Τετάρτη, 26 Ιουλίου 2017

Guideline recommendations and antimicrobial resistance: the need for a change

Objectives

Antimicrobial resistance has become a global burden for which inappropriate antimicrobial use is an important contributing factor. Any decisions on the selection of antibiotics use should consider their effects on antimicrobial resistance. The objective of this study was to assess the extent to which antibiotic prescribing guidelines have considered resistance patterns when making recommendations for five highly prevalent infectious syndromes.

Design

We used Medline searches complemented with extensive use of Web engine to identify guidelines on empirical treatment of community-acquired pneumonia, urinary tract infections, acute otitis media, rhinosinusitis and pharyngitis. We collected data on microbiology and resistance patterns and identified discrete pattern categories. We assessed the extent to which recommendations considered resistance, in addition to efficacy and safety, when recommending antibiotics.

Results

We identified 135 guidelines, which reported a total of 251 recommendations. Most (103/135, 79%) were from developed countries. Community-acquired pneumonia was the syndrome mostly represented (51, 39%). In only 16 (6.4%) recommendations, selection of empirical antibiotic was discussed in relation to resistance and specific microbiological data. In a further 69 (27.5%) recommendations, references were made in relation to resistance, but the attempt was inconsistent. Across syndromes, 12 patterns of resistance with implications on recommendations were observed. 50% to 75% of recommendations did not attempt to set recommendation in the context of these patterns.

Conclusion

There is consistent evidence that guidelines on empirical antibiotic use did not routinely consider resistance in their recommendations. Decision-makers should analyse and report the extent of local resistance patterns to allow better decision-making.



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Associations of anthropometry since birth with sagittal posture at age 7 in a prospective birth cohort: the Generation XXI Study

Objectives

Adult sagittal posture is established during childhood and adolescence. A flattened or hypercurved spine is associated with poorer musculoskeletal health in adulthood. Although anthropometry from birth onwards is expected to be a key influence on sagittal posture design, this has never been assessed during childhood. Our aim was to estimate the association between body size throughout childhood with sagittal postural patterns at age 7.

Design

Prospective cohort study.

Setting and participants

A subsample of 1029 girls and 1101 boys taking part in the 7-year-old follow-up of the birth cohort Generation XXI (Porto, Portugal) was included. We assessed the associations between anthropometric measurements (weight, height and body mass index) at birth, 4 and 7 years of age and postural patterns at age 7. Postural patterns were defined using latent profile analysis, a probabilistic model-based technique which allows for simultaneously including anthropometrics as predictors of latent profiles by means of logistic regression.

Results

Postural patterns identified were sway, flat and "neutral to hyperlordotic"in girls, and "sway to neutral", flat and hyperlordotic in boys; with flat and hyperlordotic postures representing a straightened and a rounded spine, respectively. In both girls and boys, higher weight was associated with lower odds of a flat pattern compared with a sway/"sway to neutral"pattern, with stronger associations at older ages: for example, ORs were 0.68 (95% CI 0.53 to 0.88) per SD increase in birth weight and 0.36 (95% CI 0.19 to 0.68) per SD increase in weight at age 7 in girls, with similar findings in boys. Boys with higher ponderal index at birth were more frequently assigned to the hyperlordotic pattern (OR=1.44 per SD; p=0.043).

Conclusions

Our findings support a prospective sculpting role of body size and therefore of load on musculoskeletal spinopelvic structures, with stronger associations as children get older.



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Profiles of children's social-emotional health at school entry and associated income, gender and language inequalities: a cross-sectional population-based study in British Columbia, Canada

Objectives

Early identification of distinct patterns of child social–emotional strengths and vulnerabilities has the potential to improve our understanding of child mental health and well-being; however, few studies have explored natural groupings of indicators of child vulnerability and strengths at a population level. The purpose of this study was to examine heterogeneity in the patterns of young children's social and emotional health and investigate the extent to which sociodemographic characteristics were associated.

Design

Cross-sectional study based on a population-level cohort.

Setting

All kindergarten children attending public schools between 2004 and 2007 in British Columbia (BC), Canada.

Participants

35 818 kindergarten children (age of 5 years) with available linked data from the Early Development Instrument (EDI), BC Ministry of Health and BC Ministry of Education.

Outcome measure

We used latent profile analysis (LPA) to identify distinct profiles of social–emotional health according to children's mean scores across eight social–emotional subscales on the EDI, a teacher-rated measure of children's early development. Subscales measured children's overall social competence, responsibility and respect, approaches to learning, readiness to explore, prosocial behaviour, anxiety, aggression and hyperactivity.

Results

Six social–emotional profiles were identified: (1) overall high social–emotional functioning, (2) inhibited-adaptive (3) uninhibited-adaptive, (4) inhibited-disengaged, (5) uninhibited-aggressive/hyperactive and (6) overall low social–emotional functioning. Boys, children with English as a second language (ESL) status and children with lower household income had higher odds of membership to the lower social–emotional functioning groups; however, this association was less negative among boys with ESL status.

Conclusions

Over 40% of children exhibited some vulnerability in early social–emotional health, and profiles were associated with sociodemographic factors. Approximately 9% of children exhibited multiple co-occurring vulnerabilities. This study adds to our understanding of population-level distributions of children's early social–emotional health and identifies profiles of strengths and vulnerabilities that can inform future intervention efforts.



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Respiratory syncytial virus: a systematic scientometric analysis of the global publication output and the gender distribution of publishing authors

Objective

Worldwide, the respiratory syncytial virus (RSV) represents the predominant viral agent causing bronchiolitis and pneumonia in children. To conduct research and tackle existing healthcare disparities, RSV-related research activities around the globe need to be described. Hence, we assessed the associated scientific output (represented by research articles) by geographical, chronological and socioeconomic criteria and analysed the authors publishing in the field by gender. Also, the 15 most cited articles and the most prolific journals were identified for RSV research.

Design

Retrospective, descriptive study.

Setting

The NewQIS (New Quality and Quantity Indices in Science) platform was employed to identify RSV-related articles published in the Web of Science until 2013. We performed a numerical analysis of all articles, and examined citation-based aspects (eg, citation rates); results were visualised by density equalising mapping tools.

Results

We identified 4600 RSV-related articles. The USA led the field; US-American authors published 2139 articles (46.5%% of all identified articles), which have been cited 83 000 times. When output was related to socioeconomic benchmarks such as gross domestic product or Research and Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in leading positions. A total of 614 articles on RSV (13.34% of all articles) were attributed to scientific collaborations. These were primarily established between high-income countries. The gender analysis indicated that male scientists dominated in all countries except Brazil.

Conclusions

The majority of RSV-related research articles originated from high-income countries whereas developing nations showed only minimal publication productivity and were barely part of any collaborative networks. Hence, research capacity in these nations should be increased in order to assist in addressing inequities in resource allocation and the clinical burden of RSV in these countries.



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Herbal medications for surgical patients: a systematic review protocol

Introduction

Postoperative nausea and vomiting (PONV) affect approximately 80% of surgical patients and is associated with increased length of hospital stay and systemic costs. Preoperative and postoperative pain, anxiety and depression are also commonly reported. Recent evidence regarding their safety and effectiveness has not been synthesised. The aim of this systematic review is to evaluate the efficacy and safety of herbal medications for the treatment and prevention of anxiety, depression, pain and PONV in patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgical procedures.

