Augmented monomials in terms of power sums

The problem of base changes for the classical symmetric functions has been solved a long time ago and has been incorporated into most computer software packages for symmetric functions. In this paper, we develop a simple recursive formula for the expansion of the augmented monomial symmetric functions into power sum symmetric functions. As corollaries, we present two algorithms that can be used to expressing the augmented monomial symmetric functions in terms of the power sum symmetric functions.Mathematics Subject Classification: 05E05, 11P81.

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Fungal annexins: a mini review

The large family of annexins is composed of more than a thousand members which are typically phospholipid-binding proteins. Annexins act in a number of signalling networks and membrane trafficking events which are fundamental to cell physiology. Annexins exert their functions mainly through their calcium-dependent membrane binding abilities; however, some calcium-independent interactions have been documented in the literature. Although mammalian and plant annexins have been well characterized, little is known about this family in fungi. This mini review summarizes the available data on fungal annexins.

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Underestimation of prevalence of raised blood sugar from history compared to biochemical estimation: support for the WHO rule of halves in a population based survey in Eritrea of 2009

To ascertain the prevalence of diabetes mellitus from history and biochemical estimation so as to attest the WHO Rule of halves in a lean population. A population based national survey on diabetes mellitus was carried out in 2009. History and fingerpicks blood analysis were examined according to recommended procedures of the WHO STEPwise approach and the WHO recommended automated machine to compare the two modalities of estimating diabetes prevalence. Over 6000 people with a response rate of 95 % and a prevalence of raised blood glucose of 5.0 %. The prevalence from history of raised blood sugar was 2.2 %. Less than half (47 %) of the persons with high blood glucose were aware of their status with less than half on treatment. Of those on treatment less than half (30 %) were well controlled. Prevalence of raised fasting blood glucose was more than double that estimated from history, with less than half of the people aware of their status and of those on treatment nearly half are under good control. The underestimation of the disease through history supports the WHO rule of halves and calls for the use of biochemical tests when estimating prevalence of diabetes in the general population or at least doubling the rate from history alone.

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Effects of dietary allspice, Pimenta dioica powder on physiological responses of Oreochromis mossambicus under low pH stress

This study investigated the effects of the supplementation with allspice (0, 5, 10, 15, or 20 g kg −1 ) on the haemato-immunological and biochemical variables in tilapia, Oreochromis mossambicus under acidic stress condition. In a 60-day feeding trial, 15 aquariums (80-L) were stocked with 18 fish (20.05 ± 0.10 g) each. Then, acidic stress was achieved by exposing the sampled fish to acidic water (pH 5.5) for 3 days. Allspice supplementation influenced the haematological indices, serum glucose, protein, globulin and innate immune parameters such as respiratory burst activity, lysozyme, and myeloperoxidase activities. In general, at acidic pH decreased circulating red blood cell numbers (RBC), increased mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and the innate immune parameters were observed. On the other hand, the inclusion of allspice prevented an increase in blood glucose MCV and MCH, decreases in albumin, RBC, lysozyme activity and respiratory burst avtivity. In conclusion, this study demonstrated that allspice supplementation at 10 g kg −1 for 60 days, has adequate beneficial effects on improvement of haemato-immunological and biochemical status of O. mossambicus after stressful management.

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Almost automorphic solutions for shunting inhibitory cellular neural networks with time-varying delays

This paper is concerned with the shunting inhibitory cellular neural networks with time-varying delays. Under some suitable conditions, we establish some criteria on the existence and global exponential stability of the almost automorphic solutions of the networks. Numerical simulations are given to support the theoretical findings.Mathematics Subject Classification: 39A60, 39A12.

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Impact evaluation and association with EuroQol 5D health-related utility values in Ménière’s disease

The study was aimed at evaluating the validity of impact measures among patients with Ménière's disease (MD) with outcome variables of EuroQol generic health-related quality of life (HRQoL) measures (i.e., EQ-5D) by using Visual Analogue Scale (VAS) and EQ-5D index values. 183 members (out of 200 contacted) of the Finish Ménière Association returned the questionnaires that they had filled out. Various open-ended and structured questionnaires focusing on diagnostic aspects of symptoms and impairment caused by the disease were used. For activity limitation and participation restriction, standardized questionnaires were used. Open-ended questions on impact of the disease were asked, and subsequently classified based on the WHO-ICF classification. The general HRQoL was evaluated with EQ-5D index value and EQ VAS instruments. Correlation and linear regression analyses were used to explore the association between HRQoL and other aspects. Based on the explanatory power of different models the disease specific semeionic model provides the most accurate prediction in EQ-5D index calculations (38 % of the variance explained). In EQ VAS scores, HRQoL is most accurately determined by participation restriction (53 % of the variance explained), but the worst prediction was in ICF-based limitations (8 % of the variance explained). Interestingly, attitude and personal trait explained the reduction of HRQoL somewhat better than ICF-based variables. Activity limitation and participation restrictions are significant components of MD, but are less frequently recognized as significant factors in self-evaluating the effect of MD on the quality of life. The current study results suggest that MD patients seem to have problem identifying factors causing activity limitation and participation restrictions and hence use the semiotic description focusing on complaints.

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Dead Nano-Sized Lactobacillus plantarum Inhibits Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer in Balb/c Mice

Journal of Medicinal Food , Vol. 0, No. 0.


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The Female Sexual Function Index (FSFI): Translation, Validation, and Cross-Cultural Adaptation of an Urdu Version “FSFI–U”

Abstract

Introduction

Female sexual dysfunction (FSD) is a common problem, and many self-report questionnaires are available for its evaluation. Pakistani women with sexual problems feel shy to consult with their physician. A validated self-report questionnaire, in the local language with modest expressions is required for these women.

Aim

The aim of this study was to translate, cross-culturally adapt, and perform a psychometric validation of an Urdu translation of the Female Sexual Function Index (FSFI).

Methods

The FSFI was translated in Urdu, and its precision was ascertained through reverse translation. It was pretested on 22 bilingual women and refined again to reach at a reliable Urdu version of the questionnaire FSFI-U. One hundred sixteen bilingual women, in a stable sexual relationship over the previous 6 months were finally asked to fill out the FSFI and FSFI-U. Their sexual function was then clinically evaluated and responses were compared with the clinical assessment as well as with each other.

Main Outcome Measures

The responses were analyzed through descriptive statistics for reliability, face validity, agreement between the responses to the original English version and to the FSFI-U, and also for test–retest consistency. The data were analyzed statistically using Cronbach's alpha analysis, Intraclass correlation coefficients, Pearson correlation, and Student's t-test.

Results

FSFI was found to be easily understandable and capable of adequately evaluating and measuring various aspects of female sexual function. A high degree of internal consistency was demonstrated on Cronbach's alpha analysis. Cronbach's α coefficient for various domains was sufficiently high ranging from 0.84 to 0.97. The clinical assessment of the presence and severity of FSD also matched with the self-report questionnaire. Similarly, various domains of FSFI had high degree of correlation in the Urdu version of FSFI (P < 0.001).

Conclusion

The Urdu translation version of FSFI is valid and reliable for use in the literate population of Pakistan. Rehman KU, Asif Mahmood M, Sheikh SS, Sultan T, Khan MA. The Female Sexual Function Index (FSFI): Translation, Validation, and Cross-Cultural Adaptation of an Urdu Version "FSFI–U". Sex Med **;**:**–**.

