Combined Monte Carlo and finite-difference time-domain modeling for biophotonic analysis: implications on reflectance-based diagnosis of epithelial precancer.
Monte Carlo (MC) modeling of photon transport in tissues is generally performed using simplified functions that only approximate the angular scattering properties of tissue constituents. However, such approximations may not be sufficient for fully characterizing tissue scatterers such as cells. Finite-difference time-domain (FDTD) modeling provides a flexible approach to compute realistic tissue phase functions that describe probability of scattering at different angles. We describe a computational framework that combines MC and FDTD modeling, and allows random sampling of scattering directions from FDTD phase functions. We carry out simulations to assess the influence of incorporating realistic FDTD phase functions on modeling spectroscopic reflectance signals obtained from normal and precancerous epithelial tissues. Simulations employ various fiber optic probe designs to analyze the sensitivity of different probe geometries to FDTD-generated phase functions. Combined MC/FDTD modeling results indicate that the form of the phase function used is an important factor in determining the reflectance profile of tissues, and detected reflectance intensity can change up to approximately 30% when a realistic FDTD phase function is used instead of an approximating function. The results presented need to be taken into account when developing photon propagation models or implementing inverse algorithms to extract optical properties from measurements.


Mechanistic investigation of adult myotube response to exercise and drug treatment in vitro using a multiplexed functional assay system.
The ability to accurately measure skeletal muscle functional performance at the single-cell level would be advantageous for exercise physiology studies and disease modeling applications. To that end, this study characterizes the functional response of individual skeletal muscle myotubes derived from adult rodent tissue to creatine treatment and chronic exercise. The observed improvements to functional performance in response to these treatments appear to correlate with alterations in hypertrophic and mitochondrial biogenesis pathways, supporting previously published in vivo and in vitro data, which highlights the role of these pathways in augmenting skeletal muscle output. The developed system represents a multiplexed functional in vitro assay capable of long-term assessment of contractile cellular outputs in real-time that is compatible with concomitant molecular biology analysis. Adoption of this system in drug toxicity and efficacy studies would improve understanding of compound activity on physical cellular outputs and provide more streamlined and predictive data for future preclinical analyses.


Induction of a transient acidosis in the rumen simulation technique.
Feeding high concentrate diets to cattle results in an enhanced production of short-chain fatty acids by the micro-organisms in the rumen. Excessive fermentation might result in subclinical or clinical rumen acidosis, characterized by low pH, alterations in the microbial community and lactate production. Here, we provide an in vitro model of a severe rumen acidosis. A transient acidosis was induced in the rumen simulation technique by lowering bicarbonate, dihydrogen phosphate and hydrogen phosphate concentrations in the artificial saliva while providing a concentrate-to-forage ratio of 70:30. The experiment consisted of an equilibration period of 7 days, a first control period of 5 days, the acidosis period of 5 days and a second control period of 5 days. During acidosis induction, pH decreased stepwise until it ranged below 5.0 at the last day of acidosis (day 17). This was accompanied by an increase in lactate production reaching 11.3 mm at day 17. The daily production of acetate, propionate and butyrate was reduced at the end of the acidosis period. Gas production (methane and carbon dioxide) and NH3 -N concentration reached a minimum 2 days after terminating the acidosis challenge. While the initial pH was already restored 1 day after acidosis, alterations in the mentioned fermentation parameters lasted longer. However, by the end of the experiment, all parameters had recovered. An acidosis-induced alteration in the microbial community of bacteria and archaea was revealed by single-strand conformation polymorphism. For bacteria, the pre-acidotic community could be re-established within 5 days, however, not for archaea. This study provides an in vitro model for a transient rumen acidosis including biochemical and microbial changes, which might be used for testing feeding strategies or feed additives influencing rumen acidosis.


Synthesis of functionalized indole- and benzo-fused heterocyclic derivatives through anionic benzyne cyclization.
The development of a new method for the regioselective synthesis of functionalized indoles and six-membered benzo-fused N-, O-, and S-heterocycles is reported. The key step involves the generation of a benzyne-tethered vinyl or aryllithium compound that undergoes a subsequent intramolecular anionic cyclization. Reaction of the organolithium intermediates with selected electrophiles allows the preparation of a wide variety of indole, tetrahydrocarbazole, dihydrofenantridine, dibenzopyran, and dibenzothiopyran derivatives. Finally, the application of this strategy to the appropriate starting materials allows the preparation of some tryptamine and serotonin analogues.


Management of Small Bowel Neuroendocrine Tumors.
Small bowel neuroendocrine tumors (NETs) are increasing in incidence and are now the most common primary malignancies of the small intestine. Despite this increase, the vague presentation and slow growth of these tumors lead to long delays in diagnosis, and many patients present with metastases. Patients with metastatic small bowel NETs have a favorable disease prognosis, particularly when contrasted with other GI malignancies, and benefit from aggressive, multimodal therapy. During the past decade, the options for the diagnosis and treatment of small bowel NETs have increased considerably. This review provides a practical framework for the physician who seek to understand the epidemiology, presentation, diagnosis, and management of small bowel NETs.


Aggressive progression of penetrating atheromatous ulcer of the descending thoracic aorta.
The treatment of acute aortic pathologies continues to evolve with enhanced imaging capabilities. This case report highlights the rapid progression of penetrating atherosclerotic ulcer to pseudoaneurysm development and subsequent treatment with thoracic endovascular stent graft.


Assistance is continuously on tap.
The application of a special, permanent antimicrobial coating to taps and mixers is being heralded as a significant step towards reducing healthcare-acquired infection rates. Nicholas Marshall reports.


Differences in responses to X-ray exposure between osteoclast and osteoblast cells.
Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss.


Infectious mononucleosis complicated by haemolytic anaemia due to the Donath Landsteiner antibody and by severe neutropenia.
A young man developed infectious mononucleosis complicated by profound anaemia due to haemolysis. The Donath Landsteiner antibody was found in his serum. He was treated successfully by blood transfusion but subsequently developed severe neutropenia. Both complications have been reported previously but not in the same individual. No underlying immune deficiency could be identified.


Developing a New Generation of Antimicrobial and Bioactive Dental Resins.
Dental caries is prevalent, and secondary caries causes restoration failures. This article reviews recent studies on developing a new generation of bioactive resins with anticaries properties. Extensive effects were made to develop new antimicrobial composites, bonding agents, and other resins containing quaternary ammonium methacrylates to suppress plaque buildup and bacterial acid production. The effects of alkyl chain length and charge density and the antimicrobial mechanisms for chlorhexidine, nano-silver, quaternary ammonium methacrylates, and protein-repellent agents were discussed. Synergistic effects of contact-killing and protein-repellent properties were shown to yield the greatest biofilm-inhibition effects. The combination of antimicrobial, protein-repellent, and calcium phosphate nanoparticle remineralization was suggested to provide maximal anticaries effects. In addition, for use orally, cytotoxicity and biocompatibility were important considerations for the new bioactive materials. Furthermore, rather than kill all bacteria, it would be more desirable to modulate the oral biofilm compositions via bioactive resins to suppress cariogenic/pathogenic species and promote benign species. For widespread clinical use of the new antimicrobial and therapeutic materials, whether they would induce bacterial drug resistance needs to be determined, which requires further study. Nonetheless, the new generation of bioactive anticaries resins with therapeutic and biofilm acid-inhibiting properties has the potential to substantially benefit oral health.


Spectrum of peritoneal mesothelioma in childhood: clinical and histopathologic features, including DNA cytometry.
Different types of peritoneal mesothelioma (PM) occur in children and adults. All these share certain histopathologic features but differ in other aspects, such as age of occurrence, site and sex predominance, etiology, and biologic behavior. The article describes four patients, two with cystic PM (one of whom had multiple recurrences) and two with malignant PM (one of whom had pleural metastases). These cases illustrate the variable behavior of this tumor in childhood and highlight the difficulties encountered in diagnosis and treatment. Three different groups of mesothelioma are recognized: a classic, asbestos-related, malignant mesothelioma of adults, typically occurring in the pleural cavity; a multicystic mesothelioma, predominantly affecting the pelvic peritoneum of young women and associated with a good prognosis; and mesotheliomas in children, which are not associated with asbestos exposure and have an unpredictable biologic behavior requiring individual treatment strategies. In the patients studied, DNA index measured by flow cytometry showed a difference between the cystic (aneuploid) and malignant (diploid) tumors. The proliferative rate (S phase) of the tumor was low in all four cases.


Medial scapular muscle detachment: clinical presentation and surgical treatment.
This study describes the clinical presentation and preliminary outcomes in a cohort of patients treated for detachment of the medial scapular stabilizing muscles. The study included 72 patients who underwent reattachment of the lower trapezius and rhomboid muscles. Patients presented with a history of a high level of medial scapular border pain during activity and inability to perform overhead or forward flexion activities. Clinical examination demonstrated palpable tenderness along the medial scapular border, palpable defect along the medial border muscles, scapular dyskinesis, decreased scapular/rotator cuff strength, and modification of symptoms by manual scapular repositioning. Surgical exploration revealed detachment of the lower trapezius muscle or rhomboid muscles, requiring muscle reattachment to the scapula. Clinical outcomes were measured by the American Shoulder and Elbow Surgeons (ASES) self-report form, with comparisons made between the overall scores and subcomponents obtained at initial evaluation, discharge from active care, and postdischarge follow-up. Time from injury to treatment averaged 52 months, and time from surgery to discharge was 7.4 months. ASES scores significantly improved from initial evaluation (39 ± 16) to discharge (63 ± 21) (P < .001). At medium-term follow-up (n = 23), ASES scores significantly improved from initial evaluation (38 ± 14) to discharge (69 ± 20) (P < .001). Scapular muscle detachment appears to be a clinically identifiable syndrome with a homogeneous set of history and physical findings. Surgical treatment can significantly reduce pain and improve functional outcomes.