Methods and analysis

The following electronic databases will be searched up to 1 October 2016 without language or publication status restrictions: CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science and LILACS. Randomised clinical trials enrolling adult surgical patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgeries and managed with herbal medication versus a control group (placebo, no intervention or active control) prophylactically or therapeutically will be considered eligible. Outcomes of interest will include the following: anxiety, depression, pain, nausea and vomiting. A team of reviewers will complete title and abstract screening and full-text screening for identified hits independently and in duplicate. Data extraction, risk of bias assessments and evaluation of the overall quality of evidence for each relevant outcome reported will be conducted independently and in duplicate using the Grading of Recommendations Assessment Development and Evaluation classification system. Dichotomous data will be summarised as risk ratios; continuous data will be summarised as standard average differences with 95% CIs.

Ethics and dissemination

This is one of the first efforts to systematically summarise existing evidence evaluating the use of herbal medications in laparoscopic, obstetrical/gynaecological and cardiovascular surgical patients. The findings of this review will be disseminated through peer-reviewed publications and conference presentations.

Systematic review registration

PROSPERO CRD42016042838.



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Medication incidents in primary care medicine: a prospective study in the Swiss Sentinel Surveillance Network (Sentinella)

Objectives

To describe the type, frequency, seasonal and regional distribution of medication incidents in primary care in Switzerland and to elucidate possible risk factors for medication incidents.

Design

Prospective surveillance study.

Setting

Swiss primary healthcare, Swiss Sentinel Surveillance Network.

Participants

Patients with drug treatment who experienced any erroneous event related to the medication process and interfering with normal treatment course, as judged by their physician. The 180 physicians in the study were general practitioners or paediatricians participating in the Swiss Federal Sentinel reporting system in 2015.

Outcomes

Primary: medication incidents; secondary: potential risk factors like age, gender, polymedication, morbidity, care-dependency, previous hospitalisation.

Results

The mean rates of detected medication incidents were 2.07 per general practitioner per year (46.5 per 1 00 000 contacts) and 0.15 per paediatrician per year (2.8 per 1 00 000 contacts), respectively. The following factors were associated with medication incidents (OR, 95% CI): higher age 1.004 per year (1.001; 1.006), care by community nurse 1.458 (1.025; 2.073) and care by an institution 1.802 (1.399; 2.323), chronic conditions 1.052 (1.029; 1.075) per condition, medications 1.052 (1.030; 1.074) per medication, as well as Thurgau Morbidity Index for stage 4: 1.292 (1.004; 1.662), stage 5: 1.420 (1.078; 1.868) and stage 6: 1.680 (1.178; 2.396), respectively. Most cases were linked to an incorrect dosage for a given patient, while prescription of an erroneous medication was the second most common error.

Conclusions

Medication incidents are common in adult primary care, whereas they rarely occur in paediatrics. Older and multimorbid patients are at a particularly high risk for medication incidents. Reasons for medication incidents are diverse but often seem to be linked to communication problems.



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Ability to join the workforce and work productivity among drug users under methadone maintenance treatment in a mountainous area of Northern Vietnam: a cross-sectional study

Objectives

A major measure of treatment success for drug users undergoing rehabilitation is the ability to enter the workforce and generate income. This study examines the absenteeism and productivity among people who inject drugs (PWID) enrolled in methadone maintenance treatment (MMT) in Northern Vietnam.

Setting

We conducted a cross-sectional study in two clinics in Tuyen Quang province.

Participants

A total of 241 patients enrolled in MMT.

Primary and secondary outcome measures

Patients’ work productivity was measured using the WPAI-GH instrument (Work Productivity and Activity Impairment Questionnaire: General Health V2.0). We also collected additional characteristics about participants’ employment history, such as proficient jobs, whether they actively found a new job and be accepted by employers.

Results

Most of the participants (>90%) were employed at the time of the study. Rates of absenteeism (missed work), presenteeism (impairment while working) and overall loss of productivity were 15.8%, 5.6% and 11.2%, respectively, as measured by the WPAI-GH questionnaire. The most proficient job was ‘freelancer’ (17.5%), followed by ‘blue-collar worker’ (10.6%) and ‘farmer’ (10.2%). Only 26.8% of patients reported that they actively sought jobs in the past. About half of them had been refused by employers because of their drug use history and/or HIV status. We found no statistically significant difference between patients enrolled in MMT for <1 year and those who had been enrolled >1 year. Factors associated with higher work productivity included not endorsing problems in mobility, self-care or pain; being HIV-negative and having greater MMT treatment adherence.

Conclusion

Our study highlights the high employment rate and work productivity among PWID in MMT programmes in remote areas of Northern Vietnam. The results can help to improve the quality and structure of MMT programmes across Vietnam and in other countries.



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Common attributes in retired professional cricketers that may enhance or hinder quality of life after retirement: a qualitative study

Objectives

Retired professional cricketers shared unique experiences and may possess specific psychological attributes with potential to influence quality of life (QOL). Additionally, pain and osteoarthritis can be common in retired athletes which may negatively impact QOL. However, QOL in retired athletes is poorly understood. This study explores the following questions from the personal perspective of retired cricketers: How do retired cricketers perceive and experience musculoskeletal pain and function in daily life? Are there any psychological attributes that might enhance or hinder retired cricketers’ QOL?

Design

A qualitative study using semistructured interviews, which were subject to inductive, thematic analysis. A data-driven, iterative approach to data coding was employed.

Setting

All participants had lived and played professional cricket in the UK and were living in the UK or abroad at the time of interview.

Participants

Eighteen male participants, aged a mean 57±11 (range 34–77) years had played professional cricket for a mean 12±7 seasons and had been retired from professional cricket on average 23±9 years.

Results

Fifteen participants reported pain or joint difficulties and all but one was satisfied with their QOL. Most retired cricketers reflected on experiences during their cricket career that may be associated with the psychological attributes that these individuals shared, including resilience and a positive attitude. Additional attributes included a high sense of body awareness, an ability to self-manage pain and adapt lifestyle choices to accommodate physical limitations. Participants felt fortunate and proud to have played professional cricket, which may have further contributed to the high QOL in this group of retired cricketers.

Conclusions

Most retired cricketers in this study were living with pain or joint difficulties. Despite this, all but one was satisfied or very satisfied with their QOL. This may be partly explained by the positive psychological attributes that these retired cricketers shared.



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Recruitment and retention in a 10-month social network-based intervention promoting diabetes self-management in socioeconomically deprived patients: a qualitative process evaluation

Objectives

Socioeconomically deprived patients with type 2 diabetes often face challenges with self-management, resulting in more diabetes-related complications. However, these groups are often under-represented in self-management interventions. Evidence on effective recruitment and retention strategies is growing, but lacking for intensive self-management interventions. This study aims to explore recruitment, retention and effective intervention strategies in a 10-month group-based intervention among Dutch, Moroccan, Turkish and Surinamese patients from socioeconomically deprived neighbourhoods.

Methods

Participants were recruited through general practitioners (GPs) and participated in a 10-month social network-based intervention (10 groups, n=69): Powerful Together with Diabetes. This intervention also targeted the significant others of participants and aimed to increase social support for self-management and to decrease social influences hindering self-management. A qualitative process evaluation was conducted. Retention was measured using log books kept by group leaders. Further, we conducted 17 in-depth interviews with participants (multiethnic sample) and 18 with group leaders. Interviews were transcribed, coded and analysed using framework analyses.

