Patient characteristics associated with objective measures of digital health tool use in the United States: A literature review.
The study sought to determine which patient characteristics are associated with the use of patient-facing digital health tools in the United States. We conducted a literature review of studies of patient-facing digital health tools that objectively evaluated use (eg, system/platform data representing frequency of use) by patient characteristics (eg, age, race or ethnicity, income, digital literacy). We included any type of patient-facing digital health tool except patient portals. We reran results using the subset of studies identified as having robust methodology to detect differences in patient characteristics. We included 29 studies; 13 had robust methodology. Most studies examined smartphone apps and text messaging programs for chronic disease management and evaluated only 1-3 patient characteristics, primarily age and gender. Overall, the majority of studies found no association between patient characteristics and use. Among the subset with robust methodology, white race and poor health status appeared to be associated with higher use. Given the substantial investment in digital health tools, it is surprising how little is known about the types of patients who use them. Strategies that engage diverse populations in digital health tool use appear to be needed. Few studies evaluate objective measures of digital health tool use by patient characteristics, and those that do include a narrow range of characteristics. Evidence suggests that resources and need drive use.


Partial Leidenfrost Evaporation-Assisted Ultrasensitive Surface-Enhanced Raman Spectroscopy in a Janus Water Droplet on Hierarchical Plasmonic Micro-/Nanostructures.
The conventional methods of creating superhydrophobic surface-enhanced Raman spectroscopy (SERS) devices are by conformally coating a nanolayer of hydrophobic materials on micro-/nanostructured plasmonic substrates. However, the hydrophobic coating may partially block hot spots and therefore compromise Raman signals of analytes. In this paper, we report a partial Leidenfrost evaporation-assisted approach for ultrasensitive SERS detection of low-concentration analytes in water droplets on hierarchical plasmonic micro-/nanostructures, which are fabricated by integrating nanolaminated metal nanoantennas on carbon nanotube (CNT)-decorated Si micropillar arrays. In comparison with natural evaporation, partial Leidenfrost-assisted evaporation on the hierarchical surfaces can provide a levitating force to maintain the water-based analyte droplet in the Cassie-Wenzel hybrid state, i.e., a Janus droplet. By overcoming the diffusion limit in SERS measurements, the continuous shrinking circumferential rim of the droplet, which is in the Cassie state, toward the pinned central region of the droplet, which is in the Wenzel state, results in a fast concentration of dilute analyte molecules on a significantly reduced footprint within several minutes. Here, we demonstrate that a partial Leidenfrost droplet on the hierarchical plasmonic surfaces can reduce the final deposition footprint of analytes by 3-4 orders of magnitude and enable SERS detection of nanomolar analytes (10-9 M) in an aqueous solution. In particular, this type of hierarchical plasmonic surface has densely packed plasmonic hot spots with SERS enhancement factors (EFs) exceeding 107. Partial Leidenfrost evaporation-assisted SERS sensing on hierarchical plasmonic micro-/nanostructures provides a fast and ultrasensitive biochemical detection strategy without the need for additional surface modifications and chemical treatments.


Pyramidal fractal dimension for high resolution images.
Fractal analysis (FA) should be able to yield reliable and fast results for high-resolution digital images to be applicable in fields that require immediate outcomes. Triggered by an efficient implementation of FA for binary images, we present three new approaches for fractal dimension (D) estimation of images that utilize image pyramids, namely, the pyramid triangular prism, the pyramid gradient, and the pyramid differences method (PTPM, PGM, PDM). We evaluated the performance of the three new and five standard techniques when applied to images with sizes up to 8192 × 8192 pixels. By using artificial fractal images created by three different generator models as ground truth, we determined the scale ranges with minimum deviations between estimation and theory. All pyramidal methods (PM) resulted in reasonable D values for images of all generator models. Especially, for images with sizes ≥1024×1024 pixels, the PMs are superior to the investigated standard approaches in terms of accuracy and computation time. A measure for the possibility to differentiate images with different intrinsic D values did show not only that the PMs are well suited for all investigated image sizes, and preferable to standard methods especially for larger images, but also that results of standard D estimation techniques are strongly influenced by the image size. Fastest results were obtained with the PDM and PGM, followed by the PTPM. In terms of absolute D values best performing standard methods were magnitudes slower than the PMs. Concluding, the new PMs yield high quality results in short computation times and are therefore eligible methods for fast FA of high-resolution images.


Inhibition of dimethyl sulfoxide-stimulated Friend cell erythrodifferentiation by hydrocortisone and other steroids.
Erythrodifferentiation and hemoglobin synthesis in dimethyl sulfoxide-stimulated Friend erythroleukemia cells were inhibited by hydrocortisone (HC) and four other steroids: dexamethasone, deoxycorticosterone, corticosterone, and aldosterone. The effect was specific, because no significant cytotoxicity occurred with any of these compounds at the concentrations that were inhibitory. The mechanism of action of HC was studied in detail. In the absence of dimethyl sulfoxide, it had no effect on hemoglobin levels; but, in the presence of this inducer, the synthesis of heme and globin were each inhibited by approximately 90%. There was no alteration in the synthesis of any major protein other than globin, as determined by gel electrophoresis of cell lysates. The activities of two enzymes in the heme biosynthetic pathway, delta-aminolevulinate dehydratase and uroporphyrinogen-I synthase, were inhibited by 80% and 70%, respectively. Globin mRNA induction was reduced by approximately 90%. This demonstrated that the HC inhibition of globin synthesis occurred at a pretranslational step. The dimethyl sulfoxide-induced single-stranded breaks in DNA, which have been suggested to play a role in Friend leukemia cell differentiation, were reduced in number but not eliminated. HC reduced the dimethyl sulfoxide-stimulation of virus release into the medium by approximately 50%. HC treatment in the absence of dimethyl sulfoxide doubled the production of virus.


Enhanced Visible-Light Photodetection with Undoped and Doped ZnO Thin-Film Self-Powered Photodetectors.
Photodetection plays an essential role in the visible-light zone and is important in modern science and technology owing to its potential applications in various fields. Fabrication of a stable photodetector remains a challenge for researchers. We demonstrated a high-response/recovery and self-powered undoped ZnO (UZO) and Cu-doped ZnO (CZO) thin film-based visible-light photodetector fabricated on a cost-effective Si substrate using reactive cosputtering. The structural, morphological, and optical properties of CZO and UZO thin films have been examined using X-ray diffraction, field emission scanning electron microscopy, X-ray photoelectron spectroscopy, atomic force microscopy, and photoluminescence spectroscopy. The results of the CZO/n-Si photodetector compared with those of the undoped ZnO (UZO)/n-Si photodetector show that the CZO/n-Si exhibits a higher on/off ratio, responsivity, and detectivity than UZO/n-Si. Also, the CZO/n-Si photodetector shows high stability and reproducibility over 20 cycles after 180 days. A relative study of CZO/n-Si- and UZO/n-Si-based photodetectors reveals the enhanced performance of the CZO/n-Si photodetector, which has a high on/off ratio of ∼300 with a high specific detectivity of 2.8 × 1010 Jones for 75 mW visible light. The prepared self-powered CZO/n-Si/Ag thin film-based visible-light photodetector paves the way for the development of high-performance photodetector designs.


Patient Satisfaction After Outpatient Appendectomy.
Outpatient laparoscopic appendectomy has been shown to be safe, with low morbidity and readmission rates, but whether outpatient appendectomy produces poorer patient satisfaction has been questioned. Preoperatively, patients with uncomplicated appendicitis were counselled regarding outpatient management and instructed on postoperative care, follow-up appointments, and contact information. Telephone surveys of patients who underwent an outpatient laparoscopic appendectomy for uncomplicated appendicitis from January through October 2013 were performed. A Likert scale from very dissatisfied (1) to very satisfied (5) was employed. Patients were also queried that if, given the opportunity, they would have chosen to stay in the hospital. Qualified patients included 41 men and 31 women with an average age of 36 years (range 19-79 years). Fifty-four (75%) were reached for satisfaction surveys. Patients were dismissed from the recovery room following a previously published protocol for outpatient management from 6 a.m. to noon (24%), noon to 6 p.m. (17%), 6 p.m. to midnight (22%), and midnight to 6 a.m. (37%). The average satisfaction score for outpatient management was 4.6 (range 2-5). Six patients (11%) stated that they would have preferred hospitalization, if given the opportunity. The reasons included inadequate pain control (2 patients); lack of home assistance (2 patients); nausea and vomiting (1 patient); and prolonged drowsiness (1 patient). Four of these patients violated the outpatient management guidelines (pain controlled on oral analgesics and adequate home assistance). Outpatient laparoscopic appendectomy can be performed with high patient satisfaction, but adherence to protocol guidelines for outpatient management is important to properly select patients for outpatient management and to maximize patient satisfaction.


Safety of Sublingual Immunotherapy: A Secondary Analysis of Post-marketing Adverse Events Reports Using a Japanese Public Database.
Purpose Allergic rhinitis impacts a significant portion of the Japanese population, leading to the rise of sublingual immunotherapy (SLIT) as an alternative treatment. Despite its growing popularity, there is limited safety information. Therefore, this study aimed to consolidate data on its adverse effects in an academic context. Methods We conducted a secondary analysis of adverse events reported in the Pharmaceutical Adverse Events Information Database for three SLIT drugs (Actair®, Cedarcure®, and Miticure®) approved in Japan. A descriptive analysis concerning age, gender, underlying diseases, symptoms, time of onset, and outcomes was performed. Results We identified 98 cases of adverse reactions reported for the SLIT drugs. These cases were mainly from the pediatric to adolescent group (73.7%). Males made up 59.5% of reports. Recovery or improvement was noted in 97.7% of reports. Anaphylactic reactions were the most common adverse event (42.6%), followed by respiratory distress (12.2%). Reactions typically occurred within one week of starting treatment (54.1%). Conclusions Our research illuminated the safety of SLIT drugs in Japan, revealing a favorable profile. It underscores the need for vigilance, particularly among younger patients and during initial doses, emphasizing the importance of proper patient selection and further research to enhance the treatment's efficacy.


