A Comparative Investigation on Phenolic Composition, Characterization and Antioxidant Potentials of Five Different Australian Grown Pear Varieties.
Pear (Pyrus communis L.) is widely spread throughout the temperate regions of the world, such as China, America and Australia. This fruit is popular among consumers due to its excellent taste and perceived health benefits. Various bioactive compounds, which contribute to these health benefits, have been detected in the pear fruits, including a range of phenolic compounds. Five Australian grown pear varieties, which include Packham's Triumph, Josephine de Malines, Beurre Bosc, Winter Nelis and Rico were selected for this study to examine the phenolic compounds in pears. Beurre Bosc exhibited the highest total polyphenol content (TPC) (3.14 ± 0.02 mg GAE/g), total tannin content (TTC) (1.43 ± 0.04 mg CE/g) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) (5.72 ± 0.11 mg AAE/g), while the Josephine de Malines variety was high in total flavonoid content (TFC) (1.53 ± 0.09 mg QE/g), ferric reducing antioxidant power (FRAP) (4.37 ± 0.04 mg AAE/g), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (4.44 ± 0.01 mg AAE/g) and total antioxidant capacity (TAC) (5.29 ± 0.09 mg AAE/g). The liquid chromatography coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) data indicate that a total of 73 phenolic compounds were detected in Beurre Bosc (37 compounds), Josephine de Malines (34), Rico (22), Packham's Triumph (15) and Winter Nelis (9), respectively. From HPLC-PDA quantification, the Beurre Bosc pear variety showed significantly higher in phenolic acids (chlorogenic acid; 17.58 ± 0.88 mg/g) and while flavonoids were significantly higher in Josephine de Malines (catechin; 17.45 ± 1.39 mg/g), as compared to other pear varieties. The analyses suggest that the Australian grown pears might contain an ideal source of phenolic compounds which benefit human health. The information provided by the present work can serve as practical supporting data for the use of pears in the nutraceutical, pharmaceutical and food industries.


The effects of post-growth annealing on the structural and magnetic properties of BaFe2As2.
We investigate the effects of post-growth annealing on the structural and magnetic properties of BaFe2As2. Magnetic susceptibility measurements, which exhibit a signal corresponding to the magnetic phase transition, and high-resolution x-ray diffraction measurements, which directly probe the structural order parameter, show that annealing causes the ordering temperatures of both the phase transitions to increase, sharpen and converge. In the as grown sample, our measurements show two distinct transitions corresponding to structural and magnetic ordering, which are separated in temperature by approximately 1 K. After 46 days (d) of annealing at 700 °C, the two become concurrent in temperature. These measurements demonstrate that the structural phase transition is second-order like when the magnetic and structural phase transitions are separated in temperature, and first-order like when the two phase transition temperatures coincide. This observation indicates that annealing causes the system to cross a hitherto undiscovered tricritical point. In addition, x-ray diffraction measurements show that the c-axis lattice parameter increases with annealing up to 30 d, but remains constant for longer annealing times. Comparisons of BaFe2As2 to SrFe2As2 are made when possible.


Bioinspired Fibrillary Hydrogel with Controlled Swelling Behavior: Applicability as an Artificial Vitreous.
The vitreous humor of the eye is mainly composed of fibrillary collagen and semiflexible hyaluronic acid (HA). To mimic this macromolecular composition of the vitreous, we previously developed an injectable two-component hydrogel composed of a fibrillary gellan and a semiflexible polyelectrolyte, poly[methacrylamide-co-(methacrylic acid)], both endowed with thiol cross-linkers. We optimized the hydrogel formulations for optical, physical, mechanical, and transport properties approximating those of the vitreous. Here, we studied 11 hydrogel formulations with varying concentrations of each component, and, as expected, we found that they all swelled in physiological solution. The two formulations that most closely matched the vitreous properties were investigated further. Judged against nonsurgical control and silicone oil, a clinically accepted vitreous replacement, both hydrogel formulations were biocompatible in rabbits for 30 days. Both hydrogels maintained optical clarity, physiological intraocular pressure, and intact retinal layers that displayed normal electroretinography. The swelling behavior of the gel led us to postulate that the native vitreous may also exhibit controlled swelling, where ionic HA's swelling capacity is restricted by fibrillary collagen. In conclusion, the two hydrogels merit further in vivo evaluation as an artificial vitreous for an extended duration and additionally in mini-pigs for their similarity to human eyes in size.


External validity of risk models: Use of benchmark values to disentangle a case-mix effect from incorrect coefficients.
Various performance measures related to calibration and discrimination are available for the assessment of risk models. When the validity of a risk model is assessed in a new population, estimates of the model's performance can be influenced in several ways. The regression coefficients can be incorrect, which indeed results in an invalid model. However, the distribution of patient characteristics (case mix) may also influence the performance of the model. Here the authors consider a number of typical situations that can be encountered in external validation studies. Theoretical relations between differences in development and validation samples and performance measures are studied by simulation. Benchmark values for the performance measures are proposed to disentangle a case-mix effect from incorrect regression coefficients, when interpreting the model's estimated performance in validation samples. The authors demonstrate the use of the benchmark values using data on traumatic brain injury obtained from the International Tirilazad Trial and the North American Tirilazad Trial (1991-1994).


Steady flow of couple stress fluid through tubes of slowly varying cross-sections--application to blood flows.
Steady laminar flow of a non-Newtonian fluid based on couple stress fluid theory, through narrow tubes of varying cross-sections has been studied theoretically. Asymptotic solutions are obtained for the basic equations and the expressions for the velocity field and the wall shear stress are derived for a general cross-section. Computation and discussions are carried out for the geometries which occur in the context of physiological flows or in particular blood flows. The tapered tubes and constricted tubes are of special importance. It is observed that increase in certain parameters results in erratic flow behaviour proximal to the constricted areas which is further enhanced by the increase in the geometric parameters. This elucidates the implications of the flow in the development of vascular lesions.