Influence of the exon 3-deleted/full-length growth hormone (GH) receptor polymorphism on the response to GH replacement therapy in adults with severe GH deficiency.
There is considerable individual variation in the clinical response to GH replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. The aim of the study was to assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD. A total of 124 adult GHD patients (79 men; median age, 50 yr) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (group 1) and those bearing at least one d3-GHR allele (group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). GH dose was individually titrated to obtain normal serum IGF-I levels. GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. Seventy-two (58%) patients had fl/fl genotype and were classified as group 1, whereas 52 (42%) had at least one d3-GHR allele and were classified as group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.


Volatile anesthetics compete for common binding sites on bovine serum albumin: a 19F-NMR study.
There is controversy as to the molecular nature of volatile anesthetic target sites. One proposal is that volatile anesthetics bind directly to hydrophobic binding sites on certain sensitive target proteins. Consistent with this hypothesis, we have previously shown that a fluorinated volatile anesthetic, isoflurane, binds saturably [Kd (dissociation constant) = 1.4 +/- 0.2 mM, Bmax = 4.2 +/- 0.3 sites] to fatty acid-displaceable domains on serum albumin. In the current study, we used 19F-NMR T2 relaxation to examine whether other volatile anesthetics bind to the same sites on albumin and, if so, whether they vary in their affinity for these sites. We show that three other fluorinated volatile anesthetics bind with varying affinity to fatty acid-displaceable domains on serum albumin: halothane, Kd = 1.3 +/- 0.2 mM; methoxyflurane, Kd = 2.6 +/- 0.3 mM; and sevoflurane, Kd = 4.5 +/- 0.6 mM. These three anesthetics inhibit isoflurane binding in a competitive manner: halothane, K(i) (inhibition constant) = 1.3 +/- 0.2 mM; methoxyflurane, K(i) = 2.5 +/- 0.4 mM; and sevoflurane, K(i) = 5.4 +/- 0.7 mM--similar to each anesthetic's respective Kd of binding to fatty acid displaceable sites. These results illustrate that a variety of volatile anesthetics can compete for binding to specific sites on a protein.


Application of modelling and nanotechnology-based approaches: The emergence of breakthroughs in theranostics of central nervous system disorders.
The limited efficiency of the current treatment options against the central nervous system (CNS) disorders has created increasing demands towards the development of novel theranostic strategies. The enormous research efforts in nanotechnology have led to the production of highly-advanced nanodevices and biomaterials in a variety of geometries and configurations for targeted delivery of genes, drugs, or growth factors across the blood-brain barrier. Meanwhile, the richness or reliability of data, drug delivery methods, therapeutic effects or potential toxicity of nanoparticles, occurrence of the unexpected phenomena due to the polydisperse or polymorphic nature of nanomaterials, and personalized theranostics have remained as challenging issues. In this respect, computational modelling has emerged as a powerful tool for rational design of nanoparticles with optimized characteristics including the selectivity, improved bioactivity, and reduced toxicity that might lead to the effective delivery of therapeutic agents. High-performance simulation techniques by shedding more light on the dynamical behaviour of neural networks and pathomechanisms of CNS disorders may provide imminent breakthroughs in nanomedicine. In the present review, the importance of integration of nanotechnology-based approaches with computational techniques for targeted delivery of theranostics to the CNS has been highlighted.


The Importance of Scar Cosmesis across the Surgical Specialties: Factors, Perceptions, and Predispositions.
Existing disparities in the perception of scars between patients and practitioners can translate into undesirable physical and psychological outcomes. An understanding of the determinants of surgeons' perceptions on the importance of scar cosmesis is a first step toward bridging this gap. In an online survey, surgeons were asked about the extent to which various patient and technical factors affect the importance of scar cosmesis. Additional data were obtained on surgeon characteristics, including their specialty, gender, years of experience, and work sector to investigate potential relationships. A total of 303 responses were obtained from surgeons across six specialties. Based on the survey, the importance of scar cosmesis was rated highest among plastic surgeons and obstetricians and gynecologists, and lowest among orthopedic and vascular surgeons. Compared with surgeons in private practice, publicly employed surgeons' rating of the importance of cosmesis was lower. The patient's request for a cosmetic outcome was the most highly rated factor. Regarding the influence of patient demographics on surgeons' attitudes, scar cosmesis in young and female patients was favored in comparison with older and male patients. Factors that reduced the importance of cosmesis were emergency and late-night surgeries followed by lengthy procedures, large incisions, and busy operative lists. These initial findings highlight a need to investigate means of fostering a more holistic, impartial approach toward scar cosmesis, as well as addressing potential workplace barriers that may prevent surgeons from seeking a more cosmetic result. Greater alignment between the priorities of surgeons and patients may manifest in objective and subjective improvements in patient's scars and well-being.


Molybdenum-cofactor deficiency: an easily missed cause of neonatal convulsions.
Intractable seizures in the neonatal period may be caused by molybdenum-cofactor deficiency, an inborn error which combines the deficiencies of sulphite oxidase and xanthine dehydrogenase. The neurological symptoms of molybdenum cofactor and isolated sulphite oxidase deficiencies are identical. Two new cases are reported, and the literature on neonatal convulsions due to molybdenum-cofactor and sulphite deficiencies is reviewed. Because of the high incidence of neonatal convulsions a search for this deficiency is advocated in each case of unexplained refractory neonatal convulsions. Diagnosis may be missed or delayed on standard metabolic screening for several reasons discussed. By simply using a sulphite strip test in a fresh urine sample an indication for the defect can be obtained. Antenatal diagnosis can be performed by assay of sulphite oxidase activity in a chorionic villus sample.


Activity-dependent expression of parathyroid hormone-related protein (PTHrP) in rat cerebellar granule neurons. Requirement of PTHrP for the activity-dependent survival of granule neurons.
To identify genes whose expression is neuronal activity-dependent, we used an mRNA differential display technique and discovered that parathyroid hormone-related protein (PTHrP) is expressed in an activity-dependent manner in primary cultures of rat cerebellar granule neurons. PTHrP mRNA was expressed as early as 1 h by the addition of KCl to a final concentration of 25 mM to the culture medium. This expression was induced by Ca2+ influx through voltage-dependent L-type Ca2+ channels and regulated at the transcriptional step. PTHrP mRNA was persistently expressed before and after the time of commitment of granule neurons to apoptosis when they are cultured in the presence of 25 mM KCl or both 150 microM N-methyl-D-aspartic acid and 15 mM KCl, both of which promote the survival of these neurons. PTHrP was rapidly secreted into the culture medium in a depolarization-dependent manner. Parathyroid hormone/PTHrP receptor mRNA was also expressed in the primary cultures, and its expression was up-regulated by KCl and/or N-methyl-D-aspartic acid. The addition of anti-PTHrP antiserum to the culture medium resulted in a reduction of the activity-dependent survival of the granule neurons. These results suggest that PTHrP is involved in an autocrine loop and required for the survival of granule neurons.


BRAF Fusion as a Novel Mechanism of Acquired Resistance to Vemurafenib in BRAFV600E Mutant Melanoma.
Purpose: Many patients with BRAFV600E mutant melanoma treated with BRAF inhibitors experience a rapid response, but ultimately develop resistance. Insight into the mechanism of resistance is critical for development of more effective treatment strategies.Experimental Design: Comprehensive genomic profiling of serial biopsies was performed in a patient with a BRAFV600E mutant metastatic melanoma who developed resistance to vemurafenib. An AGAP3-BRAF fusion gene, identified in the vemurafenib-resistant tumor, was expressed in BRAFV600E melanoma cell lines, and its effect on drug sensitivity was evaluated.Results: Clinical resistance to vemurafenib in a melanoma harboring a BRAFV600E mutation was associated with acquisition of an AGAP3-BRAF fusion gene. Expression of the AGAP3-BRAF fusion in BRAFV600E mutant melanoma cells induced vemurafenib resistance; however, these cells remained relatively sensitive to MEK inhibitors. The patient experienced clinical benefit following treatment with the combination of a BRAF and a MEK inhibitor. Rebiopsy of the tumor at a later time point, after BRAF and MEK inhibitors had been discontinued, showed loss of the AGAP3-BRAF fusion gene. Mixing experiments suggest that cells harboring both BRAFV600E and AGAP3-BRAF only have a fitness advantage over parental BRAFV600E cells during active treatment with a BRAF inhibitor.Conclusions: We report acquisition of a BRAF fusion as a novel mechanism of acquired resistance to vemurafenib in a patient with melanoma harboring a BRAFV600E mutation. The acquisition and regression of clones harboring this fusion during the presence and absence of a BRAF inhibitor are consistent with rapidly evolving clonal dynamics in melanoma. Clin Cancer Res; 23(18); 5631-8. ©2017 AACR.


Ameloblastoma of the mandible treated by resection, preservation of the inferior alveolar nerve, and bone grafting.
The results of five cases of ameloblastoma of the mandible treated by resection, preservation of the inferior alveolar nerve, and immediate bone grafting are reported. The incisions in all cases healed by first intention. Lip sensation on the operated side returned to normal in four to six weeks in four cases and slight numbness persisted to the eighth week in one case. All patients were followed postoperatively for 13-15 years. In one case the tumor recurred in the mucous membrane seven years after surgery at the original intraoral site and invaded the underlying bone graft. The indications and contraindications for surgery and details of the procedures, including measures to prevent recurrence, are presented.