Functional interface micromechanics of 11 en-bloc retrieved cemented femoral hip replacements.
Despite the longstanding use of micromotion as a measure of implant stability, direct measurement of the micromechanics of implant/bone interfaces from en bloc human retrievals has not been performed. The purpose of this study was to determine the stem-cement and cement-bone micromechanics of functionally loaded, en-bloc retrieved, cemented femoral hip components. 11 fresh frozen proximal femurs with cemented implants were retrieved at autopsy. Specimens were sectioned transversely into 10-mm slabs and fixed to a loading device where functional torsional loads were applied to the stem. A digital image correlation technique was used to document micromotions at stem-cement and cement-bone interfaces during loading. There was a wide range of responses with stem-cement micromotions ranging from 0.0006 mm to 0.83 mm (mean 0.17 mm, SD 0.29) and cement-bone micromotions ranging from 0.0022 mm to 0.73 mm (mean 0.092 mm, SD 0.22). There was a strong (linear-log) inverse correlation between apposition fraction and micromotion at the stem-cement interface (r(2) = 0.71, p < 0.001). There was a strong inverse log-log correlation between apposition fraction at the cement-bone interface and micromotion (r(2) = 0.85, p < 0.001). Components that were radiographically well-fixed had a relatively narrow range of micromotions at the stem-cement (0.0006-0.057 mm) and cement-bone (0.0022-0.029 mm) interfaces. Minimizing gaps at the stem-cement interface and encouraging bony apposition at the cement-bone interface would be clinically desirable. The cement-bone interface does not act as a bonded interface in actual use, even in radiographically well-fixed components. Rather, the interface is quite compliant, with sliding and opening motions between the cement and bone surfaces.


Renal patients' views on generic prescribing and substitution: example from the United Arab Emirates.
This survey examined current patient awareness and understanding of generic substitution. We surveyed 188 renal patients using 36 multiple-choice questions in 2 hospitals in the United Arab Emirates. We found that 70% of patients were aware of the availability of generic medicines, 60% understood the terms "generic" and "branded" in relation to medicines and 64% were conscious of generic substitution practice. However, 32% did not know if they were taking generics and 31% felt that generics were not equivalent or only sometimes equivalent to branded medicines. Nearly half (47%) the patients stated they would refuse generic substitution of ciclosporin when it became available if this was just to save the health authority money. In our opinion, random generic substitution should not be implemented because there is still uncertainty and lack of knowledge among patients.


Demonstration of extensive brainstem projections to medial and lateral thalamus and hypothalamus in the rat.
We use the method of retrograde transport of colloidal gold with silver intensification to map locations of brainstem neurons projecting to various nuclei of the medial and lateral thalamus (Menetrey, Histochemistry 83, 391-395, 1985; Seeley and Field, Brain Res. 449, 177-191, 1988). In rats injections of less than 1.0 microliters of a gold-wheatgerm agglutinin-horseradish peroxidase complex were restricted to the centrum medianum, centralis lateralis, medialis dorsalis, zona incerta, ventrobasal thalamic complex, or medial or lateral hypothalamus. Injections in the centralis lateralis, with some involvement of centrum medianum and medial medialis dorsalis, labeled numerous neurons throughout the rostrocaudal extent of the midbrain periaqueductal gray, and adjacent reticular formation, dorsal raphe nucleus and substantia nigra. These labeled neurons were distributed bilaterally, but with a preponderance ipsilaterally. Numerous neurons in the deep layers of the ipsilateral superior colliculus and in the anterior pretectal nucleus were also labeled. Many neurons in the pontomedullary raphe nuclei (including nucleus raphe magnus), locus coeruleus and dorsolateral parabrachial nuclei, and in the pontomedullary reticular formation, were labeled bilaterally. Fewer were seen bilaterally in the lateral reticular nucleus and nucleus of the solitary tract, with relatively few in the dorsal aspect of the trigeminal nucleus caudalis. Injections restricted largely to the centrum medianum labeled fewer cells in the brainstem, but with similar distributions. An injection restricted to the centralis lateralis also resulted in a similar distribution of labeled neurons in midbrain and nucleus raphe magnus but did not label neurons at more caudal medullary levels. An injection restricted to zona incerta labeled numerous neurons in a distribution similar to that following medial thalamic injections, except that many more were observed in the contralateral sensory trigeminal nucleus and in the dorsal column nuclei. Injections of the ventrobasal thalamic nucleus labeled many neurons in the trigeminal and dorsal column nuclei, but many fewer neurons in the midbrain, periaqueductal gray and reticular formation compared with medial thalamic injections. Labeled neurons were also seen in the superior and inferior colliculi, due presumably to involvement by the injection of the lateral posterior and magnocellular medial geniculate nuclei, respectively. Injections in the lateral hypothalamus labeled numerous neurons in a distribution similar to that seen following medial thalamic injections.(ABSTRACT TRUNCATED AT 400 WORDS)


Antioxidant and Antidiabetic Properties of Phlorotannins from Ascophyllum nodosum Seaweed Extracts.
Seaweeds have gained considerable attention in recent years due to their potential health benefits and high contents of bioactive compounds. This review focuses on the exploration of seaweed's health-promoting properties, with particular emphasis on phlorotannins, a class of bioactive compounds known for their antioxidant and antidiabetic properties. Various novel and ecofriendly extraction methods, including solid-liquid extraction, ultrasound-assisted extraction, and microwave-assisted extraction are examined for their effectiveness in isolating phlorotannins. The chemical structure and isolation of phlorotannins are discussed, along with methods for their characterization, such as spectrophotometry, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and chromatography. Special attention is given to the antioxidant activity of phlorotannins. The inhibitory capacities of polyphenols, specifically phlorotannins from Ascophyllum nodosum against digestive enzymes, such as α-amylase and α-glucosidase, are explored. The results suggest that polyphenols from Ascophyllum nodosum seaweed hold significant potential as enzyme inhibitors, although the inhibitory activity may vary depending on the extraction conditions and the specific enzyme involved. In conclusion, seaweed exhibits great potential as a functional food ingredient for promoting health and preventing chronic diseases. Overall, this review aims to condense a comprehensive collection of high-yield, low-cost, and ecofriendly extraction methods for obtaining phlorotannins with remarkable antioxidant and antidiabetic capacities.


Computational simulation of the lifetime of the methoxymethyl cation in water. A simple model for a glycosyl cation: when is an intermediate an intermediate?
A two-dimensional free-energy surface is constructed for transfer of the methoxymethyl cation between two water molecules. These atoms are treated quantum mechanically within a box of >1000 classical solvent water molecules, and the molecular dynamics of the whole system is considered at 300 K. This provides a simple model for glycosyl transfer in water. The best surface obtained (MPWB1K/6-31+G(d,p) corrected AM1/TIP3P) contains a shallow free-energy well corresponding to an oxacarbenium ion intermediate in a stepwise mechanism. Molecular dynamics analysis at three temperatures leads to a classical estimate of the lifetime of the methoxymethyl cation in water; when quantum corrections for vibrational zero-point energy are included, the lifetime is estimated to be 1 ps. This result is in complete agreement with the best experimental estimate and suggests that computational simulation is a reliable tool for elucidation of glycosyl-transfer mechanisms in enzymes and whether these involve glycosyl cations as intermediates.


Molecular structure and rheological properties of short-side-chain heavily glycosylated porcine stomach mucin.
The current accepted model for high-molecular-weight gastric mucins of the MUC family is that they adopt a polydisperse coil conformation in bulk solutions. We develop this model using well-characterized highly purified porcine gastric mucin Orthana that is genetically close to the human MUC6 type. It has short side chains and low levels of sialic acid residues and includes minute amounts of cysteine residues that, if abundant, can be responsible for the self-polymerization of mucin. We have established that the mucin structure in bulk solutions corresponds to a daisy-chain random coil. Dynamic light scattering experiments probe the internal dynamics of globular subunits (individual daisies) at the approximately 9 nm length scale, whereas viscosity and light scattering measurements indicate that the size of the whole mucin chains is much larger, approximately 50 nm. The bulk viscosity (eta) scales with mucin concentration (c) in a manner similar to that found for short-side-chain synthetic comb polyelectrolytes and is characterized by a transition between semidilute (eta approximately c1/2) and entangled (eta approximately c3/2) regimes.


Papillary tumour of the pineal region.
Papillary tumour of the pineal region (PTPR) is a relatively new and rare pathological entity, which appears to run a spectrum of clinical courses. We add another case with detailed description of the clinical course documented with serial imaging over the total of 7 years. In accordance with previous reports we recommend total surgical resection with subsequent focal radiotherapy. Clinical and radiological follow up of the entire cerebrospinal axis is mandatory.


An Automatic-Vertical Profile Monitoring System for Fresh-Saline Water Zones in Coastal Aquifer.
Coastal aquifers are complex systems governed by fresh-saline water interactions and ocean tidal effects. The vertical electrical conductivity (EC) and temperature (T) are general indicators for detecting the fresh-saline water interface (FSI) and sea water intrusion in groundwater wells located in coastal aquifers. In this method brief, we developed a cost-effective Arduino-based automatic-vertical profile monitoring system (A-VPMS) to continuously record vertical EC and T in groundwater wells, with the aim of testing its effectiveness in spatiotemporal monitoring of the FSI in a coastal aquifer located in eastern Korea. By analyzing the high-density EC and T data obtained by the A-VPMS, we evaluated the characteristics of the FSI, such as depth and spatial distribution. Our established EC and T data collection method using the A-VPMS proved to be efficient and reliable, providing an excellent tool for fine-scale temporal and spatial understanding of sea water intrusion. The results of this study demonstrate the potential of the A-VPMS for continuous monitoring of the FSI in coastal aquifers, which is crucial for sustainable management of groundwater resources.


Refined experimental design may increase the value of murine models for estimation of bluetongue virus virulence.
Bluetongue is a serious non-contagious vector-borne viral disease in ruminants, causing poor animal welfare and economic consequences globally. Concern has been raised about the development of novel bluetongue virus (BTV) strains and their possibly altered virulence through the process of viral reassortment. Virulence is traditionally estimated in lethal dose 50 (LD50) studies in murine models, but agreement with both in vitro and virulence in ruminants is questionable, and a refined experimental design is needed. Specific reassortants between wild-type and vaccine strains of BTV-1, -6 and -8 have previously been developed by reverse genetics. The aim of the present study was to rank the in vivo virulence of these parental and reassortant BTV strains by calculating LD50 in a murine model by using an experimental design that is new to virology: a between-patient optimised three-level response surface pathway design. The inoculation procedure was intracranial. Fifteen suckling mice were used to establish LD50 for each strain. Three parental and five reassortant virus strains were included. The LD50s varied from of 0.1 (95% confidence interval (CI) 0-0.20) to 3.3 (95% CI 2.96-3.72) tissue culture infectious dose 50/ml. The results support the hypothesis that reassortment in BTV may lead to increased virulence in mice with potential negative consequences for the natural ruminant host. The ranking showed low agreement with in vitro properties and virulence in ruminants according to existing literature. Refined design such as response surface pathway design was found suitable for use in virology, and it introduces significant ethical and scientific improvements.


