Neoplasm of endolymphatic sac origin: clinical, radiological and pathological features.
This paper reports on a 55-year-old female who had undergone middle ear surgery 12 years previously and was admitted with a 6-months history of unilateral hearing loss and facial weakness. MRI and CT demonstrated a space-occupying lesion arising from the temporal bone and extending into the posterior fossa. Treatment consisted in complete tumour removal. Temporal and mastoid bone destruction associated with typical histological features led to the diagnosis of neoplasm of endolymphatic sac origin. Clinical, histological, radiological and intra-operative features of these rare tumours are described and discussed. The pertinent literature is reviewed.


Visual function in goldfish with unilateral and bilateral tectal ablation.
Following complete bilateral tectal ablation, the ability to detect light recovers in about three weeks. The non-tectal retinal connections which may mediate detection are about one log unit less sensitive than the retinotectal connections. At moderate illumination levels, tectumless fish do not react visually to objects. Tectumless fish integrate luminous flux over a very wide area (at least 25 degrees diameter) while the critical diameter for the normal in this experiment is smaller. Subcortical structures may mediate the interocular transfer of a brightness discrimination. The ipsilateral retinotectal projection following unilateral tectal removal is functional, with normal sensitivity to detection of light.


Value of early operation in blunt testicular contusion with hematocele.
The use of ultrasound for evaluation of blunt testicular injury with hematocele allows contusion to be differentiated from rupture, and some authors advocate reserving surgical management for rupture. Our experience with the conservative management of 20 men with testicular contusion and hematocele was not encouraging. Of the patients 8 (40 per cent) required delayed exploration that involved orchiectomy in 3 (15 per cent) because of unresorbed hematoma or infection despite antibiotic use. In contrast, early surgical exploration in 19 patients reduced the morbidity and duration of disability, and resulted in an orchiectomy rate of 0.


Post-concussion syndrome: Still forgotten? From the disappearance of the DSM-5 to a multidisciplinary consultation.
Following the presence of both post-traumatic stress disorder (PTSD) and post-concussion syndrome (PCS) in the nosography since the publication of DSM-IV, large-scale studies investigated the links between these two entities: exposure to a mild traumatic brain injury was correlated with the presence of PTSD and vice versa, and the strongest factor associated with PCS was the presence of PTSD. But PCS entity was recently suppressed from the 5th edition of the American diagnostic and statistical classification of neuropsychiatric disorders (DSM-5, 2013). In the 11th edition of the CIM, PCS is also likely to be omitted. This elimination raises more questions if we take into consideration the emancipation of PTSD, which now includes the full category of "disorders related to trauma and stressors" to which PCS could have legitimately been added. We discuss current scientific literature and clinical practices with a socio-anthropological point of view. Post-concussion and post-traumatic clinical entities often show similar anamnestic temporalities, with an initial acute phase where memory (amnesia following TBI; dissociative post-traumatic amnesia) and consciousness (initial loss of consciousness secondary to TBI; peri-traumatic psychic dissociation) impairments predominate, followed by a pauci-symptomatic latency phase. Finally, a symptomatic phase occurs in which similar symptoms for both entities are observed (sleep disorders, anxiety and depression, irritability, fatigue, attention disorder, tendency to avoidance). If similar therapies (pharmacological and psychological) are effective in treating the clinical consequences of head and mental trauma, this suggests that they have common etiopathogenic origins. Yet, post-concussion syndrome remains a clinical-biological reality. If a diffusion tensor imaging MRI in the acute phase is likely to provide predictive elements for subsequent cognitive dysfunctions, it would appear useful to consider combining biomarkers, and linguistics markers, with the creation of a clinical-radio-bio- neuropsychological score in order to differentiate benign outcomes from neuro- and/or psycho-traumatic disorders.


Increase in aldose reductase mRNA in dog lens epithelial cells under hypertonic conditions.
Aldose reductase (AR) mRNA levels increase when dog lens epithelial cells are exposed to hypertonic conditions. Hybridization of mRNA to an AR cDNA, using Northern and slot blots, showed that AR mRNA is elevated at least fourfold when primary dog lens epithelial cells are grown in media (300 mosmol kg-1) supplemented with 150 mM NaCl (600 mosmol kg-1 final). A time course showed an increase in AR mRNA of approximately twofold by 24 hr with a maximum increase of between four- and eightfold by 48 hr. AR mRNA remained elevated for the duration of the experiment, 8 days. The addition of Tolrestat, an inhibitor of aldose reductase, had no effect on the increased level of AR mRNA in these hypertonically stressed cells. Cells grown in media supplemented with 250 mM sorbitol also showed a substantial increase in AR mRNA. These data indicate, as in other cell types, the lens, a target tissue of diabetes, responds to hypersomotic stress with an induction of AR expression and suggests that AR may play a role in intracellular osmotic regulation.


Microarrays--analysis of signaling pathways.
Microarrays provide a powerful means of analyzing the expression level of multiple transcripts in two sample populations. In this study, we have used microarray technology to identify genes that are differentially regulated in response to activin-treated ovarian cancer cells. We find a number of biologically relevant genes that are involved in regulating activin signaling and genes potentially contributing to activin-mediated growth arrest appear to be differentially regulated. Thus, microarrays are an important tool for dissecting gene expression changes in normal physiological processes and disease.


Best practice in early psychosis intervention for Australian indigenous communities: indigenous worker consultation and service model description.
The aim of this study was to identify promising elements of best practice relevant to mainstream mental health service (MHS) delivery of early psychosis intervention (EPI) to Indigenous communities. In a companion paper, a comprehensive literature review identified a promising service model with potential for delivering EPI: an Indigenous sub-team embedded within a mainstream health service. This paper describes a consultation process with Indigenous Mental Health Workers (IMHWs) in south eastern Queensland. A case study of the Sunshine Coast Cultural Healing Program (CHP-SC) was carried out during the consultation process. IMHWs agreed that the Australian clinical guidelines for early psychosis were relevant to improving outcomes for Indigenous patients. IMHWs unanimously identified the CHP-SC as a best practice mainstream MHS for delivering EPI. The CHP-SC, which represented an Indigenous sub-team model, was found to be associated with substantially improved engagement of Indigenous young people. We provisionally conclude that specialist EPI could be delivered by specialist Indigenous sub-teams (rather than specialist EPI teams) embedded in mainstream MHSs that incorporate culturally safe practice and are fully integrated with Indigenous primary care services, and recommend that the model be formally evaluated.


[Spanish Society of Anaesthesia (SEDAR) guidelines for pre-anaesthesia checking procedures].
We present this document as a guide to preparing a specific institutional pre-anaesthesia checklist, as recommended in the Helsinki declaration on patient safety in anaesthesiology. Also, the recently recommended WHO "safe surgery check-list" includes a check-list for anaesthesia. A working group was established in accordance with the charter of the Spanish Society of Anaesthesiology and Resuscitation (Sociedad Española de Anestesiología y Reanimación [SEDAR]). The new patient safety culture introduced into medicine, and the recommendations of European anaesthesia societies has led us to design and update protocols in order to improve results in this important part of our speciality. We have prepared these recommendations or guidelines using, as examples, updates of pre-anaesthesia check-lists by other American (ASA), British, or Canadian societies of anaesthesia. With that aim, we enlisted the help of anaesthesia ventilator experts and the participation and advice of experienced anaesthesiologists from all parts of Spain. After various corrections and modifications, the document was available at www.sedar.es, so that any anaesthesiologist could propose any correction, or give their opinion. Finally, these guidelines have been approved by the SEDAR Board of Directors, before it was sent for publication in this journal. The aims of this document are to provide: a guideline applicable to all anaesthesia machines, a descriptive pre-anaesthesia check-list that include everything necessary for the anaesthesia procedure, and a resumed check-list to be available in all the anaesthesia machines or other equivalent, but prepared for each institution, which should include anaesthetic equipment and drugs. So, in order to ensure the aims and requirements of the European Board of Anaesthesiology, the European Society of Anaesthesiology, and the WHO are met, each institution should have a protocol for checking equipment and drugs. These guidelines are applicable to any anaesthesia equipment, enabling every institution to develop their own checking protocols, adapted to their anaesthesia machines and their procedures. With the consent of the SEDAR, this group will collaborate with anaesthesia machines providers in order to develop specific checklists for each of their models that will be available at www.sedar.es.


Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted great interest in novel broad-spectrum antivirals, including perylene-related compounds. In the present study, we performed a structure-activity relationship analysis of a series of perylene derivatives, which comprised a large planar perylene residue, and structurally divergent polar groups connected to the perylene core by a rigid ethynyl or thiophene linker. Most of the tested compounds did not exhibit significant cytotoxicity towards multiple cell types susceptible to SARS-CoV-2 infection, and did not change the expressions of cellular stress-related genes under normal light conditions. These compounds showed nanomolar or sub-micromolar dose-dependent anti-SARS-CoV-2 activity, and also suppressed the in vitro replication of feline coronavirus (FCoV), also termed feline infectious peritonitis virus (FIPV). Perylene compounds exhibited high affinity for liposomal and cellular membranes, and efficiently intercalated into the envelopes of SARS-CoV-2 virions, thereby blocking the viral-cell fusion machinery. Furthermore, the studied compounds were demonstrated to be potent photosensitizers, generating reactive oxygen species (ROS), and their anti-SARS-CoV-2 activities were considerably enhanced after irradiation with blue light. Our results indicated that photosensitization is the major mechanism underlying the anti-SARS-CoV-2 activity of perylene derivatives, with these compounds completely losing their antiviral potency under red light. Overall, perylene-based compounds are broad-spectrum antivirals against multiple enveloped viruses, with antiviral action based on light-induced photochemical damage (ROS-mediated, likely singlet oxygen-mediated), causing impairment of viral membrane rheology.