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Corrigendum to “Inhibition of human topoisomerase I and II and anti-proliferative effects on MCF-7 cells by new titanocene complexes” [Bioorg. Med. Chem. 23 (2015) 7302–7312]

Publication date: Available online 23 November 2015
Source:Bioorganic & Medicinal Chemistry
Author(s): Adele Chimento, Carmela Saturnino, Domenico Iacopetta, Rosaria Mazzotta, Anna Caruso, Maria Rosaria Plutino, Annaluisa Mariconda, Anna Ramunno, Maria Stefania Sinicropi, Vincenzo Pezzi, Pasquale Longo




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Design Synthesis and Structure–Activity Relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)Propionamide Derivatives as Opioid Ligands

Publication date: Available online 23 November 2015
Source:Bioorganic & Medicinal Chemistry
Author(s): Srinivas Deekond, David Rankin, Peg Davis, Josephine Lai, Todd. W. Vanderah, Frank Porecca, Victor J. Hruby
Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5^th position of the (tetrahydronaphthalen-2-yl)methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850 nM–4 nM) and were selective towards the μ opioid receptor over the δ opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5^th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM respectively and 1000 fold selectivity towards the μ opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75+/- 21 nM, and 190+/- 42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170+/- 42 nM, in contrast to its binding affinity results.

Graphical abstract

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Benzenesulfonamides incorporating bulky aromatic/heterocyclic tails with potent carbonic anhydrase inhibitory activity

Publication date: Available online 23 November 2015
Source:Bioorganic & Medicinal Chemistry
Author(s): Murat Bozdag, Ahmed M. Alafeefy, Daniela Vullo, Fabrizio Carta, Nurcan Dedeoglu, Abdul-Malek S. Al-Tamimi, Nabila A. Al-Jaber, Andrea Scozzafava, Claudiu T. Supuran
Three series of sulfonamides incorporating long, bulky tails were obtained by applying synthetic strategies in which substituted anthranilic acids, quinazolines and aromatic sulfonamides have been used as starting materials. They incorporate long, bulky diamide-, 4-oxoquinazoline-3-yl- or quinazoline-4-yl moieties in their molecules, and were investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4..2.1.1) isoforms, the cytosolic human (h) hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides showed excellent inhibitory effects against the four isoforms, with KIs of 7.6 - 322 nM against hCA I, of 0.06 - 85.4 nM against hCA II; of 6.7 - 152 nM against hCA IX and of 0.49 - 237 nM against hCA XII; respectively. However no relevant isoform-selective behavior has been observed for any of them, although hCA II and XII, isoforms involved in glaucoma-genesis were the most inhibited ones. The structure-activity relationship for inhibiting the four CAs with these derivatives is discussed in detail.

Graphical abstract

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The Generality of Kinase-Catalyzed Biotinylation

Publication date: Available online 23 November 2015
Source:Bioorganic & Medicinal Chemistry
Author(s): Chamara Senevirathne, D. Maheeka Embogama, Thilani A. Anthony, Ahmed E. Fouda, Mary Kay H. Pflum
Kinase-catalyzed protein phosphorylation is involved in a wide variety of cellular events. Development of methods to monitor phosphoproteins in normal and diseased states is critical to fully characterize cell signalling. Towards phosphoprotein analysis tools, our lab reported kinase-catalyzed labeling where γ-phosphate modified ATP analogs are utilized by kinases to label peptides or protein substrates with a functional tag. In particular, the ATP-biotin analog was developed for kinase-catalyzed biotinylation. However, kinase-catalyzed labeling has been tested rigorously with only a few kinases, preventing use of ATP-biotin as a general tool. Here, biotinylation experiments, gel or HPLC-based quantification, and kinetic measurements indicated that twenty-five kinases throughout the kinome tree accepted ATP-biotin as a cosubstrate. With this rigorous characterization of ATP-biotin compatibility, kinase-catalyzed labeling is now immediately useful for studying phosphoproteins and characterizing the role of phosphorylation in various biological events.

Graphical abstract

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Tinnitus Research 2015

Tinnitus research 2015 has brought some exciting news to people who suffer from this common and sometimes debilitating condition. While research into tinnitus causes and treatments has been going on for decades, only in the last few years have real breakthroughs been seen, and 2015 has been a banner year for new treatments for this troublesome disorder.

Tinnitus Symptoms and Causes

Tinnitus has one main symptom; a relentless ringing, hissing or whooshing sound heard in the ears or head of the sufferer. For many, the condition begins after exposure to loud sound or a traumatizing event. For others, the symptoms start without any obvious cause. As time goes on, those with serious cases of tinnitus can become depressed and discouraged.

The Boston Marathon bombing and soldiers returning from Iraq and Afghanistan brought on a new wave of studies into treatments for tinnitus. Recent studies at the Universities of New York, Virginia, and Iowa have explored a new theory about what causes tinnitus.

Previously, scientists thought that tinnitus was caused by physical damage to the tiny hairs inside the ear. It was believed that when these hairs were missing or not working right, auditory signals were getting blocked on their way to the brain. The brain was then thought to be compensating by making up sounds to fill in the gaps.

Now, real-time imaging of a tinnitus sufferer's brain at the University of Iowa has shown that tinnitus involves dysfunction in multiple brain centers, including all auditory areas, as well as the centers for emotion, memory, and attention.

Newly Developed Tinnitus Treatment

The most exciting tinnitus research 2015 involved studies that resulted in the development of the Ultraquiet therapy. This new treatment uses a CD disc player, amplifier, and a set of headphones.

The disc player has a special feature, allowing it to turn the music into vibrations and sending them directly into the bones of the skull, bypassing the middle ear. This causes the cochlea to temporarily regain sensitivity to higher frequency sounds, reducing or eliminating tinnitus symptoms for as long as two weeks.

At least, that was the result for all of the nine tinnitus research 2015 studies. Participants with disabling tinnitus who had the Ultraquiet treatment for two, half hour sessions a week for four weeks were able to see these results.

Although this is not a permanent cure, retreatment every two weeks appears to keep the condition at bay indefinitely, bringing cause for celebration to tinnitus sufferers everywhere.

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Structure and function of echinoderm telomerase RNA [ARTICLE]

Telomerase is a ribonucleoprotein (RNP) enzyme that requires an integral telomerase RNA (TR) subunit, in addition to the catalytic telomerase reverse transcriptase (TERT), for enzymatic function. The secondary structures of TRs from the three major groups of species, ciliates, fungi, and vertebrates, have been studied extensively and demonstrate dramatic diversity. Herein, we report the first comprehensive secondary structure of TR from echinoderms—marine invertebrates closely related to vertebrates—determined by phylogenetic comparative analysis of 16 TR sequences from three separate echinoderm classes. Similar to vertebrate TR, echinoderm TR contains the highly conserved template/pseudoknot and H/ACA domains. However, echinoderm TR lacks the ancestral CR4/5 structural domain found throughout vertebrate and fungal TRs. Instead, echinoderm TR contains a distinct simple helical region, termed eCR4/5, that is functionally equivalent to the CR4/5 domain. The urchin and brittle star eCR4/5 domains bind specifically to their respective TERT proteins and stimulate telomerase activity. Distinct from vertebrate telomerase, the echinoderm TR template/pseudoknot domain with the TERT protein is sufficient to reconstitute significant telomerase activity. This gain-of-function of the echinoderm template/pseudoknot domain for conferring telomerase activity presumably facilitated the rapid structural evolution of the eCR4/5 domain throughout the echinoderm lineage. Additionally, echinoderm TR utilizes the template-adjacent P1.1 helix as a physical template boundary element to prevent nontelomeric DNA synthesis, a mechanism used by ciliate and fungal TRs. Thus, the chimeric and eccentric structural features of echinoderm TR provide unparalleled insights into the rapid evolution of telomerase RNP structure and function.

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Prevalence of foot disease and risk factors in general inpatient populations: a systematic review and meta-analysis

Objective

To systematically review studies reporting the prevalence in general adult inpatient populations of foot disease disorders (foot wounds, foot infections, collective 'foot disease') and risk factors (peripheral arterial disease (PAD), peripheral neuropathy (PN), foot deformity).

Methods

A systematic review of studies published between 1980 and 2013 was undertaken using electronic databases (MEDLINE, EMBASE and CINAHL). Keywords and synonyms relating to prevalence, inpatients, foot disease disorders and risk factors were used. Studies reporting foot disease or risk factor prevalence data in general inpatient populations were included. Included study's reference lists and citations were searched and experts consulted to identify additional relevant studies. 2 authors, blinded to each other, assessed the methodological quality of included studies. Applicable data were extracted by 1 author and checked by a second author. Prevalence proportions and SEs were calculated for all included studies. Pooled prevalence estimates were calculated using random-effects models where 3 eligible studies were available.