Surgical considerations after chemotherapy and radiation therapy for inflammatory breast cancer.
Eighteen patients seen between 1974 and 1982 with the clinical diagnosis of inflammatory breast carcinoma underwent modified radical mastectomy after preoperative chemotherapy and radiation therapy. In 17 of the 18 patients (94%), residual carcinoma was detected in either the resected breast or the axillary nodes. All mastectomies were accomplished without major technical difficulty. Seven wound complications, including three infections, occurred. Local recurrence was noted in 29% (five of 17 patients) and distant metastasis was detected in 89% (16 of 18 patients). Only three patients are presently alive without evidence of disease 19, 21, and 21 months since the onset of symptoms. Eleven patients have died, the median survival being 23 months since the development of symptoms, and four are alive with distant metastasis. Modified radical mastectomy can be accomplished in patients with inflammatory breast cancer after preoperative chemotherapy and radiation therapy and may have a role in reducing local tumor burden.


Current Status of Human Papillomavirus Infection and Introduction of Vaccination to the National Immunization Program in Korea: an Overview.
Human Papillomavirus (HPV) infection is the most common sexually transmitted infection and is associated with the development of cervical cancer. The purpose of this report is to provide the literature evidences on selecting the HPV vaccine for national immunization program (NIP) in Korea. To complete these tasks, we reviewed domestic and foreign literature on the current status of HPV infection, efficacy and effectiveness of HPV vaccine, safety of vaccine and cost effectiveness analysis of vaccination business. Given that the median age of first sexual intercourse is continuing to fall, this may have serious implications for HPV infection and cervical cancer incidence at the age of 20s. The World Health Organization recommends that the HPV vaccination should be included in the NIP being implemented in each country. Both the bivalent and quadrivalent vaccines have a 90% or greater preventive efficacy on cervical intraepithelial lesion 2-3 and cervical cancer by the HPV 16 or HPV 18. In the future, if HPV vaccination rate as part of NIP increases, it is expected that the incidence of HPV infection, genital warts, and cervical precancerous lesions will be decreased in the vaccination age group. Therefore, in order to increase the HPV vaccination rate at this point in Korea, social consensus and efforts such as the introduction and promotion of HPV vaccine to the NIP according to appropriate cost-effectiveness analysis are required.


A possible role for hepcidin in the detection of iron deficiency in severely anaemic HIV-infected patients in Malawi.
Iron deficiency is a treatable cause of severe anaemia in low-and-middle-income-countries (LMIC). Diagnosing it remains challenging as peripheral blood markers poorly reflect bone-marrow iron deficiency (BM-ID), especially in the context of HIV-infection. Severely anaemic (haemoglobin ≤70g/l) HIV-infected adults were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. BM-ID was evaluated. Accuracy of blood markers (including hepcidin, mean corpuscular volume, mean cellular haemoglobin concentration, serum iron, serum ferritin, soluble transferrin receptor (sTfR), sTfR index, sTfR-ratio) to detect BM-ID was evaluated by ROC area under the curve (AUCROC). Seventy-three patients were enrolled and 35 (48.0%) had BM-ID. Although hepcidin and MCV performed best (AUCROC of 0.593 and 0.545 respectively) all markers performed poorly in identifying BM-ID (ROC<0.6). The AUCROC of hepcidin in males was 0.767 (sensitivity 80%, specificity 78%) and in women 0.490 (sensitivity 60%, specificity 61%). BM-ID deficiency was common in severely anaemic HIV-infected patients. It is an important and potential treatable contributor to severe anaemia but lack of definitive biomarkers makes it difficult to accurately assess iron status in these patients. Further investigation of the potential of hepcidin is needed, including exploration of the differences in hepcidin results between males and females.


Corticosteroids in sepsis and community-acquired pneumonia.
Sepsis and septic shock, which are often caused by pneumonia, impact millions of people every year. Despite adequate antibiotic therapy, mortality remains high, up to 45% in septic shock, which is characterized by an inappropriate, excessive immune response of the host. Moreover, critical illness-related corticosteroid insufficiency often coexists. Against this background, several trials and meta-analyses evaluated corticosteroid therapy as adjuvant therapy with heterogeneous results. Indeed, before 2000, high-dosage, short courses of corticosteroid treatment resulted in no benefit on mortality and a higher rate of adverse events. After 2000, thanks to a deeper understanding of the pathophysiology, low-dosage with longer courses of treatment were tested. With this regimen, a faster decrease in inflammation and faster resolution of shock, with a low rate of mild adverse events, was demonstrated although no clear effect on mortality was shown. To date, guidelines on sepsis and septic shock and guidelines on severe community-acquired pneumonia suggest corticosteroid use in selected patients. Furthermore, by utilizing latent class analysis, phenotypes of sepsis patients who benefit the most from corticosteroid treatment were recently identified. Future research should be guided by a precision medicine approach to identify adequate dosage and duration of corticosteroid treatment for appropriate patients. This article is freely available.


Laparoscopic adhesiolysis in patients with chronic abdominal pain.
The purpose of this review was to evaluate the indications, safety, and efficacy of laparoscopic adhesiolysis and its prevention in patients with chronic abdominal pain. The safety of laparoscopic adhesiolysis can be improved by using an optic trocar for laparoscopy, by using an ultrasonic technique for adhesiolysis, and by taking care with regard to risk factors. Although many studies have reported pain reduction after laparoscopic adhesiolysis, a recent randomized study showed no more pain relief than with diagnostic laparoscopy alone. The regrowth of adhesions after adhesiolysis is less after the laparoscopic technique compared with open surgery. Liquid products can prevent the formation of adhesions, but their clinical efficacy has not yet been proved in randomized studies in humans. Older patients with a greater number of previous abdominal operations are more prone to complications in laparoscopic surgery. The introduction of a Veress needle into the ninth intercostal space, the use of an optic trocar and ultrasonic dissection can reduce the incidence of iatrogenic bowel perforations. For chronic pain, diagnostic laparoscopy is encouraged, but laparoscopic adhesiolysis is no longer recommended; its benefit being no greater than that of diagnostic laparoscopy alone.