DNAase hydrolysis of chromatin DNA in intact sea urchin sperm cells. Effect of the ionic strength on the digestion parameters.
Chromatin DNA in intact functional Sphaerechinus granularis sperm cells has been digested with micrococcal nuclease at three different ionic strength conditions. The results show a highly-flexible chromatin organization similar to that found in sperm heads. The rate of digestion, the limit value of acid-soluble material and the fragmentation pattern show that the sensitivity of nucleosome and internucleosome DNA regions to nuclease hydrolysis depends on a delicate balance of polar and non polar interactions. At low ionic strength, both nucleosome and internucleosome regions are rapidly and completely hydrolysed at the same time and a transient subunit fragment of 120 b.p. average length is formed. At high ionic strength, internucleosome regions are preferentially hydrolysed; there is a limit digest value and a stable subunit fragment of 140 b.p. average length is formed. A supernucleosome organization in the high ionic strength environment of the sperm cells is suggested by the transient preferential formation of heptamers of nucleosome DNA fragments.


Intracranial/Extracranial meningioma arising in the hypoglossal canal: case report.
A case of a patient with a posterior fossa meningioma extending through the hypoglossal canal to the cervical region as described in this article has not been previously described in the literature. Investigations and surgical management are outlined and pathological classifications are discussed. A literature review including recent reports of extracranial meningiomas is presented. Extracranial meningiomas are exceedingly rare and a high index of suspicion is necessary to make the diagnosis.


Novel cinnamohydroxamic acid derivatives as HDAC inhibitors with anticancer activity in vitro and in vivo.
A novel series of cinnamohydroxamic acid derivatives were synthesized and their biological activities against HDAC were assessed. Our results showed that the compound with more strong inhibitory activity to HDAC would exhibited more significant anti-proliferative effect on tumor cells. Among these compounds, 7e displayed clearly inhibitory effects on HDAC and tumor cell growth. Furthermore, HDAC isoforms enzyme data indicated that, compared to HDAC pan-inhibitor SAHA, 7e owned an enhanced inhibitory effect on HDAC1, 3 and 6 isoforms. Meanwhile, it also significantly suppressed cell growth of lung cancer cells compared to SAHA, but with lower toxicity in normal cells. Mechanistically, 7e prompted acetylation of histone3 and histone4, led to up-regulation of p21, and then mediated cell cycle arrest and pro-apoptosis. Moreover, the in vivo study indicated that compound 7e could retard tumor growth of A549 xenograft models. These findings support the further investigation on the anti-tumor potential of this class of compounds as HDAC inhibitor.


Biliary obstruction and susceptibility to biliary sepsis in rats.
The effect of retrograde intrabiliary (RI) injection of E. coli was studied in Sprague-Dawley rats with biliary obstruction of different duration (3 days; 2, 4, and 6 weeks). By the injection of 10(5) colony-forming units (CFU) immediately after occlusion of the common bile duct (CBD), 15 of 18 normal rats survived without clinical signs of infection. In contrast, six of 11 animals in 3-day obstruction (P = 0.04), seven of 12 in 2-week obstruction (P = 0.02), ten of 12 in both 4-week and 6-week obstruction (P = 0.0004) died of E. coli sepsis after injection of the same amount of bacteria. Animals with longstanding jaundice (4 and 6 weeks) were more susceptible than those with a shorter duration of jaundice (3 days and 2 weeks, P = 0.04). The results warrant the early decompression of the biliary tract in biliary obstruction.


Stability-indicating HPTLC method for simultaneous determination of nateglinide and metformin hydrochloride in pharmaceutical dosage form.
A stability indicating high performance thin layer chromatography (HPTLC) method was developed and validated for determination of two anti-diabetic drugs, nateglinide and metformin hydrochloride in co-formulations. Study was performed on pre-coated silica gel HPTLC plates using chloroform:ethyl acetate:acetic acid (4:6:0.1 v/v/v) as the mobile phase. A TLC scanner set at 216 nm was used for direct evaluation of the chromatograms in the reflectance/absorbance mode. Method was validated according to ICH guidelines. The correlation coefficients of calibration curves were found to be 0.996 and 0.995 in the concentration range of 200-2400 and 500-3000 ng band(-1) for nateglinide and metformin, respectively. The method had an accuracy of 99.72% for nateglinide and 100.08% for metformin hydrochloride. The method had the potential to determine these drugs simultaneously from dosage forms without any interference of the tablets excipients. Nateglinide and metformin hydrochloride were also subjected to acid, base, oxidation, wet, heat and photo-degradation studies. The degradation products obtained were well resolved from the pure drugs with significantly different Rf values. As the method could effectively separate the drugs from its degradation products, it can be used for stability-indicating analysis.


Actigraphy-based sleep analysis in sedentary and overweight/obese adults with primary hypertension: data from the EXERDIET-HTA study.
The aim of this study was to analyze actigraphy-based sleep quantity and quality in sedentary and overweight/obese adults with primary hypertension (HTN) divided by sex and cardiorespiratory fitness (CRF) and to assess the association of sleep parameters with body composition, blood pressure (BP), and CRF. This is a cross-sectional design utilizing data from the EXERDIET-HTA study conducted in 154 non-physically, obese adults with HTN (53.3 ± 7.8 years). Sleep parameters (total bedtime; total sleep time, TST; and sleep efficiency = (TST/total bedtime) × 100)) were calculated from raw accelerometer data (ActiGraph GT3X+). Peak oxygen uptake (V̇O2peak) determined the CRF. Blood pressure was assessed with the 24-h ambulatory BP monitoring. The distributions of V̇O2peak were divided into tertiles (low, medium, and high CRF) in each sex. Series of linear regression analyses were conducted between sleep, fitness, and health-related variables. Short sleep duration (6.2 h) both on weekdays and weekends, poor sleep quality (< 85% of efficiency), and no significant differences in sleep variables between women and men, nor among CRF groups, were observed. The short sleeping pattern was negatively associated (P < 0.05) with mean and night systolic BP (mmHg, β = - 0.2), and sleep efficiency with waist circumference (cm, β = - 0.08, P = 0.05). Actigraphy-based sleep analysis reinforces that sleep disorders, such as short sleep duration and poor sleep quality, are associated with high BP and abdominal obesity in sedentary adults with overweight/obesity and HTN. Sleep pattern did not appear to be related with CRF level in this population.


New signs to encourage the use of Automated External Defibrillators by the lay public.
Public Access Defibrillation - the use of Automated External Defibrillators (AEDs) by lay bystanders before the arrival of Emergency Medical Services - is an important strategy in delivering prompt defibrillation to victims of out-of-hospital cardiac arrest and can greatly improve survival rates. Such public-access AEDs are used rarely: one barrier might be poor understanding and content of current signage to indicate their presence. The aim of this project was to develop a sign, with public consultation, that better indicated the function of an AED, and an associated poster to encourage its use. Two public surveys were undertaken, in July and December 2015, to investigate perceptions of the current AED location sign recommended for use in the UK and to produce an improved location sign and associated information poster. There were 1895 and 2115 respondents to the surveys. Fewer than half (47.9%, 895/1870) understood what the current location sign indicated. One of four design options for a location sign best explained the indication for (preferred by 56.0%, 1023/1828) and best encouraged the use of a public AED (51.8%, 946/1828). 83.5% (1766/2115) preferred an illustration of a stylised heart trace to the lightning bolt used at present. From five wording options, 'Defibrillator - Heart Restarter' was the most popular (29.4%, 622/2115). An associated poster was developed using design features from the new location sign, findings from the surveys and expert group input regarding its content. This is the first time that public consultation has been used to design a public AED location sign. Effective signage has the potential to help break down the barriers to more widespread use of AEDs in public places.


The influence of vinblastine and colchicine on renin secretion in vivo and in vitro.
The effect of the microtubule inhibitors colchicine and vinblastine on renin release in vivo and in vitro was studied. Injection of 0.5 mg/100 g i.v. of colchicine or vinblastine to furosemide treated rats on a low salt diet resulted in a decrease of plasma renin as well as plasma angiotensinogen concentration during a 5 h observation period. Renin release from rat kidney slices was diminished by vinblastine (5 x 10(-5) M), when basal or stimulated (by isobutylmethylxanthine and isoproterenol) renin release was measured. Colchicine at 5 x 10(-5) M had no effect under these conditions. Renin release from the isolated perfused rat kidney was increased 2--3 fold by vinblastine (10(-5) M) or colchicine (10(-4) M). The maximal response of renin release to isoproterenol (10(-7) M) was not changed when vinblastine (10(-5) M) or colchicine (10(-4) M) were present in the perfusion medium. The contrasting results cast considerable doubts on the suitability of microtubule inhibitors in studies on renin secretion.


C-reactive protein and coronary events following percutaneous coronary angioplasty.
We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P <0.0001). In a multivariate logistic regression model, an increased C-reactive protein level was an independent predictor of death or nonfatal myocardial infarction (RR = 3.6; 95% CI: 1.8 to 7.2; P =0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (+/- SD) C-reactive protein level (5.8 +/- 9.7 mg/L vs. 7.2 +/- 12.1 mg/L, P =0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.


Photosensitivity during the hypersomnic phase in a patient with Kleine-Levin syndrome.
The case of an adolescent with Kleine-Levin syndrome is presented who exhibited a consistent and predictable photoparoxysmal self-limited response to intermittent photic stimulation during all relapses of his hypersomnic phase. A possible cause of this association that has not been previously reported is speculated based on observations concerning the two disorders.


EB1 identifies sites of microtubule polymerisation during neurite development.
EB1 is a microtubule associated protein which interacts with the APC tumour suppressor protein and components of the cytoplasmic dynein/dynactin complex. EB1 is also a specific marker of growing microtubule tips. Here we demonstrate that EB1 protein levels are increased during axon but not dendrite formation in differentiated N2A neuroblastoma cells, and that EB1 localises to microtubule tips throughout extending neurites in these cells. In N2A axons, analysis of the ratio of EB1/beta-tubulin fluorescence demonstrated that the distal tip region contained the highest proportion of polymerising microtubules. Time-lapse confocal imaging of an EB1-GFP fusion protein in transfected N2A cells directly revealed the dynamics of microtubule extension in neurites, and demonstrated the existence of unusual, discrete knots of microtubule polymerisation at the periphery of non-process bearing cells which may represent an early event in neurite outgrowth. We conclude that EB1 localisation can be used to identify and analyse sites of microtubule polymerisation at a high resolution during neurite development, a process to which it may contribute.