Inappropriate prescribing in chronic kidney disease: A systematic review of prevalence, associated clinical outcomes and impact of interventions.
Adjusting doses of renally cleared medications and/or avoidance of nephrotoxic medications are standard clinical practices in chronic kidney disease (CKD), albeit the prevalence of inappropriate prescribing (IP) in these patients remains high. Therefore, this work sought to systematically review the prevalence of IP and compare the relative effectiveness of available interventions in reducing IP in CKD. Studies were identified searching PubMed/Medline, EMBASE, Cochrane Library, IPA, Web of Science, Ovid/Medline, CINAHL, and PsychINFO databases. Studies defining CKD based on laboratory markers and quantifying prevalence of IP were included. Forty-nine studies from 23 countries met the inclusion criteria. An IP prevalence of 9.4%-81.1% and 13%-80.50% was reported in hospital and ambulatory settings, respectively; whereas, in long-term care facilities the prevalence ranged between 16% and 37.9%. Unsurprisingly, IP was associated with adverse drug events like increased hospital stay (Mean [SD] of 4.5 [4.8] vs 4.3 [4.5]) and high risk of mortality [40%]. Twenty-one studies reported the impact of interventions on IP; manual and computerised alerts were the main forms of interventions (n=19). The most significant reduction in IP was observed when physicians received immediate concurrent feedback from a clinical pharmacist (P<.001). Polypharmacy, comorbidities, and age were identified as predictors of IP. IP has led to poor patient outcomes. Although pharmacist-based and computer-aided approaches have shown promising results, there is still room for improvement. Future studies should focus on developing a multifaceted intervention to address the widespread prevalence of IP and associated clinical outcomes in CKD patients.


Altered mental status and a not-so-benign rash.
Introduction. The authors are presenting a case of Thrombotic Thrombocytopenic Purpura (TTP) that presented with complaints of altered mental status and found to have petechiae. Case Presentation. An 81-year-old female patient presented to the Emergency Department (ED) of a tertiary care hospital with chief complains of dizziness, slurred speech, and weakness. She was found to have lower extremity petechiae on physical examination. On blood exam, she had thrombocytopenia, and her peripheral blood smear showed schistocytes. Her renal function was also impaired. The CT scan of head was without any abnormality. She was finally diagnosed as having TTP and transferred to ICU but ultimately passed away. Conclusion. TTP is a rare syndrome with preventable mortality if diagnosed early and managed appropriately with plasmapheresis. The Emergency Department physicians should be aware of the presenting symptoms and signs of TTP.


Bedtime dosing of glyburide and the treatment of type II diabetes mellitus.
Suppression of nocturnal hepatic glucose production is key in the treatment of noninsulin-dependent diabetes mellitus (NIDDM). In this article, the authors compare the effectiveness of dosing glyburide at bedtime versus in the morning on glycemic control in patients with NIDDM under suboptimal control. In a placebo-controlled, double-blind crossover trial, 32 patients with NIDDM with suboptimal control on chronic glyburide treatment fulfilling entry criteria were randomized to receive one of two regimens: (1) glyburide at bedtime and placebo in morning or (2) placebo at bedtime and glyburide in the morning. After 6 months of a regimen, patients crossed over to the other treatment and completed an additional 6-month period. After baseline assessment, fasting blood sugar, history, physical exam, and compliance assessments were performed monthly. HbA1c was measured bimonthly and Sustacal tolerance tests were performed at the end of each 6-month treatment period. During the initial 6-month comparison fasting, blood sugar concentration decreased 5% in bedtime ingesters and rose 10% in the morning patients. These changes were not statistically significant. HbA1c decreased significantly in the morning group but remained unchanged in the bedtime group. At the end of 12 months, nighttime dosing resulted in better home glucose monitoring values, fasting blood sugar results, and Sustacal tolerance profiles, but the differences were not statistically significant. No hypoglycemia was observed in the monitored data collected. Bedtime dosing of glyburide resulted in measurable improvement in fasting blood sugar and carbohydrate tolerance curves, but not to a degree justifying general recommendation of this technique in patients with NIDDM with secondary failure to oral agents.


Effects of isotretinoin and acitretin on neuroregeneration in experimental spinal cord injury.
This study aimed to determine whether isotretinoin and acitretin have beneficial effects on neural tissue damage following acute spinal cord injury. Thirty-six rats were randomly divided into 6 groups: control, sham spinal cord injury, spinal cord injury with isotretinoin 15 mg/kg for 14 days, spinal cord injury with isotretinoin 15 mg/kg for 28 days, spinal cord injury with acitretin 10 mg/kg for 14 days, and spinal cord injury with acitretin 10 mg/kg for 28 days. The damage to the spinal cord was formed by the clip compression technique. A neurological evaluation was conducted on days 1, 14, and 28. All rats were sacrificed following the treatment period, and samples of their spinal cords were collected for histopathological analysis. The inclined plane angle was significantly increased on the 14th and 28th days in the isotretinoin 15 mg and acitretin 10 mg groups, compared to the spinal injury group (P=.049 and P=.009, respectively). The Drummond-Moore criterion was significantly higher in the acitretin 10 mg group than in the injury group (P=.026). Cleaved Caspase-3 expression was similar in the isotretinoin 15 mg day 28 group and the control group (P > .05), but significantly decreased in the acitretin 10 mg 14th-day and acitretin 10 mg 28th-day groups compared to spinal injury isotretinoin 15 mg 14th-day and isotretinoin 15 mg 28th-day groups (P < .05). This was the first study elaborating that isotretinoin and acitretin reduced neuronal apoptosis and improved functional recovery after spinal cord injury. These neuroprotective effects might open a window of opportunity for patients.


Insights into the Role of Galectin-3 as a Diagnostic and Prognostic Biomarker of Atrial Fibrillation.
Atrial fibrillation (AF) is an irregular atrial activity and the most prevalent type of arrhythmia. Although AF is easily diagnosed with an electrocardiogram, there is a keen interest in identifying an easy-to-dose biomarker that can predict the prognosis of AF and its recurrence. Galectin-3 (Gal-3) is a beta-galactoside binding protein from the lectin family with pro-fibrotic and -inflammatory effects and a pivotal role in a variety of biological processes, cell proliferation, and differentiation; therefore, it is implicated in the pathogenesis of many cardiovascular (e.g., heart failure (HF)) and noncardiovascular diseases. However, its specificity and sensitivity as a potential marker in AF patients remain debated and controversial. This article comprehensively reviewed the evidence regarding the interplay between Gal-3 and patients with AF. Clinical implications of measuring Gal-3 in AF patients for diagnosis and prognosis are mentioned. Moreover, the role of Gal-3 as a potential biomarker for the management of AF recurrence is investigated. The association of Gal-3 and AF in special populations (coronary artery disease, HF, metabolic syndrome, chronic kidney disease, and diabetes mellitus) has been explored in this review. Overall, although further studies are needed to enlighten the role of Gal-3 in the diagnosis and treatment of AF, our study demonstrated the high potential of this molecule to be used and focused on by researchers and clinicians.


Influencing Factors for Choosing Korean Medicine Treatments after Spinal Surgery or Spinal Surgery Recommendation in Patients with Spinal Pain: A Semi-Structured Interview Study.
This study is a qualitative study based on 1:1 semi-structured interviews designed to explore the treatment selection process and factors that influence the treatment decisions of patients with spinal pain undergoing surgery or Korean medicine treatment. Patients admitted to a Korean hospital for treatment after either undergoing or receiving a recommendation for spinal surgery, aged 19-74 years, able to communicate in Korean, and who provided informed consent were invited to participate in the study. Of the 15 participants selected, 9 underwent spinal surgery, while 6 had spinal surgery recommended but did not choose to have it. Three main themes emerged from the interviews: positive factors for Korean medicine; positive factors for surgery; difficulties in decision-making. Recommendations by and cases of people around them had the greatest influence on patients who chose Korean medicine treatment (their own situation). Patients who chose surgery tended to be influenced by their physicians, whose opinions had the greatest influence on their choice. Treatment decisions are influenced by: recommendation by or cases of personal acquaintances; fear of surgery; trust in physician; physician's competence; experience of pain; lack of information; patient's situation. The factors that influence the choice of Korean medicine treatment and surgery clearly differ. The findings would be useful for clinicians and patients who must decide between various treatments modality recommendations.


Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana.
The recent Ebola Virus Disease (EVD) epidemic that hit some countries in West Africa underscores the need to train front line high-risk health workers on disease prevention skills. Although Ghana did not record (and is yet to) any case, and several health workers have received numerous training schemes, there is no record of any study that assessed preparedness of healthcare workers (HCWS) regarding EVD and any emergency prone disease in Ghana. We therefore conducted a hospital based cross sectional study involving 101 HCWs from two facilities in Kumasi, Ghana to assess the level of preparedness of HCWs to respond to any possible EVD. We administered a face-to-face questionnaire using an adapted WHO (2015) and CDC (2014) Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. A total 92 (91.09%) HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% (n = 26) considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% (n = 9) could correctly identify the right disinfectant (χ2 = 28.52, p = 0.001). Our study demonstrates poor knowledge and ill preparedness and unwillingness of many HCWs to attend to EVD. Beyond knowledge acquisition, there is the need for more training from time to time to fully prepare HCWs to handle any possible EVD case.


Long-range transition state theory.
The implementation of variational transition state theory (VTST) for long-range asymptotic potential forms is considered, with particular emphasis on the energy and total angular momentum resolved (microJ-VTST) implementation. A long-range transition state approximation yields a remarkably simple and universal description of the kinetics of reactions governed by long-range interactions. The resulting (microJ-VTST) implementation is shown to yield capture-rate coefficients that compare favorably with those from trajectory simulations (deviating by less than 10%) for a wide variety of neutral and ionic long-range potential forms. Simple analytic results are derived for many of these cases. A brief comparison with a variety of low-temperature experimental studies illustrates the power of this approach as an analysis tool. The present VTST approach allows for a simple analysis of the applicability conditions for some related theoretical approaches. It also provides an estimate of the temperature or energy at which the "long-range transition state" moves to such short separations that short-range effects, such as chemical bonding, steric repulsion, and electronic state selectivity, must be considered.