Analysis of temporal gene expression during Bacillus subtilis spore germination and outgrowth.
Bacillus subtilis forms dormant spores upon nutrient depletion. Under favorable environmental conditions, the spore breaks its dormancy and resumes growth in a process called spore germination and outgrowth. To elucidate the physiological processes that occur during the transition of the dormant spore to an actively growing vegetative cell, we studied this process in a time-dependent manner by a combination of microscopy, analysis of extracellular metabolites, and a genome-wide analysis of transcription. The results indicate the presence of abundant levels of late sporulation transcripts in dormant spores. In addition, the results suggest the existence of a complex and well-regulated spore outgrowth program, involving the temporal expression of at least 30% of the B. subtilis genome.


Effects of training on reproductive tissue blood flow in exercising pregnant rats.
The purpose of this study were to investigate 1) whether treadmill training would attenuate the reduction in reproductive (RBF) and visceral tissue blood flow (VBF) that occurs during an acute bout of submaximal exercise (EX) in pregnant rats and 2) whether fetal number of fetal weight would be affected by training. One group (T) of female rats trained on a treadmill (10 degrees incline, 30 m/min) for 1 h/day 5 days/wk for 10 wk before becoming pregnant. A second group (UT) was run at the same speed and incline for 10 min/day 5 days/wk for 2 wk. T and UT rats were bred until pregnant. Skeletal muscle blood flow, RBF, and VBF were measured at pre-EX and at 1 and 10 min of EX (10 degrees incline, 30 m/min). No differences were observed before or during exercise between the two groups in RBF and VBF, heart rate, or mean arterial pressure. Both groups experienced decreases in VBF (except liver) and RBF from pre-EX to EX. In most muscles skeletal muscle blood flow increased for both groups from pre-EX to EX. Neither group experienced a change in mean arterial pressure from pre-EX to EX, but heart rate increased significantly for both groups. No differences were observed between groups in fetal number, fetal weight, or fetal resorptions. It was concluded that training does not significantly attenuate the reduction in RBF and VBF in pregnant rats that occurs during an acute bout of submaximal EX and that training does not affect fetal weight or fetal number.


The risk of serious illness among oral contraceptive users: evidence from the RCGP's oral contraceptive study.
So far, no-one has attempted to evaluate the overall balance of serious, but not necessarily fatal, disease among a cohort of oral contraceptive users. To emprirically assess the balance of risk of serious illness among a cohort of oral contraceptive users followed up for up to 28 years. Oral contraceptive-associated serious disease was defined as that which is often life-threatening and/or associated with long-term disability, and which has been found, or postulated, to be associated with use of combined oral contraceptives. Data from the Royal College of General Practitioners' (RCGP) Oral Contraception Study were examined to determine the rate of such conditions during 335,181 woman-years of observation in 'ever users' and 228,727 woman-years in 'never users'. The rates were standardized for age, parity, social class, and smoking. Compared with never users, ever users had a small increased risk of any serious disease (relative risk = 1.17; 95% confidence interval = 1.09-1.25). Ever users had an excess risk of cerebrovascular disease, pulmonary embolism, and venous thromboembolism, and reduced risk of ovarian and endometrial cancer. The increased risk was seen only in younger women; by the age of 50, ever users had the same risk as never users. The risk appeared to be confined to women using older oral contraceptives containing 50 micrograms or more of oestrogen. Past users of older, higher dose oral contraceptives can be reassured that the small increased risk of serious disease seen during current use does not persist after stopping, and that latent effects do not appear later in life. Currently available oral contraceptives, containing less than 50 micrograms of oestrogen accompanied by the progestogen, levonorgestrel, or norethisterone acetate, do not appear to be associated with an increased net risk of serious disease.


Lower extent but similar rhythm of osteogenic behavior in hBMSCs cultured on nanofibrous scaffolds versus induced with osteogenic supplement.
Nanotopographic cues from biomaterials exert powerful effects on the osteogenic differentiation of mesenchymal stem cells because of their niche-mimicking features. However, the biological mechanisms underlying cell lineage determination by surface nanotopography have not been clearly elucidated. Here, we explored the osteogenic behavior of human bone marrow mesenchymal stem cells (hBMSCs) on poly-l-lactide nanofibers with different orientations and monitored the dynamic changes in global gene expression triggered by topographical cues. RT-PCR analysis of osteogenic marker genes and ALP activity assays demonstrated that hBMSCs cultured on random nanofibers showed enhanced osteogenic-specific fate compared with those on aligned nanofibers. Microarray analysis demonstrated a similar temporal change in gene expression patterns between hBMSCs cultured on random nanofibers and those induced with an osteogenic supplement (OS). However, the extent of osteogenic differentiation on the fibrous scaffold was much lower than that driven by chemical OS. In-depth pathway analysis revealed that focal adhesion kinase, TGF-β, Wnt, and MAPK pathways were involved in the activation of osteogenic differentiation in hBMSCs on random nanofibers. These findings suggested that a lower extent but similar rhythm of dynamic cellular behavior was induced on random nanofibers when compared with the OS condition and that mechanotransduction could trigger nonspecific and multilevel responses in hBMSCs. This study provides insight into the regulation of osteogenesis directed by substratum surfaces.