Results

The GP's letter and reminder calls, an informational meeting and the intervention's informal nature facilitated recruitment. During the first months, positive group atmosphere, the intervention's perceived usefulness, opportunities to socialise and a reduction in practical barriers facilitated retention. After the first months, conflicting responsibilities and changes in the intervention's nature and planning hindered retention. Calls from group leaders and the prospect of a diploma helped participants overcome these barriers.

Conclusion

To promote retention in lengthy self-management interventions, it seems important that patients feel they are going on an outing to a social gathering that is enjoyable, recreational, useful and easy to attend. However, rewards and intensive personal recruitment and retention strategies remained necessary throughout the entire intervention period.

Trial registration number

Dutch Trial Register NTR1886; Results.



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In Vitro Maturation of Human iPSC-Derived Neuroepithelial Cells Influences Transplant Survival in the Stroke-Injured Rat Brain

Tissue Engineering Part A , Vol. 0, No. 0.


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Effect of superheated-steam roasting on physicochemical properties of peanut ( Arachis hypogea ) oil

Abstract

Peanut (Arachis hypogaea) is an important source of protein and lipid globally. The effect of superheated-steam roasting on quality of peanut oil was evaluated based on physicochemical quality parameters. Three roasting temperatures (150, 200, and 250 °C) were used for different periods of roasting time and the obtained results were compared with those of conventional roasting. At 250 °C, superheated-steam roasted peanuts yielded more oil (26.84%) than conventionally roasted peanuts (24.85%). Compared with conventional roasting, superheated-steam roasting resulted in lower oil color, peroxide, p-anisidine, free fatty acid, conjugated diene and triene, and acid values and higher viscosity and iodine values in the roasted peanut oil. These values were significantly different from each other (p < 0.05). The fatty acids in roasted peanut oils were affected by roasting temperature and time for both the roasting modes. The superheated steam technique can be used to roast peanuts while maintaining their favorable characteristics.



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Health Matters: How to treat an underactive thyroid? - Grand Forks Herald

Grand Forks Herald
Health Matters: How to treat an underactive thyroid?
Grand Forks Herald
Although patients and physicians may worry that the symptoms reflect a serious disease like cancer, infection or inflammatory bowel disease, most diagnostic workups of people with the above symptoms are negative. Various treatments may help, including ...



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Simultaneous occurrence of fibroblastic osteosarcoma and hypertrophic osteopathy (Marie’s disease) in a German shepherd dog

Abstract

Osteosarcoma, as a progressive tumor, accounts for approximately 80% of malignant bone tumors in dogs. Since it is a highly metastatic tumor, it develops pulmonary metastasis in the majority of cases. The considerable site preference of the tumor in dogs and the possibility of hypertrophic osteopathy in a number of cases must be considered. Clinical examination of a 12-year female German shepherd dog with lameness, weakness, and cachexia revealed an abnormal thickening in the left forelimb and a severe swelling in the left proximal humerus. Radiographic examinations showed severe swelling in the arm’s soft tissue, proximal humerus osteolysis, and irregular and palisade periosteal reaction in most bones of thoracic and pelvic limbs as well as soft-tissue masses in the thoracic cavity. In postmortem examination, a semi-hard destructive mass extended from the central cavity of humerus to the surrounding soft tissue, pulmonary and splenic metastases were observed. According to microscopic features, the tumoric bone lesion was diagnosed as fibroblastic osteosarcoma. Hypertrophic osteopathy (Marie’s disease) was also diagnosed due to gross characteristics of the forearm and palm along with radiographic findings of the forearm and tibia. This is the first report of simultaneous occurrence of fibroblastic osteosarcoma and Marie’s disease in Iranian dogs.



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Half the atoms inside your body came from across the universe

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Intergalactic winds carry gas and dust from one galaxy to the next, bringing half of the matter in our galaxy from up to a million light years away

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Galectin-8 regulates targeting of Gp135/podocalyxin and lumen formation at the apical surface of renal epithelial cells [Research]

Establishment of apical–basal polarity, through correct targeting of polarity determinants to distinct domains of the plasma membrane, is a fundamental process for the development of functioning epithelial tubules. Here we report that galectin (Gal)-8 regulates apical-basal polarity of Madin-Darby canine kidney (MDCK) cells via apical targeting of 135-kDa glycoprotein (Gp135). Gal-8 interacts with newly synthesized Gp135 in a glycan-dependent manner. Gal-8 knockdown induces aberrant lumens at the lateral domain and mistargeting of Gp135 to this structure, thus disrupting the kidney epithelial polarity of MDCK cells, which organize lumens at the apical surface. The O-glycosylation deletion mutant of Gp135 phenocopies the effect of Gal-8 knockdown, which suggests that Gal-8 is the decoding machinery for the apical sorting signals of Gp135 residing at its O-glycosylation–rich region. Collectively, our results reveal a new role of Gal-8 in the development of luminal organs by regulating targeting of apical polarity protein Gp135.—Lim, H., Yu, C.-Y., Jou, T.-S. Galectin-8 regulates targeting of Gp135/podocalyxin and lumen formation at the apical surface of renal epithelial cells.



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Half the atoms inside your body came from across the universe

Intergalactic winds carry gas and dust from one galaxy to the next, bringing half of the matter in our galaxy from up to a million light years away

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Palmitoylation is a prerequisite for dimerization-dependent raftophilicity of rhodopsin [Membrane Biology]

The visual photopigment rhodopsin (Rh) is a prototypical G protein-coupled receptor (GPCR) responsible for initiation of the phototransduction cascade in rod photoreceptors. Similar to other GPCRs, Rh can form dimers or even higher oligomers, and tends to have a supramolecular organization that is likely important in the dim light response. Rh also exhibits high affinity for lipid rafts (raftophilicity) upon light-dependent binding with cognate G protein transducin (Gt), suggesting the presence of lipid raft-like domains in the retinal disk membrane and their importance in phototransduction. However, the relationship between Rh oligomerization and lipid rafts in the disk membrane remains to be explored. Given previous findings that Gt binds to dimeric Rh and Rh is post-translationally modified with two highly raftophilic palmitoyl moieties, we hypothesized that Rh becomes raftophilic upon dimerization. Here, we tested this hypothesis biochemically. First, we found that Rh*-Gt complexes in the detergent-resistant membrane (DRM) are partially resistant to cholesterol depletion by methyl-β-cyclodextrin (MCD), and the stoichiometry of Rh to Gt in this MCD-resistant complex is 2:1. We then found that IgG-crosslinking renders Rh highly raftophilic, supporting the premise that Rh becomes raftophilic upon dimerization. Depalmitoylation of Rh with the reduction of thioester linkages by dithiothreitol blocked the translocation of IgG-crosslinked Rh to the DRM, highlighting the importance of the two palmitoyl moieties in the dimerization-dependent raftophilicity of Rh. These results indicate that palmitoylated GPCRs, such as Rh, may acquire raftophilicity upon G protein-stabilized dimerization and thereby organize receptor-cluster rafts by recruiting raftophilic lipids.