Hip and pelvic injuries in the young athlete.
Hip and pelvic injuries are relatively rare in the young athlete. Contusions and musculotendinous sprains are the most common injuries about the hip and pelvis. Apophyseal avulsion fractures and stress fractures are the most frequently encountered skeletal injuries. Each of these entities can be successfully treated with guided physical therapy following conservative management with rest, anti-inflammatory medications, and ice massage until the patient is pain free. Epiphyseal, diaphyseal, or pathologic fractures are rare entities that are secondary to violent trauma. These injuries are severe and often require operative intervention. Femoral neck fractures have a high rate of complications from avascular necrosis, nonunion, or malunion. Pelvic fractures have frequent associated genitourinary, abdominal, neurologic, and musculoskeletal injuries. Pathologic fractures are most commonly secondary to benign lesions, such as unicameral bone cysts, and less likely owing to malignancy. Finally, in children with hip pain during athletic activities, even with antecedent trauma, the sports clinician must screen for slipped capital femoral epiphysis, Perthes' disease, congenital subluxation of the hip, toxic synovitis, systemic neoplasia, or infectious process.


Bioconversion of stilbenes in genetically engineered root and cell cultures of tobacco.
It is currently possible to transfer a biosynthetic pathway from a plant to another organism. This system has been exploited to transfer the metabolic richness of certain plant species to other plants or even to more simple metabolic organisms such as yeast or bacteria for the production of high added value plant compounds. Another application is to bioconvert substrates into scarcer or biologically more interesting compounds, such as piceatannol and pterostilbene. These two resveratrol-derived stilbenes, which have very promising pharmacological activities, are found in plants only in small amounts. By transferring the human cytochrome P450 hydroxylase 1B1 (HsCYP1B1) gene to tobacco hairy roots and cell cultures, we developed a system able to bioconvert exogenous t-resveratrol into piceatannol in quantities near to mg L-1. Similarly, after heterologous expression of resveratrol O-methyltransferase from Vitis vinifera (VvROMT) in tobacco hairy roots, the exogenous t-resveratrol was bioconverted into pterostilbene. We also observed that both bioconversions can take place in tobacco wild type hairy roots (pRiA4, without any transgene), showing that unspecific tobacco P450 hydroxylases and methyltransferases can perform the bioconversion of t-resveratrol to give the target compounds, albeit at a lower rate than transgenic roots.


Diacylglycerol acyl transferase: A pathogenicity related gene in Colletotrichum gloeosporioides.
To gain more insight into the molecular mechanisms of Colletotrichum gloeosporioides pathogenesis, restriction enzyme-mediated integration (REMI) mutagenesis identified the mutants of C. gloeosporioides impaired in pathogenicity. Transformants screened for defects in pathogenicity using detached leaves and fruits. Of the 20 REMI transformants tested, two mutants (H4 and H7) showed reduced pathogenicity on leaves of apple, kiwi, mango, peach, and fruits of guava, apple, and capsicum. One tagged gene from the genome sequence of mutant H4 was recovered by inverse PCR. Sequence analysis of the tagged site in mutant H4 revealed insertion in diacylglycerol acyltransferase gene which encodes diacylglycerol acyltransferase enzyme, catalyzing the steps involved in the biosynthesis of triacylglycerol, an important component of biological membranes and source of energy. Therefore, tagging of diacylglycerol acyltransferase gene in mutant H4 resulted in reduced pathogenicity, indicating possible role of this gene in pathogenicity of C. gloeosporioides.


Oleodaphnoic acid and coriaceol, two new natural products from the stem bark of Wikstroemia coriacea.
Fractionation of the chloroform extract of Wikstroemia coriacea led to the isolation of two new compounds, oleodaphnoic acid (1), a guaiane-type sesquiterpenoid, and coriaceol (2), an 1,5-diphenyl-1-pentanone analogue, together with nine known compounds. The structures of 1 and 2 were elucidated by extensive spectroscopic data analysis. The known compounds were oleodaphnal (3), indicanone (4), (5R,8R,8aR)-3,8-dimethyl-4,5,6,7,8,8a-hexahydro-5-(1-methylethenyl)-2(1H)-azulenone, (5), 1,5 diphenyl-1-pentanone (6), (+)-3-hydroxy-1,5-diphenyl-1-pentanone (7), umbelliferone (8), daphnoretin (9), β-sitostenone (10) and (-)-hinokinin (11).


Variety of subphase emerging sequences, the frustration of three main phases, SmC_{A}^{*}, SmC^{*}, and SmA, and the long-range interlayer interactions.
Prompted by the existence of biaxial subphases 1/4, 2/5, and 3/7 [Phys. Rev. E 96, 012701 (2017)2470-004510.1103/PhysRevE.96.012701], we reconsidered the three-phase frustration and the resulting degeneracy lifting by combining the phase diagram of SmC_{A}^{*}, SmC^{*}, and SmA with the discrete flexoelectric effect. We systematically calculated the phase diagrams and tried to understand the overall picture of the phenomena by means of a simple and intuitively clear way in terms of minimal number of parameters. The treatment naturally explains the highly distorted helical structures of the biaxial subphases as well as the microscopic helical short-pitch of SmC_{α}^{*} which increases or decreases accordingly with rising temperature. The regular subphase emerging sequence is SmC_{A}^{*}(SmC_{α}^{*})-1/4-1/3-2/5-3/7-1/2-SmC^{*}(SmC_{α}^{*}), where the subphases other than 1/3 and 1/2 may or may not emerge. At the same time, we can see a variety of irregular sequences; in particular, any one of the biaxial subphases may singly emerge between SmC_{A}^{*}(SmC_{α}^{*}) and (SmC^{*})SmC_{α}^{*}. Moreover, the experimentally confirmed extraordinary subphase emerging sequence SmC^{*}-1/2-SmC_{α}^{*} appears for particular parameter values. Contrastingly to these affirmative aspects, some calculated results are contradictory to the previously reported experimental results: the change from SmC_{A}^{*} and SmC^{*} to SmC_{α}^{*} is always continuous, the 6-layer 2/3 subphase is not stabilized, and the subphase emerging sequence SmC_{A}^{*}-1/3-SmC^{*} does not appear. The causes of inconsistency and how to resolve them were discussed in comparisons with experimental findings.


Soluplus®/TPGS mixed micelles for co-delivery of docetaxel and piperine for combination cancer therapy.
In this study, mixed micelles of Soluplus® and TPGS were developed for co-administering docetaxel (DTX) and piperine (PIP) for exerting the synergistic effect, which increased the cytotoxicity and improved the anti-cancer activity in HepG2 cell lines compared to free DTX. These in vitro (MTT assay, intracellular uptake of micelles) and in vivo (pharmacokinetic study, immunostaining, TUNEL analysis) studies exhibited the advantages of co-delivery of anticancer drugs with Soluplus®/TPGS by mixed micelles and furthermore established that co-delivery of DTX and PIP via the mixed micelles of Soluplus®/TPGS could be a promising strategy for the treatment of liver cancer.


[Distribution of probon in various organs in acute poisoning].
Toxicological analysis of a Hungarian analgetics - Probon - of new chemical structure was carried out in experiment. A new technique was developed for quantitative analysis of the drug and its main metabolits in biological material. Distribution of Probon in various organs, grade of the metabolization in acute intoxication was also studied.


Mapping epitopes for 20 monoclonal antibodies to CR1.
Complement receptor type one (CR1; CD35) binds and processes C3b and C4b opsonized immune complexes and regulates complement activation. We have characterized the epitopes of 13 previously reported and seven new MoAbs to human CR1. The MoAbs formed seven groups based on their reactivity with a panel of deletion forms of CR1. Seventeen of the MoAbs reacted with CR1 at more than one site, a consequence of its repetitive sequence. All five of the MoAbs recognizing epitopes in the nearly identical repeats 3, 10, and 17, as well as one MoAb which reacted with repeats 8 or 1/2 of 9 and 15 or 1/2 of 16, blocked cofactor activity for C3b. Knowledge of the repeats bearing the epitopes for these MoAbs should facilitate the further characterization of CR1.


Spliceosomal cleavage generates the 3' end of telomerase RNA.
Telomeres cap the ends of chromosomes and provide a means to complete replication. The DNA portion of telomeres is synthesized by the enzyme telomerase using part of an RNA subunit as a template for reverse transcription. How the mature 3' end of telomerase RNA is generated has so far remained elusive. Here we show that in Schizosaccharomyces pombe telomerase RNA transcripts must be processed to generate functional telomerase. Characterization of the maturation pathway uncovered an unexpected role for the spliceosome, which normally catalyses splicing of pre-messenger RNA. The first spliceosomal cleavage reaction generates the mature 3' end of telomerase RNA (TER1, the functional RNA encoded by the ter1(+) gene), releasing the active form of the RNA without exon ligation. Blocking the first step or permitting completion of splicing generates inactive forms of TER1 and causes progressive telomere shortening. We establish that 3' end processing of TER1 is critical for telomerase function and describe a previously unknown mechanism for RNA maturation that uses the ability of the spliceosome to mediate site-specific cleavage.


[Risk of transmission of enterovirus from the surface of toilets].
Experimental studies using dyes and microbial agents as indicators showed that a viral contamination of the various surfaces of the water closets is possible through the droplets formed when one flushes the W.C. pan. An investigation conducted in several public water closets allowed to reveal the presence of enteroviruses in 2.8% to 5.8% of the samples collected from various surfaces of the water closets. The results of the investigations showed that the hinged seats were contaminated the most frequently (6.8% of the samples).


Solitary fibrous tumor of the parapharyngeal space.
Solitary fibrous tumors are benign neoplasms of mesenchymal origin. They usually arise from the visceral or parietal pleura and peritoneum, although they have been found in many areas throughout the body. We report a case of solitary fibrous tumor of the parapharyngeal space. Microscopically, the tumor contained spindle cells with areas of marked hypercellularity without a definitepattern. Consistent with a benign lesion, there were few mitoses and no necrosis. The tumor cells stained strongly positive for CD34 and vimentin. At the 2-year follow-up, the patient was well and free of local and/or distant disease.