Critical role of neutrophil alkaline phosphatase in the antimicrobial function of neutrophils.
To investigate the roles of neutrophil alkaline phosphatase (NAP) in the migration, reactive oxygen species (ROS) generation and apoptosis of neutrophils. NAP was overexpressed in neutrophil-like differentiated HL-60 cells via transfecting coding sequence of NAP by lentivirus. NAP overexpression in HL-60 cells was confirmed by the methods of quantitative RT-PCR and Western blotting. HL-60 cells were induced to differentiate into neutrophil-like cells by exposure to 1.5% dimethylsulfoxide (DMSO). The migration of neutrophil-like cells were detected by Transwell migration assay. ROS generation of neutrophil-like cells were determined by flow cytometry. Neutrophil-like cells continued to be cultured for 24h, and were then harvested for apoptosis and Western blotting. After GFP-NAP infection by lentivirus, the expression of NAP was up-regulated in HL-60 cells. HL-60 cells were allowed to differentiate into neutrophil-like cells after 5-day exposure to 1.5% DMSO. Overexpression of NAP in neutrophil-like cells resulted in an increase in the number of migrated cells, intracellular ROS and cell apoptosis followed by a rise in the expression of Caspase 3, Caspase 9 and Bax, while those results were reversed in the NEG and CON group. NAP might play a critical role in the anti-microbial function of neutrophils by promoting its migration and ROS generation, as well as accelerating apoptosis in neutrophils.


Jet ventilation for surgical interventions in the upper airway.
The clinical applications of jet ventilation (JV) in ear, nose, and throat surgery can be best understood by the characteristics that distinguish this form of ventilation from conventional positive pressure ventilation. By definition, JV is based on the application of gas portions under high pressure through an unblocked catheter into the airway, which is open to the ambient air. Beneficial opportunities arise in JV, which otherwise are not available in regular ventilation.


Tomographic mapping of brain intracellular pH and extracellular water space in stroke patients.
Functional images of regional intracellular pH (pHi) and of fractional volume of extracellular water (FVECW) were obtained in 10 patients with recent hemispheric infarction (between 10 and 19 days after onset of symptoms) using positron emission tomography (PET). The volume of extracellular water relative to that of total water was evaluated in each pixel of the PET scan 7-8 h after injection of 76Br. The pHi image was calculated from the data obtained after injection of [11C]5,5-dimethyl-2,4-oxazolidinedione and from the FVECW image. Regional CBF, oxygen extraction, and oxygen metabolism were also measured in the same patients. In normal hemisphere, mean +/- SD values for FVECW and pHi were 0.12 +/- 0.01 and 6.86 +/- 0.11, respectively. FVECW was increased in the infarcted area in most patients. pHi was increased in the infarct in seven patients and unchanged in three. The increase in pHi was not correlated with changes in FVECW, CBF, or CMRO2, but there was a significant correlation with the decrease in oxygen extraction fraction in the same region. Thus, the decreased H+ content in the infarcted area was correlated with the occurrence of perfusion in excess of metabolic demand. An alkaline shift in pHi enhances the glycolysis rate and could explain why the glucose metabolism is less affected than the oxygen metabolism in recent cerebral infarction. The pHi measured in the infarct could represent mainly the pHi of phagocytic cells that use aerobic glycolysis to synthesize hydrogen peroxide.


Oncologic treatment landscape for head and neck squamous cell carcinoma : Treatment infrastructure in German-speaking countries.
The treatment of head and neck squamous cell carcinoma (HNSCC) is highly complex and requires a multimodal approach. However, guidelines for the treatment of most forms of HNSCC do not exist in German-speaking countries with the exception of oral cavity cancer. The aim of this cross-sectional study was to describe the current treatment landscape and infrastructure in German-speaking countries. From November 2013 to July 2014, 204 departments of otorhinolaryngology (ORL) in Germany, Austria, and the German-speaking part of Switzerland were contacted and invited to take part in a web-based survey on the treatment of HNSCC. In order to cover the study in its entirety, we published three consecutive papers of which this paper is the first. In all, 62 treatment centers (30.4 %) participated in the survey. These centers included 21 university hospitals, 16 certified cancer centers, and 35 large centers, which diagnose at least 75 HNSCC patients annually. In 91.9 % of all cases, there were outpatient consultation hours (that were monodisciplinary in 61.4 %). A multidisciplinary tumor board was existent in 98.4 % of the cases. Of 62 ORL departments, 50 had a hospital cancer registry, 41 of 62 conducted oncological studies, and 35 of 62 assessed their patients' quality of life. The infrastructure of the treatment for HNSCC can be considered mostly well-developed and supports interdisciplinary cooperation. Potential improvements can be made regarding the standardization of tumor boards, the participation in clinical trials, and the availability of cancer registries and the data gathered therein.


Clobetasol propionate ointment reduces inflammation after cryotherapy.
A double-blind, randomized, placebo-controlled trial was carried out comparing the effects of clobetasol propionate ointment and the ointment base on the inflammation induced by cryotherapy of basal cell carcinomata and warts. A single application of the steroid was shown to be significantly better at reducing erythema, pain and swelling than the ointment base.


Dissection of the molecular parameters for T-cell recognition of a myoglobin antigenic site.
Previous studies from this laboratory have resulted in the determination of the antigenic structure of sperm-whale myoglobin (Mb). In the present work, we have investigated the fine specificity requirements for T-cell recognition of one of the Mb antigenic sites (antigenic site 5). The antigenic site (peptide 145-153) and seven progressively longer peptides, increasing in length stepwise by two residues at a time up to 22 residues in length (peptide 132-153), were synthesized. In addition, four truncated peptides were synthesized with intentional deletions at Tyr-151 and Ala-144. The T-cell recognition of these purified synthetic peptides was examined here in detail in three strains of mice (BALB/cByJ, B10.D2/n and SJL/J). Mb-primed mice afforded T-cells which proliferated to smaller peptides (two or four residues longer than the site; i.e. peptides 145-153 and 143-153) and more so to the longer peptides 135-153 and 132-153 and to Mb. No response was obtained to the truncated peptides, thus underscoring the fine specificity of T-cells. No response was obtained also to intermediate-sized peptides. The latter result, due to an unfavorable mode of folding, suggested a conformational dependency in T-lymphocyte recognition and was confirmed by additional studies employing peptide priming. Thus priming with either the 11- or 22-residue peptides afforded T-cells which proliferated to both of these two peptides, but not to intermediate-sized peptides. More importantly, peptide-primed cells did not proliferate on challenge in vitro with Mb. This indicated that the in vivo recognition (priming) was to the unfolded peptide and these cells will not therefore recognize native Mb in vitro. Tolerization of neonatal mice with native Mb, which was total for the native protein at the T-cell level, had no effect on in vivo recognition (priming) and in vitro proliferation due to the unfolded peptide. Conversely, tolerization by any unfolded peptide had little or no effect on in vivo recognition of, and proliferation to, native Mb. It was concluded that T-cell recognition of native proteins (or at least of Mb) is dependent on protein conformation. A peptide may not cause proliferation of native protein-primed T-cells even though it contains an antigenic site. Finally, macrophage presentation of protein antigens is not related to processing via fragmentation of antigen by macrophage.


Lack of effect of high dose vitamin E on xanthoma regression in homozygous familial hypercholesterolaemia.
There is increasing evidence that oxidative modification of low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Homozygous familial hypercholesterolaemia (HFH) is characterized by premature, severe atherosclerosis. Drugs available at present are ineffective in lowering the markedly elevated LDL levels in this condition; antioxidant therapy to protect the LDL against oxidation may be of benefit. Probucol, the only drug shown to induce xanthoma regression in HFH, is a potent antioxidant, but it also lowers high-density lipoprotein cholesterol (HDL-C) levels, causing some concern. Vitamin E is a naturally occurring antioxidant that does not affect HDL-C levels. We have therefore evaluated the effect of long-term high dose vitamin E on xanthoma regression in HFH. Ten subjects with HFH, mean age 17 years (range 4-34), received vitamin E (400-1000 mg/dl alpha-tocopherol acetate/day) for a period of 23 months (range 12-27). There was a 4.2-fold increase in the mean serum vitamin E level (mean (S.D.) 49.7 (19.9) to 177.9 (45.6) mumol/l; P < 0.005), but no change in serum lipid or lipoprotein concentrations. Although there was an increase in the in vitro resistance of LDL to oxidation as determined by the duration of the lag phase during copper-mediated oxidation (116 (8.34) vs. 141.5 (9.23) min; P < 0.005) there was no xanthoma regression; in fact they progressed in 4 subjects. Unlike probucol, high dose long-term vitamin E has no demonstrable effect on xanthoma regression in HFH.


Cell reprogramming during regeneration in Drosophila: transgression of compartment boundaries.
We discuss recent work about cellular reprogramming during regeneration of the imaginal discs of Drosophila. These contain various lineage blocks, compartments, which express distinct genetic programmes. It has been found that after massive damage to a compartment cells from a neighbour compartment can transgress the compartment border and contribute to its regeneration. The transgressing cells are genetically reprogrammed and acquire a new identity, a process facilitated by up regulation of the JNK pathway and transient loss of epigenetic control by the Pc-G and trx-G genes. The final acquisition of the new identity appears to be mediated by induction by neighbour cells, a phenomenon akin the Community Effect described for the specification of amphibian muscle cells.


Nutrient uptake by a diverse spring ephemeral community.
Net production by the six most abundant species in a diverse spring ephemeral community was 66.8 g/m2, and net uptake of nitrogen and potassium were 5.5 and 4.5 kg/ha respectively. These uptake rates are relatively large compared to those reported previously and to other fluxes of these nutrients in the site.