Results

Of the 4972 studies initially identified, 78 studies reporting 84 different cohorts (total 60 231 517 participants) were included. Foot disease prevalence included: foot wounds 0.01–13.5% (70 cohorts), foot infections 0.05–6.4% (7 cohorts), collective foot disease 0.2–11.9% (12 cohorts). Risk factor prevalence included: PAD 0.01–36.0% (10 cohorts), PN 0.003–2.8% (6 cohorts), foot deformity was not reported. Pooled prevalence estimates were only able to be calculated for pressure ulcer-related foot wounds 4.6% (95% CI 3.7% to 5.4%)), diabetes-related foot wounds 2.4% (1.5% to 3.4%), diabetes-related foot infections 3.4% (0.2% to 6.5%), diabetes-related foot disease 4.7% (0.3% to 9.2%). Heterogeneity was high in all pooled estimates (I²=94.2–97.8%, p<0.001).

Conclusions

This review found high heterogeneity, yet suggests foot disease was present in 1 in every 20 inpatients and a major risk factor in 1 in 3 inpatients. These findings are likely an underestimate and more robust studies are required to provide more precise estimates.

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Palliative care coding practices in Canada since the introduction of guidelines and the HSMR indicator

Objectives

This study examines palliative care (PC) coding practices since the introduction of a national coding standard and assesses a potential association with hospital standardised mortality ratio (HSMR) results.

Setting

Acute-care hospitals in Canada.

Participants

~16 million hospital discharges recorded in Canadian Institute for Health Information (CIHI)'s Discharge Abstract Database from April 2006 to March 2013.

Primary and secondary outcome measures

In-hospital mortality, patient characteristics and service utilisation among all hospitalisations, HSMR cases and palliative patients.

Methods

We assessed all separations in the Discharge Abstract Database between fiscal years 2006–2007 and 2012–2013 for PC cases at national, provincial and facility levels. In-hospital mortality was measured among all hospitalisations (including HSMR cases) and palliative patients. We calculated a variant HSMR-PC that included PC cases.

Results

There was an increase in the frequency of PC coding over the study period (from 0.78% to 1.12% of all separations), and year-over-year improvement in adherence to PC coding guidelines. Characteristics and resource utilisation of PC patients remained stable within provinces. Crude mortality among HSMR cases declined from 8.7% to 7.3%. National HSMR declined by 22% during the study period, compared with a 17% decline in HSMR-PC. Provincial results for HSMR-PC are not significantly different from regular HSMR calculation.

Conclusions

The introduction of a national coding standard resulted in increased identification of palliative patients and services. Aside from PC coding practices, we note numerous independent drivers of improving HSMR results, notably, a significant reduction of in-hospital mortality, and increase in admissions accompanied by a greater number of coded comorbidities. While PC impacts the HSMR indicator, its influence remains modest.

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Diffusion of anti-VEGF injections in the Portuguese National Health System

Objectives

To analyse the temporal and geographical diffusion of antivascular endothelial growth factor (anti-VEGF) interventions, and its determinants in a National Health System (NHS).

Setting

NHS Portuguese hospitals.

Participants

All inpatient and day cases related to eye diseases at all Portuguese public hospitals for the period 2002–2012 were selected on the basis of four International Classification of Diseases 9th revision, Clinical Modification (ICD-9-CM) codes for procedures: 1474, 1475, 1479 and 149.

Primary and secondary outcome measures

We measured anti-VEGF treatment rates by year and county. The determinants of the geographical diffusion were investigated using generalised linear modelling.

Results

We analysed all hospital discharges from all NHS hospitals in Portugal (98 408 hospital discharges corresponding to 57 984 patients). National rates of hospitals episodes for the codes for procedures used were low before anti-VEGF approval in 2007 (less than 12% of hospital discharges). Between 2007 and 2012, the rates of hospital episodes related to the introduction of anti-VEGF injections increased by 27% per year. Patients from areas without ophthalmology departments received fewer treatments than those from areas with ophthalmology departments. The availability of an ophthalmology department in the county increased the rates of hospital episodes by 243%, and a 100-persons greater density per km² raised the rates by 11%.

Conclusions

Our study shows a large but unequal diffusion of anti-VEGF treatments despite the universal coverage and very low copayments. The technological innovation in ophthalmology may thus produce unexpected inequalities related to financial constraints unless the implementation of innovative techniques is planned and regulated.

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Diagnosing Potentially Preventable Hospitalisations (DaPPHne): protocol for a mixed-methods data-linkage study

Introduction

Rates of potentially preventable hospitalisations (PPH) are used as a proxy measure of effectiveness of, or access to community-based health services. The validity of PPH as an indicator in Australia has not been confirmed. Available evidence suggests that patient-related, clinician-related and systems-related factors are associated with PPH, with differences between rural and metropolitan settings. Furthermore, the proportion of PPHs which are actually preventable is unknown. The Diagnosing Potentially Preventable Hospitalisations study will determine the proportion of PPHs for chronic conditions that are deemed preventable and identify potentially modifiable factors driving these, in order to develop effective interventions to reduce admissions and improve measures of health system performance.

Methods and analysis

This mixed methods data linkage study of approximately 1000 eligible patients with chronic PPH admissions to one metropolitan and two regional hospitals over 12 months will combine data from multiple sources to assess the: extent of preventability of chronic PPH admissions; validity of the Preventability Assessment Tool (PAT) in identifying preventable admissions; factors contributing to chronic PPH admissions. Data collected from patients (quantitative and qualitative methods), their general practitioners, hospital clinicians and hospital records, will be linked with routinely collected New South Wales (NSW) Admitted Patient Data Collection, the NSW Registry of Births, Death and Marriages death registration and Australian Bureau of Statistics mortality data. The validity of the PAT will be assessed by determining concordance between clinician assessment and that of a 'gold standard' panel. Multivariable logistic regression will identify the main predictor variables of admissions deemed preventable, using study-specific and linked data.

Ethics and dissemination

The NSW Population and Health Services Research Ethics Committee granted ethical approval. Dissemination mechanisms include engagement of policy stakeholders through a project Steering Committee, and the production of summary reports for policy and clinical audiences in addition to peer-review papers.

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Phenolic profile and antioxidant potential of wild watercress (Nasturtium officinale L.)

Phenolic profile, antioxidant potential and pigment contents of wild watercress (Nasturtium officinale L.) were studied to assess the potential for future studies and its applications in neutraceuticals and bioactive functional ingredients. Different extracts of watercress (roots, stem and leaves) were analysed for pigment composition, total phenolic contents, and radical scavenging activity. The phenolic profile of the leaves and roots was studied using reversed phase HPLC–DAD. Results showed that total phenolic compounds in all samples were higher in the methanolic extracts than its corresponding aqueous extracts. The RSA of methanolic extracts was higher than aqueous extracts. Fourteen phenolic compounds were identified in the leaves, where coumaric acid and its derivatives, caftaric acid and quercetin derivatives were present in higher amounts. In roots, a total of 20 compounds was tentatively identified, with coumaric acid and its derivatives, sinapic acid, caftaric acid and quercetin derivatives were the major phenolic compounds. In conclusion, watercress has significant antioxidant activity and contains important phenolic compounds, which could be of potential biological interest.