The effect of microphone wind noise on the amplitude modulation of wind turbine noise and its mitigation.
Microphone wind noise can corrupt outdoor recordings even when wind shields are used. When monitoring wind turbine noise, microphone wind noise is almost inevitable because measurements cannot be made in still conditions. The effect of microphone wind noise on two amplitude modulation (AM) metrics is quantified in a simulation, showing that even at low wind speeds of 2.5 m/s errors of over 4 dBA can result. As microphone wind noise is intermittent, a wind noise detection algorithm is used to automatically find uncorrupted sections of the recording, and so recover the true AM metrics to within ±2/±0.5 dBA.


Patient perspectives on symptoms, health-related quality of life, and treatment experience associated with relapsed/refractory multiple myeloma.
This study aimed to better understand the patient perspective and treatment experience of relapsed and/or refractory multiple myeloma (RRMM). This qualitative study enrolled adult RRMM patients from 6 US clinics who had ≥ 3 months of life expectancy, ≤ 6 prior lines of therapy, and ≥ 1 treatment regimen with a proteasome inhibitor and immunomodulator, or a CD38 monoclonal antibody or an alkylating agent, and a steroid. In-person semi-structured qualitative interviews were conducted to capture concepts that were relevant and important to patients. Topics included RRMM symptoms and impacts and the mode of administration, frequency, duration, convenience, side effects, and overall experience with RRMM treatment. A total of 22 patients completed interviews. At enrollment, 59.1% of participants were using regimens containing dexamethasone, 36.4% daratumumab, 27.3% carfilzomib, and 18.2% lenalidomide. More participants had experience using intravenous or injectable therapy alone (40.9%) than oral therapy alone (18.2%). Back pain and fatigue were the most frequently reported symptoms (40.9% each); 27.3% reported no symptoms. Most participants reported physical function limitations (86.4%), emotional impacts (77.3%), MM-related activity limitations (72.7%), and sleep disturbances (63.6%). Most participants perceived treatment effectiveness based on physician-explained clinical signs (68.2%) and symptom relief (40.9%). Participants experienced gastrointestinal adverse events (59.1%), fatigue (59.1%), sleep disturbances (31.8%), and allergic reactions (31.8%) with treatment. Key elements of treatment burden included the duration of a typical treatment day (68.2%), treatment interfering with daily activities (54.5%), and infusion duration (50.0%). These results provide treatment experience-related data to further understand RRMM treatment burden and better inform treatment decision-making.


A novel urotensin II receptor antagonist, KR-36676, prevents ABCA1 repression via ERK/IL-1β pathway.
Urotensin II (U-II), the most potent vasoconstrictor peptide known to date, is expressed at a high level in vascular smooth muscle cells (VSMC) and endothelial cells, whereas its receptor, urotensin (UT) receptor, is abundant in monocytes and macrophages of atherosclerotic lesions. U-II is highly present in the coronary arteries of the atherosclerotic patients compared to normal subjects. Recently, U-II was shown to down-regulate ATP binding cassette transporter-A1 (ABCA1) expression, which is responsible for reverse cholesterol transport in macrophages of atherosclerotic lesions. However, the mechanism of this observation was not clearly elucidated. Previous studies also revealed that the proinflammatory cytokine interleukin-1β (IL-1β) repressed ABCA1 expression. To clarify the signaling pathway involved with respect to U-II-induced ABCA1 down-regulation, we investigated whether IL-1ß was involved. Our results provided that U-II repressed ABCA1 through an ERK/ IL-1ß pathway. We further demonstrated that U-II receptor antagonist KR-36676 decreased IL-1ß production and significantly led to a recovery of ABCA1 expression at both mRNA and protein levels. In previous investigations, U-II receptor antagonists have been shown to protect atherosclerosis in cell and animal models. Our results imply that U-II receptor antagonist KR-36676 might be a potent candidate for treating atherosclerosis, and leading to a recovery of ABCA1 expression, affected by the ERK/IL-1ß pathway.


Shining LIGHT on the metabolic role of the cytokine TNFSF14 and the implications on hepatic IL-6 production.
The cytokine Tumor Necrosis Factor Superfamily member 14, TNFSF14 (or LIGHT), is a controversial player in numerous diseases. We investigated the role of endogenously expressed TNFSF14 in diet-induced obesity in vivo. Firstly, we studied the effects of Tnfsf14 ablation on the development of obesity, glucose intolerance, insulin resistance, steatosis, tissue inflammation, and mitochondrial respiration in the liver. Secondly, we examined the role of TNFSF14 expression in hematopoietic cells on obesity and insulin sensitivity. Male Tnfsf14 knockout (KO) and wild type mice were fed chow or high fat diet (HFD) for 12 weeks and were assessed for weight gain, glucose intolerance, insulin resistance, hepatosteatosis, mitochondrial dysfunction, and cytokine expression. Wild-type mice were also reconstituted with bone marrow cells from Tnfsf14 knockout mice and were fed chow or HFD for 12 weeks. These mice were examined for weight gain and insulin resistance. HFD fed mice had elevated circulating levels of serum TNFSF14. Liver and white adipose tissue are potential sources of this elevated TNFSF14. Tnfsf14 deficient mice displayed increased obesity, glucose intolerance, insulin resistance, hepatosteatosis, and mitochondrial dysfunction compared to control mice on a HFD. Hepatic cytokine profiling pointed to a potential novel role of decreased IL-6 in the metabolic disturbances in obesogenic Tnfsf14 knockout mice. Bone marrow cells from Tnfsf14 deficient mice appeared to promote diet-induced obesity, insulin resistance and reduced FGF21 levels in white adipose tissue and liver. Our novel data suggest that Tnfsf14 ablation exacerbates parameters of the metabolic syndrome under high fat feeding conditions and provides evidence to support the development of TNFSF14 agonists as potential therapeutics in diet-induced obesity.


Selenite Reduction by Proteus sp. YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles.
Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). However, the current knowledge of the molecular mechanism of selenite reduction remains limited. In this study, a selenite-resistant bacterium was isolated and identified as Proteus sp. YS02. Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. It is revealed that 197 genes were significantly upregulated, and 276 genes were significantly downregulated under selenite treatment. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs.


Congenital hernia of the abdominal wall: a differential diagnosis of fetal abdominal wall defects.
A 28-year-old woman was referred at 33 weeks of gestation with suspected fetal intestinal atresia. Sonography showed a large extra-abdominal mass on the right of the normal umbilical cord insertion. Following Cesarean section at 36 weeks and immediate surgical treatment, the malformation was not definable either as an omphalocele or as gastroschisis. This reported case involves a previously undocumented malformation of the fetal abdominal wall described as a 'hernia' of the fetal abdominal wall.


Development of a Method To Prioritize Protein-Ligand Pairs on Beads Using Protein Conjugated to a Near-IR Dye.
The development of techniques to screen one-bead-one-compound (OBOC) libraries remains a critical step in identifying small molecules that bind target proteins. While great strides have been made, there remains a need to continue to develop OBOC screening techniques that not only reliably identify hit molecules but also can distinguish poor from excellent binders in a single screen. Similarly, relatively strong binding between a small molecule and protein target is required to be considered a hit from the initial pool of screened molecules. Here, we present the framework for a method to screen OBOC libraries using proteins and antibodies stained with a near-infrared (NIR)-emitting fluorophore. These labeled proteins provide significant signal at very low concentrations because of their fluorescence quantum yield. This work revealed that we can detect proteins and antibodies interacting with a known binding partner at low nanomolar concentrations; binding is specific, and known binders to carbonic anhydrase can be detected and ranked.


Cell killing and kinetic effects of diglycolaldehyde on dividing and nondividing mammalian cells in vitro.
The effects of the anticancer drug diglycolaldehyde (NSC-118994) were studied on Chinese hamster ovary cells growing in vitro. Dividing cells, specifically those in S-phase, were more sensitive to the drug than were nondividing cells, although a large fraction of nondividing cells was also killed by doses up to 800 microgram/ml. Dose-dependent effects on cell progression kinetics were observed in all phases of the cell cycle except in mitosis, during which treated cells progressed at control rates into G1-phase. The inhibition of cell progression from G1- into S-phase (most sensitive phase of the cell cycle) put self-limiting restrictions on the cell killing effects of the drug.


Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis.
Both haplo-identical transplant (haplo) and umbilical cord transplant (UC) are valuable graft options for patients without available matched relative. Previous studies showed inconsistent outcomes comparing Post transplant Cyclophosphamide based haplo (PTCy-haplo) and UC; therefore, we attempt to compare the studies by mean of meta-analysis. We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database and Google scholar that compared transplantation with PTCy-haplo versus UC. We conducted a random-effect meta-analysis of seven studies involving a total of 3434 participants and reported the pooled odd ratios (OR) of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse and overall survival (OS) between PTCy-haplo and UC groups. We found a significantly decreased risk of aGVHD and relapse in the PTCy-haplo group compared to the UC group with a pooled OR of 0.78, 95% Confidence Interval (CI) 0.67-0.92, I2=0%, and 0.74, 95% CI 0.57-0.97, I2=23.9% respectively. We also found a significantly increased rate of cGVHD and OS with a pooled OR of 1.41, 95% CI 1.02-1.95, I2=56.8%, and 1.77, 95% CI 1.1-2.87, I2=82.5%, respectively. Our meta-analysis of clinical trials demonstrated superior outcome from PTCy-haplo group compared to the UC group in terms of decreased rate of aGVHD and relapse as well as the increased rate of OS but inferior in terms of increased cGVHD risk compared to UC transplant.


