was first isolated from the pulp of Rosa laevigata Michx fruit. Structural characterization showed that PPRLMF-2 consisted of rhamnose (7.6%), arabinose (26.5%), xylose (3.5%), mannose (0.9%), glucose (5.7%), galactose (31.9%) and galacturonic acid (23.9%). The methylation and NMR (1D and 2D) analysis revealed that PPRLMF-2 contained 16 types of glycosidic linkages. The immunomodulatory activity assays indicated that PPRLMF-2 could significantly enhance phagocytosis, the secretion and mRNA expression of cytokines in RAW 264.7 cells. Additionally, SR, GR, TLR-2, and TLR-4 were the main pattern recognition receptors (PRRs) of PPRLMF-2 to upregulate the p-ERK, p-JNK, p-p38, and p-p65. These results suggested that PPRLMF-2 could recognize the PRRs of the macrophages to enhance the immunomodulatory activity via activation of the MAPKs and NF-κB signaling pathways. This study provides important implications of PPRLMF-2 as an attractive immunomodulatory functional food.


Haemodialysis is an effective treatment in acute metabolic decompensation of maple syrup urine disease.
Acute metabolic decompensation in maple syrup urine disease can occur during intercurrent illness and is a medical emergency. A handful of reports in the medical literature describe the use of peritoneal dialysis and haemodialysis as therapeutic inventions. We report the only patient from our centre to have haemodialysis performed in this setting. Combined with dietary BCAA restriction and calorific support, haemodialysis allows rapid reduction in plasma leucine concentrations considerably faster than conservative methods.


The Effect of Supportive-Educational Interventions on Stress and Adaptation to Maternal Role: A Quasi-Experimental Study.
Preterm delivery is a stressful event and stress can affect adaptation to maternal role. The purpose of this study is to determine the effect of supportive-educational interventions on stress and adaptation to the maternal role among women with premature infants hospitalized in the neonatal intensive care unit. This quasi-experimental study was conducted on 60 women with premature infants hospitalized in the neonatal intensive care unit. A control group (n = 30) was initially selected from eligible female participants. Sampling was stopped for three weeks and then the intervention group was sampled. The entire sampling process was carried out from December 2018 to June 2019. The control group received usual care at the hospital and the intervention group (n = 30) received three sessions of supportive-educational intervention in addition to routine care. Data were collected through the perceived stress and the maternal role adaptation questionnaires completed by both groups at the time of infant discharge, and also at the follow-up period (one month after discharge). The results showed that maternal stress score changed considerably over time and a significant difference between the two groups was observed (P < 0.05). Additionally, adaptation to the maternal role changed substantially over time and the difference between the two groups was statistically significant (P < 0.05). The supportive-educational program reduced the stress of mothers with premature infants hospitalized in the neonatal intensive care unit and increased their adaptation to the maternal role.


The differential distribution of the growth-associated protein-43 in first and higher order thalamic nuclei of the adult rat.
Corticothalamic axons from layer 5 of primary and secondary auditory and visual areas have large terminals that make multiple synaptic contacts on proximal dendrites of relay cells in higher order thalamic nuclei and have been termed "driver" inputs. The corticothalamic cells express mRNA for the presynaptic growth-associated protein-43, in the adult rat [Feig SL (2004) Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex express GAP-43 mRNA in the adult rat. J Comp Neurol 468:96-111]. In contrast, ascending driver afferents to first order nuclei (e.g. retinal, inferior collicular, and lemniscal) lose growth-associated protein-43 as mature synaptic terminals are established. Levels of immunoreactivity for growth-associated protein-43 are compared for first and higher order visual (lateral geniculate and lateral posterior), auditory (ventral and dorsal divisions of the medial geniculate), and somatosensory (ventral posterior and posterior) thalamic nuclei. At one week postnatal, staining for growth-associated protein-43 is uniform throughout first and higher order thalamic nuclei. By three weeks and thereafter, staining is denser in the higher order than first order thalamic nuclei. Electron microscopy shows growth-associated protein-43 in profiles with characteristics of afferents from layer 5 in LP and medial geniculate nucleus and no such label in retinal afferents in lateral geniculate nucleus. In these nuclei, approximately 25% of the profiles with characteristics of cortical afferents from layer 6 have label for growth-associated protein-43. The superficial layers of the superior colliculus also show growth-associated protein-43 positive profiles with characteristics of terminals from cortical layer 5. Some growth-associated protein-43 positive terminals were also positive for GABA in the thalamic nuclei studied and in the superior colliculus. The data suggest that sensory afferents to first order thalamocortical relays become stabilized once mature synaptic patterns are established, but the higher stages of information processing involving higher order thalamic relays, via cells in cortical layer 5, retain plasticity related to growth-associated protein-43 in the adult.