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In situ ∼2.0 Ma trees discovered as fossil rooted stumps, lowermost Bed I, Olduvai Gorge, Tanzania

Publication date: January 2016
Source:Journal of Human Evolution, Volume 90
Author(s): Jörg M. Habermann, Ian G. Stanistreet, Harald Stollhofen, Rosa M. Albert, Marion K. Bamford, Michael C. Pante, Jackson K. Njau, Fidelis T. Masao
The discovery of fossil rooted tree stumps in lowermost Lower Bed I from the western Olduvai Basin, Tanzania, age-bracketed by the Naabi Ignimbrite (2.038 ± 0.005 Ma) and Tuff IA (1.88 ± 0.05 Ma), provides the first direct, in situ, and to date oldest evidence of living trees at Olduvai Gorge. The tree relicts occur in an interval dominated by low-viscosity mass flow and braided fluvial sediments, deposited at the toe of a largely Ngorongoro Volcano-sourced volcaniclastic fan apron that comprised a widely spaced network of ephemeral braided streams draining northward into the Olduvai Basin. Preservation of the trees occurred through their engulfment by mass flows, post-mortem mold formation resulting from differential decay of woody tissues, and subsequent fluvially-related sediment infill, calcite precipitation, and cast formation. Rhizolith preservation was triggered by the interaction of root-induced organic and inorganic processes to form rhizocretionary calcareous root casts. Phytolith analyses were carried out to complete the paleoenvironmental reconstruction. They imply a pronounced seasonality and indicate a wooded landscape with grasses, shrubs, and sedges growing nearby, comparable to the low, open riverine woodland (unit 4c) along the Garusi River and tributaries in the Laetoli area. Among the tree stump cluster were found outsized lithic clasts and those consisting of quartzite were identified as Oldowan stone tool artifacts. In the context of hominin activity, the identification of wooded grassland in association with nearby freshwater drainages and Oldowan artifacts significantly extends our paleoenvironmental purview on the basal parts of Lower Bed I, and highlights the hitherto underrated role of the yet poorly explored western Olduvai Gorge area as a potential ecologically attractive setting and habitat for early hominins.



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Recent advances in choroideremia

Zinkernagel MS, MacLaren RE

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Genetics and diabetic retinopathy

Hampton BM, Schwartz SG, Brantley MA Jr, Flynn HW Jr

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Identification and characterization of microsatellite loci in two socially complex old world tropical babblers (Family Timaliidae)

Background: Although the highest diversity of birds occurs in tropical regions, little is known about the genetic mating systems of most tropical species. We describe microsatellite markers isolated in the chestnut-crested yuhina (Staphida everetti), endemic to the island of Borneo, and the grey-throated babbler (Stachyris nigriceps), widely distributed across Southeast Asia. Both species belong to the avian family Timaliidae and are highly social, putatively cooperatively breeding birds in which helpers attend the nests of members of their social group. We obtained DNA from individuals in social groups breeding in Kinabalu Park, Malaysian Borneo. Results: We used a shotgun sequencing approach and 454-technology to identify 36 microsatellite loci in the yuhina and 40 in the babbler. We tested 13 primer pairs in yuhinas and 20 in babblers and characterized eight polymorphic loci in 20 unrelated female yuhinas and 21 unrelated female babblers. Polymorphism at the yuhina loci ranged from 3 to 9 alleles, observed heterozygosities from 0.58 to 1.00, and expected heterozygosities from 0.64 to 0.81. Polymorphism at the babbler loci ranged from 3 to 12 alleles, observed heterozygosities from 0.14 to 0.90 and expected heterozygosities from 0.14 to 0.87. One locus in the yuhina deviated significantly from Hardy–Weinberg equilibrium. We detected nonrandom allele associations between two pairs of microsatellite loci in each species. Conclusions: Microsatellite markers will be used to describe the genetic mating system of these socially complex species and to measure genetic parentage and relatedness within social groups.

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Magnetic Separation-Assistant Fluorescence Resonance Energy Transfer Inhibition for Highly Sensitive Probing of Nucleolin

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b03064

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Direct Interface between Digital Microfluidics and High Performance Liquid Chromatography–Mass Spectrometry

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b03616

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Meeting the Challenges of Intervention Research in Health Science: An Argument for a Multimethod Research Approach

Abstract

Research within health science is often based on developing, implementing and evaluating interventions in a randomized controlled trial (RCT) design, with patients or other health care users as the target group. The results of RCTs can have limited generalizability. Since a trial often takes place in a controlled setting, it may be difficult to implement the results in other settings. Successful implementation in practice requires knowledge of the context and the social mechanisms and processes through which an intervention works. It is therefore important to secure such knowledge of high quality. The aim of this paper was to present and discuss how intervention research in RCT designs can be developed and strengthened by using a multimethod research approach. First, we focus on four considerations relating to the use of RCTs, namely objectivity and linearity, contextual dimensions, generalizability, and complex interventions. Second, a multimethod research approach including the terms 'research style' and 'forms of integration' is presented to address the four considerations. Third, a Danish intervention study is presented in order to discuss the potential of this multimethod research approach. We conclude by suggesting that future intervention studies should consider the potential for combining different research styles and forms of integration to the benefits of the patients and other health care users as the target group.

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Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus A Prospective Cohort Study

Background:

Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain.

Objective:

To evaluate lactation and the 2-year incidence of DM after GDM pregnancy.

Design:

Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030)

Setting:

Integrated health care system.

Participants:

1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011.

Measurements:

Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders.

Results:

Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios.

Limitation:

Randomized design is not feasible or desirable for clinical studies of lactation.

Conclusion:

Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery.

Primary Funding Source:

National Institute of Child Health and Human Development.

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Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus

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Four-Week Direct-Acting Antiviral Regimens in Noncirrhotic Patients With Hepatitis C Virus Genotype 1 Infection An Open-Label, Nonrandomized Trial

Background:

Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) for 6 weeks achieves sustained virologic response (SVR) rates of 95% in some patients. If effective, shorter therapeutic courses could improve adherence and treatment costs.

Objective:

To determine factors predictive of SVR to 4 weeks of DAA treatment in patients with stage F0 to F2 liver fibrosis.

Design:

Open-label, nonrandomized, phase 2a trial. (Clinical Trials.gov: NCT01805882)

Setting:

Single-center.

Patients:

50 treatment-naive and predominantly African American patients with HCV genotype 1 infection and early-stage liver fibrosis were sequentially enrolled into 2 treatment groups.

Intervention:

25 participants received a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 for 4 weeks, and 25 received a 4-drug regimen consisting of ledipasvir, sofosbuvir, GS-9451, and GS-9669 for 4 weeks.

Measurements:

The primary efficacy end point was SVR12 (HCV RNA level below the lower limit of quantification at posttreatment week 12).

Results:

Forty percent (10 of 25) (95% CI, 21% to 61%) of patients in the 3-drug group and 20% (5 of 25) (CI, 7% to 41%) of those in the 4-drug group achieved SVR12. Exploratory analysis suggested that lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12. Ten patients had baseline HCV variants conferring greater than 20-fold resistance in vitro to at least 1 study DAA; all had viral relapse. Forty-eight percent (12 of 25) of patients receiving the 3-drug regimen and 72% (18 of 25) of those receiving the 4-drug regimen had adverse events, most of which were mild. One participant was lost to follow-up.

Limitation:

Nonrandomized study design and small sample of patients with early-stage fibrosis.

Conclusion:

Combination DAA therapy with 3 or 4 drugs for 4 weeks was well-tolerated but resulted in limited cure rates.

Primary Funding Source:

National Institute of Allergy and Infectious Diseases, National Cancer Institute, and Clinical Center Intramural Program; supported in part by a cooperative research and development agreement between the National Institutes of Health and Gilead Sciences.

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HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors A Randomized, Controlled Trial

Background:

Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials.

Objective:

To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents.

Design:

Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394)

Setting:

Outpatient HIV clinics.

Participants:

Treatment-experienced patients with HIV infection and viral resistance.

Intervention:

Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs.

Measurements:

The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment.

Results:

360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, −6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group.

Limitation:

Unblinded study design, and the study may not be applicable to resource-poor settings.

Conclusion:

Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population.

Primary Funding Sources:

National Institute of Allergy and Infectious Diseases, Boehringer Ingelheim, Janssen, Merck, ViiV Healthcare, Roche, and Monogram Biosciences (LabCorp).

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Improving Adherence to Therapy and Clinical Outcomes While Containing Costs: Opportunities From the Greater Use of Generic Medications: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians

Description:

The discrepancy between health care spending and achieved outcomes in the United States has fueled efforts to identify and address situations where unnecessarily expensive therapies are used when less costly, equally effective options are available. The underuse of generic medications is an important example.