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The Alzheimer's Disease-protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool [Glycobiology and Extracellular Matrices]

The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset Alzheimers disease (LOAD), an apparently human-specific post-reproductive disease. CD33 generates two splice variants: a full-length CD33M transcript produced primarily by the LOAD-risk allele and a shorter CD33m isoform lacking the sialic acid-binding domain, produced primarily from the LOAD-protective allele. A SNP that modulates CD33 splicing to favor CD33m is associated with enhanced microglial activity. Individuals expressing more protective isoform accumulate less brain Beta-amyloid and have a lower LOAD risk. How the CD33m isoform increases Beta-amyloid; clearance remains unknown. We report that the protection by the CD33m isoform may not be conferred by what it does, but rather from what it cannot do. Analysis of blood neutrophils and monocytes and a microglial cell line revealed that unlike CD33M, the CD33m isoform does not localize to cell surfaces; instead, it accumulates in peroxisomes. Cell stimulation and activation did not mobilize CD33m to the surface. Thus, the CD33m isoform may neither interact directly with amyloid plaques nor engage in cell-surface signaling. Rather, production and localization of CD33m in peroxisomes is a way of diminishing the amount of CD33M and enhancing Beta-amyloid clearance. We confirmed intracellular localization by generating a CD33m-specific monoclonal antibody. Of note, CD33 is the only Siglec with a peroxisome-targeting sequence, and this motif emerged by convergent evolution in toothed whales, the only other mammals with a prolonged post-reproductive lifespan. The CD33 allele that protects post-reproductive individuals from LOAD may have evolved by adaptive loss-of-function, an example of the less-is-more hypothesis.

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Crystal structure of the human Polε B-subunit in complex with the C-terminal domain of the catalytic subunit [Protein Structure and Folding]

The eukaryotic B-family DNA polymerases include four members, Polα, Polδ, Polϵ, and Polζ, which share common architectural features, such as the exonuclease/polymerase and C-terminal domains (CTDs) of catalytic subunits bound to indispensable B-subunits, which serve as scaffolds that mediate interactions with other components of the replication machinery. Crystal structures for the B-subunits of Polα and Polδ/Polζ have been reported; the former within the primosome and separately with CTD, and the latter with the N-terminal domain (NTD) of the C-subunit. Here we present the crystal structure of the human Polϵ B-subunit (p59) in complex with CTD of the catalytic subunit (p261C). The structure revealed a well-defined electron density for p261C and the phosphodiesterase (PDE) and oligonucleotide/oligosaccharide-binding domains of p59. However, electron density was missing for the p59 NTD and for the linker connecting it to the PDE domain. Similar to Polα, p261C contains a three-helix bundle in the middle and zinc-binding modules (Zn1 and Zn2) on each side. Intersubunit interactions involving 11 hydrogen bonds and numerous hydrophobic contacts account for stable complex formation with a buried surface area of 3094 Å2. Comparative structural analysis of p59-p261C with the corresponding Polα complex revealed significant differences between the B-subunits and CTDs as well as their interaction interfaces. The B-subunit of Polδ/Polζ also substantially differs from B-subunits of either Polα or Polϵ. This work provides a structural basis to explain biochemical and genetic data on the importance of B-subunit integrity in replisome function in vivo.

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Search for DNA Damage by Human Alkyladenine DNA Glycosylase Involves Early Intercalation by an Aromatic Residue [Enzymology]

DNA repair enzymes recognize and remove damaged bases that are embedded in the duplex. To gain access, most enzymes use nucleotide flipping , whereby the target nucleotide is rotated 180 degree into the active site. In human alkyladenine DNA glycosylase (AAG), the enzyme that initiates base excision repair of alkylated bases, the flipped-out nucleotide is stabilized by intercalation of the side chain of tyrosine 162 that replaces the lesion nucleobase. Previous kinetic studies provided evidence for the formation of a transient complex that precedes the stable flipped-out complex, but it is not clear how this complex differs from nonspecific complexes. We used site-directed mutagenesis and transient-kinetic approaches to investigate the timing of Y162 intercalation for AAG. The tryptophan substitution (Y162W) appeared to be conservative, because the mutant protein retained a highly favorable equilibrium constant for flipping the 1,N6-ethenoadenine (εA) lesion and the rate of N-glycosidic bond cleavage was identical to that of the wild-type enzyme. We assigned the tryptophan fluorescence signal from Y162W by removing two native tryptophan residues (W270A/W284A). Stopped-flow experiments then demonstrated that the change in tryptophan fluorescence of the Y162W mutant is extremely rapid upon binding to either damaged or undamaged DNA, much faster than the lesion-recognition and nucleotide-flipping steps that were independently determined by monitoring the εA fluorescence. These observations suggest that intercalation by this aromatic residue is one of the earliest steps in the search for DNA damage, and that this interaction is important for the progression of AAG from nonspecific searching to specific-recognition complexes.

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Thrombospondin-1 (TSP-1), a new bone morphogenetic protein-2 and -4 (BMP-2/4) antagonist identified in pituitary cells [Protein Structure and Folding]

Bone morphogenetic proteins (BMPs) regulate diverse cellular responses during embryogenesis and in adulthood including cell differentiation, proliferation and death in various tissues. In the adult pituitary, BMPs participate in the control of hormone secretion and cell proliferation suggesting a potential endocrine/paracrine role for BMPs, but some of the mechanisms are unclear. Here, using a bioactivity test based on embryonic cells (C3H10T1/2) transfected with a BMP-responsive element, we sought to determine whether pituitary cells secrete BMPs or BMP antagonists. Interestingly, we found that pituitary-conditioned medium contains a factor that inhibits action of BMP-2 and -4. Combining surface plasmon resonance (SPR) and high-resolution mass spectrometry helped pinpoint this factor as thrombospondin-1 (TSP-1). SPR and co-immunoprecipitation confirmed that recombinant human TSP-1 can bind BMP-2 and -4 and antagonize their effects on C3H10T1/2 cells. Moreover, TSP-1 inhibited the action of serum BMPs. We also report that the von Willebrand type C (VWC) domain of TSP-1 is likely responsible for this BMP-2/4 binding activity, an assertion based on sequence similarity that TSP-1 shares with the VWC domain of Crossveinless 2 (CV-2), a BMP antagonist and member of the chordin family. In summary, we identified for the first time TSP-1 as a BMP-2/-4 antagonist and presented structural basis for the physical interaction between TSP-1 and BMP-4. We propose that TSP-1 could regulate bioavailability of BMPs, either produced locally or reaching the pituitary via the blood circulation. In conclusion, our findings provide new insights into the involvement of TSP-1 in the BMP-2/-4 mechanisms of action.