Interactions between TGFβ1 and cyclic strain in modulation of myofibroblastic differentiation of canine mitral valve interstitial cells in 3D culture.
The mechanisms of myxomatous valve degeneration (MVD) are poorly understood. Transforming growth factor-beta1 (TGFβ1) induces myofibroblastic activation in mitral valve interstitial cells (MVIC) in static 2D culture, but the roles of more physiological 3D matrix and cyclic mechanical strain are unclear. In this paper, we test the hypothesis that cyclic strain and TGFβ1 interact to modify MVIC phenotype in 3D culture. MVIC were isolated from dogs with and without MVD and cultured for 7 days in type 1 collagen hydrogels with and without 5 ng/ml TGFβ1. MVIC with MVD were subjected to 15% cyclic equibiaxial strain with static cultures serving as controls. Myofibroblastic phenotype was assessed via 3D matrix compaction, cell morphology, and expression of myofibroblastic (TGFβ3, alpha-smooth muscle actin - αSMA) and fibroblastic (vimentin) markers. Exogenous TGFβ1 increased matrix compaction by canine MVIC with and without MVD, which correlated with increased cell spreading and elongation. TGFβ1 increased αSMA and TGFβ3 gene expression, but not vimentin expression, in 15% cyclically stretched MVIC. Conversely, 15% cyclic strain significantly increased vimentin protein and gene expression, but not αSMA or TGFβ3. 15% cyclic strain however was unable to counteract the effects of TGFβ1 stimulation on MVIC. These results suggest that TGFβ1 induces myofibroblastic differentiation (MVD phenotype) of canine MVIC in 3D culture, while 15% cyclic strain promotes a more fibroblastic phenotype. Mechanical and biochemical interactions likely regulate MVIC phenotype with dose dependence. 3D culture systems can systematically investigate these phenomena and identify their underlying molecular mechanisms.


Dendritic cells activated by cross-linking B7-DC (PD-L2) block inflammatory airway disease.
Allergic asthma is an increasing clinical problem that might be addressed with immunologically based interventions. A novel human antibody that activates human and mouse dendritic cells (DCs) by cross-linking B7-DC has strong immunomodulatory properties and blocks antigen-induced inflammatory lung disease in mice. We sought to evaluate the ability of activated DCs to mediate an antibody-induced protective response against inflammatory lung disease. An adoptive transfer strategy was used to test the ability of antibody treatments to activate DCs, inducing a protective response against inflammatory lung disease in mice presensitized to ovalbumin (OVA). After transfer of activated DCs, recipient mice were exposed repeatedly to airway antigen and evaluated for changes in immune reactivity and airway inflammatory disease. Animals presensitized to OVA receiving either systemic treatments with B7-DC cross-linking antibody (XAb) or adoptively transferred antibody-activated DCs were completely protected from airway inflammatory responses normally induced by repeated exposure to OVA. Lymphocytes isolated from spleens or lung-draining lymph nodes of treated animals were highly responsive to OVA and secreted TNF-alpha, IFN-gamma, and IL-10. In contrast, IL-4 was not produced by cells isolated from animals receiving B7-DC XAb. Activation of DCs with B7-DC XAb ex vivo before adoptive transfer into presensitized mice is sufficient to protect animals completely from inflammatory lung disease induced by subsequent repeated airway exposure to the offending antigen. This finding is consistent with our hypothesis that in vivo administration of B7-DC XAb modulates the immune response by activating endogenous DCs.


Histocompatibility antigens in multiple sclerosis patients participating in a multicentre trial of azathioprine. British & Dutch Multiple Sclerosis Azathioprine Trial Group.
The human leucocyte antigen (HLA) types of 283 patients with multiple sclerosis participating in a trial of azathioprine treatment were studied. The prevalence of HLA types was compared with those of over 3,300 controls from tissue typing centres in the UK. The prevalence of HLA A3 (38.5% cp 26.1%), HLA B7 (44.9% cp 27.3%) and HLA DR2 (58.3% cp 30.6%) was increased in the multiple sclerosis patients compared with the controls. Age at onset, disease status (relapsing-remitting or currently progressive) and disease severity did not show an association with any particular HLA type.


Progesterone receptors in the human uterus and their possible role in parturition.
An overview is given on the role of progesterone in parturition in the human. Progesterone withdrawal is considered to be a major event for the beginning of parturition. However, in the human, no evidence exists in favour of a decline in placental progesterone production prior to labour. Progesterone actions are mediated by two functionally different but structurally highly related intranuclear proteins, progesterone receptor (PR) A and PRB. In the human, functional progesterone withdrawal is thought to play a role. This may be mediated by a change in the expression of the two isoforms of the PR, with an increase in the PRA:PRB ratio, and this is accompanied by an increase in the expression of the estrogen receptor. These mechanisms are considered to be critical for the endocrine control of parturition.