Detection of the metabolic response to drought stress using hyperspectral reflectance.
Drought is the most important limitation on crop yield. Understanding and detecting drought stress in crops is vital for improving water use efficiency through effective breeding and management. Leaf reflectance spectroscopy offers a rapid, non-destructive alternative to traditional techniques for measuring plant traits involved in a drought response. We measured drought stress in six glasshouse-grown agronomic species using physiological, biochemical, and spectral data. In contrast to physiological traits, leaf metabolite concentrations revealed drought stress before it was visible to the naked eye. We used full-spectrum leaf reflectance data to predict metabolite concentrations using partial least-squares regression, with validation R2 values of 0.49-0.87. We show for the first time that spectroscopy may be used for the quantitative estimation of proline and abscisic acid, demonstrating the first use of hyperspectral data to detect a phytohormone. We used linear discriminant analysis and partial least squares discriminant analysis to differentiate between watered plants and those subjected to drought based on measured traits (accuracy: 71%) and raw spectral data (66%). Finally, we validated our glasshouse-developed models in an independent field trial. We demonstrate that spectroscopy can detect drought stress via underlying biochemical changes, before visual differences occur, representing a powerful advance for measuring limitations on yield.


Diversity of Rickettsiae in Feeding and Questing Ticks Collected From a Malaysian Forest Reserve Area.
High seropositivity to Rickettsia conorii and Rickettsia felis has been reported in Malaysian indigenous community living in settlements adjacent to forest areas. The current study was conducted to determine the type and distribution of rickettsiae in feeding and questing ticks that were collected from a forest reserve area at Kuala Lompat in Pahang, Malaysia. Using PCR assays targeting citrate synthase (gltA), outer membrane protein A (ompA) and B (ompB) genes, rickettsiae were detected from approximately one-third of 98 ticks (mainly Dermacentor and Haemaphysalis spp.) collected from the forest reserve. BLAST analysis reveals the predominance of Rickettsia sp. RF2125 in both feeding and questing ticks and Rickettsia sp. TCM1 in the questing ticks. Sequences exhibiting close genetic relationship with Rickettsia raoultii, Rickettsia tamurae, Rickettsia heilongjiangensis, and Rickettsia asiatica were also detected from the ticks. This study highlights the diversity of rickettsial species and potential tick vectors which may contribute to the high seropositivity observed among the local communities.


Histologic classification and immunophenotyping of canine non-Hodgkin's lymphomas: unexpected high frequency of T cell lymphomas with B cell morphology.
Using three different classification schemes (Rappaport, the Working Formulation, and the Kiel classification), 116 canine malignant lymphomas were classified histologically. The number of lymphomas with a completely follicular growth pattern was low (14.9%). The majority of the lymphomas (50.8%) had a diffuse type of architecture, while 34.3% were diffuse with some nodularity. In the Rappaport scheme, 69.3% of the canine lymphomas were classified as histiocytic lymphomas, but these consisted of a group of tumors with different morphologic and immunologic cell types. The Working Formulation and the Kiel classification could be applied to differentiate the canine lymphomas cytomorphologically. In both the Working Formulation and the Kiel classification, only a minority of lymphomas (16.4 and 12.0%, respectively) were low-grade malignant lymphomas. Large cell or centroblastic lymphomas were the most frequently encountered in the Working Formulation or the Kiel classification, respectively. Immunophenotyping of 95 lymphomas was performed with the aid of a panel of monoclonal and polyclonal antibodies. The majority of the lymphomas were of B cell origin (58.9%) while three were classified as non-B/non-T cell lymphomas. Contrary to the distribution pattern of human non-Hodgkin's lymphoma (NHL) in western countries, there was a high percentage of T cell lymphomas (37.9%) in the canine. However, the phenotype could not be predicted by the morphologic characteristics alone.


Recent Progress on Cellulose-Based Electro-Active Paper, Its Hybrid Nanocomposites and Applications.
We report on the recent progress and development of research into cellulose-based electro-active paper for bending actuators, bioelectronics devices, and electromechanical transducers. The cellulose electro-active paper is characterized in terms of its biodegradability, chirality, ample chemically modifying capacity, light weight, actuation capability, and ability to form hybrid nanocomposites. The mechanical, electrical, and chemical characterizations of the cellulose-based electro-active paper and its hybrid composites such as blends or coatings with synthetic polymers, biopolymers, carbon nanotubes, chitosan, and metal oxides, are explained. In addition, the integration of cellulose electro-active paper is highlighted to form various functional devices including but not limited to bending actuators, flexible speaker, strain sensors, energy harvesting transducers, biosensors, chemical sensors and transistors for electronic applications. The frontiers in cellulose paper devices are reviewed together with the strategies and perspectives of cellulose electro-active paper and cellulose nanocomposite research and applications.


A metabolic daylength measurement system mediates winter photoperiodism in plants.
Plants have served as a preeminent study system for photoperiodism due to their propensity to flower in concordance with the seasons. A nearly singular focus on understanding photoperiodic flowering has prevented the discovery of other photoperiod measuring systems necessary for vegetative health. Here, we use bioinformatics to identify photoperiod-induced genes in Arabidopsis. We show that one, PP2-A13, is expressed exclusively in, and required for, plant fitness in short, winter-like photoperiods. We create a real-time photoperiod reporter, using the PP2-A13 promoter driving luciferase, and show that photoperiodic regulation is independent of the canonical CO/FT mechanism for photoperiodic flowering. We then reveal that photosynthesis combines with circadian-clock-controlled starch production to regulate cellular sucrose levels to control photoperiodic expression of PP2-A13. This work demonstrates the existence of a photoperiod measuring system housed in the metabolic network of plants that functions to control seasonal cellular health.


Correlations of noncarious cervical lesions and occlusal factors determined by using pressure-detecting sheet.
The purpose of this clinical study was to examine the relationships of v-shaped noncarious cervical lesion (NCCL) formation with occlusal factors. A total of 159 male self-defense force officials with a mean age of 36.2 years participated in this study. All present teeth were examined for the presence and type of NCCL using the Tooth Wear Index (TWI). The subjects were then interviewed about bruxing and toothbrushing habit. Finally, occlusal force, occlusal contact area and average pressure were measured using a pressure-detecting sheet. Subject-level logistic regression was carried out to assess the associations of factors with presence of v-shaped NCCL teeth. Subjects without v-shaped NCCL were designated as control subjects. Totally, 4518 teeth were examined. Seventy-eight subjects (49.1%) had one or more teeth with typical v-shaped NCCL (259 teeth). The number of teeth with v-shaped NCCL of grade 2 (defect less than 1mm in depth) was 195 (4.3%), and the number of teeth with v-shaped NCCL of grade 3 (defect 1-2mm in depth) was 54 (1.2%). The prevalence of teeth with v-shaped NCCL was significantly higher in the maxilla than in the mandible. Most of the NCCL teeth were premolars. There was no significant difference between teeth with NCCL on the right side and those on the left side. Subject-level logistic regression analysis revealed that age (OR=1.11), toothbrushing pressure (400g, OR=2.43) and occlusal contact area (>23.0mm(2), OR=4.15) were associated with the presence of NCCL teeth. It is concluded that aging, toothbrushing pressure and occlusal contact area are associated with the presence of NCCLs.


Helminth infection alters IgE responses to allergens structurally related to parasite proteins.
Immunological cross-reactivity between environmental allergens and helminth proteins has been demonstrated, although the clinically related implications of this cross-reactivity have not been addressed. To investigate the impact of molecular similarity among allergens and cross-reactive homologous helminth proteins in IgE-based serologic assessment of allergic disorders in a helminth-infected population, we performed ImmunoCAP tests in filarial-infected and noninfected individuals for IgE measurements to allergen extracts that contained proteins with high levels of homology with helminth proteins as well as IgE against representative recombinant allergens with and without helminth homologs. The impact of helminth infection on the levels and function of the IgE to these specific homologous and nonhomologous allergens was corroborated in an animal model. We found that having a tissue-invasive filarial infection increased the serological prevalence of ImmunoCAP-identified IgE directed against house dust mite and cockroach, but not against timothy grass, the latter with few allergens with homologs in helminth infection. IgE ELISA confirmed that filaria-infected individuals had higher IgE prevalences to those recombinant allergens that had homologs in helminths. Mice infected with the helminth Heligmosomoides polygyrus displayed increased levels of IgE and positive skin tests to allergens with homologs in the parasite. These results show that cross-reactivity among allergens and helminth proteins can have practical implications, altering serologic approaches to allergen testing and bringing a new perspective to the "hygiene hypothesis."


Evaluation of accuracy and precision of adenovirus absorptivity at 260 nm under conditions of complete DNA disruption.
A simple, accurate, and precise method to determine adenovirus particle concentration using 260-nm absorbance was developed as an enhancement to the method of Maizel et al. (1968, Virology 36, 115-125). This modified method ensures complete disruption of virus particles and viral DNA prior to absorbance measurements, therefore eliminating absorbance measurement errors due to hyperchromic shift and thus providing an extinction coefficient at 260 nm that is directly related to protein concentration as measured by the method of Lowry et al. (1951, J. Biol. Chem. 193, 265-275). Application of this modified method will reduce interlaboratory variability in determining adenovirus particle concentrations, as current practices reflected in the literature utilize varying sample preparation procedures and calculation methods which cause underestimation of adenovirus concentration by almost twofold. The sample pretreatment conditions used in this modified method entail incubation in 1% sodium dodecyl sulfate at 100 degrees C for 4 min and result in an adenovirus 260-nm absorptivity of 1.8 x 10(12) viral particles per milliliter per absorbance unit in a 1-cm-pathlength cell.