Messengers of renal graft quality during warm and cold ischemia: a porcine microdialysis study.
Little is known about local graft metabolism during warm and cold ischemia before renal transplantation. We sought to characterize local metabolic changes in renal grafts during storage to understand acceptable ischemia time. Kidneys from 60- or 15-kg pigs were randomized to cold (4°C) or warm (37°C) storage. Local renal graft metabolism was monitored for 24 hours by use of microdialysis and measurements of glycerol, glutamate glucose and lactate. For all metabolites, there was a significant interaction between time, storage temperature, and kidney size (all P < .0001). For local glycerol and glutamate, a significant increase was observed initially during warm storage, reaching a high steady state level. Glycerol remained low in cold kidneys for 80 minutes, but after 100 minutes there was an ongoing increase (P = .003) with no steady-state maximum level reached during the first 24 hours. The curves in the 2 size groups were parallel (P = .384) with 74% higher glycerol content in large kidneys (P = .005). Glutamate increased in cold kidneys in a similar manner in the 2 size groups (P = .924). Warm storage caused a rapid glucose decline within 60-100 minutes. In cold storage, glucose remained at a steady level until 480 minutes. Reducing cold ischemia time is of great importance, because concentrations of ischemic metabolites continuously increase in renal grafts. Furthermore, small kidney grafts from growing individuals are more resistant to cold ischemia but more susceptible to warm ischemia. In the setting of donation after circulatory death with prolonged warm ischemia, ongoing catabolism in the potential renal graft may be measured by microdialysis to achieve optimal timing of transplantation.


Safety and efficacy needs to be tested in an appropriate design.
The Chungpyesagan-tang was developed for one of four human constitutional types in Korea. In order to test the effectiveness and efficacy, randomized controlled trials and placebo controlled trials, respectively are required. The safety question should be answered through control studies within the same constitutional population.


A conceptual framework for road safety and mobility applied to cycling safety.
Scientific literature lacks a model which combines exposure to risk, risk, and the relationship between them. This paper presents a conceptual road safety framework comprising mutually interacting factors for exposure to risk resulting from travel behaviour (volumes, modal split, and distribution of traffic over time and space) and for risk (crash and injury risk). The framework's three determinants for travel behaviour are locations of activities; resistances (generalized transport costs); needs, opportunities, and abilities. Crash and injury risks are modelled by the three 'safety pillars': infrastructure, road users and the vehicles they use. Creating a link in the framework between risk and exposure is important because of the 'non-linear relationship' between them, i.e. risk tends to decrease as exposure increases. Furthermore, 'perceived' risk (a type of travel resistance) plays a role in mode choice, i.e. the perception that a certain type of vehicle is unsafe can be a deterrent to its use. This paper uses theories to explain how the elements in the model interact. Cycling is an area where governments typically have goals for both mobility and safety. To exemplify application of the model, the paper uses the framework to link research on cycling (safety) to land use and infrastructure. The model's value lies in its ability to identify potential consequences of measures and policies for both exposure and risk. This is important from a scientific perspective and for policy makers who often have objectives for both mobility and safety.


Long-Term Treatment of Cancer-Associated Thrombosis (CAT) Beyond 6 Months in the Medical Practice: USCAT, a 432-Patient Retrospective Non-Interventional Study.
extended anticoagulant therapy beyond the initial 6 months is suggested in patients with cancer-associated thrombosis (CAT) and active cancer. Few data are available on patient management and outcomes on the period between 6 and 12 months after the venous thromboembolism (VTE) event. our objective was to document patient management and outcomes beyond 6 months and up to 12 months in CAT patients initially treated for 6 months with tinzaparin. adult CAT patients with a cancer still alive at the end of an initial 6-month treatment period were eligible to participate in this retrospective non-interventional French multicenter study. a total of 432 patients aged 66.5 ± 12.7 years were available to participate in this study. Out of the patients included in the study, the anticoagulant treatment was maintained in 348 of 422 documented patients (82.5%) while it was discontinued in 74 (17.5%) patients (before the end or at the end of the initial 6-month treatment period). Between 6 and 12 months, 24 patients (5.7%) experienced VTE recurrence, while 21 (5.1%) patients had clinically relevant bleeding, 11 patients (2.7%) had major bleeding and 96 patients (22.3%) died, mostly from cancer. VTE recurrence was more frequent in patients with lung (14.3%) and colorectal cancer (6.0%) while major bleeding was more frequent in patients with colorectal cancer (6.0%). clinical outcomes were consistent with previous observations and variable according to the type of cancer. Further clinical research is required to orient the management of patients with CAT beyond 6 months based on cancer-specific treatment strategies.


Relationship of thermal quenching of protein fluorescence to intramolecular structural mobility.
Temperature dependence (over the range from 5 to 75 degrees C) of the fluorescence quantum yield--the parameter sensitive to the rapid (ns) mobility--has been investigated. For native proteins containing 1--2 fluorescing chromophores this dependence in the non-denaturing temperature range can be described by the equation 1/q = a + b . T/eta (a and b are temperature-independent constants, T is the temperature (K), eta is the viscosity of water, (cP). The linearity of the plot of 1/q vs. T/eta probably indicates that the internal mobility of different parts of the protein globule is limited by the diffusion of the molecules of the solvent. The peculiarity of individual protein structures is reflected by various absolute values of the constants of quenching rates. The results of the studies indicate that an analysis of the temperature dependence of the protein fluorescence quantum yield (thermal quenching curves) might be a new experimental approach to the study of the mobility of protein structures. The thermal quenching curves of proteins could be used as a measure of the temperature dependence of the rapid reverse structural mobility.


Predicting cervical intraepithelial neoplasia recurrence in HIV-infected and -noninfected women by detecting aberrant promoter methylation in the CDH1, TIMP3, and MGMT genes.
Aberrant DNA methylation is present in virtually all types of human cancer. There is no clear evidence that methylation status can predict bad prognosis in patients with CIN recurrence in HIV infected. This study evaluates the relationship between aberrant methylation of CpG islands of CDH1, TIMP3 and MGMT genes and CIN recurrence in HIV-infected and -noninfected women. This is a nested case-control study involving 33 cases with CIN recurrence and 114 controls without recurrence, HIV infected and noninfected, treated with LEEP, between 1999 and 2004. Recurrence diagnosis was established after biopsy. Genes methylation profile was assessed by MSP-PCR technique in formalin-fixed, paraffin-embedded cone specimens. Statistical analysis was performed to compare categorical variables, using χ2 test with Yates correction and Fisher's exact test. Multivariate analysis was carried out using logistic regression. CIN recurrence was more frequent in women with glandular involvement (OR 11.6; 95% CI 2.93-45.89) and compromised surgical margins (OR 2.5; 95% CI 0.87-7.27) in the cervical cone and in HIV-infected women (OR 2.47; 95% CI 0.87-7.05). One methylated allele of CDH1, TIMP3 and MGMT genes was present in 87.9% women with CIN recurrence. Promoter hypermethylation of TIMP3 and MGMT was detected in women with CIN recurrence and without CIN recurrence independent of HIV infection with significant difference between groups (p = 0.04 and p = 0.02, respectively). CIN recurrence was associated with glandular involvement and compromised margins in cone biopsy and HIV infection. The presence of CpG islands hemimethylation in TIMP3 and MGMT genes is a promising triage method in CIN recurrence.


Cellular glutathione content, in vitro chemoresponse, and the effect of BSO modulation in samples derived from patients with advanced ovarian cancer.
The objective was to assess the relationship between glutathione content and drug sensitivity with glutathione modulation in ovarian cancer in a pilot study using 31 samples of freshly obtained ovarian tumor material from 26 patients with advanced disease. Processed tumor samples were screened to determine the glutathione content using an enzyme recycling assay modified for use in a 96-well plate format. Chemosensitivity testing (MTT assay) was used to assess sensitivity to cisplatin and doxorubicin and modulation using buthionine sulfoximine. Multidrug-resistance-associated protein MRP1 (putative drug-glutathione conjugate transporter) expression was also assessed. There was a significant increase in the tumor cell GSH levels in samples from patients who had received previous chemotherapy (9) versus those from chemotherapy-naïve patients (20), P = 0.005. In vitro chemosensitivity testing with doxorubicin and cisplatin (using LC(50) values, i.e., drug dose causing 50% reduction in cell survival relative to untreated control) failed to show a relationship with glutathione levels. Coincubation of cisplatin and doxorubicin with buthionine sulfoximine resulted in a significant increase in sensitivity to both of these drugs overall (cisplatin, P = 0.05; doxorubicin, P = 0.025), with 20 samples showing sensitization to a drug to which they were previously resistant. MRP1 expression failed to show a correlation with drug sensitivity and glutathione levels. Our study supports the use of glutathione modulation using agents such as buthionine sulfoximine in patients with heavily pretreated, drug-resistant ovarian cancer.


Heterogeneity of Triple-Negative Breast Cancer: Differences in Clinicopathologic and Ultrasound Features Between Premenopausal and Postmenopausal Patients.
The aim of this study was to determine whether any salient differences exist in triple-negative breast cancer (TNBC) between premenopausal and postmenopausal patients by comprehensively comparing the ultrasound (US) and clinicopathologic features of these patients. A detailed evaluation of the US and clinicopathologic features of 60 tumors from 60 patients with a diagnosis of TNBC (36 premenopausal and 24 postmenopausal women) was conducted in this retrospective study. Triple-negative breast cancer in premenopausal patients was more likely to show a round or oval shape and microlobulated margins, more commonly exerted effects on surrounding tissue, and showed grade 3 blood flow according to the method of Adler et al (Ultrasound Med Biol 1990; 16:553-559) compared with tumors in postmenopausal women. Triple-negative breast cancer in postmenopausal patients showed some similar US features as those observed in estrogen receptor-positive tumors, including irregular shapes, angular or spiculated margins, and nonparallel growth to the skin (P < .05 for all). Although US cannot be used to unequivocally identify TNBC, it can distinguish some salient US features regarding TNBC between premenopausal and postmenopausal women. Such information can then provide some valuable predictive information on the diagnosis of TNBC for clinicians.


A 10-km CMIP6 downscaled dataset of temperature and precipitation for historical and future Vietnam climate.
High-resolution climate projections are mandatory for many applications and impact assessments in environmental and management studies. In response to the needs in Vietnam, this study constructs a new precipitation and temperature daily dataset for Vietnam, at a high spatial resolution of 0.1° × 0.1°, based on the outputs of 35 global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6). The Bias Correction and Spatial Disaggregation (BCSD) method is adopted to bias-correct monthly GCM simulations using observation data, then subsequently temporally disaggregate them into daily data. The new dataset is called CMIP6-VN, covering the present-time period 1980-2014 and future projections for 2015-2099 from both CMIP6 tier-1 (Shared Socioeconomic Pathways (SSPs) 1-1.26, 2-4.5, 3-7.0, and 5-8.5) and tier-2 (SSPs 1-1.9, 4-3.4, 4-6.0) experiments. Results indicated the good performance of CMIP6-VN for the historical period, suggesting that the dataset could be used for studies on climate change assessment and impacts in Vietnam.