Unilateral massive ovarian edema (MOE): a case report.
Massive ovarian edema is an unusual cause of ovarian enlargement in young patients. Venous end lymphatic obstruction producing edema is thought to be the reason for enlargement of the ovaries in most cases. We report the case of a 23-year-old woman with unilateral massive ovarian edema, findings on ultrasound imaging, and a review of the literature. The ultrasound findings have been reported as a solid tumour-like mass or as a solid mass containing a cystic component, which is non-specific and can mimic neoplasia. Thus, the definitive diagnosis requires histological examination. Because conservative treatment with preservation of the ovaries is often possible, ovarian edema is an important condition to consider in a young patient with a complex but non-specific ovarian mass and appropriate preoperative clinical treatment should be started.


Bioaugmentation of chlorothalonil-contaminated soil with hydrolytically or reductively dehalogenating strain and its effect on soil microbial community.
Although bioaugmentation of pollutant-contaminated sites is a great concern, there are few reports on the relationships among indigenous microbial consortia, exogenous inocula, and pollutants in a bioaugmentation process. In this study, bioaugmentation with Pseudochrobactrum sp. BSQ1 and Massilia sp. BLM18, which can hydrolytically and reductively dehalogenate chlorothalonil (TPN), respectively, was studied for its ability to remove TPN from soil; the alteration of the soil microbial community during the bioaugmentation process was investigated. The results showed that TPN (50 mg/kg) was completely removed in both bioaugmentation treatments within 35 days with half-lives of 6.8 and 9.8 days for strains BSQ1 and BLM18 respectively. In high concentration of TPN-treated soils (100 mg/kg), the bioaugmentation with strains BSQ1 and BLM18 respectively reduced 76.7% and 62.0% of TPN within 35 days. The TPN treatment significantly decreased bacterial richness and diversity and improved the growth of bacteria related to the elimination of chlorinated organic pollutants. However, little influence on soil microbial community was observed for each inoculation treatment (without TPN treatment), showing that TPN treatment is the main force for the shift in indigenous consortia. This study provides insights into the effects of halogenated fungicide application and bioaugmentation on indigenous soil microbiomes.


A preconsultation web-based tool to generate an agenda for discussion in diabetes outpatient clinics to improve patient outcomes (DIAT): a feasibility study.
To test the feasibility of running a randomised controlled trial of a preconsultation web-based intervention (Presenting Asking Checking Expressing (PACE-D)) to improve the quality of care and clinical outcomes in patients with diabetes. A feasibility study (with randomisation) conducted at outpatient diabetes clinics at two secondary care hospitals in Devon, UK. People with diabetes (type 1 and type 2) attending secondary care general diabetes outpatient clinics. The PACE-D, a web-based tool adapted for patients with diabetes to use before their consultation to generate an agenda of topics to discuss with their diabetologist. The percentage of eligible patients who were recruited and the percentage of participants for whom routine glycosylated haemoglobin (HbA1c) data (the putative primary outcome) could be extracted from medical notes and who completed secondary outcome assessments via questionnaire at follow-up were reported. In contrast with the planned recruitment of 120 participants, only 71 participants were randomised during the 7-month recruitment period. This comprised 18.7% (95% CI 14.9% to 23.0%) of those who were eligible. Mean (SD) age of the participants was 56.5 (12.4) years and 66.2% had type 1 diabetes. Thirty-eight patients were randomised to the intervention arm and 33 to the control arm. HbA1c data were available for only 73% (95% CI 61% to 83%) of participants at the 6 months follow-up. The questionnaire-based data were collected for 66% (95% CI 54% to 77%) of the participants at 6 months follow-up. Participants reported that the PACE-D tool was easy to use. A randomised controlled trial of the preconsultation web-based intervention as set out in our current protocol is not feasible without significant modification to improve recruitment and follow-up of participants. The study also provides insights into the feasibility and challenges of conducting complex intervention trials in everyday clinical practice. ISRCTN75070242.


Swallowable sensing device for long-term gastrointestinal tract monitoring.
This paper presents a swallowable sensor device that can be ingested orally, later arriving to the stomach, where the device can indwell for a long term and can be egested at any time after it is triggered using wireless communication. This device can inflate a silicone balloon in the gastrointestinal tract using a chemical reaction. The balloon can be deflated later using electrolysis of water at the time of egestion. A motorless chemical-reaction-based egestion method is proposed to minimize the sensor device size. This device can achieve long-term monitoring in the gastrointestinal tract.


Bovine coccidiosis: protective effects of low-level infection and coccidiostat treatments in calves.
Twenty coccidia-free Holstein bull calves were allotted to groups to study effects of treatment with lasalocid and decoquinate on subsequent resistance to coccidiosis (Eimeria spp infections). Calves fed medicated rations of either drug at dosages of 50 mg/kg of feed (approx 1.2 mg/kg of body weight) had significantly fewer oocysts (P less than 0.01) than did nontreated controls regardless of other procedures used. Treated calves premunized with 2,000 oocysts/day for 5 days and later challenge inoculated with 200,000 oocysts did not develop diarrhea, unless the drugs were withdrawn from feed. Animals premunized (2,000 oocysts/day for 5 days) in absence of drug were no more resistant to the challenge inoculation than nonpremunized animals. These results indicated that lasalocid and decoquinate were efficacious coccidiostats and protected calves as long as they were administered. Cessation of drug treatment usually resulted in appearance of oocysts in feces and diarrhea. Premunization alone cannot be expected to prevent coccidiosis when animals are exposed to large numbers of oocysts.


Phase coarsening in multicomponent systems.
A theory for phase coarsening in multicomponent systems is developed in which both the multicomponent thermodynamic effect and kinetic effect from a nonzero volume fraction are considered. In contrast to previous theory, a diffusion screening zone for a coarsening particle due to nonzero volume fraction is introduced. The evolution equation for phase coarsening in multicomponent systems is derived in a rigorous way in the framework of the maximum rate of dissipation with the constraints of mass and energy conservation. Existing previous relations are recovered and generalized. Some findings such as the relationship between the maximum particle size and volume fraction and particle size distribution in multicomponent systems are discovered.


"I beg you…breastfeed the baby, things changed": infant feeding experiences among Ugandan mothers living with HIV in the context of evolving guidelines to prevent postnatal transmission.
For women living with HIV (WLWH) in low- and middle-income countries, World Health Organization (WHO) infant feeding guidelines now recommend exclusive breastfeeding until six months followed by mixed feeding until 24 months, alongside lifelong maternal antiretroviral therapy (ART). These recommendations represent the sixth major revision to WHO infant feeding guidelines since 1992. We explored how WLWH in rural Uganda make infant feeding decisions in light of evolving recommendations. We conducted semi-structured interviews with 20 postpartum Ugandan WLWH accessing ART, who reported pregnancy < 2 years prior to recruitment. Interviews were conducted between February-August 2014 with babies born between March 2012-October 2013, over which time, the regional HIV treatment clinic recommended lifelong ART for all pregnant and breastfeeding women (Option B+). Content analysis was used to identify major themes. Infant feeding experiences was an emergent theme. NVivo 10 software was used to organize analyses. Among 20 women, median age was 33 years [IQR: 28-35], number of livebirths was 3 [IQR: 2-5], years on ART was 2.3 [IQR: 1.5-5.1], and 95% were virally suppressed. Data revealed that women valued opportunities to reduce postnatal transmission. However, women made infant feeding choices that differed from recommendations due to: (1) perception of conflicting recommendations regarding infant feeding; (2) fear of prolonged infant HIV exposure through breastfeeding; and (3) social and structural constraints shaping infant feeding decision-making. WLWH face layered challenges navigating evolving infant feeding recommendations. Further research is needed to examine guidance and decision-making on infant feeding choices to improve postpartum experiences and outcomes. Improved communication about changes to recommendations is needed for WLWH, their partners, community members, and healthcare providers.


Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin.
Apoptosis is a noninflammatory, programmed form of cell death. One mechanism underlying the non-phlogistic nature of the apoptosis program is the swift phagocytosis of the dying cells. How apoptotic cells attract mononuclear phagocytes and not granulocytes, the professional phagocytes that accumulate at sites of inflammation, has not been determined. Here, we show that apoptotic human cell lines of diverse lineages synthesize and secrete lactoferrin, a pleiotropic glycoprotein with known antiinflammatory properties. We further demonstrated that lactoferrin selectively inhibited migration of granulocytes but not mononuclear phagocytes, both in vitro and in vivo. Finally, we were able to attribute this antiinflammatory function of lactoferrin to its effects on granulocyte signaling pathways that regulate cell adhesion and motility. Together, our results identify lactoferrin as an antiinflammatory component of the apoptosis milieu and define what we believe to be a novel antiinflammatory property of lactoferrin: the ability to function as a negative regulator of granulocyte migration.


DNA barcoding and genetic diversity analyses of fishes of Kaladan River of Indo-Myanmar biodiversity hotspot.
Species are considered as a fundamental unit of biodiversity. Therefore, the prerequisite for biodiversity management and conservation is to know the number of species one is dealing with. Consequently, the need of the present study was conceptualized, which dealt with the comprehensive molecular appraisal of Kaladan's Fish fauna. A total of 291 specimens representing 49 species, 28 genera, 11 families, and 4 orders, were collected from 11 sampling stations situated along the main Kaladan River and its four major tributaries, i.e. Tiau, Tuipui, Mat, and Tuichang, flowing in Mizoram state of India (part of Indo-Myanmar biodiversity hotspot) and COI sequences of all the 291 samples were generated. All the analyses conducted in the present study, i.e. K2P genetic divergence, bPTP and Neighbour-Joining suggest that DNA Barcoding is an efficient and reliable tool for species identification and deciding the species boundary. Most of the species of Kaladan showed the clear existence of barcode gap. However, the presence of intra-specific and inter-specific genetic distance overlap in two species revealed the existence of putative sibling species or hidden taxa. This study also revealed the presence of two cryptic species and putative previously unknown species of genus Garra and Schistura. The COI barcode database of Kaladan's fish fauna, established in the present study, may serve as a reference library for accurate identification of fishes and will help ichthyologist, researcher, students, biodiversity managers and policy makers in proper planning with regard to conservation and management of the resources.