Enhancing ambient noise correlation processing using vector sensors.
Ambient noise cross-correlations between separated sensors can yield estimates of the Green's function between them. Vector sensors (which record both pressure and acoustic velocity vector components) can leverage their directionality to reject ambient noise sources that do not contribute to the emergence of the Green's function, thus improving performance over standard omnidirectional hydrophones. To quantify this performance gain, a time-domain analytical expression for the correlation between each component of a vector sensor in the presence of an isotropic ambient noise field is derived. Improvement of the velocity channel correlations relative to pressure channel correlations is examined for varying bandwidth, sensor separation distance, and additive channel noise levels. Last, the experimentally measured reduction in variance for the velocity channels correlations vs pressure correlations, using drifting vector sensors deployed in the Long Island Sound, were found to be comparable to the theoretical prediction. Overall, both theoretical and experimental results indicate modest gains are obtained when extracting the Green's function from velocity correlations over using pressure correlations. Thus, vector sensors can be used to reduce the required averaging time for this noise correlation processing, which may be especially useful, for instance, in a fluctuating environment or for drifting sensors.


Evaluation of custom multiplex real - time RT - PCR in comparison to fast - track diagnostics respiratory 21 pathogens kit for detection of multiple respiratory viruses.
Severe acute respiratory infections in children can be fatal, rapid identification of the causative agent and timely treatment can be life saving. Multiplex real time RT-PCR helps in simultaneous detection of multiple viruses saving cost, time and labour. Commercially available multiplex real time RT-PCR kits are very expensive. Therefore the aim of the present study was to develop a cost effective multiplex real time RT-PCR for the detection of 18 respiratory viruses and compare it with an in-vitro diagnostics approved Fast Track Diagnostic Respiratory Pathogens 21 Kit (FTD). Nasopharyngeal aspirates and throat swabs were collected and processed for extraction of nucleic acid using an automated extraction system and multiplex real time RT-PCR was performed using the FTD kit and a custom assay on 356 samples. Custom and FTD assays detected one or more respiratory viruses in 268 (75.29 %) and 262 (73.60 %) samples respectively. The concordance between the custom assay and the FTD assay was 100 % for HCoV OC43, HCoV 229E, HPIV-1, HPIV-2, HBoV, HPeV, Flu A, and Influenza A(H1N1)pdm09 and 94.66 - 99.71 % for the remaining viruses; Flu B (99.71 %), HRV (99.71 %), HPIV-3 (98.87 %), HPIV-4 (99.43 %), HCoV NL63 (99.71 %), HMPV A/B (99.71 %), RSV A/B (94.66 %), EV (98.31 %), HCoV HKU1 (99.71 %), HAdV (99.71 %). Major discrepancy was observed for RSV A/B, which was over detected in 18 samples by the custom assay as compared to the FTD assay. The custom assay was much cheaper than the FTD assay and the time taken was only 29 min more. The custom primer and probe mix was found to be comparable to the FTD assay with good concordance but was much cheaper and the time taken for reporting was only 29 min more. The low cost custom multiplex RT-PCR can be a useful alternative to the costly FTD kit for rapid identification of viral aetiology in resource limited settings.


Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guerin and with or without irradiation in operable breast cancer. A prospective randomized trial.
Between May 1977 and April 1980, 238 patients with operable breast cancer were treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy. All patients were randomized to receive FAC alone or FAC with nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) vaccine. A randomization for routine postoperative irradiation was included in the study in May 1978. At the median follow-up of 33 months, 53 patients had developed recurrent disease. Up to the present time, there have been no significant differences in the disease-free survival of patients treated with FAC alone from those treated with FAC + BCG (P = 0.21). The disease-free survival for patients treated with and without routine postoperative irradiation was similar (P = 0.99). Disease-free survival of premenopausal and postmenopausal women was similar. The overall estimate of disease-free survival was 72% at 3 years.


Should Immigration Status Information Be Considered Protected Health Information?
In response to a case of an undocumented patient who was reported to immigration authorities, this commentary considers whether a patient's immigration status should be deemed protected health information (PHI) under the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. A legal argument, supported by clinical data, is offered that immigration status should be regarded as PHI not subject to valid exception for release without patient authorization. This argument concludes that covered entities (eg, hospitals and health care professionals) are legally precluded under the HIPAA Privacy Rule from disclosing a patient's immigration status.


Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses.
We performed quantitative metabolic phenotyping of blood plasma in parallel with cytokine/chemokine analysis from participants who were either SARS-CoV-2 (+) (n = 10) or SARS-CoV-2 (-) (n = 49). SARS-CoV-2 positivity was associated with a unique metabolic phenotype and demonstrated a complex systemic response to infection, including severe perturbations in amino acid and kynurenine metabolic pathways. Nine metabolites were elevated in plasma and strongly associated with infection (quinolinic acid, glutamic acid, nicotinic acid, aspartic acid, neopterin, kynurenine, phenylalanine, 3-hydroxykynurenine, and taurine; p < 0.05), while four metabolites were lower in infection (tryptophan, histidine, indole-3-acetic acid, and citrulline; p < 0.05). This signature supports a systemic metabolic phenoconversion following infection, indicating possible neurotoxicity and neurological disruption (elevations of 3-hydroxykynurenine and quinolinic acid) and liver dysfunction (reduction in Fischer's ratio and elevation of taurine). Finally, we report correlations between the key metabolite changes observed in the disease with concentrations of proinflammatory cytokines and chemokines showing strong immunometabolic disorder in response to SARS-CoV-2 infection.


[Combination therapy in early rheumatoid arthritis: the COBRA study].
The scheme 'Combination therapy in rheumatoid arthritis' (COBRA) in early rheumatoid arthritis (RA) involves administration of not only sulfasalazine but also prednisolone and methotrexate during the first six months. The trial showed that the COBRA scheme over a period of 1.5 years was superior to sulfasalazine alone: less disease activity in the major part of the year of treatment, less articular damage on radiographs, fewer side effects and equal or reduced costs. An 'aggressive' treatment in patients with early RA is indicated, with (re)assessment of the use of corticosteroids.


Quantitative Sensory Testing (QST) Estimation of Regional Cutaneous Thermal Sensitivity During Waking State, Neutral Hypnosis, and Temperature Specific Suggestions.
This study aimed to determine the effects of neutral hypnosis and hypnotic temperature suggestions in thermal and pain thresholds compared to resting state. Sixteen healthy medium or high hypnotizable volunteers were enrolled. Hypnotizability was assessed with the Hypnotic Induction Profile (HIP); QST was checked in resting state, in neutral hypnosis, after suggestions of heat and cold, and after deinduction. A significant increase in heat threshold was recorded during hypnosis with both cold and heat suggestions compared to neutral hypnosis. HIP induction score showed a linear correlation with changes of temperature thresholds after heat and cold suggestions. Thermal suggestions may result in a significant increase of heat perception thresholds with respect to neutral hypnosis. HIP score is related to thermal threshold changes. QST is a valuable and manageable tool to measure temperature threshold change during hypnosis.


Site-selective intramolecular hydrogen-bonding interactions in phosphorylated serine and threonine dipeptides.
To study the phosphorylation effect on the peptide conformation, we carried out nuclear magnetic resonance (NMR), circular dichroism (CD), Fourier transform (FT)-IR, and vibrational circular dichroism (VCD) experiments with serine and threonine dipeptides (SD and TD) and their phosphorylated ones (pSD and pTD). It is found that both unphosphorylated and phosphorylated serine and threonine dipeptides adopt two conformations, polyproline II (P(II)) and beta-strand. The pH-dependent NMR study shows that the side-chain dianionic phosphoryl group can form direct intramolecular hydrogen bonds with the backbone amide protons at both the acetyl and amide ends of pTD, but only at the acetyl end of pSD. Temperature- and pH-dependent CD studies reveal that, unlike pSD, pTD undergoes conformational transition from P(II) to beta-strand upon double ionization of the phosphoryl group. The subtle but distinct differences between pTD and pSD in site-selective intramolecular hydrogen-bonding interaction and charge-dependent conformational transition may sometimes become significant when choosing between serine and threonine for the conformational control of peptides and proteins by phosphorylation.


Transfection of a rearranged viral DNA fragment, WZhet, stably converts latent Epstein-Barr viral infection to productive infection in lymphoid cells.
An Epstein-Barr viral gene (ZEBRA) is identified that, in human lymphoblastoid cells, activates a switch causing the virus to shift from the latent to the replicative phase of its life cycle. We have shown that a 2.7-kilobase-pair rearranged Epstein-Barr virus DNA fragment of this gene (BamHI fragment WZhet) induced transient expression of viral replicative antigens and polypeptides when it was transfected into a somatic cell hybrid, which was derived from the fusion of an epithelial line cell with a Burkitt lymphoma cell. We now show that this rearranged WZhet fragment, when introduced stably into lymphoblastoid cells, will activate expression of the complete viral replicative cycle in 1-10% of the lymphoblastoid cells, leading to production of biologically active virions that can immortalize primary lymphocytes. The transfected plasmid appears to be regulated in a manner analogous to the complete Epstein-Barr virus genome.


Degeneracy in cryptophane-xenon complex formation in aqueous solution.
The reversible binding of xenon to cryptophane molecules is currently heavily explored for application as a reporter system in NMR. Herein, for aqueous solution, first evidence of degenerate exchange in this host-guest system is presented based on a novel approach using hyperpolarized (129)Xe.


Hirschsprung's disease in twin to twin transfusion syndrome: a case report.
Twin to twin transfusion syndrome (TTTS) is caused by aberrant vascular connections between infant twins and results in high morbidity and mortality in the perinatal period. In donor infants with TTTS and symptoms of intestinal obstruction, small-bowel lesions have been reported in most cases. We report on a 33(+6) gestational wk donor infant with TTTS who had intermittent obstructive episodes, including delayed meconium passage and colonic dilatation on abdominal X-ray. The diagnosis of Hirschsprung's disease was based on a lateral pelvic film with a reversed rectosigmoid ratio. A subsequent barium colon study and rectal suction biopsy indicated a short segment aganglionosis of the colon.