Distance-based reconstruction of protein quaternary structures from inter-chain contacts.
Predicting the quaternary structure of protein complex is an important problem. Inter-chain residue-residue contact prediction can provide useful information to guide the ab initio reconstruction of quaternary structures. However, few methods have been developed to build quaternary structures from predicted inter-chain contacts. Here, we develop the first method based on gradient descent optimization (GD) to build quaternary structures of protein dimers utilizing inter-chain contacts as distance restraints. We evaluate GD on several datasets of homodimers and heterodimers using true/predicted contacts and monomer structures as input. GD consistently performs better than both simulated annealing and Markov Chain Monte Carlo simulation. Starting from an arbitrarily quaternary structure randomly initialized from the tertiary structures of protein chains and using true inter-chain contacts as input, GD can reconstruct high-quality structural models for homodimers and heterodimers with average TM-score ranging from 0.92 to 0.99 and average interface root mean square distance from 0.72 Å to 1.64 Å. On a dataset of 115 homodimers, using predicted inter-chain contacts as restraints, the average TM-score of the structural models built by GD is 0.76. For 46% of the homodimers, high-quality structural models with TM-score ≥ 0.9 are reconstructed from predicted contacts. There is a strong correlation between the quality of the reconstructed models and the precision and recall of predicted contacts. Only a moderate precision or recall of inter-chain contact prediction is needed to build good structural models for most homodimers. Moreover, GD improves the quality of quaternary structures predicted by AlphaFold2 on a Critical Assessment of Techniques for Protein Structure Prediction-Critical Assessments of Predictions of Interactions dataset.


[Heterogeneity of Shigella flexneri during selective synchronization].
The study of a number of main growth characteristics of S. flexneri (S) cells during the first and second cycles of their cultivation in a solid culture medium in Peshkov's chamber from seed material, nonsynchronized and synchronized by C. E. Helmstetter's method, has revealed that this method does not permit obtaining completely synchronized cultures. Four physiological cell clusters, differing in the time of generation, growth rate, size at the beginning and the end of the cycle and the time of adaptation, have been detected.


Vascular cognitive impairment - Past, present, and future challenges.
Vascular cognitive impairment (VCI) is a lifelong process encompassing a broad spectrum of cognitive disorders, ranging from subtle or mild deficits to prodromal and fully developed dementia, originating from cerebrovascular lesions such as large and small vessel disease. Genetic predisposition and environmental exposure to risk factors such as unhealthy lifestyles, hypertension, cardiovascular disease, and metabolic disorders will synergistically interact, yielding biochemical and structural brain changes, ultimately culminating in VCI. However, little is known about the pathological processes underlying VCI and the temporal dynamics between risk factors and disease mechanisms (biochemical and structural brain changes). This narrative review aims to provide an evidence-based summary of the link between individual vascular risk/disorders and cognitive dysfunction and the potential structural and biochemical pathophysiological processes. We also discuss some key challenges for future research on VCI. There is a need to shift from individual risk factors/disorders to comorbid vascular burden, identifying and integrating imaging and fluid biomarkers, implementing a life-course approach, considering possible neuroprotective influences of positive life exposures, and addressing biological sex at birth and gender differences. Finally, this review highlights the need for future researchers to leverage and integrate multidimensional data to advance our understanding of the mechanisms and pathophysiology of VCI.


Prevention of preterm delivery after successful tocolysis in preterm labor by 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial.
The objective of the study was to evaluate the use of 17 alpha-hydroxyprogesterone caproate (17P) to reduce preterm delivery. This open-label, multicenter, randomized controlled trial included women with singleton pregnancies admitted at 24-31 weeks' gestation and cervical length less than 25 mm for preterm labor successfully arrested by tocolytic treatment. Randomization assigned them to receive (or not) 500 mg of intramuscular 17P after tocolysis ended, repeated semiweekly until 36 weeks or preterm delivery. The primary outcome was the time from randomization to delivery. Outcome data were available for 184 of 188 women randomized. The 17P and control groups (similar for most baseline characteristics) did not differ significantly for median [interquartile range] time to delivery (64 [42-79] and 67 [46-83] days, respectively) or rates of delivery before 37, 34, or 32 weeks of gestation or adverse perinatal outcomes. Semiweekly injections of 17P did not prolong pregnancy significantly in women with tocolysis-arrested preterm labor.


The dataset on rural women's awareness and attitudes about residential constructions in accordance with the health standards A case study of Gilan-e-Gharb, Iran.
Residence can affect various aspects of one׳s physical, psychological and social health. Therefore, the present dataset aimed to assess the level of rural housewives' awareness and attitudes towards the importance of residence and its compliance with health standards. To collect the present dataset, four villages were selected from the Gilan-e-Gharb township using the randomized cluster sampling method, then 25 subjects were chosen from each village (totaling 100 altogether). Furthermore, the subjects' awareness and attitudes were measured using a researcher-made questionnaire, and the data were then analyzed using the SPSS Statistical Software Version 21.0. The obtained data demonstrated that rural housewives' awareness and attitudes towards the subject were significantly different in terms of education and age group (P< 0.05), but the opposite was true in terms of the variables of marital status and training by health practitioners (P> 0.05). Based on the obtained data, the awareness and attitudes of rural women towards the importance and necessity of health standards of residence were low and moderate, respectively. In addition, providing rural women with effective training in various ways to raise their awareness and attitudes is of prime significance.


Impact of second-generation transoral incisionless fundoplication on atypical GERD symptoms: a systematic review and meta-analysis.
Transoral incisionless fundoplication (TIF) using the EsophyX device (EndoGastric Solutions, Inc, Redmond, Wash, USA) is a minimally invasive endoscopic fundoplication technique. Our study aimed to assess the efficacy of TIF for atypical GERD symptoms in patients with chronic or refractory GERD. A systematic search of 4 major databases was performed. All original studies assessing atypical GERD using a validated symptom questionnaire (the reflux symptom index [RSI]) were included. The RSI score was assessed before and after TIF at a 6- and 12-month follow-up. Data on technical success rate, adverse events, proton pump inhibitor (PPI) use, and patient satisfaction were also collected. Only TIF procedures currently in practice using the EsophyX device (ie, TIF 2.0) and TIF with concomitant hiatal hernia repair were included in the review. Ten studies (564 patients) were included. At the 6- and 12- month follow-up, there was a mean reduction of 15.72 (95% confidence interval, 12.15-19.29) and 14.73 (95% confidence interval, 11.74-17.72) points, respectively, in the RSI score post-TIF, with a technical success rate of 99.5% and a pooled adverse event rate of 1%. At both time intervals, more than two-thirds of the patients were satisfied with their health condition and roughly three-fourths of the patients were off daily PPIs. Our study shows that TIF using the EsophyX device is safe and effective in reducing atypical GERD symptoms at 6 and 12 months of follow-up. It improves patient-centered outcomes and can be a minimally invasive therapeutic option for patients suffering from atypical GERD symptoms on chronic medical therapy.


A Patient-Centered Transitions Framework for Persons With Complex Chronic Conditions.
Hospitals are under increasing pressures by governing bodies to meet mandated performance standards and fiscal targets. As a result, hospitals are incentivized by funders to discharge patients efficiently and effectively. Gaining insight into the patient experience of discharge, as well as understanding patient needs and concerns, is prudent. Leveraging this knowledge may expedite patient discharge and potentially minimize hospital readmission rates. The purpose of this study was to better understand the discharge experiences and concerns of patients with multiple chronic diseases-a population currently understudied. In this study, qualitative survey data were analyzed from a large scale, mixed methods study that took place in 2011 at Bridgepoint Hospital, a complex continuing care and rehabilitation facility in Toronto, Canada. One hundred and sixteen patients were interviewed individually using a self-designed survey composed of open- and close-ended questions. All data pertaining to hospital discharge were extracted and examined using qualitative descriptive analysis. Key discharge concerns were related to process (next steps in the care plan, friction in the provider-patient relationship, premature discharge), consequences (relocation, impact on family, leaving the comforts and security of the hospital), and needs (availability of home care, managing daily activities, navigating the predisability home). Our findings are presented in a patient-centered framework that can be used as a guide for future discharge strategies for complex patient populations.


Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes.
Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing. We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ≥0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes. A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients). This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.


Effects of Ovariectomy and Prolactin on Mammary Gland Expressions of Transforming Growth Factor alpha and Epidermal Growth Factor Receptor mRNAs in Mice.
Beginning 15 days after ovariectomy (OVX), a high mammary tumor strain of SHN virgin mice at 3 months of age received subcutaneous injections of danazol (0.5 mug / 0.1 ml olive oil, once a day), perphenazine (0.05 mg / 0.1 ml saline, twice a day) or ovine prolactin (oPRL: 0.25 mg / 0.05 ml buffer, twice a day) for 3 days to modulate their circulating PRL levels. The serum PRL level was significantly decreased by danazol and increased by perphenazine compared to the intact and OVX-control groups. The expression of both transforming growth factor alpha (TGFalpha) mRNA and epidermal growth factor receptor (EGFR) mRNA in the mammary gland was increased by danazol. However, TGFalpha mRNA expression was decreased by perphenazine. Meanwhile, mammary end-bud formation was inhibited in danazol-treated group. All findings suggest that the manifestation of the effect of TGFalpha on mammary gland is rather suppressed by PRL, while mammary gland growth needs the participation of PRL; in other words, PRL is dominant to TGFalpha on the mammary gland growth. OVX resulted in a significant decrease of TGFalpha mRNA expression in the mammary gland despite of little alteration in serum PRL, confirming the previous observations. The similar trend was observed in ICR mice; however, the response to hormonal modulation is generally less susceptible than SHN mice.