Chronic expanding hematoma after spinal surgery.
Chronic expanding hematoma after spinal surgery is extremely rare, with no case previously reported in the literature. To report a rare case of a chronic expanding hematoma of the spine that occurred 24 years after thoracic laminectomy and spinal cord tumor resection. Case report. A 71-year-old man presented with a spinal mass located approximately at the level of the sixth thoracic vertebral body. The patient had undergone thoracic laminectomy with tumor resection 24 years previously. The mass had appeared 5 years after this and had gradually enlarged over 19 years. The tumor was resected en bloc. The lamina and spinous processes had been partially eroded by the tumor at the fifth and sixth thoracic vertebrae, but the dura was intact. Histopathologic examination confirmed the diagnosis of chronic expanding hematoma. The hematoma had not recurred at the 1-year follow-up. We report herein an extremely rare case of chronic expanding hematoma after spinal surgery. This entity may be considered a late complication after surgery regardless of the number of years that have passed since the index surgery.


Application of triphenylphosphine organic compounds constructed with O, S, and Se in aluminum ion batteries.
Due to their high reactivity and theoretical capacity, chalcogen elements have been favored and applied in many battery studies. However, the high surface charge density and high solubility of these elements as electrode materials have hindered their deeper exploration due to the shuttle effect. In this article, organic structural triphenylphosphine is used as a molecular main chain structure, and chalcogen elements O, S, and Se are introduced to combine with P as active sites. This approach not only takes advantage of the beneficial effects of the aromatic ring on the physical and chemical properties of the chalcogen element but also allows for the optimization of its advantages. By utilizing Triphenylphosphine selenide (TP-Se) as the cathode material in aluminum-ion batteries(AIBs), a high-performance Al-organic battery was fabricated, which exhibited a high initial capacity of 180.6 mAh g-1 and stable cycling for up to 1000 cycles. Based on density functional theory (DFT) calculations, TP-Se exhibits a smaller energy gap, which renders it favorable for chemical reactions. Moreover, the calculated results suggest that TP-Se tends to undergo redox reactions with AlCl2+. The molecular structure of triphenylphosphine and its combination with Se offers an enticing pathway for designing cathode materials in aluminum-organic batteries.


Ghrelin Gene Variants Influence on Metabolic Syndrome Components in Aged Spanish Population.
The role of genetic variations within the ghrelin gene on cardiometabolic profile and nutritional status is still not clear in humans, particularly in elderly people. We investigated six SNPs of the ghrelin gene and their relationship with metabolic syndrome (MS) components. 824 subjects (413 men/411 women, age 77.31±5.04) participating in the Mataró aging study (n = 310) and the Hortega study (n = 514) were analyzed. Anthropometric variables, ghrelin, lipids, glucose and blood pressure levels were measured, and distribution of SNPs -994CT (rs26312), -604GA (rs27647), -501AC (rs26802), R51Q (rs34911341), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene evaluated. Genotypes were determined by multiplex PCR and SNaPshot minisequencing. MS (IDF criteria) was found in 54.9%. No association between any of the SNPs and levels of total fasting circulating ghrelin levels was found. C/A-A/A genotype of M72L was associated with increased risk of central obesity according to IDF criteria, while G/A-G/G genotypes of -604GA with reduced risk. A/A genotype of -501AC polymorphism was associated to decreased BMI. In relation to lipid profile, the same genotypes of -604GA were associated with increased total cholesterol and LDL-cholesterol and -501AC with reduced triglycerides. There were no associations with systolic or diastolic blood pressure levels or with hypertension, glucose levels or diabetes and ghrelin polymorphisms. However, G/G genotype of -604GA was associated with glucose >100 mg/dL. Haplotype analysis showed that only one haplotype is associated with increased risk of waist circumference and central obesity. The analysis of subjects by gender showed an important and different association of these polymorphisms regarding MS parameters. Ghrelin gene variants -604GA, -501AC and M72L are associated with certain components of MS, in particular to BMI and lipid profile in elderly Spanish subjects.


Hematologic complications of diabetes mellitus.
In summary, hematologic abnormalities in diabetes affect the function, morphology, and metabolism of blood cells, and the coagulation system. These complications can contribute to the development of anemia, infection, and hypercoagulability in diabetic dogs and cats. Some hematologic changes, such as glycosylated hemoglobin and fructosamine, play an important role as markers of glycemic control. Hematologic changes also serve as important models for changes occurring in other tissues, such as cataract formation and nephropathy. Further study of blood alterations will enhance our knowledge of the biochemistry and pathophysiology of diabetes and diabetic complications and stimulate the development of effective preventative and therapeutic measures.