Replacement of surgical vasectomy through the use of wild-type sterile hybrids.
For the production and rederivation of mouse strains, pseudopregnant female mice are used for embryo transfer and serve as surrogate mothers to support embryo development to term. Vasectomized males are commonly used to render pseudopregnancy in females, generated by surgical procedures associated with considerable pain and discomfort. Genetically modified mouse strains with a sterility phenotype provide a non-surgical replacement and represent an important application of the 3Rs (Replacement, Reduction, Refinement). However, the maintenance of such genetically modified mouse strains requires extensive breeding and genotyping procedures, which are regulated procedures under national legislation. As an alternative, we have explored the use of sterile male hybrids that result when two wild-type mouse subspecies, Mus musculus musculus and Mus musculus domesticus, interbreed. We find the male STUSB6F1 hybrid, resulting from the mating of female STUS/Fore with male C57BL/6J, ideally suited and demonstrate that its performance for the production of oviduct and uterine transfer recipients is indistinguishable when compared to surgically vasectomized mice. The use of these sterile hybrids avoids the necessity for surgical procedures or the breeding of sterile genetically modified lines and can be generated by the simple mating of two wild-type laboratory strains-a non-regulated procedure. Furthermore, in contrast with the breeding of genetically sterile mice, all male offspring are sterile and suitable for the generation of pseudopregnancy, allowing their efficient production with minimal breeding pairs.


Characterization of Sarcoptes scabiei Tropomyosin and Paramyosin: Immunoreactive Allergens in Scabies.
Scabies is a human skin disease due to the burrowing ectoparasite Sarcoptes scabiei var. hominis resulting in intense itching and inflammation and manifesting as a skin allergy. Because of insufficient mite material and lack of in vitro propagation system for antigen preparation, scabies is a challenging disease to develop serological diagnostics. For allergen characterization, full-length S. scabiei tropomyosin (Sar s 10) was cloned, expressed in pET-15b, and assessed for reactivity with IgE antibodies from human sera. IgE binding was observed to Sar s 10 with sera collected from subjects with ordinary scabies, house dust mite (HDM)-positive and naive subjects and a diagnostic sensitivity of < 30% was observed. S. scabiei paramyosin (Sar s 11) was cloned, and expressed in pET-28a in three overlapping fragments designated Sspara1, Sspara2, and Sspara3. IgE and IgG binding was observed to Sspara2 and Sspara3 antigens with sera collected from ordinary scabies, and HDM-positive subjects, but no binding was observed with sera collected from naive subjects. Sspara2 displayed excellent diagnostic potential with 98% sensitivity and 90% specificity observed for IgE binding and 70% sensitivity for IgG. In contrast, the diagnostic sensitivity of Sspara3 was 84% for IgE binding and 40% for IgG binding. In combination, Sspara2 and Sspara3 provided an IgE sensitivity of 94%. This study shows that IgE binding to Sspara2 and Sspara3 is a highly sensitive method for diagnosis of scabies infestation in clinical practice. The developed enzyme-linked immunosorbent assay helps direct future development of a specific diagnostic tool for scabies.


Modulation of gap junction transcript and protein expression during pregnancy in the rat.
The expression of three different gap junction transcripts, alpha 1 (Cx43), beta 1 (Cx32), and beta 2 (Cx26) was examined in several organs during pregnancy in the rat. In all of the organs that were examined--uterus, ovary, heart, and liver--there was a strong correlation between levels of gap junction mRNA and gap junction antigens that were detected at different stages of pregnancy. A striking change in alpha 1 transcript levels (a 5.5-fold increase) was detected in the uterine myometrium on the day before parturition. This elevation of the alpha 1 transcript is thought to be associated with the formation of gap junctions that are required for synchronizing the contractility of the myometrial cells during parturition. 2 d before parturition, there was a detectable elevation of beta 2 transcripts and protein in the endometrial epithelium, which was then followed by a dramatic decrease in beta 2 gap junctional protein on the day before parturition. There was also a substantial elevation of alpha 1 transcripts (a 6.7-fold increase) in the stromal regions of the ovary on the day before parturition that was identical to the temporal pattern of alpha 1 expression in the myometrium. In all three instances--the alpha 1 transcripts in the myometrium, beta 2 transcripts in the endometrium, and alpha 1 transcripts in the ovary--the transcript modulation appeared to be cell specific, because the changes in transcript levels of these three gene products occurred independently of the poly(A) + RNA concentrations at the same pregnancy stages in the respective organs. There were no specific changes detected in gap junction transcript levels in the heart and liver during pregnancy. These observations indicate that a cell-specific modulation of gap junction expression occurs in two regions of the uterus and the ovary during pregnancy. Further, it appears that the same gap junction gene in different organs, such as the alpha 1 gene in the uterine myometrium and the heart, can be differentially regulated.


Impact of insecticides and surfactant on lettuce physiology and yield.
Insecticides are used extensively on lettuce, Lactuca sativa L., grown in southwestern Arizona because of heavy insect pressure that can potentially reduce lettuce productivity. Multiple sprays are made per season to manage these insects in lettuce. One of the major concerns related to extensive insecticide applications in lettuce is the potential subtle impact of insecticides that may reduce lettuce photosynthesis and yield. We conducted field and greenhouse experiments to examine the impact of multiple insecticides and surfactant spray applications on lettuce photosynthesis and yield. Lettuce was planted in the field in 1998, insecticides and surfactant were applied, and lettuce gas-exchange and dry weights were determined. Treatments were arranged in a split-plot consisting of insecticides as main plot and surfactant as subplot treatments in a randomized complete block design with four replications. Photosynthetic rates of lettuce were significantly reduced by endosulfan, methomyl, acephate, and surfactant at seedling stage 4 h and 2 d after the spray application was made. However, the reduction in lettuce photosynthesis by these insecticides and surfactant was only transient, and lettuce photosynthesis recovered 5 d after the spray application was made. Photosynthetic rates were not altered by zeta-cypermethrin, emamectin benzoate, and spinosad at the seedling stage. Insecticides or surfactant (Kinetic, a nonionic surfactant) did not significantly affect lettuce photosynthesis after rosette formation. In addition, lettuce dry weight was not significantly altered. These studies suggest that lettuce photosynthesis may be susceptible to some insecticides at the seedling stage. Consequently, we found that biorational insecticides, introduced to manage insect pests in lettuce, have no influence on lettuce physiology at the seedling stage, unlike the chlorinated hydrocarbons, organophosphates, or carbamates tested in this study. In a greenhouse study, we found that lettuce photosynthesis and yield were not altered by Bacillus thuringiensis application. Our results indicate that B. thuringiensis and the newer insecticides, particularly biorationals, can be used to manage lettuce insect pests without significantly altering lettuce gas-exchange and yield.