Folate-chitosan Coated Quercetin Liposomes for Targeted Cancer Therapy.
Although quercetin exhibits promising anti-tumor properties, its clinical application is limited due to inherent defects and a lack of tumor targeting. This study aimed to prepare and characterize active targeting folate-chitosan modified quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitro and in vivo was also studied. Box-Behnken Design (BBD) response surface method was used to select the optimal formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitro of QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in healthy Wistar mice and S180 tumor-bearing mice, respectively. The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP were 261.6±8.5 nm, 22.3±1.7 mV, and 98.63±1.28 %, respectively. FA-CS-QUE-LP had a sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol (P<0.01). There was a significant difference in AUC, t1/2, CL and other pharmacokinetic parameters among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P<0.05). In in vivo antitumor activity study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and 37.35%, respectively. FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180 tumor-bearing mice, thus offering novel avenues for cancer treatment.


Sustained release of vascular endothelial growth factor from calcium-induced alginate hydrogels reinforced by heparin and chitosan.
A possible alternative for immunosuppression is a microencapsulation technique using hydrogels, which have been utilized for cell immobilization and drug delivery systems. Angiogenesis is crucial for delivery of the metabolic products to the host tissues as well as to supply oxygen and nutrients to cells. The local delivery of angiogenic growth factors, such as VEGF and basic FGF, has been recently studied to enhance angiogenesis on peripheral tissue of graft. In this study, we evaluated sustained VEGF release with a model using hydrogels coated with chitosan and heparin in vitro. We fabricated calcium alginate gels and chitosan-coated calcium alginate gels. Heparinized chitosan-coated calcium-induced alginate hydrogel beads were prepared by soaking chitosan-coated calcium alginate gels in heparin solution. We compared the stability and VEGF release manner between three kinds of hydrogels. To compare the stability, 5 mL of each hydrogel was incubated with 20 mL PBS under the rotational culture. Compression forces were measured using a rheometer. The amount of VEGF released from the gels was measured by ELISA. The heparin-coated chitosan alginate hydrogels showed the highest surface stability among the three hydrogels. VEGF from the heparinized gel was released in sustained manner up to 10 days in vitro. Chitosan-coated alginate gels released 90% of loaded VEGF within 5 days. These results suggest that local delivery of VEGF using a heparinized hydrogel may provide a long-term supply of angiogenic growth factor that might induce new vessel formation in vivo.


The perfect blend.
'NURSING THE dying is an art, as well as a science. It cannot be reduced to a process of drug administration or a series of required nursing tasks, however important these are.'


Nutrition transition and double burden of undernutrition and excess of weight in Brazil.
Brazil, a unique Latin American country recognized as 1 of the 8 major economies of the world, is experiencing a significant deterioration in health equality in the past decade, despite its universal and free-of-charge health service that is governed by its national constitution. The objective was to describe the double burden at the national, household, and individual levels as well as its major trends across all demographic strata in the past 40 y. The data were collected from 6 Brazilian national surveys conducted in 1974-1975, 1989, 1996, 2002-2003, 2006, and 2008-2009. Anthropometric indicators were estimated for all age groups and anemia indicators for children aged <5 y and women aged >15 y according to WHO recommendations. The annual increment rate was calculated for all indicators to assess the different time points among surveys. In 2008-2009, 1 of every 7 citizens was obese. From 1974-1975 to 2008-2009, the annual obesity increment rate for men was 4.7% each year and was 2.5% each year for women. A large decrease in undernutrition in adults was observed from 1974-1975 to 1989. In children <5 y of age, no increase in the prevalence of overweight across the analyzed periods was observed, whereas a major decrease in the prevalence of undernutrition was detected from 1996 to 2006-2007. The prevalence of the obese mother-underweight child pair was low. No association between anemia and any other child anthropometric indicator was detected. Prevalence trends of adult obesity stratified by quintiles of per capita household income showed different trajectories for men and women across the surveys. In the last period, the poorest and richest adults showed positive incremental rates of obesity. In Brazil, the current prevalence of excess weight is at least 3-fold higher than that of undernutrition. The lowest prevalence rate in the last period analyzed was observed in children <5 y of age. Inclusive social policies have succeeded in reducing poverty and in identifying new challenges related to obesity control or reduction.


Comparative cytogenetics of hamsters of the genus Allocricetulus argyropulo 1932 (Cricetidae, Rodentia).
Chromosome painting and G-banding analyses were used to delimit homologous chromosomal segments among 4 taxa of the hamsters genus Allocricetulus Argyropulo 1932 (Cricetidae, Murоidea, Rodentia)--A. curtatus (2n = 20), A. eversmanni eversmanni, A. eversmanni pseudocurtatus, and the hybrid A. eversmanni beljaevi × A. eversmanni pseudocurtatus (all 2n = 26). Comparative maps between the 4 karyotypes were established based on chromosome painting of chromosome-specific probes from the Syrian hamster (Mesocricetus auratus, 2n = 44). A putative ancestral karyotype for the genus Allocricetulus (AAK) was proposed and contains 12-13 ancestral autosomal elements. Integrated maps demonstrate extended conservation of syntenies within this rodent genus and show the predominant role of Robertsonian rearrangements in the karyotype evolution of the genus Allocricetulus. At the cytogenetic level, we clearly demonstrate karyological differences between karyotypes of species (A. curtatus vs. A. eversmanni) and subspecies A. e. eversmanni and A. e. beljaevi versus A. e. pseudocurtatus, but the karyotypes of A. e. eversmanni and A. e. beljaevi are identical at this level of resolution.


Effect of narrowband ultraviolet B phototherapy on melanocytic naevi.
Melanocytic naevi have been observed to undergo morphological changes following exposure to narrowband ultraviolet (NB-UV)B radiation. To analyse changes in naevi exposed to NB-UVB in a large cohort of patients. Subjects referred for phototherapy had macroscopic and dermoscopic images taken of prominent melanocytic naevi at the following time points: immediately prior to NB-UVB treatment, after 10 exposures, after 30 exposures or at the end of treatment if earlier, and 3 months after discontinuing treatment. Four dermatologists, by consensus, examined each naevus for specific clinical and dermoscopic features at each time point. The size (area) of each naevus was determined by plenimetry. Complete sets of images were taken for 36 out of 51 patients. The most common global dermoscopic patterns in the 440 naevi examined were reticular (50%) and globular (32%). Following NB-UVB exposure, blurring or merging of lines was observed in 45% of reticular naevi. An increase in colour intensity and in the number of dots or globules was observed in 63% of globular naevi, and 167 naevi (40%) underwent a change in size. Of these, 91/167 (54%) decreased in size, with a median area reduction of 8% (0·9-42%); while 76/167 (46%) increased in size, with a median area increase of 9% (1-76%). Around half of naevi exposed to a course of NB-UVB treatment undergo size or morphological changes. Naevi that enlarged tended to revert to pretreatment size 3 months after discontinuation of phototherapy.


Contextual influences on early drinking: Characteristics of drinking and nondrinking days.
Research characterizing the adolescent drinking context is limited, often relies on samples of current drinkers reporting on recent/last or typical drinking experiences, and provides little information about the context of very early use. The present study uses repeated monthly assessments to describe the context of drinking days and matched nondrinking days to determine the unique risk associated with different drinking-related characteristics. Additionally, we used latent class analysis to empirically identify key configurations of drinking-related characteristics and both family- and nonfamily-related environmental characteristics (social context, physical location, source of alcohol). Data included 688 days (344 drinking days, 344 nondrinking days) from 164 middle-school students enrolled in a prospective study on drinking initiation and progression (62% female; 26% non-White, 11% Hispanic). Results supported 4 patterns: (a) heavier drinking occurring in a peer context, lighter drinking occurring in (b) a family context or (c) a peer context, and (d) drinking alcohol obtained at home without permission. Latent classes varied as a function of gender, age, peer norms, and parenting behaviors as well as alcohol type and perceived alcohol availability. Findings indicated that highly endorsed contexts were not necessarily the riskiest ones, and simply targeting an oft-reported source of alcohol, physical location, or social context may not be an effective strategy for reducing underage drinking. Additionally, although greater monitoring and anticipated parent reaction to drinking are typically protective against adolescent drinking, we found they were associated with parent-sanctioned drinking, suggesting the role of parenting practices must be considered in the context of drinking pattern. (PsycINFO Database Record


Paediatric chest wall trauma causing delayed presentation of ventricular arrhythmia.
This report describes a paediatric patient presenting with haemodynamically stable non-sustained ventricular tachycardia 1 day after minor blunt chest trauma. Initial laboratory studies, chest X-ray and echocardiography were normal; however, cardiac MRI revealed precordial haematoma, myocardial contusion and small pericardial effusion. Throughout her hospital course, she remained asymptomatic aside from frequent couplets and triplets of premature ventricular contractions. Ectopy was controlled with oral verapamil. This case highlights how significant cardiac injury may be missed with standard diagnostic algorithms.


Highly Efficient Water Decontamination by Using Sub-10 nm FeOOH Confined within Millimeter-Sized Mesoporous Polystyrene Beads.
Millimeter-sized polymer-based FeOOH nanoparticles (NPs) provide a promising option to overcome the bottlenecks of direct use of NPs in scaled-up water purification, and decreasing the NP size below 10 nm is expected to improve the decontamination efficiency of the polymeric nanocomposites due to the size and surface effect. However, it is still challenging to control the dwelled FeOOH NP sizes to sub-10 nm, mainly due to the wide pore size distribution of the currently available polymeric hosts. Herein, we synthesized mesoporous polystyrene beads (MesoPS) via flash freezing to assemble FeOOH NPs. The embedded NPs feature with α-crystal form, tunable size ranging from 7.3 to 2.0 nm and narrow size distribution. Adsorption of As(III/V) by the resultant nanocomposites was greatly enhanced over the α-FeOOH NPs of 18 × 60 nm, with the iron mass normalized capacity of As(V) increasing to 10.3 to 14.8 fold over the bulky NPs. Higher density of the surface hydroxyl groups of the embedded NPs as well as their stronger affinity toward As(V) was proved to contribute to such favorable effect. Additionally, the as-obtained nanocomposites could be efficiently regenerated for cyclic runs. We believe this study will shed new light on how to fabricate highly efficient nanocomposites for water decontamination.