Endoscopic Management of Pancreatic Cysts.
Management of pancreatic cystic lesions relies on patients' clinical presentation, imaging, and endoscopic ultrasound. Current research in basic science, radiology, and endoscopy is evolving and making progress in this condition which is relatively common in the general population. This review focuses on the recent endoscopic ultrasound approaches to the diagnosis of these pancreatic disorders.


Basic fibroblast growth factor dilates rat pial arterioles.
Basic fibroblast growth factor (bFGF) is a polypeptide that promotes the survival and differentiation of brain neurons, glia, and endothelial cells. It has been shown recently that intravenously administered bFGF lowers blood pressure by systemic vasodilation; this effect is mediated, in part, by nitric oxide (NO)-dependent mechanisms. In the current study, we directly evaluated the effect of bFGF on pial arterioles of pentobarbital-anesthetized Sprague-Dawley rats (n = 18) using the closed cranial window technique. Basic FGF (5-200 ng/ml) produced dose-dependent vasodilation; maximal vessel diameter (approximately 120% of control) was reached at 100 ng/ml. No vasodilation was found when bFGF was heat inactivated, or preincubated with blocking antibody. Moreover, bFGF-induced vasodilation was attenuated by coadministration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), consistent with an NO-dependent mechanism. These results suggest that bFGF may play an important role in the regulation of cerebrovascular tone and cerebral blood flow.


Synergistic effect of novel chitosan combined metformin drug on streptozotocin-induced diabetes mellitus rat.
Metformin is widely used as a frontline medicine of type-II diabetes. Frequent overdose side-effects and their consequent adversative need to be reduced. The novel source of marine hydrozoa, Thyroscyphus ramosus derived chitosan combined metformin drug was administrated to evaluate the antidiabetic potential on a high-fat diet (HFD) with streptozotocin (STZ) induced diabetic rats. The primary analysis of In vitro antioxidant activity was tested for various solvent dissolved chitosan. Based on their IC50 dose values, CsnAA was chosen for further experiments. The chitosan was combined with metformin by sonication and confirmed through XRD, FTIR and SEM analysis. The enhanced activity was observed in 100 mg/kg metformin combined with CSN500mg/kg. The level of serum bilirubin, total protein, SGH, liver glycogen, Glucose-6-phosphatase and fructose-1,6- phosphatase values were significantly similar to metformin 300 mg/kg treated group. With this beneficiary, the novel chitosan was recommended to administrate with metformin to improve the drug efficacy and reduction of overdose lethal effects.


Assessment and management of obesity in childhood and adolescence.
The increased prevalence of obesity in childhood and adolescence highlights the need for effective treatment approaches. Initial assessments of these patients should include taking a careful history (investigating comorbidities, family history and potentially modifiable behaviors) and physical examination with BMI plotted on a BMI-for-age chart. The degree of investigation is dependent on the patient's age and severity of obesity, the findings on history and physical examination, and associated familial risk factors. There are several broad principles of conventional management: management of comorbidities; family involvement; taking a developmentally appropriate approach; the use of a range of behavior change techniques; long-term dietary change; increased physical activity; and decreased sedentary behaviors. Orlistat can be useful as an adjunct to lifestyle changes in severely obese adolescents and metformin can be used in older children and adolescents with clinical insulin resistance. Bariatric surgery should be considered in those who are severely obese, with recognition of the need for management in centers with multidisciplinary weight management teams and for surgery to be performed in tertiary institutions experienced in bariatric surgery. Finally, given the high prevalence and chronic nature of obesity, coordinated models of care for health-service delivery for the management of pediatric obesity are needed.


ViaChip for Size-based Enrichment of Viable Cells.
Live cells acquire different fates including apoptosis, necrosis, and senescence in response to stress and stimuli. Rapid and label-free enrichment of live cells from a mixture of cells adopting various cell fates remains a challenge. We developed a ViaChip for high-throughput enrichment of Viable cells via size-based separation on a multi-stage microfluidic Chip. Our chip takes advantage of the characteristic increase in cell size during cellular senescence and decreases during apoptosis and necrosis, in comparison to their viable and healthy counterparts. The core component of our ViaChip is a slanted and tunable 3D filter array in the vertical direction (z-gap) for rapid and continuous cell sieving. The shape of the 3D filter array is optimized for target cells to prevent clogging during continuous separation. We demonstrated enrichment of live human and mouse mesenchymal stem cells in culture and from live animals, as well as the removal of senescent and necrotic MSCs, respectively, achieving an enrichment efficiency of ~67% with the continuous flow at 1.5 mL/hour. With further improvements in throughput and separation efficiency, our ViaChip could find applications in cell-based drug screening for anti-cancer and anti-aging cell therapies.