[Effect of a bone marrow stimulator of antibody producers on virus-specific antibody formation in animals infected with flaviviruses].
The injection of the marrow stimulator of antibody-producing cells (SAPC) into animals infected with Japanese encephalitis and tick-borne encephalitis viruses stimulated the formation of virus-specific antibodies in the infected animals, increasing antibody production 8- to 16-fold. Such SAPC-induced stimulation of the formation of virus-specific antibodies is observed in cases of both acute and chronic virus infection. The prospects of using the preparation of SAPC are discussed.


Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms.
Electrical vagus nerve (VN) stimulation during sepsis attenuates tumor necrosis factor (TNF) production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36) on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP). The septic rats were subsequently treated with EA-ST36 (CLP+ST36), and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P < 0.05), and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms.


Synthesis and evaluation of poly(oxyethylene glycol) polymer (POP) supports.
Mono- and alpha,omega-bis-styryl-oligo(oxyethylene glycol) ethers have been constructed in an efficient two-step synthesis. From these precursors, poly(oxyethylene glycol) polymer (POP) supports of varying monomer and cross-linker composition have been produced. The swelling properties and mass-solvent uptake of these novel materials have been evaluated in a variety of solvents, demonstrating that POP supports exhibit enhanced solvent compatibilities over the commercial resins TENTA-GEL, ARGO-GEL, and Merrifield's resin. The utility of POP supports in solid-phase organic chemistry has also been demonstrated successfully. It is anticipated that these high-loading polymeric supports will have generic application in the solid-phase synthesis of combinatorial libraries and the in situ screening of these libraries in the aqueous environment of a bioassay.


Evaluation of the anti-gout effect of Sonchus Arvensis on monosodium urate crystal-induced gout arthritis via anti-inflammatory action - an in vivo study.
Sonchus arvensis is an Indonesian plant with strong therapeutic effects. Various studies have shown that this plant is useful in treating kidney stone disorders, and recent studies have shown that S. arvensis extract can reduce inflammation caused by monosodium urate crystal deposition in the synovial tissue. This study was aimed to explore the extract of Sonchus arvensis, via fractionation, to optimize the specific content of S. arvensis with anti-inflammatory potential in gout arthritis. The study included 30 rats (Rattus norvegicus) Wistar strain obtained from the Eureka Research Laboratory (Palembang, Indonesia) weighing between 200 - 250 grams. After one week of acclimatization, the rats were randomly divided into six groups, each group containing five animals; normal control group, monosodium urate group (negative control), colchicine group, hexane fraction of S. arvensis group, ethyl-acetate fraction of S. arvensis group and water fraction group. Before monosodium urate administration, rats in the colchicine group, as a positive control group, were given orally for seven days with 0.28 mg/kg/day colchicine. IL-1β levels in joint synovial fluid were examined with Rat ELISA interleukin-1β. S. arvensis water fraction showed the most significant reduction in inflammatory cells compared to the hexane or ethyl acetate fractions. The water fraction of S. arvensis group had an equal effect with positive control in reducing the infiltration of inflammatory cells in the synovial tissue. Sonchus arvensis water fraction has anti-gout effects in monosodium urate-induced gout arthritis in rats by decreasing the inflammatory response in the synovial joint.


Efficacy and safety of direct oral anticoagulants vs vitamin K antagonists in patients with atrial fibrillation and end-stage renal disease on hemodialysis: A systematic review and meta-analysis.
The prevalence of atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) on chronic hemodialysis is increasing. The optimal anticoagulant choice in this population is unclear since these patients were excluded from the pivotal randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in the general AF population. We aimed to assess the efficacy and safety of DOACs vs. VKAs in patients with AF and ESRD on chronic hemodialysis through a systematic review and meta-analysis of all available evidence. We performed a systematic search in MEDLINE and Scopus for RCTs or observational studies of patients with AF and ESRD on chronic hemodialysis who were treated with DOACs or VKAs. The outcomes of interest included ischemic stroke, the composite of ischemic stroke or systemic embolism, major bleeding, gastrointestinal bleeding, minor bleeding events and all-cause mortality. Among 397 studies identified from the literature search, six studies (three RCTs and three observational studies) were included in the meta-analysis. Compared with VKA-treated patients, those treated with DOACs had similar risk of ischemic stroke (RR:0.76, 95% CI:0.41-1.41), ischemic stroke or systemic embolism (RR:0.65, 95% CI:0.38-1.10), major bleeding (RR:0.79, 95% CI:0.49-1.28) and all-cause death (RR:0.79, 95% CI:0.56-1.12). The risk of gastrointestinal bleeding was lower in DOAC- vs VKA-treated patients in three eligible observational studies (RR:0.73, 95% CI: 0.54-0.99, I2 = 79%) but this was not confirmed in two eligible RCTs (RR:0.69, 95% CI: 0.33-1.43, I2 = 0%). Among AF patients with ESRD on chronic hemodialysis, the risk of ischemic stroke, ischemic stroke or systemic embolism, minor bleeding, major bleeding, and all-cause mortality is similar in patients treated with DOACs compared to VKAs. Given that the meta-analysis of RCTs on gastrointestinal bleeding did not confirm the results of the meta-analysis of the observational studies, it cannot be concluded that gastrointestinal bleeding is lower among DOAC-treated patients. PROSPERO CRD42023391966.