Rhodococcus sp. F92 immobilized on polyurethane foam shows ability to degrade various petroleum products.
This work reports on the immobilization and performance of a hydrocarbon-degrading microorganism on polyurethane foam (PUF) in the bioremediation of petroleum hydrocarbons. The ability of four different microorganisms to immobilize on PUF and to degrade various petroleum products (Arabian light crude (ALC), Al-Shaheen crude (ASC), diesel and oil slops) was assessed by measuring the n-alkane fraction remaining in the petroleum products over time. A Rhodococcus sp. (designated as F92) had the highest number of immobilized viable cells (10(9) cells per cm3 PUF) and a maximum attachment efficiency of 90% on PUF of a density of 14 kg/m3. Scanning electron microscopy showed the presence of extracellular structures that could play an important role in the immobilization of F92 on PUF. Analysis by GC-MS revealed that both free and immobilized F92 cells were able to degrade approximately 90% of the total n-alkanes in the petroleum products tested within 1 week at 30 degrees C. Rhodococcus sp. F92 was efficiently immobilized onto PUF and the immobilized cells were able to degrade a variety of petroleum products such as ALC, ASC, diesel and oil slops. The results suggest the potential of using PUF-immobilized Rhodococcus sp. F92 to bioremediate petroleum hydrocarbons in an open marine environment.


Distribution of erm genes among MRSA isolates with resistance to clindamycin in a Chinese teaching hospital.
The objective of this study was to analyze erythromycin and clindamycin resistance patterns among different MRSA lineages in China. Antimicrobial susceptibility testing, resistance determinant screening, plasmid electroporation and sequence comparisons were performed. High rates of clindamycin (92.5%, 270/292) and erythromycin (92.8%, 271/292) resistance were observed. Additionally, 88.2% (60/68) of the ST59 MRSA isolates and 78.9% (15/19) of the ST239 MRSA isolates had constitutive resistance to clindamycin, while 82.0% (123/150) of the ST5 MRSA isolates showed inducible clindamycin resistance. The ermB gene was identified in 80.9% (55/68) of the ST59 isolates but was not detected in ST5 and ST239 MRSA isolates. Detection rates of ermA were high in the ST5 (99.3%, 149/150) and ST239 (89.5%, 17/19) MRSA isolates, but no ermA-positive ST59 MRSA isolates were identified. The ermC gene, observed to be harbored on similar, transmissible plasmids ranging in size from 2402 to 2473 bp, were found in different MRSA lineages. Summarily, high erythromycin and clindamycin resistance rates were observed in MRSA isolates. ST59 and ST239 MRSA isolates primarily exhibited constitutive resistance, while ST5 MRSA isolates showed inducible resistance phenotypes. ermA and ermB genes were frequently carried by specific MRSA clones, while ermC gene was present within small transmissible plasmids in all lineages. Erythromycin and clindamycin resistance genes transfer between MRSA isolates in healthcare settings remains a problem, and infection control procedures should be applied.


Comparison between skin testing and in vitro testing for diagnosis of allergen in asthmatic children.
This study was designed to compare the skin testing and in vitro testing for the diagnosis of most common inhalant allergens in asthmatic children. Sixty-two asthmatic children positive to most common allergens in the area of skin tests and multiple allergosorbent chemiluminescent assay (MAST-CLA) were subjected to another Pharmacia CAP test (CAP). The agreement between the results of MAST-CLA and CAP was variable. The correlation coefficient for CAP with MAST-CLA was significant for five allergens except candida, dog dander and Willow pollen when the diagnostic levels of MAST-CLA and CAP were compared with skin test reactions. For all the allergens tested, MAST-CLA showed a sensitivity of 51%, a specificity of 84% and an efficiency of 73%, compared with 57%, 80% and 74%, respectively, in the CAP analysis. MAST-CLA and CAP can be used as a screening test to measure allergen IgE level. Both MAST-CLA and CAP were comparable in their ability to diagnose of allergy to tested allergens.


Triazole hybrid compounds: A new frontier in malaria treatment.
Reviewing the advancements in malaria treatment, the emergence of triazole hybrid compounds stands out as a groundbreaking development. Combining the advantages of triazole and other moieties, these hybrid compounds offer a new frontier in the battle against malaria. Their potential as effective antimalarial agents has captured the attention of researchers and holds promise for overcoming the challenges posed by drug-resistant malaria strains. We focused on their broad spectrum of antimalarial activity of diverse hybridized 1,2,3-triazoles and 1,2,4-triazoles, structure-activity relationship (SAR), drug-likeness, bioavailability and pharmacokinetic properties reported since 2018 targeting multiple stages of the Plasmodium life cycle. This versatility makes them highly effective against both drug-sensitive and drug-resistant strains of P. falciparum, making them invaluable tools in regions where resistance is prevalent. The synergistic effects of combining the triazole moiety with other pharmacophores have resulted in even greater antimalarial potency. This approach has the potential to circumvent existing resistance mechanisms and provide a more sustainable solution to malaria treatment. While triazole hybrid compounds show great promise, further research and clinical trials are warranted to fully evaluate their safety, efficacy and long-term effects. As research progresses, these compounds can potentially revolutionize the field and contribute to global efforts to eradicate malaria, ultimately saving countless lives worldwide.


Noninvasive monitoring of carbon dioxide in infants and children with congenital heart disease: end-tidal versus transcutaneous techniques.
End-tidal CO2 (ET(CO2)) monitoring and transcutaneous (TC) CO2 monitoring were prospectively compared in 53 patients, 1 month to 16 years of age, with congenital heart disease (CHD). There were 32 patients with cyanotic CHD and 21 with acyanotic CHD. The TC-Pa(CO2) difference was 2 +/- 1 mm Hg and the ET-Pa(CO2) difference was 5 +/- 3 mm Hg (P < .0001). The TC-Pa(CO2) difference was < or = 2 mm Hg in 30 of 53 patients and < or = 5 mm Hg in 53 of 53 patients. The ET-Pa(CO2) difference was < or = 2 mm Hg in 9 of 53 patients and < or = 5 mm Hg in 30 of 53 patients (P < .001). No variation in the TC-Pa(CO2) difference was noted based on the type of CHD (acyanotic vs cyanotic) or age. The ET-Pa(CO2) difference was greater in patients with cyanotic versus acyanotic CHD (7 +/- 3 mm Hg vs 4 +/- 2 mm Hg, P < .0001) and in patients < or = 1 year of age versus patients > or = 1 year of age (6 +/- 3 mm Hg vs 4 +/- 2, P = .008). In infants and children with CHD, TC monitoring provides a more accurate estimation of Pa(CO2) than ET monitoring.


Dealing with microscopic peritoneal metastases of epithelial ovarian cancer. A surgical challenge.
Understanding biology and progression mechanisms of peritoneal metastases of epithelial ovarian cancer (EOC) is a cornerstone in the knowledge and the comprehensive management of the disease. Despite clinical remission after the association of complete cytoreductive surgery and platinum-based chemotherapy, peritoneal recurrence still occurs in 60% of patients. Eligible studies, published from 1980 to June 2016, were retrieved through ClinicalTrials.gov, MEDLINE, Cochrane databases and bibliography searches. We reviewed all publications that deals with microscopic peritoneal metastases of EOC in French and English. To discuss expected benefits of intraperitoneal (IP) chemotherapy, fluorescence-guided surgery or IP photodynamic therapy, we reviewed most recent and relevant studies. The final reference list was generated on the basis of originality and relevance to the broad scope of this review. Published data concerning early-stage ovarian cancer suggest that occult peritoneal or epiploic metastases are present in 1.2%-15.1% of cases. In the frequent case of advanced-stage disease, residual microscopic lesions are ignored by conventional surgery. We are convinced that microscopic peritoneal metastases are a relevant surgical therapeutic target. This article discusses existing data on microscopic peritoneal metastases, the treatment indications, the diagnostic and therapeutic surgical approaches to be developed and their expected benefits. A local therapeutic strategy to target microscopic lesions is needed in addition to complete macroscopic cytoreductive surgery to decrease the rate of peritoneal recurrence. Intraperitoneal chemotherapy, and targeted photodynamic therapy could play a role in this new paradigm. The roles of these different options must be defined by future researches.


Vaccination as a social practice: towards a definition of personal, community, population, and organizational vaccine literacy.
A comprehensive and agreed-upon definition of vaccine literacy (VL) could support the understanding of vaccination and help policy-makers and individuals make informed decisions about vaccines. To shed some light on this debate and provide clarity, a scoping review was conducted to collect, summarize, and analyse available definitions of VL. Based on the findings of the scoping review, a new and comprehensive definition was proposed by a panel of experts. Fifty-three articles were included, and two of them appeared to be the milestones around which the other definitions were grouped. The new definition proposed by the panel of experts included not only the personal perspective, but also the community, population, and organizational perspectives. Moreover, due to the increasing complexity of the social context with respect to the ability to navigate, understand, and use information and services, the definition of organizational vaccine literacy and the attributes of a vaccine literate healthcare organization have been proposed. The new definition can contribute to the overall paradigm of health literacy and its distinct component of vaccine literacy, possibly improving the implementation of public health strategies to allow vaccination to be understood as a social practice by the entire community. This study describes the conceptual foundations, the competencies, and the civic orientation to be considered when developing measurement tools devoted to assessing VL at the different levels and in different contexts.


Analysis of starch grains trapped in human dental calculus in Áspero, Peru during the Initial Formative Period (3000-1800 BCE).
The objective of this research is to identify the plants consumed and to determine their dietary importance in Áspero, an urban center on the coast of the Supe Valley, Peru. Consequently, starch grains trapped in the human dental calculus of nine individuals were recovered, while the results from one individual from the Sacred City of Caral, located in the interior of Supe Valley, are presented. Eight species of food plants were identified, among them C3 plants: sweet potato, squash, potato, chili pepper, algarrobo, manioc and bean and C4 plant: maize. Previous isotopic analysis indicates that C3 plants formed the foundation of the diet at Áspero and Caral. Our results indicate a high ubiquity of C3 plants like sweet potato (100%) and squash (90%) suggesting, with caution, that these taxa were an important C3 source in the menu. Maize, C4 plant, showed a similar ubiquity (100%) to sweet potato and squash, however, previous isotopic analysis indicate that maize was a marginal food in Áspero and Caral. These results support that the absence and abundance of starch grains cannot be employed to directly infer the frequency of intake of C3 and C4 plants within a small population, as suggested by previous studies.