Elevated ApoB/ApoA-Ι ratio is associated with poor outcome in acute ischemic stroke.
Apolipoproteins are known atherogenic factors that play important roles in many mechanisms related to acute ischemic stroke (AIS). However, it is unclear whether the ApoB/ApoA-Ι ratio is related to the prognosis of patients with AIS. We conducted a prospective cohort study in the Department of Neurology, Yangpu Hospital, School of Medicine, Tongji University and investigated the association between ApoB/ApoA-Ι ratio and poor outcomes at 3 months of AIS. 1,247 patients that met the eligibility criteria were enrolled in our study. We found that ApoA-Ι (Adjusted odds ratios (adjOR) 0.529, 95 %CI 0.327-0.855), ApoB (adjOR 3.015, 95 %CI 1.746-5.207), and ApoB/ApoA-Ι ratio (adjOR 3.986, 95 %CI 2.220-7.155) were independently associated with poor outcomes in acute ischemic stroke. During subgroup analysis, the ApoB/ApoA-Ι ratio was more likely associated with poor AIS outcomes in males and patients younger than 80 with SAO(Small Artery Occlusion) and no history of diabetes or statin use. Restricted cubic spline analyses explored the correlation between poor outcomes and ApoB/ApoA-Ι ratio. Higher ApoB, lower ApoA-Ι, and higher ApoB/ApoA-Ι ratios were independently associated with poor outcomes in AIS. However, ApoB and ApoA-Ι were not related to hemorrhagic transformation in AIS.


Direct input of monitoring data into a mechanistic ecological model as a way to identify the phytoplankton growth-rate response to temperature variations.
We present an approach (knowledge-and-data-driven, KDD, modeling) that allows us to get closer to understanding the processes that affect the dynamics of plankton communities. This approach, based on the use of time series obtained as a result of ecosystem monitoring, combines the key features of both the knowledge-driven modeling (mechanistic models) and data-driven (DD) modeling. Using a KDD model, we reveal the phytoplankton growth-rate fluctuations in the ecosystem of the Naroch Lakes and determine the degree of phase synchronization between fluctuations in the phytoplankton growth rate and temperature variations. More specifically, we estimate a numerical value of the phase locking index (PLI), which allows us to assess how temperature fluctuations affect the dynamics of phytoplankton growth rates. Since, within the framework of KDD modeling, we directly include the time series obtained as a result of field measurements in the model equations, the dynamics of the phytoplankton growth rate obtained from the KDD model reflect the behavior of the lake ecosystem as a whole, and PLI can be considered as a holistic parameter.


The human HIP gene, overexpressed in primary liver cancer encodes for a C-type carbohydrate binding protein with lactose binding activity.
HIP was originally identified as a gene expression in primary liver cancers, and in normal tissues such as pancreas and small intestine. Based on gene data base homologies, the HIP protein should consist of a signal peptide linked to a single carbohydrate recognition domain. To test this hypothesis HIP and the putative carbohydrate recognition domain encoded by the last 138 C-terminal amino acids, were expressed as glutathione-S-transferase proteins (GST-HIP and GST-HIP-142, respectively). Both recombinant proteins were purified by a single affinity purification step from bacterial lysates and their ability to bind saccharides coupled to trisacryl GF 2000M were tested. Our results show that HIP and HIP-142 proteins bind to lactose, moreover the binding requires divalent cations. Thus the HIP protein is a lactose-binding lectin with the characteristics of a C-type carbohydrate recognition domain of 138 amino acids in the C-terminal region.


Disposition and tissue distribution of ML12 in rats.
To investigate the disposition and tissue distribution of ML12 after intravenous (iv) administration in rats, the compound in plasma or in tissue was extracted into ethyl acetate under basic condition and was determined by HPLC after extracted by dilute sulfuric acid. Excitation wavelength and emission wavelength of fluorescence detection were 278 nm and 307 nm, respectively. The data were processed with the software 3P97 to calculate the main pharmaceutical parameters of ML12. At dose of 5 and 10 mg/kg, the elimination of the drug from plasma was found to be kinetically linear, but when the dosage was 20 mg/kg, a non-linear feature was observed. The highest level of ML12 was found in the kidney. Distribution of ML12 after iv administration was extensive and the concentration-time profile was found to be fitted to an open two-compartment model.