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Efficient Methylation of C2 in L-Tryptophan by the Cobalamin-dependent Radical S-Adenosylmethionine Methylase TsrM Requires an Unmodified N1 Amine [Metabolism]

TsrM catalyzes the methylation of C2 in Ltryptophan (Trp). This reaction is the first step in the biosynthesis of the quinaldic acid moiety of the thiopeptide antibiotic thiostrepton, which exhibits potent activity against Gram-positive pathogens. TsrM is a member of the radical S-adenosylmethionine (SAM) superfamily of enzymes, but does not catalyze formation of 5'-deoxyadenosin-5'-yl or any other SAM-derived radical. In addition to a [4Fe-4S] cluster, TsrM contains a cobalamin cofactor that serves as an intermediate methyl carrier in its reaction. However, how this cofactor donates a methyl moiety to the Trp substrate is unknown. Here, we show that an unmodified N1 position of Trp is important for turnover and that 1-thia-Trp and 1-oxa-Trp serve as competitive inhibitors. We also show that β-cyclopropyl-Trp undergoes C2 methylation in the absence of cyclopropyl ringopening, disfavoring mechanisms that involve unpaired electron density at C3 of the indole ring. Moreover, we show that all other indole-substituted analogs of Trp undergo methylation at varying but measurable rates, and that the analog 7-aza-Trp - which is expected to temper the nucleophilicity of C2 in Trp-is a very poor substrate. Lastly, no formation of cob(II)alamin or substrate radicals is observed during the reaction with Trp or any molecule within a tested panel of Trp analogs. In summary, our results are most consistent with a mechanism that involves two polar nucleophilic displacements, the second of which requires deprotonation of the indole nitrogen in Trp during its attack on methylcobalamin.

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Rise in e-cigarette use linked to increase in smoking cessation rates

Evidence for the effectiveness of e-cigarettes as smoking cessation aids for individual smokers, still limited to just two randomised controlled trials of now obsolete e-cigarettes, suggests they are...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=C2Pp0hePA1Q:YlhXngRGQsA:V_sGLiP recent?d=qj6IDK7rITs recent?i=C2Pp0hePA1Q:YlhXngRGQsA:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=C2Pp0hePA1Q:YlhXngRGQsA:F7zBnMy recent?i=C2Pp0hePA1Q:YlhXngRGQsA:-BTjWOF


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The antibiotic course has had its day

Antibiotics are vital to modern medicine and antibiotic resistance is a global, urgent threat to human health. The relation between antibiotic exposure and antibiotic resistance is unambiguous both...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:V_sGLiP recent?d=qj6IDK7rITs recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:F7zBnMy recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:-BTjWOF


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E-cigarette use and associated changes in population smoking cessation: evidence from US current population surveys

Objective To examine whether the increase in use of electronic cigarettes in the USA, which became noticeable around 2010 and increased dramatically by 2014, was associated with a change in overall...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=T3lIZN2c0mA:Hlmz9n1AWQM:V_sGLiP recent?d=qj6IDK7rITs recent?i=T3lIZN2c0mA:Hlmz9n1AWQM:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=T3lIZN2c0mA:Hlmz9n1AWQM:F7zBnMy recent?i=T3lIZN2c0mA:Hlmz9n1AWQM:-BTjWOF


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Push to raise head, neck cancer awareness - NEWS.com.au

Push to raise head, neck cancer awareness
NEWS.com.au
"HPV is what causes cervical cancer, but many Australians may not be aware that it can also cause head and neck cancers. This is another reason for teenage boys and girls to get vaccinated when they are offered it through our national immunisation ...

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– Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists

We thank Professor Albertsen for his interest in our study.

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Mesenchymal stem/stromal cell extracellular vesicles: From active principle to next generation drug delivery system

Publication date: 28 September 2017
Source:Journal of Controlled Release, Volume 262
Author(s): Barbara Crivelli, Theodora Chlapanidas, Sara Perteghella, Enrico Lucarelli, Luisa Pascucci, Anna Teresa Brini, Ivana Ferrero, Mario Marazzi, Augusto Pessina, Maria Luisa Torre
It has been demonstrated that the biological effector of mesenchymal stem/stromal cells (MSCs) is their secretome, which is composed of a heterogeneous pool of bioactive molecules, partially enclosed in extracellular vesicles (EVs). Therefore, the MSC secretome (including EVs) has been recently proposed as possible alternative to MSC therapy. The secretome can be considered as a protein-based biotechnological product, it is probably safer compared with living/cycling cells, it presents virtually lower tumorigenic risk, and it can be handled, stored and sterilized as an Active Pharmaceutical/Principle Ingredient (API). EVs retain some structural and technological analogies with synthetic drug delivery systems (DDS), even if their potential clinical application is also limited by the absence of reproducible/scalable isolation methods and Good Manufacturing Practice (GMP)-compliant procedures. Notably, EVs secreted by MSCs preserve some of their parental cell features such as homing, immunomodulatory and regenerative potential. This review focuses on MSCs and their EVs as APIs, as well as DDS, considering their ability to reach inflamed and damaged tissues and to prolong the release of encapsulated drugs. Special attention is devoted to the illustration of innovative therapeutic approaches in which nanomedicine is successfully combined with stem cell therapy, thus creating a novel class of “next generation drug delivery systems.”

Graphical abstract

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Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

Publication date: 28 September 2017
Source:Journal of Controlled Release, Volume 262
Author(s): Sean Allen, Omar Osorio, Yu-Gang Liu, Evan Scott
Flash nanoprecipitation (FNP) has proven to be a powerful tool for the rapid and scalable assembly of solid-core nanoparticles from block copolymers. The process can be performed using a simple confined impingement jets mixer and provides an efficient and reproducible method of loading micelles with hydrophobic drugs. To date, FNP has not been applied for the fabrication of complex or vesicular nanoarchitectures capable of encapsulating hydrophilic molecules or bioactive protein therapeutics. Here, we present FNP as a single customizable method for the assembly of bicontinuous nanospheres, filomicelles and vesicular, multilamellar and tubular polymersomes from poly(ethylene glycol)-bl-poly(propylene sulfide) block copolymers. Multiple impingements of polymersomes assembled via FNP were shown to decrease vesicle diameter and polydispersity, allowing gram-scale fabrication of monodisperse polymersomes within minutes. Furthermore, we demonstrate that FNP supports the simultaneous loading of both hydrophobic and hydrophilic molecules respectively into the polymersome membrane and aqueous lumen, and encapsulated enzymes were found to be released and remain active following vesicle lysis. As an example application, theranostic polymersomes were generated via FNP that were dual loaded with the immunosuppressant rapamycin and a fluorescent dye to link targeted immune cells with the elicited immunomodulation of T cells. By expanding the capabilities of FNP, we present a rapid, scalable and reproducible method of nanofabrication for a wide range of nanoarchitectures that are typically challenging to assemble and load with therapeutics for controlled delivery and theranostic strategies.