M-type 57 group A streptococcus bacteriocin.
All 40 tested isolates of M-type 57 group A streptococci gave the same, highly characteristic inhibitory pattern (P-type 614) when tested by deferred antagonism using a set of nine indicator strains. One component of this inhibitory activity was attributed to the production of a bacteriocinlike substance, streptococcin A-M57 (SA-M57). Production of SA-M57 was enhanced by the presence of blood and also by growth at an alkaline pH. Partially purified SA-M57 was obtained from culture supernatants by a combination of ammonium sulphate fractionation and column chromatography. On Sephadex G-100 two different molecular weight forms (SA-M57 alpha, greater than 100 000; SA-M57 beta, 33 000) were demonstrated. Both SA-M57 forms were protease and heat sensitive and had identical inhibitory activity against a collection of indicator bacteria. The adsorption to and rate of kill of sensitive cells by SA-M57 was enhanced in the presence of human plasma. Partially purified SA-M57 preparations were devoid of M-type 57 protein and curing studies showed that loss of SA-M57 did not correlate with loss of M protein production.


Anti-Ro52/TRIM21 antibodies are associated with aberrant inflammatory circuits in patients with systemic autoimmune rheumatic diseases.
Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complements C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.


Enhancement of polycyclic aromatic hydrocarbons removal during anaerobic treatment of urban sludge.
Anaerobically stabilized sewage sludge has potential to partially substitute synthetic fertilizers. The main risk with the recycling of urban sludge on agricultural soils is the accumulation of unwanted products, such as trace metals and organic micropollutants. In this context, the polycyclic aromatic hydrocarbons (PAHs) are particularly monitored because of their toxic properties at low concentrations and their high resistance to biological degradation. The aim of the present study was to optimize PAHs removal during anaerobic digestion of contaminated sewage sludge. Thirteen PAHs were monitored in laboratory-scale anaerobic bioreactors under mesophilic (35 degrees C) and thermophilic (55 degrees C) methanogenic conditions. Abiotic losses were statistically significant for the lightest PAHs, such as fluorene, phenanthrene and anthracene. It was shown that PAH removal was due to a specific biological activity. Biological PAHs removal was significantly enhanced by an increase of the temperature from 35 degrees C to 55 degrees C, especially for the heaviest PAHs. Bioaugmentation experiment was also performed by addition of a PAH-adapted bacterial consortium to a non-acclimated reactor. Significant enhancement of PAHs removal was observed. It was finally shown that PAH removal efficiencies and methanogenic performances were closely linked. The rate of biogas production may be used as an indicator of bacterial activity on PAH removal.


Syntheses and optical and electrochemical properties of porphyrin dimers linked by metal ions.
The preparation, isolation, and characterization of several new peripherally functionalized monomeric porphyrins and metalloporphyrins and of porphyrin dimers are described. These dimers are obtained by linking with metal ions two monomeric porphyrins bearing at their periphery an enaminoketone chelate fully conjugated with the aromatic ring. Porphyrin dimers linked by metal ions display large interactions in the ground state as evidenced by their electronic spectra and their electrochemical behavior. Compared to the monomeric analogue, these dimers show absorption spectra with intensified red-shifted Q-bands and their first oxidation potentials are substantially lowered and split into two distinct redox steps.


Annual Viral Expression in a Sea Slug Population: Life Cycle Control and Symbiotic Chloroplast Maintenance.
In a few well-known cases, animal population dynamics are regulated by cyclical infections of protists, bacteria, or viruses. In most of these cases, the pathogen persists in the environment, where it continues to infect some percentage of successive generations of the host organism. This persistent re-infection causes a long-lived decline, in either population size or cycle, to a level that depends upon pathogen density and infection level (1-4). We have discovered, on the basis of 9 years of observation, an annual viral expression in Elysia chlorotica, an ascoglossan sea slug, that coincides with the yearly, synchronized death of all the adults in the population. This coincidence of viral expression and mass death is ubiquitous, and it occurs in the laboratory as well as in the field. Our evidence also suggests that the viruses do not re-infect subsequent generations from an external pathogen pool, but are endogenous to the slug. We are led, finally, to the hypothesis that the viruses may be involved in the maintenance of symbiotic chloroplasts within the molluscan cells.


Sulfur-Mediated Polycarbonate Polyurethane for Potential Application of Blood-Contacting Materials.
In this study, a sulfur-mediated polycarbonate polyurethane (PCU-SS) is developed by mimicking the catalyzing ability of glutathione peroxidase (GPx) on nitric oxide (NO) in the human body. The PCU-SS is endowed with the capability to produce NO based on disulfide bonds, which could strongly improve the biocompatibility of the materials. The characterization results indicate that PCU-SS could not only decrease the adhesion of platelets but also enhance the capability of anti-thrombus. Moreover, it is shown that PCU-SS has a good compatibility with endothelial cells (ECs), while has a marked inhibition capacity of the proliferation of smooth muscle cells (SMCs) and macrophages (MA). Meanwhile, the result of animal implantation experiments further demonstrates the good abilities of PCU-SS on anti-inflammation, anti-thrombus, and anti-hyperplasia. Our results offer a novel strategy for the modification of blood-contacting materials based on disulfide bonds. It is expected that the PCU-SS could shed new light on biocompatibility improvement of cardiovascular stents.


A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris.
In a double-blind, parallel group study we compared fluconazole 150 mg once weekly with griseofulvin 500 mg once daily for 4-6 weeks in the treatment of tinea corporis or tinea cruris. Eighty-four of 114 patients (74%) (39% after 3 weeks) were clinically cured in the fluconazole group compared with 72 of 116 (62%) (39% after 3 weeks) in the griseofulvin group (P = 0.06). In the fluconazole group 78% were mycological cured compared with 80% in the griseofulvin group. In the fluconazole group nine patients (7.5%) had treatment related adverse events and in the griseofulvin group 15 patients (12.5%) had adverse events. Fluconazole 150 mg once weekly for 6 weeks is both clinically and mycologically effective in the treatment of tinea corporis and tinea cruris and few side-effects were reported.


Cyclic nucleotide content of passaged keratinocytes in culture during various growth stages.
Human newborn foreskin keratinocytes were maintained in culture in first passage for up to 60 days. An initial lag phase was followed by a growth and a final plateau phase. During this time, cell numbers, the morphologic appearance of both attached and detached cells, DNA, and cyclic nucleotide content were evaluated. Cell cycle analysis during growth phase was performed by flow cytofluorometry. High levels of cAMP and cGMP coincided with the early growth phase, when up to 70% of cells were in S, G2, or M compartments of the cell cycle. Halfway through growth phase, a fall in cyclic nucleotide levels coincided with a drop in mitotic index and increase in G1 cells. Plateau phase was characterized by increased desquamation, a gradual elevation of intracellular cAMP, cGMP, and DNA, and in later stages, an increased proportion of squamous cells in the attached layers. The oldest cultures were mostly squamous with low cyclic nucleotide levels. Results suggest that high cyclic nucleotide content is a feature of cycling, possibly S phase keratinocytes. Onset of differentiation coincides with a small but definite increase in both cAMP and cGMP, which in general vary in the same direction.


Pubertal height gain in Ullrich-Turner syndrome.
Short stature and ovarian failure are the main features in Ullrich-Turner syndrome (UTS). The aim of this retrospective analysis was to evaluate the influence of age at initiation of puberty on final height. Sixty-five girls were treated with growth hormone (GH) and had a final height of 150.6 +/- 5.7 cm; 12/65 entered puberty spontaneously. A non-GH treated group of 12 girls with UTS reached a final height of 147.3 +/- 6.6 cm. Subdividing the GH treated group (n = 53) based on the age at induction of puberty, before or after 13 years, there was no significant difference in final height. Final height was affected by the age at which GH treatment was initiated, height SDS at the beginning of puberty, and by the duration of GH therapy. Therefore, early treatment with GH for short stature in UTS should be attempted so that an age adequate initiation of puberty will be feasible.


Universal finite-size scaling functions with exact nonuniversal metric factors.
Using exact partition functions and finite-size corrections for the Ising model on finite square, plane triangular, and honeycomb lattices and extending a method [J. Phys. 19, L1215 (1986)] to subtract leading singular terms from the free energy, we obtain universal finite-size scaling functions for the specific heat, internal energy, and free energy of the Ising model on these lattices with exact nonuniversal metric factors.


Enhancement of immunoglobulin A production in Peyer's patches by oral administration of a traditional Chinese medicine, xiao-chai-hu-tang (Shosaiko-to).
The Peyer's patches contain a large number of precursor cells committed to the production of immunoglobulin A (IgA) and play an important role in IgA response in the mucosal immune system. We investigated the induction of IgA producing cells in Peyer's patches by plaque forming cell assay after oral administration of a traditional Chinese herbal medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to). The number of total IgA producing cells in the Peyer's patches detected by the protein-A plaque assay was increased about two-fold by Shosaiko-to administration and the numbers of both anti-SRBC and anti-HRBC IgA producing cells were also increased by such a treatment. On the other hand, when SRBC alone were administered orally, only the number of anti-SRBC IgA producing cells was increased. Further, we examined T-cell subpopulations in the gut-associated lymphoid tissues after oral administration of Shosaiko-to by flowcytometry. Marked alternations in T cell subpopulations were not detected in the Peyer's patches, though TcR gamma delta+T-cells in the intraepithelial lymphocytes and Thy1.2-TcR alpha beta+T cells in the mesenteric lymph nodes were slight increased. These results showed that orally administered Shosaiko-to acts as a polyclonal B-cell activator which induces IgA production in the mucosal immune system.