Proposal of a health gut microbiome index based on a meta-analysis of Korean and global population datasets.
The disruption of the human gut microbiota has been linked to host health conditions, including various diseases. However, no reliable index for measuring and predicting a healthy microbiome is currently available. Here, the sequencing data of 1,663 Koreans were obtained from three independent studies. Furthermore, we pooled 3,490 samples from public databases and analyzed a total of 5,153 fecal samples. First, we analyzed Korean gut microbiome covariates to determine the influence of lifestyle on variation in the gut microbiota. Next, patterns of microbiota variations across geographical locations and disease statuses were confirmed using a global cohort and di-sease data. Based on comprehensive comparative analysis, we were able to define three enterotypes among Korean cohorts, namely, Prevotella type, Bacteroides type, and outlier type. By a thorough categorization of dysbiosis and the evaluation of microbial characteristics using multiple datasets, we identified a wide spectrum of accuracy levels in classifying health and disease states. Using the observed microbiome patterns, we devised an index named the gut microbiome index (GMI) that could consistently predict health conditions from human gut microbiome data. Compared to ecological metrics, the microbial marker index, and machine learning approaches, GMI distinguished between healthy and non-healthy individuals with a higher accuracy across various datasets. Thus, this study proposes a potential index to measure health status of gut microbiome that is verified from multiethnic data of various diseases, and we expect this model to facilitate further clinical application of gut microbiota data in future.


Antisera of designed specificity for subunits of guanine nucleotide-binding regulatory proteins.
Antisera were raised against purified subunits of regulatory GTP-binding proteins (G proteins) and against synthetic peptides that correspond to defined regions of G proteins. Peptide antisera were generated that recognized all alpha or all beta subunits from Gs, Gi, Go, and transducin; others recognized only Gs alpha or Go alpha. Such cross-reaction or complete specificity for a given alpha subunit was not obtained when purified subunits were injected. Peptide antisera were used to identify G protein subunits in selected tissue membrane preparations by immunoblots.


Modulation of amino acid transport in rat liver slices by tissue preincubation.
In rat liver slices, a prolonged preincubation resulted in a stimulation of AIB and alanine uptake. The increase of transport of both amino acids can be ascribed to a reduction of Ki without an alteration of Vt. The enhancement of transport seems to be restricted to the A mediation as indicated by the findings that only the Na+-dependent, MeAIB-inhibitable portion of AIB transport was increased by the prolonged preincubation, and, furthermore, that the uptake of cysteine, a specific substrate for system ASC in liver cells, was not affected. The effect of an extended preincubation on AIB transport was abolished by the addition of high concentrations of AIB and alanine to the preincubation medium. Several other amino acids tested did not affect the increase of AIB transport. The observed stimulation of transport seems not to be due to the derepression of the synthesis of transport proteins, as cycloheximide and 5-azacytidine did not block the increase of AIB uptake. The enhancement of amino acid transport does not appear to be a result of a release from transinhibition since the uptake of alanine was markedly enhanced after 3 h of preincubation while the alanine concentrations in the incubated liver slices did not change significantly.


Classical kinetical Bose gas.
An autocatalytic reaction combined with spontaneous creation and annihilation processes of particles are studied in a quantum formalism of the master equation in a lattice gas representation with unrestricted occupancy. In case the system is activated by a linear coupling to a heat bath the problem can be solved exactly and the stationary particle density follows the Bose distribution. The relation to spin-flip processes with a restricted occupancy is discussed. Different from those processes the relaxation time and the density fluctuation increase in the high-temperature limit. On a small scale the mutual interaction between the particles is relevant. While in case of a repulsive interaction the stationary solution becomes unstable against short wavelength fluctuations, an attractive interaction leads to an instability for long wavelength fluctuations. The system decays in domains, the size of which can be estimated as a function of temperature and interaction strength. The model is also appropriate to study the growth of open bacterial colonies under the influence of a competitive interaction between the species.


[Application of regional arterial infusion chemotherapy in short-term neoadjuvant chemotherapy for advanced gastric cancer].
To explore the feasibility of short-term neoadjuvant chemotherapy (NACT) in patients with advanced gastric cancer (AGC), and to compare clinical efficacy of short-term neoadjuvant chemotherapy with different ways. Clinical data of 310 AGC patients treated with one course of NACT using EOF regimen(epirubicin, oxaliplatin and fluorouracil plus calcium folinate) in our hospital from January 2008 to December 2011 were retrospectively analyzes. Efficacy was compared between regional arterial infusion chemotherapy and intravenously chemotherapy. All the 310 AGC patients completed one course of NACT and none was interrupted by adverse events. Postoperative pathological remission rate was 33.9% (105/310) and 5 patients (1.6%) had complete pathological remission. The pathologic response rate in the regional arterial infusion chemotherapy group was higher than that in the intravenously chemotherapy group(42.4% vs. 23.6%, P = 0.001). Multivariate analysis revealed that chemotherapy method(HR=1.827, 95% CI:1.006-3.316, P = 0.048) was associated with significantly higher pathologic response. Pathological response rate is quite low following short-term NACT. Regional arterial infusion chemotherapy with short-term NACT can improve the pathological response rate of advanced gastric cancer.


Does male reproductive effort increase with age? Courtship in fiddler crabs.
Theory suggests that reproductive effort generally increases with age, but life-history models indicate that other outcomes are possible. Empirical data are needed to quantify variation in actual age-dependence. Data are readily attainable for females (e.g. clutch per egg size), but not for males (e.g. courtship effort). To quantify male effort one must: (i) experimentally control for potential age-dependent changes in female presence; and, crucially, (ii) distinguish between the likelihood of courtship being initiated, the display rate, and the total time invested in courting before stopping ('courtship persistence'). We provide a simple experimental protocol, suitable for many taxa, to illustrate how to obtain this information. We studied courtship waving by male fiddler crabs, Uca annulipes. Given indeterminate growth, body size is correlated with age. Larger males were more likely to wave at females and waved more persistently. They did not, however, have a higher courtship rate (waves per second). A known female preference for males with higher display rates explains why, once waving is initiated, all males display at the same rate.


Molecular mechanics methods for predicting protein-ligand binding.
Ligand binding affinity prediction is one of the most important applications of computational chemistry. However, accurately ranking compounds with respect to their estimated binding affinities to a biomolecular target remains highly challenging. We provide an overview of recent work using molecular mechanics energy functions to address this challenge. We briefly review methods that use molecular dynamics and Monte Carlo simulations to predict absolute and relative ligand binding free energies, as well as our own work in which we have developed a physics-based scoring method that can be applied to hundreds of thousands of compounds by invoking a number of simplifying approximations. In our previous studies, we have demonstrated that our scoring method is a promising approach for improving the discrimination between ligands that are known to bind and those that are presumed not to, in virtual screening of large compound databases. In new results presented here, we explore several improvements to our computational method including modifying the dielectric constant used for the protein and ligand interiors, and empirically scaling energy terms to compensate for deficiencies in the energy model. Future directions for further improving our physics-based scoring method are also discussed.


Changes in renal haemodynamis and electrolyte excretion after intraventricular infusion of carbachol in conscious sheep.
Infusion of carbachol at 10 nmol x min-1 for 30 min into one lateral cerebral ventricle of conscious sheep caused long-lasting increases in arterial blood pressure, heart rate and haematocrit. The increase in haematocrit resulted from release of red blood cells from the spleen. The systemic cardiovascular changes were accompanied by increased glomerular filtration rate (G.F.R.), renal plasma flow (R.P.F) and renal blood flow (R.B.F) which did not return to pre-carbachol levels within 180 min post-carbachol. Intracerebroventricular (ICV) infusion of carbachol increased the rates of sodium excretion and clearance, potassium excretion and clearance, osmolal clearance and solute-free water reabsorption and increased the concentration of vasopressin in arterial plasma. The increase in sodium excretion rate was caused by increased sodium filtration associated with a fall in the proportion of filtered sodium being reabsorbed. The increase in potassium excretion rate resulted mainly from increased potassium secretion possibly stimulated by increased distal sodium delivery and by increased vasopressin levels. The observed effects of ICV carbachol infusion resembled those previously reported for ICV infision of hyperosmotic sodium solutions.


Diabetes Insipidus.
Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understand the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ) . This is followed by a discussion of regulatory mechanisms underlying CDI and NDI , with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R ) and the water channel molecule, aquaporin 2 (AQP2 ). The clinical manifestation, diagnosis and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.


Comparison of fast-setting calcium phosphate bone cement and fat autograft in a rabbit model of frontal sinus obliteration.
Traditionally, chronic obstruction of the frontal recess is managed by frontal sinus obliteration (FSO). This often requires the harvest of abdominal fat as a filler with all of its associated morbidity. In this study, we investigate the efficacy of calcium phosphate bone cement (Craniofacial Repair System [CRS]) as a material for FSO. Eighteen New Zealand white rabbits were divided into three groups and carried out to two time periods. Six rabbits underwent FSO with fat autograft (control group) and 12 rabbits underwent FSO with CRS (study groups 1 and 2, respectively). At 52 weeks, six control and six study rabbits were killed. The remaining six rabbits were killed at 78 weeks. All specimens underwent radiological evaluation with spiral computed tomography (CT) followed by gross inspection. Histological evaluation was then performed to assess bony growth and to evaluate the interface of the sinus wall with the obliterative material. Sinuses obliterated with CRS showed complete obliteration radiographically. This was apparent at 52 weeks and remained static at 78 weeks. Histological analysis indicated persistent obliteration of the sinus cavity from 52 to 78 weeks and signs of osteoinduction. There were no complications observed as a result of the operative procedure or the materials used. CRS is an alternative to fat autograft for FSO in this noninfected animal model. Further studies are needed to evaluate its long-term efficacy as well as its behavior in chronically infected sinuses.


What Can Domesticated Genes Tell Us about the Intron Gain in Mammals?
Domesticated genes, originating from retroelements or from DNA-transposons, constitute an ideal system for testing the hypothesis on the absence of intron gain in mammals. Since single-copy domesticated genes originated from the intronless multicopy transposable elements, the ancestral intron state for domesticated genes is zero. A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5' UTR and coding regions, while 3' UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Surprisingly, the majority of intron gains have occurred in the ancestor of placental mammals. Domesticated genes could constitute an excellent system on which to analyse the mechanisms of intron gain. This paper summarizes the current understanding of intron gain in mammals.