Uranium transfer in grasses grown on mining waste and natural soil.
The transfer of radionuclides from soil to the food chain often begins with uptake by plant root system. The roots of most angiosperms showed symbiosis with arbuscular mycorrhizal fungi (AMF) and to understand the transfer process of these toxic elements it is important to consider different physical, chemical and biological factors in soils. In the present study, three grass species (Poaceae), Zea mays, Chrysopogon zizanioides and Aristida setifolia were cultivated with and without organic fertilization in experimental blocks on natural soils, at Fazenda Vargem Formosa (VF) with low uranium (U) contents in the soil, and in the leached ore deposit at the Uranium Concentrate Unit Mine (URA) in Caetité (Uraniferous Province of Lagoa Real - Brazil). In the present study, the biomass production of plants, their rate of root colonization by AMF, the levels of U in soils, roots and leaves, as well as different physico-chemical parameters related to soil fertility were evaluated. The data analysis was performed using Artificial Neural Networks (ANNs), specifically Self-Organizing Maps (SOMs). The levels of available uranium in the soil ranges from 0.33 to 1.11 mg kg-1 in VF and from 177.5 to 475.8 mg kg-1 in URA. The results revealed high percentage of root AMF colonization, even in soils with high U contents. There was an inverse relationship between soil U content and its transfer to the plant organs, with U transfer rates being influenced by plant species and not by soil parameters. C. zizanioides had the lowest transfer factor to the shoot and the highest mass productivity under conditions of high U content in soil. The results indicate that C. zizanioides is an important species for use in the recovery of U mining areas.


Do admission decisions predict performance during medical school? A comparison of one medical school's rejected and accepted applicants who attended other schools.
The relation of one school's admission decisions to performance in medical school was examined by comparing accepted applicants who chose to attend other institutions with rejected applicants who went to those same institutions. When differences among schools were controlled, no effect of admission decisions was observed.


Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease.
There is evidence of increased systemic expression of active GSK3B in Alzheimer's disease patients, which apparently is associated with the formation of senile plaques and neurofibrillary tangles. Due to its central role in the pathogenesis of AD, GSK3B is currently a promising target of the pharmaceutical industry. Whilst trials with specific GSK inhibitors in AD are under way, major attention has been focused on the neuroprotective effects of lithium. Whereas the direct and indirect inhibitory effects of lithium over GSK3 activity have been documented by several groups, its effects over Gsk3 transcription have not yet been addressed. We used quantitative PCR to evaluate the transcriptional regulation of Gsk3a and Gsk3b in lithium-treated primary cultures of rat cortical and hippocampal neurons. We found a significant and dose-dependent reduction in the expression of Gsk3b, which was specific to hippocampal cells. This same effect was further confirmed in vivo by measuring Gsk3 expression in different brain regions and in peripheral leukocytes of adult rats treated with lithium. Our studies show that LiCl can modulate Gsk3b transcription in vitro and in vivo. This observation suggest new regulatory effects of lithium over Gsk3b, contributing to the better understanding of its mechanisms of action, offering a new and complementary explanation for Gsk3b modulation and reinforcing its potential for the inhibition of key pathological pathways in Alzheimer's disease.


Frequency detection of imidacloprid resistance allele in Aphis gossypii field populations by real-time PCR amplification of specific-allele (rtPASA).
The Aphis gossypii Glover (Hemiptera: Aphididae) is one of the most serious pests worldwide, and imidacloprid has been widely used to control this insect pest. Just like other classes of insecticides, the resistance to imidacloprid has been found in A. gossypii. An amino acid mutation (R81T) in the nicotinic acetylcholine receptor (nAChR) beta1 subunit was detected in the imidacloprid-resistant A. gossypii collected from Langfang (LF) and Dezhou (DZ) cities. To estimate the R81T mutation frequency of A. gossypii field populations, a simple, rapid and accurate rtPASA (real-time PCR amplification of specific allele) protocol was developed. The performance of the rtPASA protocol was evaluated by comparing with the data generated by a cPASA (competitive PCR amplification of specific allele) method from 50 individual genotypes. The R81T allele frequencies of the LF population (34.7%±1.3%) and DZ population (45.2%±5.2%) estimated by the rtPASA protocol matched the frequencies (LF 38.1%, DZ 48.2%) deduced by the cPASA method in specimens. The results indicated that the rtPASA format was applicable for the detection of mutation associated with imidacloprid resistance and will allow rapid and efficient monitoring of A. gossypii resistance in field populations in a high throughput format.


Association between precocious puberty and obesity risk in children: a systematic review and meta-analysis.
The aim of this study was to evaluate the potential association between early onset puberty and the risk of different forms of obesity in children. The databases PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched for relevant studies. The odds ratio (OR) and 95% confidence interval (CI) of obesity in precocious puberty were calculated using Stata software 14.0. A fixed-effects model was used if P > 0.1 and I2 ≤ 50%. Otherwise, a random-effects model was used. Publication bias was assessed using funnel plots and Egger's test. The pooling analysis showed that precocious puberty in girls was associated with a higher risk of obesity (OR = 1.98; 95% CI: 1.76-2.24; I2 = 0.00%, P < 0.001). Girls with a history of precocious puberty were found to have an increased risk of general obesity (OR = 2.03; 95% CI: 1.62-2.55; I2 = 22.2%, P < 0.001), central obesity (OR = 1.96; 95% CI: 1.70-2.26; I2 = 0.00%, P < 0.001), and overweight (OR = 2.03; 95% CI: 1.68-2.46; I2 = 5.1%, P < 0.001). The pooled analysis showed that precocious puberty in boys was not associated with an increased risk of obesity (OR = 1.14; 95% CI: 0.86-1.51; I2 = 50.6%, P = 0.369). In boys, the occurrence of precocious puberty was not associated with an elevated risk of general obesity (OR = 0.96; 95% CI: 0.40-2.27; I2 = 79.6%, P = 0.922), central obesity (OR = 1.17; 95% CI: 0.96-1.43; I2 = 0.00%, P = 0.125), or overweight (OR = 1.03; 95% CI: 0.56-1.88; I2 = 74.4%, P = 0.930). This meta-analysis suggests that the onset of puberty at an early age in girls is associated with an increased risk of obesity, however precocious puberty in boy was not associated with an increased risk of obesity. These findings highlight that precocious puberty should be considered an independent risk factor for obesity in girls. CRD42023404479.


Structures of Escherichia coli DNA mismatch repair enzyme MutS in complex with different mismatches: a common recognition mode for diverse substrates.
We have refined a series of isomorphous crystal structures of the Escherichia coli DNA mismatch repair enzyme MutS in complex with G:T, A:A, C:A and G:G mismatches and also with a single unpaired thymidine. In all these structures, the DNA is kinked by approximately 60 degrees upon protein binding. Two residues widely conserved in the MutS family are involved in mismatch recognition. The phenylalanine, Phe 36, is seen stacking on one of the mismatched bases. The same base is also seen forming a hydrogen bond to the glutamate Glu 38. This hydrogen bond involves the N7 if the base stacking on Phe 36 is a purine and the N3 if it is a pyrimidine (thymine). Thus, MutS uses a common binding mode to recognize a wide range of mismatches.


3-Isobutyl-5,5-di-phenyl-imidazolidine-2,4-dione.
The imidazolidine ring in the title mol-ecule, C19H20N2O2, is slightly 'ruffled'. In the crystal, a layer structure is generated by N-H⋯O and C-H⋯O hydrogen bonds plus C-H⋯π(ring) inter-actions.


Quantitative trait locus analysis of nonverbal communication in autism spectrum disorder.
Autism spectrum disorder (ASD) is a neurodevelopmental syndrome marked by impairments in social interactive functioning and communication skills, and the presence of repetitive and restrictive behaviors. Twin and linkage studies provide evidence that ASD is heritable and genetically complex. Genetic analyses of familial quantitative traits in those with ASD may help to reveal underlying risk genes. We report a quantitative trait locus (QTL) analysis of nonverbal communication (NVC) in 228 families from the autism genetics resource exchange (AGRE) ascertained for at least two siblings with ASD. QTL at 1p13-q12, 4q21-25, 7q35, 8q23-24, and 16p12-13 indicate that genes at these loci may contribute to the variation in NVC among those with ASD. Using the criteria of Lander and Kruglyak, the QTL at 1p13-q12 is 'suggestive', while the other four are 'possible'. To assess whether these QTL are likely to harbor genes contributing specifically to the deficits in NVC, linkage analysis of ASD sibships with the most severe NVC scores was conducted. The sibships were identified by ordered-subset analyses (OSA), and families with the most severe NVC scores displayed lod scores of 3.4 at 8q23-24 and 3.8 at 16p12-13, indicating that these two regions are likely to harbor gene(s) contributing to ASD by predisposing to deficits in NVC.


Naïve T cells are maintained in the periphery during the first 3 months of acute HIV-1 infection: implications for analysis of thymus function.
A key determinant of T cell dynamics in HIV-1 infection is the status of thymic function. To date, most studies of the impact of HIV-1 on the thymus during early HIV-1 infection have been done in samples collected in the interval of 3-12 months after infection. In this study, we have probed the status of thymic function and peripheral naive T cells in patients with acute HIV-1 infection diagnosed 18-72 days after the onset of symptoms. We found that peripheral CD4 and CD8 T cell proliferation was initially elevated, then waned over time. The fall in T cell proliferation correlated with a reduction in HIV-1 viral RNA levels and a rise in peripheral blood CD4+ CD25+ T cells. In spite of elevated T cell proliferation early on in primary HIV-1 infection, levels of naive phenotype CD4 and CD8 T cells and T cell receptor excision circle positive cells (sjTREC(+)) remained constant. Taken together with the observation that T cell proliferation normally dilutes peripheral T cell episomal sjTREC levels, these data suggested that thymopoiesis contributes to maintenance of the naive T cell pool during the earliest stages of HIV-1 infection (18-72 days).