Methods:

A literature review was conducted to answer 5 questions about generic medications: 1) How commonly are brand-name medications used when a generic version is available? 2) How does the use of generic medications influence adherence? 3) What is the evidence that brand-name and generic medications have similar clinical effects? 4) What are the barriers to increasing the use of generic medications? 5) What strategies can be used to promote cost savings through greater generic medication use? This article was reviewed and approved by the American College of Physicians Clinical Guidelines Committee, whose members are physicians trained in internal medicine and its subspecialties and which includes experts in evidence synthesis.

Best Practice Advice:

Clinicians should prescribe generic medications, if possible, rather than more expensive brand-name medications.

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Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy A Systematic Review and Meta-analysis

Background:

Solid tumor chemotherapy regimens pose a risk for hepatitis B virus (HBV) reactivation, but screening and antiviral prophylaxis remains controversial because of insufficient evidence.

Purpose:

To determine the risk for HBV reactivation with and without antiviral prophylaxis and the effectiveness of prophylaxis in adults with solid tumors and chronic or resolved HBV infection.

Data Sources:

MEDLINE through 1 July 2015 and Web of Science, Cochrane Central Register of Controlled Trials, TOXNET, and Scopus through 1 March 2015.

Study Selection:

26 English-language observational studies and randomized, controlled trials in patients with chronic or resolved HBV receiving chemotherapy for solid tumors.

Data Extraction:

Study characteristics, quality, and risk of bias were assessed by 1 researcher and verified by another independent researcher.

Data Synthesis:

Random-effects model meta-analyses were used to estimate the risk and odds ratio (OR) of reactivation with versus without antiviral prophylaxis. Reactivation in chronic HBV without prophylaxis ranged from 4% to 68% (median, 25%) with substantial heterogeneity. Prophylaxis reduced the risk for HBV reactivation (OR, 0.12 [95% CI, 0.06 to 0.22]), HBV-related hepatitis (OR, 0.18 [CI, 0.10 to 0.32]), and chemotherapy interruption (OR, 0.10 [CI, 0.04 to 0.27]). In 3 studies of patients with resolved HBV infection, none received HBV prophylaxis and reactivation risk ranged from 0.3% to 9.0%

Limitations:

Significant heterogeneity in underlying study populations and treatment regimens, incomplete baseline data, possibility of publication bias, and limited study quality. Most studies were observational and from Asia.

Conclusion:

In patients with chronic HBV receiving solid tumor chemotherapy, the risk for HBV reactivation is similar to the risk with other types of immunosuppressive therapy. Results support HBV screening and antiviral prophylaxis before initiation of chemotherapy for solid tumors.

Primary Funding Source:

National Center for Advancing Translational Sciences and National Institutes of Health.

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Improving Adherence to Therapy and Clinical Outcomes While Containing Costs: Opportunities From the Greater Use of Generic Medications

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Prevention of Hepatitis C by Screening and Treatment in U.S. Prisons

Background:

The prevalence of hepatitis C virus (HCV) in U.S. prisoners is high; however, HCV testing and treatment are rare. Infected inmates released back into society contribute to the spread of HCV in the general population. Routine hepatitis screening of inmates followed by new therapies may reduce ongoing HCV transmission.

Objective:

To evaluate the health and economic effect of HCV screening and treatment in prisons on the HCV epidemic in society.

Design:

Agent-based microsimulation model of HCV transmission and progression of HCV disease.

Data Sources:

Published literature.

Target Population:

Population in U.S. prisons and general community.

Time Horizon:

30 years.

Perspective:

Societal.

Interventions:

Risk-based and universal opt-out hepatitis C screening in prisons, followed by treatment in a portion of patients.

Outcome Measures:

Prevention of HCV transmission and associated disease in prisons and society, costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and total prison budget.

Results of Base-Case Analysis:

Implementing risk-based and opt-out screening could diagnose 41 900 to 122 700 new HCV cases in prisons in the next 30 years. Compared with no screening, these scenarios could prevent 5500 to 12 700 new HCV infections caused by releasees, wherein about 90% of averted infections would have occurred outside of prisons. HCV screening could also prevent 4200 to 11 700 liver-related deaths. The ICERs of screening scenarios were $19 600 to $29 200/QALY, and the respective first-year prison budget was $900 to $1150 million. Prisons would require an additional 12.4% of their current health care budget to implement such interventions.

Results of Sensitivity Analysis:

Results were sensitive to the time horizon, and ICERs otherwise remained less than $50 000 per QALY.

Limitation:

Data on transmission network, reinfection rate, and opt-out HCV screening rate are lacking.

Conclusions:

Universal opt-out HCV screening in prisons is highly cost-effective and would reduce HCV transmission and HCV-associated diseases primarily in the outside community. Investing in U.S. prisons to manage hepatitis C is a strategic approach to address the current epidemic.

Primary Funding Source:

National Institutes of Health.

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Using Behavioral Economics to Design Physician Incentives That Deliver High-Value Care

Behavioral economics provides insights about the development of effective incentives for physicians to deliver high-value care. It suggests that the structure and delivery of incentives can shape behavior, as can thoughtful design of the decision-making environment. This article discusses several principles of behavioral economics, including inertia, loss aversion, choice overload, and relative social ranking. Whereas these principles have been applied to motivate personal health decisions, retirement planning, and savings behavior, they have been largely ignored in the design of physician incentive programs. Applying these principles to physician incentives can improve their effectiveness through better alignment with performance goals. Anecdotal examples of successful incentive programs that apply behavioral economics principles are provided, even as the authors recognize that its application to the design of physician incentives is largely untested, and many outstanding questions exist. Application and rigorous evaluation of infrastructure changes and incentives are needed to design payment systems that incentivize high-quality, cost-conscious care.

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Evaluating Hepatitis B Virus Reactivation During Solid Tumor Chemotherapy: Evidence to Guide Pretreatment Hepatitis B Screening and Prophylaxis

In this issue, Paul and colleagues' meta-analysis examined the risk for HBV reactivation with and without antiviral prophylaxis and its effectiveness in adults with solid tumors and chronic or resolved HBV infection. The editorialists discuss the findings and their implications for pretreatment HBV screening and prophylaxis.

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Ambient Mass Spectrometry Imaging with Picosecond Infrared Laser Ablation Electrospray Ionization (PIR-LAESI)

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b02756

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In Vitro Generation of Murine Plasmacytoid Dendritic Cells from Common Lymphoid Progenitors using the AC-6 Feeder System

In this study we present an in vitro culture system that can efficiently generate pDCs by co-culturing common lymphoid progenitors with AC-6 feeder cells in the presence of Flt3 ligand.

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A Label-free Technique for the Spatio-temporal Imaging of Single Cell Secretions

Inter-cellular communication is critical for controlling various physiological activities within and outside the cell. This paper describes a protocol for measuring the spatio-temporal nature of single cell secretions. To achieve this, a multidisciplinary approach is used which integrates label-free nanoplasmonic sensing with live cell imaging.

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A Microfluidic Platform for Precision Small-volume Sample Processing and Its Use to Size Separate Biological Particles with an Acoustic Microdevice

This protocol describes a system architecture for performing automated small volume (0.15–1.5 ml) particle separations using a microfluidic device, and discusses methods to optimize acoustofluidic device performance and operation.