Lifespan data on postural balance in multiple standing positions.
Maintaining balance is important throughout life. The Nintendo Wii Balance Board (WBB) can give reliable quantitative measures of postural balance, but reference data are lacking. Furthermore, one-leg standing balance across the adult lifespan is not fully described. The aim of the study was (1) to provide reference data on postural balance in multiple standing positions using a WBB, (2) to determine an age cut-off for the ability to stand on one-leg in men and women. This was a cross-sectional study and data was collected in two cities in Denmark (Aalborg and Odense) and Norway (Oslo and Ålesund) during spring and summer of 2016. Postural balance was assessed in individuals across the adult lifespan in three different bases of support positions (hip-wide and narrow two-legged stance, and one-legged stance) using a WBB. Reference data were analyzed and presented in 10-year intervals. A total of 354 individuals aged 20-99 years were recruited. Reference data were presented in percentiles stratified by gender for the following age categories: 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+. Data showed that the difference between men and women's balance was larger at older age with men performing worst. The cut-off ability to stand on one-leg was 72.5 years without statistical evidence of gender difference. This study reports reference data for postural balance across the entire adult lifespan using a WBB. More than half of the individuals over 72.5 years of age were unable to stand balanced on one-leg.


Helicobacter pylori in gastroduodenal disease.
Helicobacter pylori is a recently described Gram-negative micro-organism, which plays an important role in the pathogenesis of peptic ulcer disease and gastritis. In this paper an outline is given of the history and the pathophysiology of Helicobacter pylori, as well as the therapeutic studies aimed at eradication of the bacterium in various clinical entities.


Transient Interactions of a Cytosolic Protein with Macromolecular and Vesicular Cosolutes: Unspecific and Specific Effects.
Cytosolic proteins do not occur as isolated but are exposed to many interactions within a crowded cellular environment. We investigated the associations between a test cytosolic protein, human ileal bile acid binding protein (IBABP), and model cosolutes mimicking macromolecular and lipid membrane intracellular components. Using fluorescence spectroscopy, heteronuclear NMR, and molecular dynamics, we found that IBABP associated weakly with anionic lipid vesicles and experienced transient unspecific contacts with albumin. Localized dynamic perturbations were observed even in the case of apparent unspecific binding. IBABP and ubiquitin did not display mutually attractive forces, whereas IBABP associated specifically with lysozyme. A structural model of the IBABP-lysozyme complex was obtained by data-driven docking simulation. Presumably, all the interactions shown here contribute to modulating functional communication of a protein in its native environment.


A randomized controlled trial comparing isosorbide dinitrate-oxytocin versus misoprostol-oxytocin at management of foetal intrauterine death.
The metabolic activity of endogenous nitric oxide (NO) and the medical use of nitrovasodilatory drugs like isosorbide dinitrate have been shown to be potential inducers inducers of cervical ripening prior to surgical evacuation of the uterus. To assess the therapeutic efficacy and safety of combined isosorbide dinitrate-oxytocin in the management of intrauterine foetal death (IUFD). Sixty women with IUFD after 20 weeks of gestation requesting uterine evacuation were randomly selected to receive isosorbide dinitrate gel solution (80 mg/1.5 mL; n = 30) or misoprostol gel solution (100 mcg/1.5 mL; n = 30) every 3 h with a maximum of four doses or until a Bishop score >7 was reached. Subsequently, patients received a high dose of intravenous oxytocin until complete uterus evacuation was achieved. Therapeutic efficacy was evaluated by mean the relative risk of the foetal expulsion based on comparison of event rates, and the proportion of women induced to labor at 7, 10 and 15 h after the administration of isosorbide dinitrate or misoprostol. Safety was assessed on the basis of woman´s vital signs and evaluation of adverse effects, including headache, abdominal pain, pelvic pain, lower back pain, nausea, dizziness and vomiting. The foetal expulsion rate using the isosorbide dinitrate-oxytocin combination was approximately 4.4 times, and at least 2.1 times, the foetal expulsion rate with the misoprostol-oxytocin regimen at any given point in time. The proportion of women achieved vaginal delivery at 15 hours was 100% for the isosorbide dinitrate-oxytocin group and 86.7% for the misoprostol-oxytocin group. The average delivery induction interval was significantly lower when isosorbide dinitrate-oxytocin was used (8.7 ± 3.1 h) than when misoprostol-oxytocin (11.9 ± 3.1 h) was used. A total of 20% of patients in the isosorbide dinitrate-oxytocin group recorded headache, and no cases of uterine tachysystole, haemorrhage or coagulopathy were recorded. This study indicates that intravaginal isosorbide dinitrate followed by intravenous oxytocin was more effective than the conventional method used to induce labour in the medical management of foetal death in pregnancies after 20 weeks of gestation. Clinicaltrials.gov NCT02488642.