How can portal vein cavernous transformation cause chronic incomplete biliary obstruction?
Biliary disease in the setting of non-cirrhotic portal vein thrombosis (and similarly in portal vein cavernous transformation) can become a serious problem during the evolution of disease. This is mostly due to portal biliary ductopathy. There are several mechanisms that play a role in the development of portal biliary ductopathy, such as induction of fibrosis in the biliary tract (due to direct action of dilated peribiliary collaterals and/or recurrent cholangitis), loss of biliary motility, chronic cholestasis (due to fibrosis or choledocholithiasis) and increased formation of cholelithiasis (due to various factors). The management of cholelithiasis in cases with portal vein cavernous transformation merits special attention. Because of a heterogeneous clinical presentation and concomitant pathophysiological changes that take place in biliary anatomy, diagnosis and therapy can become very complicated. Due to increased incidence and complications of cholelithiasis, standard treatment modalities like sphincterotomy or balloon sweeping of bile ducts can cause serious problems. Cholangitis, biliary strictures and hemobilia are the most common complications that occur during management of these patients. In this review, we specifically discuss important issues about bile stones related to bile duct obstruction in non-cirrhotic portal vein thrombosis and present evidence in the current literature.


Health promotion in barbershops: balancing outreach and research in African American communities.
Promoting health and preventing illness among African American men, who die disproportionately from preventable diseases, is a challenging health disparity that has seen limited progress. However, focusing our efforts in places outside of traditional clinical and community settings such as the barbershop has shown promise for ameliorating these disparities. In particular, barbershop-based health promotion as conducted by the Black Barbershop Health Outreach Program has successfully reached nearly 10,000 men nationwide through a grassroots, volunteer-driven effort. At the same time, researchers have begun to conduct formal clinical trials in barbershops in order to explore interventions targeting this at-risk population. Herein, we describe, in brief a review of barbershop-based health promotion and the experience of this novel community-based organization. We argue for continuing to integrate evaluation and research using community-partnered principles into successful grassroots initiatives without dulling the practical impact of these programs is a crucial next step as we move beyond simply acknowledging health disparities and seek to find solutions.


Targeted Maytansinoid Conjugate Improves Therapeutic Index for Metastatic Breast Cancer Cells.
This study was undertaken to target cell surface receptors other than the ones typically associated with breast cancer {estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)}. It was also launched to use small molecules other than those most widely used for active targeting in general ( e.g. folate and carbonic anhydrase IX ligands). Specifically, the focus of this study was on unique small molecules that bind the TrkC receptor, which is overexpressed in metastatic breast cancer. A conjugate (1) of a TrkC-targeting small molecule and the highly cytotoxic warhead, DM4 (a maytansinoid), was prepared. Cellular studies featuring TrkC+ and TrkC- human breast cells indicated this conjugate might have a better therapeutic effect than DM4 alone. It emerged that the conjugate 1 was very efficacious in vivo, completely ablating orthotopic 4T1 breast tumor in one case and dramatically reducing the tumor size in four other mice. Throughout, no significant weight loss or obvious neurotoxic effects were observed in the animals tested.


Ethnicity, education, and the cortisol response to awakening: a preliminary investigation.
To explore the associations among ethnicity, educational attainment, and cortisol secretion. Participants include 63 white (n = 31) and African-American (n = 32) adult men and women. Subjects provided salivary cortisol samples immediately upon awakening and again, 30 minutes later. Analyses adjusted for relevant covariates revealed a steeper awakening response among whites with higher education compared to other groups. Cortisol levels were significantly lower among African-American participants with lower levels of education. All effects were independent of perceived stress. These preliminary findings demonstrate significant ethnic and education-related differences in awakening cortisol secretion responses. Our data highlight the importance of considering ethnicity and the moderating effects of social class when examining the associations among social contextual factors and cortisol secretion.


Adjuvant Chemoradiotherapy With Epirubicin, Cisplatin, and Fluorouracil Compared With Adjuvant Chemoradiotherapy With Fluorouracil and Leucovorin After Curative Resection of Gastric Cancer: Results From CALGB 80101 (Alliance).
Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma, Intergroup Trial 0116 (Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction adenocarcinoma: Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil (FU) and leucovorin (LV) compared with surgery alone. CALGB 80101 (Alliance; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival. Patients and Methods Between April 2002 and May 2009, 546 patients who had undergone a curative resection of stage IB through IV (M0) gastric or gastroesophageal junction adenocarcinoma were randomly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy (FU plus LV arm) or postoperative epirubicin, cisplatin, and infusional FU (ECF) before and after combined FU and radiotherapy (ECF arm). Results With a median follow-up duration of 6.5 years, 5-year overall survival rates were 44% in the FU plus LV arm and 44% in the ECF arm ( Plogrank = .69; multivariable hazard ratio, 0.98; 95% CI, 0.78 to 1.24 comparing ECF with FU plus LV). Five-year disease-free survival rates were 39% in the FU plus LV arm and 37% in the ECF arm ( Plogrank = .94; multivariable hazard ratio, 0.96; 95% CI, 0.77 to 1.20). In post hoc analyses, the effect of treatment seemed to be similar across all examined patient subgroups. Conclusion After a curative resection of gastric or gastroesophageal junction adenocarcinoma, postoperative chemoradiotherapy using a multiagent regimen of ECF before and after radiotherapy does not improve survival compared with standard FU and LV before and after radiotherapy.