Graphical abstract

image


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Harmful Contaminants Found In Florida Drinking Water: Study - Patch.com

Patch.com
Harmful Contaminants Found In Florida Drinking Water: Study
Patch.com
Radium-228 (linked to cancer). Found above health guidelines at 359 utilities. Chlorate (linked to impaired thyroid function, which can be harmful during pregnancy and childhood). Found above health guidelines at 239 utilities. Arsenic (linked to cancer).
Contaminants in Indy water raise some concern, new report showsIndianapolis Star
Check online for contaminants in your city's drinking waterSun Sentinel

all 56 news articles »


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Clinical Features of Psoriatic Arthritis: a Comprehensive Review of Unmet Clinical Needs

Abstract

Psoriatic arthritis (PsA) is a form of inflammatory arthritis (IA) affecting approximately 0.25% of the population. It is a heterogeneous disorder associated with joint damage, disability, disfiguring skin disease and in severe cases, premature mortality. Inherently irreversible and frequently progressive, the process of joint damage begins at, or before, the clinical onset of disease. Early recognition and intervention is thus crucial to patient outcome. At disease onset, however, PsA often resembles other forms of arthritis—especially rheumatoid arthritis (RA). Despite the similarities between PsA and RA, their distinctive pathologies require different treatments. For example, drugs that are effective in RA may not be effective in PsA and can even cause adverse effects. Since there is no currently validated test for PsA, the diagnosis is often missed or delayed and this has functional consequences for the patient. In the context of PsA and RA, making an accurate diagnosis is not the only challenge faced by rheumatologists. Choosing an effective and safe medication to manage the disease is another significant challenge and currently approximately 40% achieve meaningful responses such as minimal disease activity status. For the patient, several months may be lost as a result of trial and error testing—meanwhile, irreversible joint damage may occur. Clearly, more effective clinical tests are urgently needed to improve personalised patient care in PsA. Specifically, there is need to develop minimally invasive tests predictive of diagnosis, response to treatment and radiographic progression. In this review, we examined the biomarker development process, highlighted the importance of qualifying unmet clinical needs and emphasised the challenges that impede biomarker studies. We have compiled a comprehensive list of potentially clinically relevant biomarkers in PsA and provided a summary of proteomic technologies that might usefully support additional biomarker research in PsA.



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Expression of MicroRNA-146a and MicroRNA-155 in Placental Villi in Early- and Late-Onset Preeclampsia

We studied the expression of microRNA-146a and microRNA-155 in placental villi from 18 women (26-39 weeks of gestation) of reproductive age with early- or late-onset preeclampsia. The reference group consisted of women with physiological pregnancy and full-term gestation and with preterm birth after caesarian section on gestation week 26-31. MicroRNA-146a and microRNA-155 were detected by in situ hybridization with digoxigenin on paraffin sections. It was found that the expression of microRNA-146a in both syncytiotrophoblast of the intermediate villi and syncytial knots was lower at late-onset preeclampsia than at physiologic pregnancy of full-term period (p=0.037 and p=0.001 respectively). The expression of microRNA-155 in syncytiotrophoblast of intermediate placental villi in early-onset preeclampsia was higher than in group with preterm delivery (p=0.003). However, in syncytiotrophoblast of intermediate villi and in syncytial knots, the expression of microRNA-155 was lower at late-onset preeclampsia in comparison with full-term physiological pregnancy (p=0.005). In addition, the expression of microRNA-146a and microRNA-155 did not increase in the later terms in preeclampsia, while in the reference groups demonstrating gradual increase in the expression of these markers with increasing gestational age. Expression microRNA-146a and microRNA-155 little differed in early- and late-onset preeclampsia. These findings suggest that different variants of preeclampsia are probably characterized by common pathogenetic pathways. Damaged trophoblast cannot maintain of microRNAs synthesis at the required level, which determines the formation of a vicious circle in preeclampsia and further progression of the disease.



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Ahead of print: Comparison of two cold compression therapy protocols after tibial plateau leveling...

Objective: To evaluate two different protocols of cold compression therapy (CCT) for pain management and functional recovery in dogs undergoing tibial plateau leveling osteotomy (TPLO). Material and methods: A total of 27 adult dogs (n = 30 stifles; staged bilateral procedures: n = 3) undergoing routine TPLO were randomly allocated to three groups (n = 10/group). Dogs of group I received CCT once before and immediately after surgery. In dogs of group II CCT was performed postoperatively four times at 6-hour intervals. Dogs of the control group did not receive CCT. Circumference of the stifle joint and the following pain-related parameters were measured by a single blinded observer before surgery and 1, 10 and 42 days after surgery: stifle joint range of motion (ROM), subjective degree of lameness, and score of a modified Glasgow Pain Scale (GPS). Results: Both CCT groups showed significantly greater ROM and lower GPS scores 24 hours after surgery compared to the control group. Ten days after surgery there was a significantly lower degree of lameness in both CCT groups compared to the control group. Fourty-two days after surgery a significantly greater ROM was observed in both CCT groups compared to the control group. Group II also showed a significant improvement in the degree of lameness and GPS. There were no significant differences in any of the parameters between the two CCT groups at any time point. Conclusion: CCT applied preoperatively and immediately postoperatively showed similar short- and long-term beneficial results compared to a previously established protocol of applying CCT four times postoperatively. This protocol may be more suitable for practical use. Clinical significance: The reported data can be used to establish the new protocol of CCT in a clinical surrounding and to support postoperative rehabilitation of the canine patient....

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Pharmaceuticals released from senior residences: occurrence and risk evaluation

Abstract

One of the main pursuits, yet most difficult, in monitoring studies is to identify the sources of environmental pollution. In this study, we have identified health-care facilities from south European countries as an important source of pharmaceuticals in the environment. We have estimated that compounds consumed in by the elderly and released from effluents of senior residences can reach river waters at a concentration higher than 0.01 μg/L, which is the European Medicines Agency (EMA) threshold for risk evaluation of pharmaceuticals in surface waters. This study has been based on five health institutions in Portugal, Spain, and France, with 52 to 130 beds. We have compiled the pharmaceuticals dispensed on a daily base and calculated the consumption rates. From 54.9 to 1801 g of pharmaceuticals are consumed daily, with laxatives, analgesics, antiepileptics, antibiotics, and antidiabetic agents being the main drug families administered. According to excretion rates, dilution in the sewerage system, and elimination in wastewater treatment plants, macrogol, metformin, paracetamol, acetylcysteine, amoxicillin, and gabapentin, among others, are expected to reach river waters. Finally, we discuss the risk management actions related to the discharge of pharmaceuticals from senior residences to surface waters.



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Therapeutic Approach to the Management of Severe Asymptomatic Hyponatremia

Hyponatremia is an electrolyte imbalance encountered commonly in the hospital and ambulatory settings. It can be seen in isolation or present as a complication of other medical conditions. It is therefore a challenge to determine the appropriate therapeutic intervention. An understanding of the etiology is key in instituting the right treatment. Clinicians must not be too hasty to correct a random laboratory value without first understanding the physiologic principle. We present such a case of a patient who presented with sodium of 98 mmol/L, the lowest recorded in the current literature, and yet was asymptomatic. Following appropriate management driven by an understanding of the underlying pathophysiologic mechanism, the patient was managed to full recovery without any clinically significant neurological sequelae.

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Unilateral Headache Status after Intra-Aortic Balloon Pump Placement

Introduction. Intra-aortic balloon pump (IABP) counterpulsation is a catheter-based treatment for coronary artery disease and decompensated heart failure to increase coronary blood flow and improve cardiac output. IABP is generally well tolerated, and complications are usually related to peripheral vasculature or red blood cell and platelet consumption. The usual insertion site via femoral artery renders the patient bedbound. Recently, axillary artery has been used in patients with atherosclerotic peripheral vascular disease and documented small arteries or in those awaiting transplant to ensure ambulation and prevent deconditioning. Case Report. We present a patient with ischemic cardiomyopathy and severe left ventricular dysfunction, awaiting Orthotropic Heart Transplant. His worsening intractable angina and dyspnea necessitated IABP placement via left axillary artery, significantly improving his condition. He subsequently experienced migraine-type persistent unilateral headache refractory to standard pain management. Multiple strategies were utilized to treat his pain, but the patient insisted that his pain commenced after IABP placement. Ultimately, the removal of the pump led to complete resolution with no recurrence. Conclusion. The authors hypothesize that the unilaterally directed blood flow and direct increase in cerebral perfusion from the intra-aortic balloon pump may have caused vasodilation of the extracranial arteries, leading to a persistent and debilitating headache in this susceptible patient.