RhoB: Team Oncogene or Team Tumor Suppressor?
Although Rho GTPases RhoA, RhoB, and RhoC share more than 85% amino acid sequence identity, they play very distinct roles in tumor progression. RhoA and RhoC have been suggested in many studies to contribute positively to tumor development, but the role of RhoB in cancer remains elusive. RhoB contains a unique C-terminal region that undergoes specific post-translational modifications affecting its localization and function. In contrast to RhoA and RhoC, RhoB not only localizes at the plasma membrane, but also on endosomes, multivesicular bodies and has even been identified in the nucleus. These unique features are what contribute to the diversity and potentially opposing functions of RhoB in the tumor microenvironment. Here, we discuss the dualistic role that RhoB plays as both an oncogene and tumor suppressor in the context of cancer development and progression.


The effect of 1,25-vitamin D3 on calbindin-D and calcium-metabolic variables in the rat.
Intraperitoneal injection of 1,25-(OH)2D3 4 micrograms/kg was given to 84 calcium- and vitamin D-repleted Wistar rats and samples of plasma, duodenal mucosa and renal tissue were taken after 0, 3, 6, 12, 24, 48 and 96 hr (n = 12 at each time interval). Plasma-ionized Ca increased after 6 hr, reached a maximum after 24 hr and returned to the initial values after 96 hr. The concentrations of renal calbindin-D28k and intestinal calbindin-D9k did not increase until 48 hr after injection and remained elevated until 96 hr after. Therefore, significantly elevated concentrations of the cytosolic calbindin-D were found at a time with normal values of plasma Ca. The present data suggest that calbindin-D does not alone increase the transcellular Ca transport and, therefore, supports the view that calbindin-Ds may serve as Ca buffer proteins.


Copolymer-based progressive addition lens with graded index designed for astigmatism and distortion correction.
In this research, we propose to reduce astigmatism and distortion in a progressive addition lens (PAL) by employing a polymer-based graded-index (GRIN) material. We adopted the diffusion copolymerization method for the GRIN-PAL fabrication. The GRIN material was prepared by partial diffusion of methyl methacrylate (MMA) and 2,2,2-trifluoroethyl methacrylate (3FMA) monomers into the cross-linked benzyl methacrylate polymer gel. GRIN-PAL was prepared by polymerization of the GRIN material in a mold of commercially available PAL. As a result, methods to control Deltan, the diffusion length, and the order of the GRIN profile in polymeric GRIN materials were demonstrated. In a combination of the PBzMA gel and the MMA/3FMA diffusion monomer, 50/50 in volume provides the highest Deltan. The diffusion period mainly affects the diffusion length. These two parameters consequently determine the order of the GRIN profile and the focusing power that the GRIN provides. The difference in the ease of diffusion caused by the difference in the cross-linking density provides a method for positional control of the GRIN profile. Furthermore, GRIN-PAL using a polymeric material was successfully fabricated. Improvement in astigmatism and distortion was demonstrated using GRIN. Therefore, the GRIN material is suggested to be applicable for the further modification of the PAL with low astigmatism and distortion.


Vaccination with pure Mycobacterium leprae proteins inhibits M. leprae multiplication in mouse footpads.
In this study, we evaluated vaccination with a number of purified, as well as recombinant, Mycobacterium leprae proteins for protective efficacy in mice. BALB/c mice were immunized intradermally with various native somatic (purified) or recombinant M. leprae proteins and their synthetic polypeptides emulsified in Freund's incomplete adjuvant. The protective efficacy of these preparations was assessed by enumeration of bacilli in the footpads of mice challenged with viable M. leprae 1 to 2 months following immunization. Protection was afforded by the purified and recombinant 10-kDa M. leprae cytoplasmic heat shock protein, the recombinant cell wall-associated 65-kDa M. leprae heat shock protein, and to a lesser extent, the purified 28-kDa M. leprae cytoplasmic protein (superoxide dismutase). Vaccination with either the purified or recombinant 35-kDa M. leprae cell membrane protein, the synthetic 27-amino-acid N-terminal peptide of the 10-kDa protein, the recombinant 18-kDa M. leprae protein, or the purified 22-kDa cell membrane protein was ineffective. When the interval between immunization and challenge was increased to 6 months, the purified 10-kDa M. leprae protein and the recombinant 65-kDa M. leprae protein lost vaccine efficacy, while a sodium dodecyl sulfate-soluble protein fraction of the M. leprae cell wall (soluble proteins), as had been found previously, continued to protect, suggesting that multiple M. leprae protein epitopes are critical for solid vaccine protection.


Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data.
The recent rise in the prevalence of immune-mediated diseases has been attributed to environmental factors such as a lack of microbial challenge, or dietary change, that deviate the overall balance between mutually antagonistic subsets of T helper (Th) cells. An alternative proposal is that recent environmental changes have resulted in an immune system that is more likely to produce both Th1 and Th2 responses against benign antigens. The prediction of this hypothesis, that Th1 and Th2-mediated diseases are not mutually exclusive, and may be positively associated, is tested here in a whole population. Data from General Practices participating in the Scottish Continuous Morbidity Recording (CMR) project were used to determine the coincidence of the major Th2-mediated atopic diseases; asthma, eczema and allergic rhinitis, with the Th1-mediated autoimmune conditions; type I diabetes, rheumatoid arthritis and psoriasis. We also identified the prescription rates of inhaled therapy for asthma in patients with Th1-mediated disease. There was a significant increase in the risk of presenting with a Th1-mediated autoimmune condition in patients with a history of allergic disease (standardized prevalence ratio (95% confidence interval) 1.28 (1.18-1.37)). Likewise, the standardized prevalence ratios of presenting with either eczema (1.67 (1.48-1.87)) or allergic rhinitis (1.22 (1.02-1.44)) were significantly increased in subjects with a history of Th1-mediated disease. There was a particularly strong association between current psoriasis and current eczema (standardized prevalence ratio ofpsoriasis in subjects with eczema 2.88, 95% confidence interval (CI) 2.38-3.45). There was also a significant increase in prescriptions for inhaled asthma therapy in patients with Th1 disease. It is concluded that Th1- and Th2-mediated diseases are significantly associated in a large General Practice population. This finding supports the proposal that autoimmune and atopic diseases share risk factors that increase the propensity of the immune system to generate both Th1- and Th2-mediated inappropriate responses to non-pathological antigens.


Bacterial RNA isolation with one hour centrifugation in a table-top ultracentrifuge.
A procedure for the rapid preparation of cesium-chloride purified RNA from E. coli and the cyanobacterium Synechococcus sp. PCC7942 is described. Cells are lysed in modified sucrose, Triton X-100, EDTA, Tris buffer with phenol/chloroform. The cleared lysate is extracted further with phenol/chloroform and RNA is peleted by centrifugation through a 5.7 M CsCl cushion. High quality RNA can be prepared in three hours using this procedure.


Induction and inhibition of in vitro oocyte maturation and production of steroids in fish follicles by forskolin.
The effects of forskolin (FK) on in vitro oocyte maturation and production of steroids were examined in Oryzias latipes. When oocytes within preovulatory follicles were preincubated in the presence of FK for 2-10 hr, they matured normally after additional incubation for 10-20 hr in plain culture medium. Naked (follicle cell-free) oocytes did not mature under these conditions. FK stimulated dose-dependent production of steroids (estradiol-17 beta, E2, and 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, 17 alpha,20 beta-diOHprog) and cAMP in follicle (granulosa) cells. On the other hand, exposure to FK within 2 hr after 17 alpha,20 beta-diOH prog stimulation caused reversible inhibition of gonadotropin (PMS)- or 17 alpha,20 beta-diOH prog-induced maturation of the intrafollicular oocytes in vitro. FK also significantly inhibited the 17 alpha,20 beta-diOHprog-induced maturation of naked oocytes, suggesting the existence of adenylate cyclase in fish oocytes. These data indicate that in Oryzias latipes, FK induces oocyte maturation by stimulating follicular production of maturation-inducing steroid (MIS), probably 17 alpha,20 beta-diOH prog, via an increase in cAMP, and that it may inhibit oocyte maturation by increasing ooplasmic cAMP and some inhibitory interaction between the granulosa cells and the oocyte through intercellular communication.


RD-05, a novel anti-CD154 antibody, efficiently inhibits generation of anti-drug antibody without the risk of thrombus formation in non-human primates.
Antibody formation against therapeutic agents, such as tumor necrosis factor inhibitors and Factor VIII, that leads to treatment failure has become a major challenge in the treatment of rheumatoid arthritis and hemophilia. It is well known that anti-CD154 antibodies have the highest potential to inhibit these types of adverse immune responses. Nevertheless, the formation of thromboemboli is the major hurdle in the clinical application of these anti-CD154 blocking antibodies. For this, we attempted to derive an idea as to how this major complication can be eliminated. Consequently, we developed a novel anti-CD154 chimeric antibody, which was made by genetic modification of a portion of human IgG4 Fc. This antibody has an almost comparable antigen binding affinity to a previously developed 5C8 clone and near completely inhibited CD40-CD154 interaction and T cell-dependent B cell activation in vitro. Even under the condition, where we injected immune complexes comprised of RD-05 and CD154 antigen, the formation of thromboembolism was not seen in human FcγRIIA-transgenic mice, whereas the converse was exactly true in the case of 5C8 antibody. Notably, just two injections of RD-05 antibody was sufficient to inhibit the antibody formation against adalimumab during 3-4 months in cynomolgus macaques, in which adalimumab was repeatedly injected for 12 weeks. Based on these findings, we suggest that this RD-05 antibody can be applied to antibody-mediated autoimmune diseases, including systemic lupus erythematosus and immune thrombocytopenic purpura.


Community gun safety in Central Pennsylvania.
Firearm-related injuries are a public health issue in the United States. In rural Pennsylvania, it is a familiar way of life to have a gun or guns in the home. Safety behaviors along with gun storage in the home, specifically where there are young children (aged 6 years and younger), are a concern for this level I regional resource center in rural Pennsylvania. Head Start families were surveyed regarding gun safety habits before and after safety educational activities. A noteworthy number of families reported changing behaviors regarding better safety habits for storing and use of firearms in the home postsurvey.