[Detection of Anopheles artemievi (Diptera, Culicidae) in Uzbekistan].
An. artemievi was diagnosed by morphological and molecular genetic analyses in the Fergana valley, Uzbekistan, in 2008-2009. Four species of the genus Anopheles: An. superpictus, An. artemievi, An. hyrcanus, and An. claviger inhabiting the irrigated oases with the bulk of population were detected in the Fergana valley. An. artemievi and An. superpictus were prevalent in the foci of malaria. An. artemievi larvae inhabited the rice fields, springs, collection-drainage systems, and water reservoirs enriched in oxygen. The most attractive day's rest for mosquitoes was a cattle house where their bulk (on average 41.8%) was present. Next was cattle sheds, with the mosquitoes averaging 26.4%. An. artemievi, attacked human beings in the field conditions. This species showed a high susceptibility to test insecticides, such as propoxur, cipermethrin, deltamethrin, and lambda-Cyhalothrin.


BAFinder: A Software for Unknown Bile Acid Identification Using Accurate Mass LC-MS/MS in Positive and Negative Modes.
Most LC-MS based bile acid analyses target common bile acids. The identification of unknown bile acids remains challenging in untargeted experiments. Here, a software named BAFinder was developed to improve the identification of unknown bile acids from accurate mass LC-MS/MS data in both the positive and negative ESI modes. A wide variety of bile acid structures were covered in BAFinder, including oxidized bile acids and sugar conjugates that were often ignored. The annotation of unknown bile acids was based on a thorough investigation of MS/MS fragmentation patterns of 84 bile acid reference standards in both modes. Specifically, BAFinder took the peak alignment result and MS/MS spectra, grouped candidate features in positive and negative modes, searched their representative MS/MS spectra against a MS/MS library, and used characteristic product ions and neutral losses to annotate bile acids not covered in the library. Finally, the number of hydroxyl groups and double bonds, conjugation, and isomer information of bile acids were reported with four different levels of annotation confidence. The use of BAFinder was demonstrated through successful application to the analysis of human plasma and urine samples, in which a total of 112 and 244 bile acids were annotated and 75 and 111 of them were confirmed with standards or synthesized compounds, respectively. The software is freely available at https://bafinder.github.io/.


On the importance of anchoring and the consequences of its impairment in dyslexia.
One of the main impediments of individuals with reading difficulties and individuals with language difficulties is poor working memory. Typically measured using verbal stimuli, working memory deficits have often been considered as one aspect of the phonological difficulty putatively underlying dyslexia. Over the years it has been shown that a broad range of auditory discrimination abilities are also mildly impaired. Here we present evidence that a domain general, rather than a phonology specific, deficits in the ability to implicitly use contextual information, which we term anchoring, can account for both types of deficits. We propose that anchoring ability, which reflects a basic biological mechanism for replacing effortful mechanisms of explicit working memory with automatic mechanisms of implicit memory, and consequently boost performance in both perceptual and cognitive tasks, is a crucial factor in our ability to be expert users of oral and written language.


From the Point of View of the Chickens: What Difference Does a Window Make?
We aimed to investigate what broiler chickens prefer when given free choice between a barn side with artificial lighting only as opposed to the other barn side with natural light through glass windows and artificial light. Eighty-five 1 day-old male Cobb 500 broiler chickens were divided into 10 pens; half of each pen area was provided with only artificial light (OAL) and the other half with natural and artificial light (NAL), and birds were free to move across sides. Environmental indicators and external conditions such as temperature, relative humidity, air velocity, ammonia and illuminance were monitored inside and outside the barn. Chickens' preference was registered each three days, divided in categories: I (at 9, 12, and 15 days), II (at 18, 21, 24, and 27 days), and III (at 30, 33 and 36 days). The effect of the interaction between environmental indicators and week was statistically different only for illuminance. Chickens preferred NAL to OAL from 18 days onwards (II p < 0.001; III p = 0.016). Drinking (p = 0.034) and exploration or locomotion (p = 0.042) behaviours were more frequent, and "not visible" behaviours (p < 0.001) were less frequent, in NAL. Foraging was the only behaviour with an interaction effect between age category and light treatment, as birds during period II expressed this behaviour more frequently in NAL than OAL (p = 0.003). For our experimental conditions, the chickens preferred NAL from 18 days of age onwards, when the confounding effect of the heating light was removed, and their behavioural repertoire was also different according to each side of the barn and to their ages.


Could cannabinoids provide a new hope for ovarian cancer patients?
It is known that gynecological cancers remain a worldwide problem and as shown by the statistics, there is a need for new gynecological cancer treatments. Cannabinoids, the pharmacologically active compounds of the Cannabis sativa plant, have been used for many centuries by individuals as a symptomatic treatment to alleviate pain, nausea, vomiting, and to help stimulate appetite. Research has revealed that cannabinoids also exert anti-cancer activity such as anti-proliferative and pro-apoptotic effects through a variety of mechanisms. There is significant value in the development of these compounds as anti-cancer therapies in clinical practice as they do not produce the typical toxic side effects that exist with conventional therapies and recent clinical trials have shown their great tolerability by patients at high doses. Cannabinoids can induce psychoactive effects that could limit their progression. Therefore, non-psychoactive cannabinoids are attracting pharmacological interest due to their inability to produce psychological effects. Recent studies have focussed on non-psychoactive cannabinoids in ovarian cancer and have revealed promising pre-clinical results that indicate that these compounds may have potential benefits in the treatment of these cancers. However, there are still unanswered questions and research gaps that need to be addressed. This review summarizes the current understanding of this topic and identifies the current gaps in knowledge that provide a useful direction for future work.