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Electrochemical Evaluation of trans-Resveratrol Levels in Red Wine Based on the Interaction between Resveratrol and Graphene

trans-Resveratrol is often considered as one of the quality standards of red wine, and the development of a sensitive and reliable method for monitoring the trans-resveratrol levels in red wine is an urgent requirement for the quality control. Here, a novel voltammetric approach was described for probing trans-resveratrol using a graphene-modified glassy carbon (GC) electrode. The proposed electrode was prepared by one-step electrodeposition of reduced graphene oxide (ERGO) at a GC electrode. Compared with the bare GC electrode, the introduced graphene film on the electrode surface dramatically improved the sensitivity of the sensor response due to the π-π interaction between the graphene and trans-resveratrol. The developed sensor exhibited low detection limit of 0.2 μM with wide linear range of 0.8–32 μM and high stability. For the analysis of trans-resveratrol in red wine, the high anti-interference ability and the good recoveries indicated the great potential for practical applications.

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CVD-Graphene-Based Flexible, Thermoelectrochromic Sensor

The main idea behind this work was demonstrated in a form of a new thermoelectrochromic sensor on a flexible substrate using graphene as an electrically reconfigurable thermal medium (TEChrom™). Our approach relies on electromodulation of thermal properties of graphene on poly(ethylene terephthalate) (PET) via mechanical destruction of a graphene layer. Graphene applied in this work was obtained by chemical vapor deposition (CVD) technique on copper substrate and characterized by Raman and scanning tunneling spectroscopy. Electrical parameters of graphene were evaluated by the van der Pauw method on the transferred graphene layers onto SiO2 substrates by electrochemical delamination method. Two configurations of architecture of sensors, without and with the thermochromic layer, were investigated, taking into account the increase of voltage from 0 to 50 V and were observed by thermographic camera to define heat energy. Current-voltage characteristics obtained for the sensor with damaged graphene layer are linear, and the resistivity is independent from the current applied. The device investigated under 1000 W/m2 exhibited rise of resistivity along with increased temperature. Flexible thermoelectrochromic device with graphene presented here can be widely used as a sensor for both the military and civil monitoring.

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Hexavalent Chromium Removal from Model Water and Car Shock Absorber Factory Effluent by Nanofiltration and Reverse Osmosis Membrane

Nanofiltration and reverse osmosis are investigated as a possible alternative to the conventional methods of Cr(VI) removal from model water and industrial effluent. The influences of feed concentration, water recovery, pH, and the coexisting anions were studied. The results have shown that retention rates of hexavalent chromium can reach 99.7% using nanofiltration membrane (NF-HL) and vary from 85 to 99.9% using reverse osmosis membrane (RO-SG) depending upon the composition of the solution and operating conditions. This work was also extended to investigate the separation of Cr(VI) from car shock absorber factory effluent. The use of these membranes is very promising for Cr(VI) water treatment and desalting industry effluent. Spiegler-Kedem model was applied to experimental results in the aim to determine phenomenological parameters, the reflection coefficient of the membrane , and the solute permeability coefficient . The convective and diffusive parts of the mass transfer were quantified with predominance of the diffusive contribution.

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A Correlation between the Higgs Mass and Dark Matter

Depending on the value of the Higgs mass, the Standard Model acquires an unstable region at large Higgs field values due to RG running of couplings, which we evaluate at 2-loop order. For currently favored values of the Higgs mass, this renders the electroweak vacuum only metastable with a long lifetime. We argue on statistical grounds that the Higgs field would be highly unlikely to begin in the small field metastable region in the early universe, and thus some new physics should enter in the energy range of order of, or lower than, the instability scale to remove the large field unstable region. We assume that Peccei-Quinn (PQ) dynamics enters to solve the strong CP problem and, for a PQ-scale in this energy range, may also remove the unstable region. We allow the PQ-scale to scan and argue, again on statistical grounds, that its value in our universe should be of order of the instability scale, rather than (significantly) lower. Since the Higgs mass determines the instability scale, which is argued to set the PQ-scale, and since the PQ-scale determines the axion properties, including its dark matter abundance, we are led to a correlation between the Higgs mass and the abundance of dark matter. We find the correlation to be in good agreement with current data.

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Extraction and Optimization of Natural Dye from Hambo Hambo (Cassia singueana) Plant Used for Coloration of Tanned Leather Materials

This investigation was aimed at introducing natural dye extracted from the bark of Cassia Singueana plant for dyeing chrome tanned sheep skin crust leather. The colorant was extracted by aqueous extraction and its strength evaluated using UV-Visible spectroscopy. The extraction with the highest strength (3.9 at of 400 nm) was obtained at temperature of 95°C, concentration of 60 g/l, and time of 60 minutes. The possibility of using aloe vera juice and mango bark extract as natural mordants for leather coloration was investigated. Dyeing was conducted with and without mordant using different combinations of temperature, time, pH, and concentration of mordants. All three mordanting techniques were evaluated. The color strength , CIE values, and fastness properties (light, rubbing, and perspiration) of dyed leather samples were evaluated using appropriate instruments and according to international standards. Majority of samples exhibited that fastness result was in the range of good-excellent. Significantly better color fastness was obtained in case of leather samples premordanted with aloe vera. This study leads to the conclusion that dye extracted from bark of Cassia singueana can be used as colorant for tanned leather with the selected natural mordants.

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Nontrivial Solutions for Time Fractional Nonlinear Schrödinger-Kirchhoff Type Equations

We study the existence of solutions for time fractional Schrödinger-Kirchhoff type equation involving left and right Liouville-Weyl fractional derivatives via variational methods.

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Numerical and Experimental Investigation on the Structural Behaviour of a Horizontal Stabilizer under Critical Aerodynamic Loading Conditions

The aim of the proposed research activity is to investigate the mechanical behaviour of a part of aerospace horizontal stabilizer, made of composite materials and undergoing static loads. The prototype design and manufacturing phases have been carried out in the framework of this research activity. The structural components of such stabilizer are made of composite sandwich panels (HTA 5131/RTM 6) with honeycomb core (HRH-10-1/8-4.0); the sandwich skins have been made by means of Resin Transfer Moulding (RTM) process. In order to assess the mechanical strength of this stabilizer, experimental tests have been performed. In particular, the most critical inflight recorded aerodynamic load has been experimentally reproduced and applied on the stabilizer. A numerical model, based on the Finite Element Method (FEM) and aimed at reducing the experimental effort, has been preliminarily developed to calibrate amplitude, direction, and distribution of an equivalent and simpler load vector to be used in the experimental test. The FEM analysis, performed by using NASTRAN code, has allowed modelling the skins of the composite sandwich plates by definition of material properties and stack orientation of each lamina, while the honeycomb core has been modelled by using an equivalent orthotropic plate. Numerical and experimental results have been compared and a good agreement has been achieved.