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Variable uptake feature of focal nodular hyperplasia in Tc-99m phytate hepatic scintigraphy/single-photon emission computed tomography—A parametric analysis

Publication date: Available online 23 November 2015
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Yu-Ling Hsu, Yu-Wen Chen, Chia-Yang Lin, Yun-Chang Lai, Shinn-Cherng Chen, Zu-Yau Lin
Tc-99m phytate hepatic scintigraphy remains the standard method for evaluating the functional features of Kupffer cells. In this study, we demonstrate the variable uptake feature of focal nodular hyperplasia (FNH) in Tc-99m phytate scintigraphy. We reviewed all patients who underwent Tc-99m phytate hepatic scintigraphy between 2008 and 2012 in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Cases with FNH were diagnosed on the basis of pathology or at least one or more prior imaging with a periodic clinical follow-up. All patients received a standard protocol of dynamic flow study and planar and Tc-99m phytate single-photon emission computed tomography (E. CAM; Siemens). The correlation of variable nodular radioactivity with parameters such as tumor size and localization was analyzed. In total, 15 lesions of 14 patients in the clinic were diagnosed as FNH. The tumor size was approximately 2.9–7.4 cm (mean size 4.6 cm). Four lesions were larger than 5 cm. The major anatomic distribution was in the right hepatic lobe (10 lesions), particularly in the superior segments (7 lesions). Tc-99m phytate single-photon emission computed tomography imaging for determining the functional features of Kupffer cells included cool/cold (8 lesions), isoradioactive/warm (6 lesions), and hot (1 lesion) patterns of uptake. We did not observe any statistically significant correlation between variable nodular radioactivity and tumor size (p=0.68) or localization (p=0.04). Herein, we demonstrate the variable uptake feature of FNH in Tc-99m phytate scintigraphy. In small FNH tumors (< 5 cm), increased or equal uptake still provided specificity for the differential diagnosis of hepatic solid tumors.



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The importance of superficial basal cell carcinoma in a retrospective study of 139 patients who underwent Mohs micrographic surgery in a Brazilian university hospital

OBJECTIVE: Mohs micrographic surgery is a specialized surgical procedure used to treat skin cancer. The purpose of this study was to better understand the profile of the patients who underwent the procedure and to determine how histology might be related to complications and the number of stages required for complete removal. METHODS: The records of patients who underwent Mohs micrographic surgery from October 2008 to November 2013 at the Dermatology Division of the Hospital of the Campinas University were assessed. The variables included were gender, age, anatomical location, histology, number of stages required and complications. RESULTS: Contingency tables were used to compare the number of stages with the histological diagnosis. The analysis showed that patients with superficial basal cell carcinoma were 9.03 times more likely to require more than one stage. A comparison between complications and histological diagnosis showed that patients with superficial basal cell carcinoma were 6.5 times more likely to experience complications. CONCLUSION: Although superficial basal cell carcinoma is typically thought to represent a less-aggressive variant of these tumors, its propensity for demonstrating "skip areas" and clinically indistinct borders make it a challenge to treat. Its particular nature may result in the higher number of surgery stages required, which may, as a consequence, result in more complications, including recurrence. Recurrence likely occurs due to the inadequate excision of the tumors despite their clear margins. Further research on this subtype of basal cell carcinoma is needed to optimize treatments and decrease morbidity.

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Myocardial blood flow assessment with 82rubidium-PET imaging in patients with left bundle branch block

OBJECTIVES: Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease. OBJECTIVE: We sought to investigate rubidium-82 (82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block. METHODS: Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress 82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII). RESULTS: Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001). CONCLUSION: The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by 82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.

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Can mastalgia be another somatic symptom in fibromyalgia syndrome?

OBJECTIVE: The purposes of this study were to determine the coexistence of mastalgia and fibromyalgia, to investigate the effects of this combination on pain patterns, and to discuss the status of breast pain in the diagnostic algorithm of fibromyalgia syndrome. METHODS: Sixty-one female patients reporting breast pain during the last three months and 53 female patients diagnosed with fibromyalgia syndrome were enrolled in this study. The Breast Pain Questionnaire was administered to all participants in the mastalgia group and to those in the fibromyalgia syndrome group who had experienced mastalgia during the past three months. The patients in the fibromyalgia syndrome group were evaluated using the 2010 preliminary American College of Rheumatology classification criteria. All of the patients in the mastalgia group were evaluated for the diagnosis of fibromyalgia syndrome by a single physiatrist. The coexistence and pain patterns of mastalgia and fibromyalgia were assessed statistically. RESULTS: Approximately half of the patients with fibromyalgia syndrome (47.2%) reported having mastalgia at the time of admission and 37.7% of the patients with mastalgia met the diagnostic criteria for fibromyalgia syndrome. The patients with mastalgia in the fibromyalgia syndrome group had significantly higher total breast pain scores compared with the women in the mastalgia group. In addition, the patients with fibromyalgia syndrome in the mastalgia group had significantly higher Widespread Pain Index and Symptom Severity Scale scores than the patients with fibromyalgia syndrome. CONCLUSIONS: We suggest that mastalgia can be an aspect of the central sensitivity syndrome and can be added to the somatic symptoms of fibromyalgia.

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Serum from patients with ankylosing spondylitis can increase PPARD, fra-1, MMP7, OPG and RANKL expression in MG63 cells

OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all p<0.05). RANKL expression was higher in MG63 cells treated with serum from patients with ankylosing spondylitis or rheumatoid arthritis than in those treated with serum from controls (both p<0.05). The OPG/RANKL ratio was also higher in MG63 cells treated with serum from ankylosing spondylitis patients than in those treated with serum from controls (p<0.05). No associations were found between the expression of the five genes and the patient demographics and clinical assessments (all p>0.05). CONCLUSIONS : Serum from ankylosing spondylitis patients increases PPARD, fra-1, MMP7, OPG and RANKL expression and the OPG/RANKL ratio in MG63 cells; these effects may be due to the stimulatory effect of the serum on the Wnt pathway.

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Baropodometric analyses of patients before and after bariatric surgery

OBJECTIVE: The aim of this study was to evaluate the vertical component of the ground reaction force, plantar pressure, contact area of the feet and double-support time using static and dynamic (gait) baropodometry before and after bariatric surgery. METHODS: Sixteen individuals with a body mass index of between 35 and 55 were evaluated before and after bariatric surgery. Thirteen patients (81.3%) were female and three (18.8%) male and their average age was 46±10 (21-60) years. An FSCAN system (version 3848) was used for baropodometric analyses (1 km/h and 3 km/h). The peak plantar pressure and ground reaction force were measured for the rear foot and forefoot. The double-support time and foot contact area were measured during gait. RESULTS: There were reductions in the ground reaction force in the forefoot and rear foot and in the foot contact area in all evaluations and of the double-support time at 3 km/h, as well as a significant reduction in the body mass index at six months post-surgery. The peak pressure did not vary at 1 km/h and at 3 km/h, reductions in peak pressure were observed in the left and right rear feet and left forefoot. CONCLUSIONS: Weight loss after bariatric surgery resulted in decreases in the ground reaction force and contact area of the foot. Plantar pressure was decreased at 3 km/h, especially in the forefoot. There was an increase in rhythm because of a reduction in the double-support time at 3 km/h.

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The prevalence of adenoviral conjunctivitis at the Clinical Hospital of the State University of Campinas, Brazil

OBJECTIVES: Viral conjunctivitis is a common, highly contagious disease that is often caused by an adenovirus. The aim of this study was to evaluate the prevalence of adenoviral conjunctivitis by analyzing data from a prospective clinical study of 122 consecutively enrolled patients who were treated at the Clinical Hospital of the State University of Campinas (UNICAMP) after a clinical diagnosis of infectious conjunctivitis between November 2011 and June 2012. METHODS: Polymerase chain reaction was used to evaluate all cases of clinically diagnosed infectious conjunctivitis and based on the laboratory findings, the prevalence of adenoviral infections was determined. The incidence of subepithelial corneal infiltrates was also investigated. RESULTS: Of the 122 patients with acute infectious conjunctivitis included, 72 had positive polymerase chain reaction results for adenoviruses and 17 patients developed subepithelial corneal infiltrates (13.93%). CONCLUSIONS: The polymerase chain reaction revealed that the prevalence of adenoviral conjunctivitis was 59% in all patients who presented with a clinical diagnosis of infectious conjunctivitis from November 2011 to June 2012. The prevalence of adenoviral conjunctivitis in the study population was similar to its prevalence in other regions of the world.

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Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats

OBJECTIVES: This study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers. METHODS: Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration. RESULTS: Nigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO. CONCLUSION: The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension.