Protective effect of a standardized Ginkgo extract (ginaton) on renal ischemia/reperfusion injury via suppressing the activation of JNK signal pathway.
A new standardized Ginkgo extract (ginaton) destined for i.v. injection was investigated in rats for its protective effect on renal ischemia/reperfusion injury. We report on the elucidation of the downstream mechanism of action of JNK on the renal ischemia/reperfusion injury, which can be explained as the decrease in JNK phosphorylation at 20 min and c-Jun phosphorylation (Ser63/73) at 3h after renal ischemia. At the same time, ginaton attenuated the increased expression of FasL at 3h and caspase3 immunoreactivity at 6h after renal ischemia. Furthermore, ginaton significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that ginaton could suppress the JNK-c-Jun-FasL-caspase3 signaling cascade, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by JNK signal pathway.


Using Normalization Process Theory to Evaluate the Implementation of Montessori-Based Volunteer Visits Within a Canadian Long-Term Care Home.
Montessori-based interventions (MBIs) have potential to improve the life quality of long-term care residents with dementia. In this study, we aimed to understand the processes by which staff integrated a volunteer-led MBI into practice within a special dementia care unit, and to explore staff members ' perceptions of associated strengths and limitations. This study relied on a qualitative descriptive design. Following a 3-month period of volunteer involvement, we conducted 21 interviews with staff members to document perceptions of the new program and subjected interview transcripts to qualitative content analysis, guided by normalization process theory. During the implementation of the volunteer-led MBI, staff members developed a shared understanding of the intervention, a sense of commitment, practical ways to support the intervention, and opinions about the value of the residents. Overall, we found that the volunteer-led MBI was quickly and successfully integrated into practice and was perceived to support both residents and staff members in meaningful ways. Nevertheless, some limitations were also identified. Volunteer-delivered MBIs are a useful adjunct to practice within a special dementia care unit. This article raises attention to some strengths and limitations associated with this approach.


Influence of infarct age on reproducibility of ventricular tachycardia induction in a canine model.
The inducibility and reproducibility of ventricular tachycardia were evaluated in 97 dogs after myocardial infarction produced by single stage coronary artery ligation. Arrhythmia induction was performed with use of an endocardial electrode catheter positioned at the right ventricular apex before each study. An aggressive protocol of programmed stimulation was used, employing up to seven extrastimuli and three attempts at arrhythmia induction in each study. Electrophysiologic study was performed in individual dogs at the following times after infarction: 1) 7.7 +/- 0.3 and 15 +/- 0.2 days (34 consecutive dogs); 2) 14 +/- 0.6 and 26 +/- 1.7 days (24 selected dogs); 19 +/- 2 and 43 +/- 3 days (12 selected dogs); 4) 36 +/- 2 and 60 +/- 6 days (8 selected dogs); and 5) 59 +/- 12 and 130 +/- 10 days (3 selected dogs). Inducibility of ventricular tachycardia decreased significantly from 74% 1 week after infarction to 41% 2 weeks after infarction. Thus, early reproducibility was low (48%). Reproducibility increased thereafter, with 88% of the dogs having reproducible ventricular tachycardia between 2 and 4 weeks (p less than 0.025) and 100% having reproducibly inducible ventricular tachycardia between 4 weeks and 4 months after infarction. Dogs with no inducible arrhythmia early after infarction did not develop inducible ventricular tachycardia or fibrillation at later studies. Twelve dogs developed spontaneous ventricular tachycardia or sudden arrhythmic death late after infarction. Overall, 22% of dogs with inducible ventricular tachycardia with a cycle length greater than 140 ms developed spontaneous ventricular tachycardia or sudden death. Arrhythmia induction decreases significantly during the 1st 2 weeks after myocardial infarction, but long-term reproducibility of ventricular tachycardia induced greater than or equal to 2 weeks after infarction is very high. This canine model of long-term, reliably inducible ventricular tachycardia is suitable for investigation of antiarrhythmic drugs, surgery and other interventions.


Students' well-being in nursing undergraduate education.
Although previously the Job-Demand-Control-Support model has been successfully applied in many studies in the field of health care and education, the model was never used for the evaluation of the nursing students' well-being. The aim of this study was to promote nursing students' well-being. The objective was to verify whether the Job-Demand-Control-Support model is appropriate for the evaluation of their well-being. The Job-Demand-Control-Support model was implemented and investigated in a multiple-case study, which consisted of two phases. In phase I the students' well-being along with the perceived levels of control, support, and demand for each individual student during their study were identified. These results were used in phase II, where the usefulness of the presented model was evaluated. The study was performed at the end of the academic year 2009/2010 in two institutions: Tampere University of Applied Sciences, School of Health Care, Finland (institution 1); and the University of Primorska, Faculty of Health Sciences, Slovenia (institution 2). Participants of the study were nursing graduates who finished their studies in 2009/2010 and the Vice-Deans for education of both institutions. The final sample included 83 students in institution 1 and 79 students in institution 2. The case study was combined with a survey (phase I) and an interview (phase II). Although the students' well-being in these two institutions was different, most students of both institutions perceived their studies as low strain, placid, and only some of the students in both institutions had a high risk of malaise. The Vice-Deans for education of both institutions confirmed that the application of the Job-Demand-Control-Support model provided relevant information on the nursing students' well-being, which helped in planning improved nursing study programmes. This study demonstrated that the Job-Demand-Control-Support model is appropriate for estimating undergraduate nursing students' well-being.


Fluorescence formation from the interaction of DNA with lipid oxidation degradation products.
To clarify the mechanism of fluorescence formation between DNA and lipid degradation products in the presence of ferric chloride and ascorbic acid, a number of carbonyl compounds and decomposition products of pure methyl linolenate hydroperoxides were examined. Keto derivatives of methyl ricinoleate, linoleate, and oleate, alkanals and 2-alkenals produced little or no fluorescence with DNA in the presence of ferric chloride-ascorbic acid. 2,4-Alkadienals were more active and 2,4,7-decatrienal was the most active. Mixtures of volatile aldehydes prepared from linolenate hydroperoxide decomposed either thermally or with iron and ascorbate had the same activity as 2,4,7-decatrienal. Higher molecular-weight products from the decomposition of methyl linolenate hydroperoxides showed relatively low activity. beta-Carotene, alpha-tocopherol and other antioxidants effectively reduced the amount of fluorescence formed by linolenate hydroperoxides. The results suggest that, in addition to hydroperoxide decomposition products, singlet oxygen and/or free radical species contribute significantly to the fluorescence formed from the interaction of methyl linolenate hydroperoxides with DNA in the presence of ferric chloride and ascorbic acid.


The effects of different thermal and chemical stresses on release of outer membrane vesicles (OMVs) by ClearColi™.
The highly immunogenic properties of outer membrane vesicles (OMVs), small spherical nanoparticles commonly released by Gram-negative bacteria, led to their application as vaccine candidate. ClearColi™ is an engineered Escherichia coli strain, which does not produce endotoxic response in humans and is useful for production of OMV-based vaccines. Therefore, producing ClearColi™ OMVs with high yield attracts particular interest. As stresses can be removed by OMVs, they may affect OMVs release. We aimed to investigate the effects of culture temperature, chemical (NaCl, ethanol, EDTA, D-cycloserine, polymyxin B, 1-octanol, and H2O2) and thermal stresses on release of ClearColi™ OMVs. Herein, the growth rate of ClearColi™ was decreased in the presence of all chemical stresses with the exception of H2O2. The optimum temperature for OMVs production was 37 ℃ and their release was not increased under thermal shock. The highest and lowest OMVs release was obtained in the presence of NaCl and H2O2, respectively. Electron microscopy images confirmed that the bilayer spherical-shaped OMVs were isolated under different stresses. Furthermore, SEM and DLS analysis demonstrated that OMVs released under EDTA stress are smaller than those released from untreated cultures. It can be concluded that chemical stresses have influence on the level of ClearColi™ OMVs production. However, changes in their content should be further investigated.


Role of preprocedural glutathione concentrations in the prediction of major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention.
Poor antioxidant protection of cardiomyocytes due to cardiac ischemia and low serum levels of reduced glutathione (GSH) may be associated with enhanced risk of coronary restenosis after primary percutaneous coronary intervention (pPCI). The aim of this study was to investigate whether preprocedural serum reduced GSH, reflecting the antioxidant status, may be predictive of major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS) treated with pPCI. Preprocedural serum GSH level was evaluated in 141 patients with ACS treated with pPCI with bare-metal stent (BMS) deployment. During a 15-month follow-up, 30 patients (mean age, 61 ±10 years) experienced a MACE. The remaining 111 subjects constituted the non-MACE group (mean age, 63 ±10 years). The MACE group had significantly lower GSH levels compared with the non-MACE group (P <0.001); significant differences were also observed in a subgroup of type 2 diabetic patients (P <0.001). All patients were arbitrarily classified as having low (median, ≤1.39; 1.04-1.55 μmol/l) or high serum GSH (median, >2.26; 2.09-2.99 μmol/l; P <0.001). The Kaplan-Meier analysis showed a significantly longer MACE-free survival in patients with higher serum GSH (P <0.004). The Cox proportional hazards regression indicated that patients with lower GSH were 2.2 times more likely to experience MACE (95% confidence interval [CI], 1.2-3.9; P <0.02 for the whole group and 1.8-11.8 for diabetic patients; P <0.002). Preprocedural GSH levels may be useful in the prediction of MACE in patients with ACS scheduled for pPCI and BMS deployment, especially in diabetic subjects.


Adult respiratory distress syndrome--how many cases in the UK?
Previously reported figures for the incidence of Adult Respiratory Distress Syndrome, based largely on American results, would suggest that the average British Health District of 200,000 people could expect to see 130 cases per year. This figure is greatly in excess of that expected from our clinical experience. We have undertaken a retrospective survey of patients within a British Health Region (population, 3,599,400). Results indicate an incidence of nine for an average Health District of 200,000 population, or 2.5% of all admissions to intensive therapy units, or 0.045 per 1000 resident population.