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Evaluation of the Processing Times in Anuran Sound Classification

Nowadays, sound classification applications are becoming more common in the Wireless Acoustic Sensor Networks (WASN) scope. However, these architectures require special considerations, like looking for a balance between transmitted data and local processing. This article proposes an audio processing and classification scheme, focusing on WASN architectures. This article also analyzes in detail the time efficiency of the different stages involved (from acquisition to classification). This study provides useful information which makes it possible to choose the best tradeoff between processing time and classification result accuracy. This approach has been evaluated on a wide set of anurans songs registered in their own habitat. Among the conclusions of this work, there is an emphasis on the disparity in the classification and feature extraction and construction times for the different studied techniques, all of them notably depending on the overall feature number used.

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Bearing Fault Detection by One-Dimensional Convolutional Neural Networks

Bearing faults are the biggest single source of motor failures. Artificial Neural Networks (ANNs) and other decision support systems are widely used for early detection of bearing faults. The typical decision support systems require feature extraction and classification as two distinct phases. Extracting fixed features each time may require a significant computational cost preventing their use in real-time applications. Furthermore, the selected features for the classification phase may not represent the most optimal choice. In this paper, the use of 1D Convolutional Neural Networks (CNNs) is proposed for a fast and accurate bearing fault detection system. The feature extraction and classification phases of the bearing fault detection are combined into a single learning body with the implementation of 1D CNN. The raw vibration data (signal) is fed into the proposed system as input eliminating the need for running a separate feature extraction algorithm each time vibration data is analyzed for classification. Implementation of 1D CNNs results in more efficient systems in terms of computational complexity. The classification performance of the proposed system with real bearing data demonstrates that the reduced computational complexity is achieved without a compromise in fault detection accuracy.

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An Interstitial 4q Deletion with a Mosaic Complementary Ring Chromosome in a Child with Dysmorphism, Linear Skin Pigmentation, and Hepatomegaly

Interstitial deletions of 4q are rarely reported, vary in size, and have limited genotype-phenotype correlations. Here, genome-wide array CGH analysis identified a 21.6 Mb region of copy number loss at 4q12-q21.1 in a patient diagnosed with dysmorphism, linear skin pigmentation, and hepatomegaly. An additional small ring chromosome was detected in 5/30 cells examined via G-banding. Confirmation of the origin of the ring chromosome was obtained by FISH analysis which identified that the ring chromosome contained material from the deleted region of chromosome 4 and was therefore complementary to the 21.6 Mb deletion. Further microarray studies in the proband using a different microarray platform showed no evidence of mosaicism. This case highlights the importance of an integrated approach to cytogenetic analysis and demonstrates the value of G-banding for detecting mosaicism, as current microarray platforms are unable to detect low level mosaics.

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Efficacy of CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease of the blood affecting children, adolescents and adults. Although current treatment protocols for T-ALL have improved overall survival, a portion of T-ALL patients still experiences treatment failure. Thus, the development of novel therapies is needed. In this study, we used several patient-derived T-ALL cell lines to screen an effective drug for T-ALL. Using a panel of 378 inhibitors against different kinases, we identified the CDK inhibitor dinaciclib as a potential drug for T-ALL.

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World Head and Neck Cancer day - ABC Online

ABC Online
World Head and Neck Cancer day
ABC Online
... and the rates of HPV-related head and neck cancers around the world have reached epidemic levels. Today is World Head and Neck Cancer day, and to mark the occasion, former RN broadcaster Julie McCrossin — herself a survivor of cancer in her ...

and more »


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“Non è abbastanza malata, niente cure per lei”. Ma la donna sta morendo… - DirettaNews.it

PAY-NOT-ENOUGH-CANCER-7-300x200.jpg

DirettaNews.it
“Non è abbastanza malata, niente cure per lei”. Ma la donna sta morendo…
DirettaNews.it
Dopo diversi cicli di chemioterapia e radioterapia, il tumore di Louise si è in effetti ridimensionato, ma se ne è formato un altro sul collo, e dopo aver avuto un'emorragia i medici le hanno detto che era giunta allo stadio terminale. “Ho perso tutti ...



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Biomechanical evaluation of a novel hybrid reconstruction plate for mandible segmental defects: A finite element analysis and fatigue testing

This study develops a novel hybrid (NH) reconstruction plate that can provide load-bearing strength, secure the bone transplant at the prosthesis favored position, and also maintain the facial contour in a mandibular segmental defect. A new patient-match bending technique which uses a three-dimensional printing (3DP) stamping process is developed to increase the interfacial fit between the reconstruction plate and mandibular bone.

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The feasibility of cold atmospheric plasma in the treatment of complicated wounds in cranio-maxillo-facial surgery

Compromised wound healing in cranio-maxillo-facial surgery is a threat to the patient's rehabilitation. Therapy of chronic and/or infected wounds is time- and cost-consuming, burdensome and occasionally futile. Cold atmospheric plasma is a new approach that promises to overcome these limitations. The aim of this proof-of-concept study was to evaluate the clinical outcome of cold plasma irradiation in patients with impaired wound healing who are refractory to conservative wound therapy and/or revision surgery.

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World Head and Neck Cancer day - ABC Online

ABC Online
World Head and Neck Cancer day
ABC Online
HPV is the common human papilloma virus which can be sexually transmitted — and it's connected to a surprisingly long list of cancers in both sexes. You may remember that the Hollywood actor Michael Douglas contracted stage 4 throat cancer because of ...
Give boys vaccine to fight HPV pandemic, says expertThe Times

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World Head and Neck Cancer day - ABC Online

ABC Online
World Head and Neck Cancer day
ABC Online
... of HPV-related head and neck cancers around the world have reached epidemic levels. Today is World Head and Neck Cancer day, and to mark the occasion, former RN broadcaster Julie McCrossin — herself a survivor of cancer in her tonsils, tongue and ...
Give boys vaccine to fight HPV pandemic, says expertThe Times

all 3 news articles »


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Pathway discovery using transcriptomic profiles in adult-onset severe asthma

This study elucidates distinct gene profiles in adult-onset severe asthma compared to childhood-onset severe asthma. Identified gene profiles include those associated with eosinophils, ILC3s and mast cells, and may represent targets for new treatments.

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Liver disease predicts mortality in patients with XHIM but can be prevented by early hematopoietic stem cell transplantation

In the largest detailed study of liver disease in X-linked immunodeficiency with hyper-IgM, we show that liver disease is commoner than generally recognized and that early hematopoietic stem cell transplantation may prevent liver disease progression and improve survival.

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Rise in e-cigarette use linked to increase in smoking cessation rates

Evidence for the effectiveness of e-cigarettes as smoking cessation aids for individual smokers, still limited to just two randomised controlled trials of now obsolete e-cigarettes, suggests they are...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=C2Pp0hePA1Q:YlhXngRGQsA:V_sGLiP recent?d=qj6IDK7rITs recent?i=C2Pp0hePA1Q:YlhXngRGQsA:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=C2Pp0hePA1Q:YlhXngRGQsA:F7zBnMy recent?i=C2Pp0hePA1Q:YlhXngRGQsA:-BTjWOF


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The antibiotic course has had its day

Antibiotics are vital to modern medicine and antibiotic resistance is a global, urgent threat to human health. The relation between antibiotic exposure and antibiotic resistance is unambiguous both...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:V_sGLiP recent?d=qj6IDK7rITs recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:F7zBnMy recent?i=pdfE5e6CWoI:aOoNLr9g_Jo:-BTjWOF


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