Biosynthesis of S-adenosyl-methionine enhances aging-related defects in Drosophila oogenesis.
Tissue aging is a major cause of aging-related disabilities and a shortened life span. Understanding how tissue aging progresses and identifying the factors underlying tissue aging are crucial; however, the mechanism of tissue aging is not fully understood. Here we show that the biosynthesis of S-adenosyl-methionine (SAM), the major cellular donor of methyl group for methylation modifications, potently accelerates the aging-related defects during Drosophila oogenesis. An aging-related increase in the SAM-synthetase (Sam-S) levels in the germline leads to an increase in ovarian SAM levels. Sam-S-dependent biosynthesis of SAM controls aging-related defects in oogenesis through two mechanisms, decreasing the ability to maintain germline stem cells and accelerating the improper formation of egg chambers. Aging-related increases in SAM commonly occur in mouse reproductive tissue and the brain. Therefore, our results raise the possibility suggesting that SAM is the factor related to tissue aging beyond the species and tissues.


Obtaining informed consent to treatment: new legal dimensions.
John Tingle, Reader in Health Law at Nottingham Trent University, discusses the guidance on consent to treatment issued by the Royal College of Surgeons, which takes the implications of a landmark legal case into account.


[The interaction between drugs and oral anticoagulants of the coumarin group].
The problem of drug interactions during prolonged use of coumarin anticoagulants is important for most patients receiving anticoagulants take several other drugs. Frequent interaction causes either potentialisation of the anticoagulant effect with risk of hemorrhage or inhibition of the anticoagulant effect with risk of thrombosis. The various mechanisms which may explain most interactions are reviewed and the authors propose a list of drugs which should not be administered with coumarin.


Antineutrophil cytoplasmic antibody negative pauci-immune extracapillary glomerulonephritis.
Pauci-immune extracapillary glomerulonephritis (PEGN) is one of the most common causes of rapidly progressive glomerulonephritis and is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). However, a significant number of individuals with PEGN test negative for ANCA and this study aimed to analyze the characteristics of this subgroup of patients. Patients from two centres who were diagnosed with PEGN between 1997 and 2014 were studied retrospectively. Clinicopathological characteristics and renal outcome were compared between patients presenting with pauci-immune necrotizing extracapillary glomerulonephritis associated or not with the presence of circulating ANCA. Among the 114 patients with PEGN, 29 (25.4%) were ANCA negative. Compared with the 85 ANCA-positive patients, ANCA-negative patients were younger at the onset (54.8 ± 17.2 vs. 62 ± 14.0 years; P < 0.05). The median level of urinary protein excretion was significantly higher among ANCA-negative patients (3.1 vs. 1 g/24 h; P < 0.001), whereas no differences were found in renal function and need for dialysis between ANCA-negative and positive groups. Extrarenal involvement was present independently of ANCA status. Histological analysis showed that ANCA-negative patients were more likely to have mesangial proliferation (P < 0.05). Renal and global survival were similar between ANCA-negative and positive patients, and treatment response and relapse rates were comparable in both groups. ANCA-negative pauci-immune extracapillary glomerulonephritis is not a rare condition and is part of a systemic vasculitis disease. Although ANCA-negative patients have renal and histological characteristics that differ from ANCA-positive patients, renal survival and treatment response in PEGN are independent of ANCA status.


TNF-alpha and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion.
Vascular endothelial growth factor (VEGF) promotes angiogenesis and is associated with the invasion and metastasis of malignant tumors. It enhances vascular permeability and is expressed in inflammatory nasal as well as middle-ear mucosa. As the mechanism of VEGF induction during chronic inflammation, such as chronic paranasal sinusitis (CPS) remains to be clarified, we studied the factors regulating the production of VEGF in cultured human nasal fibroblasts and discussed the role of VEGF in the pathogenesis of CPS. We used ELISA to quantify VEGF levels in paranasal sinus effusions, nasal secretions, and serum from patients with CPS. In addition, we cultured human nasal fibroblasts isolated from nasal polyps of CPS patients and studied the effects of hypoxia, TNF-alpha, and endotoxin on their production of VEGF using ELISA and PCR. The VEGF concentration was significantly higher in paranasal sinus effusions than in nasal secretions and serum. Nasal fibroblasts produced high levels of VEGF, when cultured under hypoxic condition and this production was remarkably enhanced in the presence of TNF-alpha or endotoxin. VEGF is locally produced in paranasal sinuses as well as nasal mucosa and its production is increased in patients with CPS. Hypoxia is associated with the production of VEGF by nasal fibroblasts and TNF-alpha and endotoxin may act synergistically to enhance VEGF production in paranasal sinuses under hypoxic condition.