Invasive carcinoma of the cervix in young women.
One hundred and seventy-six cases of cancer of the cervix in women age 35 years or less from 1959 to 1980 were compared with 65 cases occurring in the 5-year period from 1982 to 1986. The incidence of the disease in this age group changed little over this time, increasing from 9% to 11%. However, the incidence of adenocarcinoma cell types increased from 10% in the first period to 25% in the more recent cases. A change in management resulted in increased surgical emphasis in treatment; only 24% were treated surgically in the earlier group compared to 80% in the recent group. There has not been an increase in advanced cases or mortality in those young patients in recent years.


Immunomodulatory role of thyroid hormones: effect on humoral immune response to Salmonella typhi O antigen.
Effect of long term administration of thyroid hormones and the removal of thyroid on humoral antibody response to S. typhi O antigen was studied in male albino rats of HM strain. Humoral antibody response to S. typhi O antigen was enhanced in animals pretreated with T3 or T4 at a dose of 10 micrograms daily for 15 days. Administration of thyroid hormones simultaneously along with antigen, resulted in suppression of antibody response. In thyroidectomized animals, the antibody titer to S. typhi O antigen was decreased; this decrease in antibody titer was restored to normal level following hormone supplementation. Thyroidectomy significantly depressed TLC as well. Total leucocyte count and absolute lymphocyte count were increased following hormone treatment. Present findings, thus show the lymphoproliferative response of thyroid hormones and their effect on antibody response suggesting the immunomodulatory role of thyroid hormones.


[Retracted] miR‑127 aggravates myocardial failure by promoting the TGF‑β1/Smad3 signaling.
After the publication of the above article, the authors have found that they are not able to reproduce certain of the results presented in their research. The authors have expressed their concern about the choice of cell line selected for their original experiments, which may account for why their results are no longer reproducible. As a consequence, the authors have requested that this article be retracted from the publication. Both authors on the paper agree to the retraction, and regret the inconvenience that this retraction will cause to the Editor and to the readership of the Journal. [the original article was published in Molecular Medicine Reports 18: 4839‑4846, 2018; DOI: 10.3892/mmr.2018.9514].


Role of injection technique in use of insulin pens: prospective evaluation of a 31-gauge, 8-mm insulin pen needle.
To evaluate the effectiveness, comfort, and ease of use of insulin pen injections with a 31-gauge, 8-mm needle. In 50 study subjects (24 patients with type 1 insulin-dependent diabetes and 26 insulin-using patients with type 2 diabetes), we assessed the delivery of insulin, residual insulin leakage, glycemic control, plunger depression pressure, and perceived pain associated with the B-D 31-gauge, 8-mm pen needles in comparison with the B-D conventional 30-gauge, 8-mm pen needles, while the patient used their own insulin pens (Novo or B-D). The study subjects injected their usual dose of regular and NPH insulin using the 30-gauge, 8-mm needle during the first 3 weeks of the study. This period was followed by two 3-week crossover segments of the study with either needle assigned in random sequence. No statistically significant differences were noted in glycemic control or perceived pain of injection between the two needles. The interaction between the two needles and the two insulin pen brands on glycemic control was not statistically significant. Plunger depression pressure increased with the increase in the gauge of the needle and with increases in size of dose of injected insulin (P<0.01). B-D pen users reported lower plunger pressure ratings in comparison with Novo pen users (P<0.01), regardless of the needle type and dose range. Both the insulin pen type and the needle type individually had statistically significant (P<0.01) effects on the residual insulin leakage from the needle tip after injection; however, their interaction was not statistically significant. Insulin doses greater than 30 units were associated with increased leakage (P<0.01). As needle retention time decreased, residual insulin leakage from the needle tip after injection increased (P<0.01), regardless of the needle used. The 31-gauge insulin pen needles are safe and effective for the delivery of insulin. With both 30-gauge and 31-gauge needles, attention to injection technique is essential to ensure complete delivery of insulin, particularly with administration of large doses.


Biological diversity of yeasts in the gastrointestinal tract of weaned piglets kept under different farm conditions.
The study was conducted to determine yeasts present in the gastrointestinal tract (GIT) of piglets kept under experimental farm (EF) and commercial farm (CF) conditions. Ninety five German Landrace full- and half-sibling piglets were sacrificed at 39 days of age. Sixty eight piglets were weaned at 28th day of life, when they were offered one diet ad libitum. Twenty seven piglets remained unweaned by their dams. None of the piglets received any creep feed before weaning. Digesta samples were collected from 1/3 distal small intestine (SI), caecum and proximal colon. One hundred seventy three colonies of isolated yeasts were characterized by sequence analysis of the PCR-amplified D1/D2 domain of the 26S rRNA gene with following alignment of the recovered sequences to GenBank entries. From the 17 phylotypes found, isolates most closely related to Galactomyces geotrichum, Kazachstania slooffiae and Candida catenulata dominated in the GIT of CF piglets. Kazachstania slooffiae and Candida glabrata dominated in GIT of EF piglets. Sørenson and Morisita-Horn similarity indices between farms were low (0.44 and 0.54 respectively) and the Simpson diversity index was higher for EF (7.58) than for CF (4.34). The study brings new data on yeasts composition in the pig GIT and shows differences in yeasts biodiversity between farms operated at different hygiene conditions.


Synthesis of 2-Oxo-1, 2-Dihydroquinoline Chemotype with Multiple Attachment Points as Novel Screening Compounds for Drug Discovery.
The 2-oxo-1, 2-dihydroquinoline Chemotype is well represented among screening compound collection. However, the chemical space of 2-oxo-1, 2-dihydroquinoline has not been thoroughly investigated. In this work we report the synthesis of a small but novel 2-oxo-1, 2-dihydroquinoline compound array for screening purposes, especially in drug discovery, possessing three convenient point of diversity.


Regulation of tight junction proteins and cell death by peroxisome proliferator-activated receptor γ agonist in brainstem of hypertensive rats.
The decrease in tight junction proteins and their adapter proteins in the hypertensive brain is remarkable. Here, we aimed to investigate tight junction proteins and peroxisome proliferator-activated receptor (PPARγ) activation as well as inflammation factors and cell death proteins in the brainstem of hypertension models, namely spontaneously hypertensive rats (SHR) and borderline hypertensive rats (BHR). At first, SHR and BHR groups were treated with PPARγ agonist, pioglitazone. Then, occludin, claudin-1, claudin-2, claudin-12, ZO-1, and NF-κB p65 gene expression levels; pIKKβ, NF-κB p65, TNF, IL-1β, caspase-3, caspase-9 levels, and PARP-1 cleavage were evaluated. Significantly lower pIKKβ, NF-κB p65, TNF, and IL-1β levels were measured in pioglitazone-treated SHR. Results from this study confirm higher occludin (1.35-fold), claudin-2 (7.45-fold), claudin-12 (1.12-fold), and NF-κB p65 subunit (4.76-fold) expressions in the BHR group when compared to the SHR group. Pioglitazone was found effective in terms of regulating gene expression in SHR. Pioglitazone significantly increased occludin (8.17-fold), claudin-2 (2.41-fold), and claudin-12 (1.85-fold) mRNA levels, which were accompanied by decreased cleaved caspase-3, caspase-9 levels, PARP-1 activation, and proinflammatory factor levels in SHR (p ˂ 0.05). Our work has led us to conclude that alterations in tight junction proteins, particularly occludin, and cell death parameters in the brainstem following PPARγ activation may contribute to neuroprotection in essential hypertension.


Segmental neurofibromatosis and malignancy.
Segmental neurofibromatosis is an uncommon variant of neurofibromatosis type I characterized by neurofibromas and/or café-au-lait macules localized to one sector of the body. Although patients with neurofibromatosis type I have an associated increased risk of certain malignancies, malignancy has only occasionally been reported in patients with segmental neurofibromatosis. The published reports of patients with segmental neurofibromatosis who developed malignancy were reviewed and the characteristics of these patients and their cancers were summarized. Ten individuals (6 women and 4 men) with segmental neurofibromatosis and malignancy have been reported. The malignancies include malignant peripheral nerve sheath tumor (3), malignant melanoma (2), breast cancer (1), colon cancer (1), gastric cancer (1), lung cancer (1), and Hodgkin lymphoma (1). The most common malignancies in patients with segmental neurofibromatosis are derived from neural crest cells: malignant peripheral nerve sheath tumor and malignant melanoma. The incidence of malignancy in patients with segmental neurofibromatosis may approach that of patients with neurofibromatosis type I.


A bacterial cell that synthesizes a protein containing the antigenic determinants of rat prolactin.
Bacterial minicells containing three different recombinant plasmids with rat prolactin cDNA sequences inserted at the Pst I site of pBR322 via the poly(dG):poly(dC) joining technique were examined for the expression of rat prolactin antigenic determinants. The three prolactin coding sequences were in the same orientation as the coding sequence of the ampicillin-resistance gene of pBR322. The presence of each of the three recombinant plasmids induced some prolactin synthesis by the bacteria as measured by immunoprecipitation with anti-prolactin antisera. About 10% of the protein synthesized from one of the plasmids, prl 3, precipitated with the antisera. These prolactin antigenic determinants were part of a larger fused protein.


Impact of wet underwear on thermoregulatory responses and thermal comfort in the cold.
The purpose of this study was to investigate the significance of wet underwear and to compare any influence of fibre-type material and textile construction of underwear on thermoregulatory responses and thermal comfort of humans during rest in the cold. Long-legged/long-sleeved underwear manufactured from 100% polypropylene in a 1-by-1 rib knit structure was tested dry and wet as part of a two-layer clothing system. In addition cotton (1-by-1 rib knit), wool (1-by-1 rib knit), polypropylene (fishnet), and a double-layer material manufactured from 47% wool and 53% polypropylene (interlock knit) was tested wet in the clothing system. In the wet condition 175 g of water was distributed in the underwear prior to the experiment. The test was done on eight men (T(a) = 10 degrees C, RH = 85%, V(a) < 0.1 m/s), and comprised a 60 min resting period. Skin temperature, rectal temperature, and weight loss were recorded during the test. Total changes in body and clothing weight were measured separately. Furthermore, subjective ratings on thermal comfort and sensation were collected. The tests demonstrated the significant cooling effect of wet underwear on thermoregulatory responses and thermal comfort. Further, the tests showed that textile construction of underwear in a two-layer clothing ensemble has an effect on the evaporation rate from clothing during rest in the cold resulting in a significant difference in mean skin temperature. The thickness of the underwear has more of an influence on the thermoregulatory responses and thermal comfort, than the types of fibres tested.