Injury prevention for older adults: A dataset of safety concern narratives from online reviews of mobility-related products.
Older adults are among the fastest-growing demographic groups in the United States, increasing by over a third this past decade. Consequently, the older adult consumer product market has quickly become a multi-billion-dollar industry in which millions of products are sold every year. However, the rapidly growing market raises the potential for an increasing number of product safety concerns and consumer product-related injuries among older adults. Recent manufacturer and consumer injury prevention efforts have begun to turn towards online reviews, as these provide valuable information from which actionable, timely intelligence can be derived and used to detect safety concerns and prevent injury. The presented dataset contains 1966 curated online product reviews from consumers, equally distributed between safety concerns and non-concerns, pertaining to product categories typically intended for older adults. Identified safety concerns were manually sub-coded across thirteen dimensions designed to capture relevant aspects of the consumer's experience with the purchased product, facilitate the safety concern identification and sub-classification process, and serve as a gold-standard, balanced dataset for text classifier learning.


Prediction of meat quality from biopsy in live pigs with different RYR1 genotypes.
To predict meat quality after slaughter, biopsy samples were taken from musculus longissimus lumborum et thoracis of live pigs at approximately 40 kg and 80 kg of weight. The obtained values from biopsies for pH1 and EC50 (electric conductivity) were compared with measurements after slaughter at a weight of approximately 110 kg. RYR1 genotypes were determined from blood samples using PCR-RFLP. Mating of Nn sows with two nn boars resulted in 72 Nn and 40 nn offspring. Significant differences between the two genotypes were found for pH1 and EC50 values for the three weights. The coefficients of correlation for the Nn genotype of the RYR1 gene between the values after slaughter and both the first and the second biopsy for pH1 and EC50 were very low (r = 0.06, r = 0.14; and r = 0.26, r = 0.26; P ? 0.05). For the nn genotype were r = -0.23, r = -0.15; and r = -0.25, r = -0.11 respectively. The values of pH1 and EC50 were highly correlated (r = -0.52 to -0.84; P < or = 0.001) both within biopsies and after slaughter.


An Aquatic Microbial Metaproteomics Workflow: From Cells to Tryptic Peptides Suitable for Tandem Mass Spectrometry-based Analysis.
Meta-omic technologies such as metagenomics, metatranscriptomics and metaproteomics can aid in the understanding of microbial community structure and metabolism. Although powerful, metagenomics alone can only elucidate functional potential. On the other hand, metaproteomics enables the description of the expressed in situ metabolism and function of a community. Here we describe a protocol for cell lysis, protein and DNA isolation, as well as peptide digestion and extraction from marine microbial cells collected on a cartridge filter unit (such as the Sterivex filter unit) and preserved in an RNA stabilization solution (like RNAlater). In mass spectrometry-based proteomics studies, the identification of peptides and proteins is performed by comparing peptide tandem mass spectra to a database of translated nucleotide sequences. Including the metagenome of a sample in the search database increases the number of peptides and proteins that can be identified from the mass spectra. Hence, in this protocol DNA is isolated from the same filter, which can be used subsequently for metagenomic analysis.


Kynurenine pathway metabolism and neuroinflammatory disease.
Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response. Under physiological conditions, QUIN is metabolized to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+), which represents an important metabolic cofactor and electron transporter. NAD+ also serves as a substrate for the DNA 'nick sensor' and putative nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP). Free radical initiated DNA damage, PARP activation and NAD+ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.


Propofol infusion syndrome: an unusual cause of renal failure.
Propofol infusion syndrome has been increasingly recognized as a syndrome of unexplained myocardial failure, metabolic acidosis, and rhabdomyolysis with renal failure. It has been described only with acute neurologic injury or acute inflammatory diseases complicated by severe infections or sepsis. It appears to develop in the context of high-dose, prolonged propofol (100 microg/kg/min) treatment in combination with catecholamines and/or steroids. This was first noted in children but is increasingly recognized in adults. This is a case report of 2 patients (a 42-year-old man and a 17-year-old girl) who had acute renal failure associated with use of propofol in the appropriate clinical setting. It examines the pathophysiology and the possible mechanisms of this condition and illustrates the need to consider it as the cause of rhabdomyolysis and acute renal failure in critically ill patients.


Synthesis of Transition-State Inhibitors of Chorismate Utilizing Enzymes from Bromobenzene cis-1,2-Dihydrodiol.
In order to survive in a mammalian host, Mycobacterium tuberculosis (Mtb) produces aryl-capped siderophores known as the mycobactins for iron acquisition. Salicylic acid is a key building block of the mycobactin core and is synthesized by the bifunctional enzyme MbtI, which converts chorismate into isochorismate via a SN2″ reaction followed by further transformation into salicylate through a [3,3]-sigmatropic rearrangement. MbtI belongs to a family of chorismate-utilizing enzymes (CUEs) that have conserved topology and active site residues. The transition-state inhibitor 1 described by Bartlett, Kozlowski, and co-workers is the most potent reported inhibitor to date of CUEs. Herein, we disclose a concise asymmetric synthesis and the accompanying biochemical characterization of 1 along with three closely related analogues beginning from bromobenzene cis-1S,2S-dihydrodiol produced through microbial oxidation that features a series of regio- and stereoselective transformations for introduction of the C-4 hydroxy and C-6 amino substituents. The flexible synthesis enables late-stage introduction of the carboxy group and other bioisosteres at the C-1 position as well as installation of the enol-pyruvate side chain at the C-5 position.


[Respiratory insufficiency due to duplications of the oesophagus].
Duplications of the oesophagus are uncommon congenital malformations with possible occurrence in any part of the gastrointestinal tract. The duplications may be cysts, diverticula or tubular-shaped. Cysts may even occur further away from the gastrointestinal tract, not necessarily having contact with it. I present a patient case, in which a 13-month-old child was brought to the emergency room due to gradually increasing dyspnea. The child made a full recovery after the surgical procedure.


Clinical applications of Sunscreens and formulation advancements.
Sunscreens cover the big market ratio in terms of cosmetic applications, but the therapeutic necessity of sunscreen still needs to be uncovered in the clinical context. Clinically, sunscreens are being employed more often nowadays as a result of the rising consequences of skin malignancies and the photodamaging effects of UV radiation. Sunscreens are essential to prevent aging by shielding the skin from the harmful effects of ultraviolet (UV) radiation. Over the recent decades, there has been a significant evolution in the usage of sunscreens as photo protectants. The demand for sunscreen formulations will inevitably rise as more people become aware of the protection that sunscreens provide against tanning, photoaging, non-melanoma skin cancers, pre-malignant skin lesions, and skin melanomas. The novel contemporary formulation techniques are also beneficial in enhancing the product's aesthetic look and quality. Recently, regulatory agencies have also started paying attention to the regulation of the clinical application, efficacy, and safety parameters related to sunscreen. This review underlines the pathophysiological response of UV exposure with the therapeutic applications of sunscreen in various dermatological conditions and the recent formulation advancements in the development of sunscreen.


Autoregulated paracellular clearance of amyloid-β across the blood-brain barrier.
The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and protecting neural tissue from damaging blood-borne agents. The barrier is characterized by endothelial tight junctions that limit passive paracellular diffusion of polar solutes and macromolecules from blood to brain. Decreased brain clearance of the neurotoxic amyloid-β (Aβ) peptide is a central event in the pathogenesis of Alzheimer's disease (AD). Whereas transport of Aβ across the BBB can occur via transcellular endothelial receptors, the paracellular movement of Aβ has not been described. We show that soluble human Aβ(1-40) monomers can diffuse across the paracellular pathway of the BBB in tandem with a decrease in the tight junction proteins claudin-5 and occludin in the cerebral vascular endothelium. In a murine model of AD (Tg2576), plasma Aβ(1-40) levels were significantly increased, brain Aβ(1-40) levels were decreased, and cognitive function was enhanced when both claudin-5 and occludin were suppressed. Furthermore, Aβ can cause a transient down-regulation of claudin-5 and occludin, allowing for its own paracellular clearance across the BBB. Our results show, for the first time, the involvement of the paracellular pathway in autoregulated Aβ movement across the BBB and identify both claudin-5 and occludin as potential therapeutic targets for AD. These findings also indicate that controlled modulation of tight junction components at the BBB can enhance the clearance of Aβ from the brain.


Renal cell carcinoma in autosomal dominant polycystic kidney disease: A case report.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the congenital cystic renal diseases with the highest incidence. ADPKD was suspected of being a risk factor for the emergence of RCC. A 65-year-old male complained of numbness in both knees for a week. The patient came to a neurosurgeon and was advised to perform a lumbosacral MRI. The patient had no complaints. The patient had a history of hypertension but was never treated. Computed tomography intravenous pyelogram (CT-IVP) revealed a heterogeneous lobulated mass in the upper to the middle of the right kidney to the right renal hilus. It also revealed multiple cysts, in both kidneys. The patient underwent an open radical nephrectomy in the right kidney with minimal bleeding. Three years revealed no pain at the surgery site or hematuria. Abdominal MRI revealed no recidive mass. This case report comprehensively described an autosomal dominant polycystic kidney disease that coexists with RCC. malignant lesions were found in ADPKD cases without any clinical symptoms of malignancy. M malignant lesions could be discovered by chance in nephrectomy specimens. Autosomal dominant polycystic kidney disease with renal cell carcinoma is a unique presentation. Despite the rarity of the situation, the patient was successfully treated.