Solid-phase microextraction for the gas chromatography mass spectrometric determination of oxazole fungicides in malt beverages.
This paper describes a method for the sensitive, selective, and solvent-free determination of six oxazole fungicide residues (hymexazol, drazoxolon, vinclozolin, chlozolinate, oxadixyl, and famoxadone) in malt beverages. Direct immersion solid-phase microextraction (DI-SPME) coupled to gas chromatography with mass spectrometry in the selected ion monitoring mode, GC-MS(SIM), is used. A comparison of the optimal fiber used, a polar carbowax-divinylbenzene 70-microm fiber, and a nonpolar polydimethylsiloxane 100-microm fiber was carried out. Optimal extraction conditions were 60 degrees C and an extraction time of 30 min under continuous stirring. Desorption was carried out at 250 degrees C for 5 min. Detection limits ranged from 0.006 to 0.3 microg L(-1) at a signal to noise ratio of 3, depending on the compound. The proposed method was successfully applied to malt beverages including malt, beer, and whisky, and none of the samples contained residues higher than detection limits.


Reduced responsiveness of HLA-B27 transgenic rat cells to TGF-beta and IL-10-mediated regulation of IFN-gamma production.
We have reported that commensal luminal bacterial components induce an active in vitro IFN-gamma response in mesenteric lymph node (MLN) and intestinal cells from specific pathogen-free (SPF) HLA-B27 transgenic (TG) rats with chronic colitis but not in cells from non-diseased SPF non-TG, germ-free (GF) non-TG or GF TG rats. The study examined IL-12 stimulation of MLN IFN-gamma responses to luminal bacteria and regulation of these responses by suppressive cytokines. Exogenous IL-12 significantly increased the bacterial lysate-induced IFN-gamma response in SPF TG MLN cells, while bacterial lysate and IL-12 synergistically induced IFN-gamma from low baseline levels in cells obtained from both SPF and GF non-TG rats, and in GF TG cells. TGF-beta fully counteracted the effects of IL-12 and bacterial lysate on non-TG cells by almost completely inhibiting IFN-gamma production. In contrast, TG cells were less responsive to TGF-beta-mediated downregulation with a substantial residual IFN-gamma response to IL-12 plus bacterial lysate. Further experiments showed that CD4+/CD25+ cells had no inhibitory effect on the IFN-gamma production and were not required for TGF-beta-mediated suppression. Addition of exogenous IL-10 also partially inhibited IFN-gamma production by non-TG cells but did not affect TG cells. Conversely, exogenous IL-12 preferentially suppressed bacterial lysate-induced TGF-beta and IL-10 production in TG rat cells. An attenuated response to regulatory signals leads to uncontrolled potentiated induction of effector IFN-gamma responses to commensal bacteria in HLA-B27 TG rats that spontaneously develop chronic intestinal inflammation.


Genome-wide identification and expression profiling of two-component system (TCS) genes in Brassica oleracea in response to shade stress.
The Two-component system (TCS) consists of Histidine kinases (HKs), Phosphotransfers (HPs), and response regulator (RR) proteins. It has an important role in signal transduction to respond to a wide variety of abiotic stresses and hence in plant development. Brassica oleracea (cabbage) is a leafy vegetable, which is used for food and medicinal purposes. Although this system was identified in several plants, it had not been identified in Brassica oleracea yet. This genome-wide study identified 80 BoTCS genes consisting of 21 HKs, 8 HPs, 39 RRs, and 12 PRRs. This classification was done based on conserved domains and motif structure. Phylogenetic relationships of BoTCS genes with Arabidopsis thaliana, Oryza sativa, Glycine max, and Cicer arietinum showed conservation in TCS genes. Gene structure analysis revealed that each subfamily had conserved introns and exons. Both tandem and segmental duplication led to the expansion of this gene family. Almost all of the HPs and RRs were expanded through segmental duplication. Chromosomal analysis showed that BoTCS genes were dispersed across all nine chromosomes. The promoter regions of these genes were found to contain a variety of cis-regulatory elements. The 3D structure prediction of proteins also confirmed the conservation of structure within subfamilies. MicroRNAs (miRNAs) involved in the regulation of BoTCSs were also predicted and their regulatory roles were also evaluated. Moreover, BoTCSs were docked with abscisic acid to evaluate their binding. RNA-seq-based expression analysis and validation by qRT-PCR showed significant variation of expression for BoPHYs, BoERS1.1, BoERS2.1, BoERS2.2, BoRR10.2, and BoRR7.1 suggesting their importance in stress response. These genes showing unique expression can be further used in manipulating the plant's genome to make the plant more resistant the environmental stresses which will ultimately help in the increase of plant's yield. More specifically, these genes have altered expression in shade stress which clearly indicates their importance in biological functions. These findings are important for future functional characterization of TCS genes in generating stress-responsive cultivars.