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A systematic review and meta-analysis of gestational weight gain recommendations and related outcomes in Brazil

Worldwide, different guidelines are used to assess the adequacy of gestational weight gain. This study identified the recommendations for gestational weight gain in Brazilian women. We also determined the proportion of women with adequate weight gain in accordance with these recommendations and the associated perinatal outcomes. A systematic review was performed. A computerized search was conducted utilizing the following databases: PubMed, MEDLINE, Web of Science, Embase, SciELO and Google Scholar. Observational studies of healthy, Brazilian, pregnant women were included. Studies were excluded if they did not provide pregestational weight and gestational weight gain or if they studied women with comorbid conditions. A meta-analysis was performed to evaluate the odds ratio of inadequate (insufficient or excessive) gestational weight gain. Seventeen studies were included in the systematic review and four studies were included in the meta-analysis. The most widely used recommendations were from the Institute of Medicine. Excessive gestational weight gain was associated with fetal macrosomia and high rates of cesarean delivery. Overweight women had a higher risk of excessive gestational weight gain than eutrophic women (OR=2.80, 95%CI=2.22-3.53). There are no standardized recommendations concerning gestational weight gain based on Brazilian population-based data. Many Brazilian women are overweight or obese at the beginning of pregnancy. Overweight pregnant women have a higher risk of excessive gestational weight gain. Excessive gestational weight gain was associated with cesarean delivery and fetal macrosomia.

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Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice

Polycystic ovary syndrome represents 80% of anovulatory infertility cases. Treatment initially includes preconception guidelines, such as lifestyle changes (weight loss), folic acid therapy to prevent the risk of fetal neural tube defects and halting the consumption of tobacco and alcohol. The first-line pharmacological treatment for inducing ovulation consists of a clomiphene citrate treatment for timed intercourse. The second-line pharmacological treatment includes the administration of exogenous gonadotropins or laparoscopic ovarian surgery (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective with cumulative live birth rates of approximately 70%. Ovarian drilling should be performed when laparoscopy is indicated; this procedure is typically effective in approximately 50% of cases. Finally, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is the third-line treatment and is recommended when the previous interventions fail. This option is also the first choice in cases of bilateral tubal occlusion or semen alterations that impair the occurrence of natural pregnancy. Evidence for the routine use of metformin in infertility treatment of anovulatory women with polycystic ovary syndrome is not available. Aromatase inhibitors are promising and longer term studies are necessary to prove their safety.

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Molbank, Vol. 2015, Article M875: (8R,10aS)-Methyl 2,4-diamino-8-(tert-butyl)-6-oxo-6,8,10,10a-tetrahydrooxazolo[3′′,4′′:1′,5′]-pyrrolo[3′,4′:5,6]pyrido[2,3-d]pyrimidine-10a-carboxylate

A fused polyheterocyclic derivative is available by annulation of a tetramate scaffold, and has been shown to have some Gram-negative, but not Gram-positive, antibacterial activity.

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Remote Sensing, Vol. 7, Pages 15702-15728: On the Use of Global Flood Forecasts and Satellite-Derived Inundation Maps for Flood Monitoring in Data-Sparse Regions

Early flood warning and real-time monitoring systems play a key role in flood risk reduction and disaster response decisions. Global-scale flood forecasting and satellite-based flood detection systems are currently operating, however their reliability for decision-making applications needs to be assessed. In this study, we performed comparative evaluations of several operational global flood forecasting and flood detection systems, using 10 major flood events recorded over 2012–2014. Specifically, we evaluated the spatial extent and temporal characteristics of flood detections from the Global Flood Detection System (GFDS) and the Global Flood Awareness System (GloFAS). Furthermore, we compared the GFDS flood maps with those from NASA's two Moderate Resolution Imaging Spectroradiometer (MODIS) sensors. Results reveal that: (1) general agreement was found between the GFDS and MODIS flood detection systems, (2) large differences exist in the spatio-temporal characteristics of the GFDS detections and GloFAS forecasts, and (3) the quantitative validation of global flood disasters in data-sparse regions is highly challenging. Overall, satellite remote sensing provides useful near real-time flood information that can be useful for risk management. We highlight the known limitations of global flood detection and forecasting systems, and propose ways forward to improve the reliability of large-scale flood monitoring tools.

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Energies, Vol. 8, Pages 13265-13283: Feasibility Study of a Solar-Powered Electric Vehicle Charging Station Model

In China, the power sector is currently the largest carbon emitter and the transportation sector is the fastest-growing carbon emitter. This paper proposes a model of solar-powered charging stations for electric vehicles to mitigate problems encountered in China's renewable energy utilization processes and to cope with the increasing power demand by electric vehicles for the near future. This study applies the proposed model to Shenzhen City to verify its technical and economic feasibility. Modeling results showed that the total net present value of a photovoltaic power charging station that meets the daily electricity demand of 4500 kWh is $3,579,236 and that the cost of energy of the combined energy system is $0.098/kWh. In addition, the photovoltaic powered electric vehicle model has pollutant reduction potentials of 99.8%, 99.7% and 100% for carbon dioxide, sulfur dioxide, and nitrogen oxides, respectively, compared with a traditional gasoline-fueled car. Sensitivity analysis results indicated that interest rate has a relatively strong influence on COE (Cost of Energy). An increase in the interest rate from 0% to 6% increases COE from $0.027/kWh to $0.097/kWh. This analysis also suggests that carbon pricing promotes renewable energy only when the price of carbon is above $20/t.

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Materials, Vol. 8, Pages 7926-7937: Compressive Behavior and Microstructural Characteristics of Iron Hollow Sphere Filled Aluminum Matrix Syntactic Foams

Iron hollow sphere filled aluminum matrix syntactic foams (AMSFs) were produced by low pressure, inert gas assisted infiltration. The microstructure of the produced AMSFs was investigated by light and electron microscopy, extended by energy dispersive X-ray spectroscopy and electron back-scattered diffraction. The investigations revealed almost perfect infiltration and a slight gradient in the grain size of the matrix. A very thin interface layer that ensures good bonding between the hollow spheres and the matrix was also observed. Compression tests were performed on cylindrical specimens to explore the characteristic mechanical properties of the AMSFs. Compared to other (conventional) metallic foams, the investigated AMSFs proved to have outstanding mechanical properties (yield strength, plateau strength, etc.) and energy absorbing capability.

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Energies, Vol. 8, Pages 13255-13264: Governing China’s Clean Energy Transition: Policy Reforms, Flexible Implementation and the Need for Empirical Investigation

In the ten years since committing to clean energy transition, China has formulated a large number of policies and programs to achieve some very ambitious targets. This paper argues that the dearth of empirical studies concerning the implementation of these new policies and programs has created a knowledge gap between official policy documents, which are vague and lacking in specifics, and official policy outcomes, which are unreliable. In particular, the merits and limitations of flexible implementation with regard to desirable outcomes need to be debated and clarified. This paper calls for more empirical investigation in four areas as a starting point: (1) the nature and extent of flexibility in the implementation; (2) implementation strategies and their impacts; (3) factors that shape the behavior of local officials responsible for implementation; and (4) the relationship between the central-local relation and policy implementation.

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Materials, Vol. 8, Pages 7913-7925: Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials

Calcium phosphate ceramic materials are extensively used for bone replacement and regeneration in orthopedic, dental, and maxillofacial surgical applications. In order for these biomaterials to work effectively it is imperative that they undergo the process of degradation and resorption in vivo. This allows for the space to be created for the new bone tissue to form and infiltrate within the implanted graft material. Several factors affect the biodegradation and resorption of calcium phosphate materials after implantation. Various cell types are involved in the degradation process by phagocytic mechanisms (monocytes/macrophages, fibroblasts, osteoblasts) or via an acidic mechanism to reduce the micro-environmental pH which results in demineralization of the cement matrix and resorption via osteoclasts. These cells exert their degradation effects directly or indirectly through the cytokine growth factor secretion and their sensitivity and response to these biomolecules. This article discusses the mechanisms of calcium phosphate material degradation in vivo.

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Materials, Vol. 8, Pages 7900-7912: Ultrasound-Assist Extrusion Methods for the Fabrication of Polymer Nanocomposites Based on Polypropylene/Multi-Wall Carbon Nanotubes

Isotactic polypropylenes (iPP) with different melt flow indexes (MFI) were used to fabricate nanocomposites (NCs) with 10 wt % loadings of multi-wall carbon nanotubes (MWCNTs) using ultrasound-assisted extrusion methods to determine their effect on the morphology, melt flow, and electrical properties of the NCs. Three different types of iPPs were used with MFIs of 2.5, 34 and 1200 g/10 min. Four different NC fabrication methods based on melt extrusion were used. In the first method melt extrusion fabrication without ultrasound assistance was used. In the second and third methods, an ultrasound probe attached to a hot chamber located at the exit of the die was used to subject the sample to fixed frequency and variable frequency, respectively. The fourth method is similar to the first method, with the difference being that the carbon nanotubes were treated in a fluidized air-bed with an ultrasound probe before being used in the fabrication of the NCs with no ultrasound assistance during extrusion. The samples were characterized by MFI, Optical microscopy (OM), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), electrical surface resistivity, and electric charge. MFI decreases in all cases with addition of MWCNTs with the largest decrease observed for samples with the highest MFI. The surface resistivity, which ranged from 1013 to 105 Ω/sq, and electric charge, were observed to depend on the ultrasound-assisted fabrication method as well as on the melt flow index of the iPP. A relationship between agglomerate size and area ratio with electric charge was found. Several trends in the overall data were identified and are discussed in terms of MFI and the different fabrication methods.

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Molecules, Vol. 20, Pages 20823-20831: Two New Cyototoxic Cardenolides from the Whole Plants of Adonis multiflora Nishikawa & Koki Ito

A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides—adonioside A (1) and adonioside B (6)—as well as four known cardenolides: tupichinolide (2) oleandrine (3), cryptostigmin II (4), and cymarin (5). Their structures were elucidated on the basis of NMR, MS, and IR spectroscopic analyses. Compounds 1, 2, 5, and 6 showed significant cytotoxicity against six human cancer cell lines (HCT-116, HepG2, HeLa, SK-OV-3, and SK-MEL-5, and SK-BR-3).

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Viruses, Vol. 7, Pages 5962-5986: Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome?

The genomes of RNA viruses are relatively small. To overcome the small-size limitation, RNA viruses assign distinct functions to the processed viral proteins and their precursors. This is exemplified by poliovirus 3CD protein. 3C protein is a protease and RNA-binding protein. 3D protein is an RNA-dependent RNA polymerase (RdRp). 3CD exhibits unique protease and RNA-binding activities relative to 3C and is devoid of RdRp activity. The origin of these differences is unclear, since crystal structure of 3CD revealed "beads-on-a-string" structure with no significant structural differences compared to the fully processed proteins. We performed molecular dynamics (MD) simulations on 3CD to investigate its conformational dynamics. A compact conformation of 3CD was observed that was substantially different from that shown crystallographically. This new conformation explained the unique properties of 3CD relative to the individual proteins. Interestingly, simulations of mutant 3CD showed altered interface. Additionally, accelerated MD simulations uncovered a conformational ensemble of 3CD. When we elucidated the 3CD conformations in solution using small-angle X-ray scattering (SAXS) experiments a range of conformations from extended to compact was revealed, validating the MD simulations. The existence of conformational ensemble of 3CD could be viewed as a way to expand the poliovirus proteome, an observation that may extend to other viruses.

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Molecules, Vol. 20, Pages 20832-20840: Identification of RNA Oligonucleotides Binding to Several Proteins from Potential G-Quadruplex Forming Regions in Transcribed Pre-mRNA

G-quadruplexes (G4s) are noncanonical DNA/RNA structures formed by guanine-rich sequences. Recently, G4s have been found not only in aptamers but also in the genomic DNA and transcribed RNA. In this study, we identified new RNA oligonucleotides working as aptamers by focusing on G4-forming RNAs located within the pre-mRNA. We showed that the G4 in the 5′ UTR and first intron of VEGFA bound to the protein encoded in VEGFA gene, VEGF165, with high affinity. Moreover, G4-forming RNAs located within the PDGFA and the PDGFB introns bound to PDGF-AA and PDGF-BB, respectively, indicating that G4 in the pre-mRNA could be an aptamer. It had been reported that the putative G4-forming RNA sequences are located in some parts of most genes, thus our strategy for aptamer identification could be applicable to other proteins. It has been reported that some G4-forming RNAs in 5′ UTRs are involved in translation control; however, G4-forming excised intronic RNA function has not been revealed previously. Therefore, these findings could not only contribute to the identification of RNA aptamers but also provide new insights into the biological functioning of G4-forming RNAs located within intronic RNA sequences.

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Molecules, Vol. 20, Pages 20805-20822: A 7-Deazaadenosylaziridine Cofactor for Sequence-Specific Labeling of DNA by the DNA Cytosine-C5 Methyltransferase M.HhaI

DNA methyltransferases (MTases) catalyze the transfer of the activated methyl group of the cofactor S-adenosyl-l-methionine (AdoMet or SAM) to the exocyclic amino groups of adenine or cytosine or the C5 ring atom of cytosine within specific DNA sequences. The DNA adenine-N6 MTase from Thermus aquaticus (M.TaqI) is also capable of coupling synthetic N-adenosylaziridine cofactor analogues to its target adenine within the double-stranded 5′-TCGA-3′ sequence. This M.TaqI-mediated coupling reaction was exploited to sequence-specifically deliver fluorophores and biotin to DNA using N-adenosylaziridine derivatives carrying reporter groups at the 8-position of the adenine ring. However, these 8-modified aziridine cofactors were poor substrates for the DNA cytosine-C5 MTase from Haemophilus haemolyticus (M.HhaI). Based on the crystal structure of M.HhaI in complex with a duplex oligodeoxynucleotide and the cofactor product, we synthesized a stable 7-deazaadenosylaziridine derivative with a biotin group attached to the 7-position via a flexible linker. This 7-modified aziridine cofactor can be efficiently used by M.HhaI for the direct, quantitative and sequence-specific delivery of biotin to the second cytosine within 5′-GCGC-3′ sequences in short duplex oligodeoxynucleotides and plasmid DNA. In addition, we demonstrate that biotinylation by M.HhaI depends on the methylation status of the target cytosine and, thus, could provide a method for cytosine-C5 DNA methylation detection in mammalian DNA.

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Viruses, Vol. 7, Pages 5987-6008: Genetic and Phylogenetic Characterization of Tataguine and Witwatersrand Viruses and Other Orthobunyaviruses of the Anopheles A, Capim, Guamá, Koongol, Mapputta, Tete, and Turlock Serogroups

The family Bunyaviridae has more than 530 members that are distributed among five genera or remain to be classified. The genus Orthobunyavirus is the most diverse bunyaviral genus with more than 220 viruses that have been assigned to more than 18 serogroups based on serological cross-reactions and limited molecular-biological characterization. Sequence information for all three orthobunyaviral genome segments is only available for viruses belonging to the Bunyamwera, Bwamba/Pongola, California encephalitis, Gamboa, Group C, Mapputta, Nyando, and Simbu serogroups. Here we present coding-complete sequences for all three genome segments of 15 orthobunyaviruses belonging to the Anopheles A, Capim, Guamá, Kongool, Tete, and Turlock serogroups, and of two unclassified bunyaviruses previously not known to be orthobunyaviruses (Tataguine and Witwatersrand viruses). Using those sequence data, we established the most comprehensive phylogeny of the Orthobunyavirus genus to date, now covering 15 serogroups. Our results emphasize the high genetic diversity of orthobunyaviruses and reveal that the presence of the small nonstructural protein (NSs)-encoding open reading frame is not as common in orthobunyavirus genomes as previously thought.

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