A combined physical and physiological dormancy controls seasonal seedling emergence of Geranium robertianum.
Temperate forest herbs with seeds exhibiting both a physical and a physiological dormancy mechanism are rare, and knowledge on the factors regulating germination of these species is fragmentary. The biennial Geranium robertianum L. grows mainly in temperate woodlands, but can also be found in exposed habitats. Seedlings of G. robertianum are known to emerge from spring until autumn, but little is known about the environmental factors regulating germination. In this study, phenology of seedling emergence and of physical dormancy loss was examined for seeds buried at shaded or sunny exposed locations. The role of temperature in regulating dormancy and germination was analysed by incubating seeds in temperature sequences simulating temperatures that seeds experience in nature. The results indicate that most seeds of G. robertianum buried in sunny conditions germinate immediately after physical dormancy loss in summer. Seeds buried in shaded conditions also lose physical dormancy mainly during summer, but remain physiologically dormant and do not germinate until late winter or early spring. Besides physical dormancy, seeds of G. robertianum also initially have a high level of physiological dormancy, which is reduced during dry storage. Physiological dormancy is reduced through chilling in winter, thus enabling the seeds to germinate at low temperatures. We conclude that a complex combination of physical and physiological dormancy ensures that G. robertianum seeds germinate in summer at exposed sites and in early spring at shaded sites.


Expression of complement component 3 (C3) from an adenovirus leads to pathology in the murine retina.
Activation of complement has been implicated as one of the major causes of age-related macular degeneration (AMD). Evidence is accumulating for a role of complement in other retinal diseases, such as diabetic retinopathy and proliferative vitreoretinopathy. Because of the paucity of animal models that directly investigate the role of complement in retinal pathology, the authors sought to develop a model of increased complement expression and activation, specifically in the murine retina. The authors constructed a recombinant adenovirus-expressing murine complement component 3 (C3, AdcmvC3). Adult mice were injected in the subretinal space with either AdcmvC3 or a control virus, AdcmvGFP. After 1 to 2 weeks of exogenous C3 expression, mice were analyzed by scotopic electroretinography and fluorescein angiography. Eyes were harvested for histologic, immunohistochemical, and quantitative RT-PCR analyses. Mice injected with C3-expressing adenovirus exhibited significantly increased vascular permeability, endothelial cell proliferation and migration, RPE atrophy, loss of photoreceptor outer segments, reactive gliosis, retinal detachment, and reduced retinal function relative to those injected with a control adenovirus. Deposition of the membrane attack complex was observed on endothelial cells and photoreceptor outer segments. Adenovirus-mediated delivery of C3 to murine RPE induces significant functional and anatomic changes that reproduce many of the features of AMD as well as those of other retinal diseases. This novel model may be useful in assessing the role of complement in retinal pathology and in developing anti-complement therapies for retinal diseases associated with complement activation.


Salidroside attenuates apoptosis in ischemic cardiomyocytes: a mechanism through a mitochondria-dependent pathway.
In the present study, we investigated cardioprotective effects of salidroside, isolated from Rhodiola rosea L, on oxygen-glucose deprivation (OGD)-induced cardiomyocyte death and ischemic injury evoked by acute myocardial infarction (AMI) in rats. Pretreatment with salidroside notably ameliorated cell viability losses in a dose-dependant manner and in parallel it alleviated morphologic injury detected by electron microscopy. Mechanistically, diminished OGD-induced cardiomyocyte apoptosis was shown in salidroside-pretreated cardiomyocytes, in accordance with minimal reactive oxygen species (ROS) burst. Moreover, salidroside markedly upregulated the Bcl-2/Bax ratio and preserved mitochondrial transmembrane potential (ΔΨm). Salidroside administration also inhibited myocardial apoptosis in AMI rats by increasing phosphorylation of Akt and decreasing activation of caspase-3. These findings suggest that salidroside reduced ischemia-mediated myocardial damage. Salidroside therefore has potential to be a promising drug for preventing and treating myocardial ischemic diseases.


[Non-specific acid nucleoside triphosphatase from cytosol and chromatin of rat liver: partial purification and general properties].
The nucleoside triphosphatase (EC 184.108.40.206) was isolated from rat liver cytosol and purified 600-fold. The enzyme hydrolyzes all NTPs and dNTPs, splits NDPs and dNDPs at a low rate and does not destroy NMPs and dNMPs. The phosphatase consists of a single subunit with molecular weight of 65 000. The chromatin fraction of the enzyme is fully bound to the membrane, whereas the cytosol fraction contains 15-30% of the membrane-bound enzyme. Both free and membrane-bound phosphatases possess identical functional properties. The enzymatic activity has a pH-optimum of 4.0--4.5, is increased in the presence of Me2+ and is unaffected by ouabain, Triton X-100, N-ethylmaleimide, NaF or DNA, but is inhibited by NaCl, Pi and PPi. The value of Km is equal to 20 microM for TTP splitting. Since the NTP pool is essentially changed throughout the cell cycle, it is suggested that the nucleoside triphosphatase can participate in the nucleotide pool regulation.


Shared (epi)genomic background connecting neurodegenerative diseases and type 2 diabetes.
The progressive aging of populations has resulted in an increased prevalence of chronic pathologies, especially of metabolic, neurodegenerative and movement disorders. In particular, type 2 diabetes (T2D), Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most prevalent age-related, multifactorial pathologies that deserve particular attention, given their dramatic impact on patient quality of life, their economic and social burden as well the etiopathogenetic mechanisms, which may overlap in some cases. Indeed, the existence of common triggering factors reflects the contribution of mutual genetic, epigenetic and environmental features in the etiopathogenetic mechanisms underlying T2D and AD/PD. On this subject, this review will summarize the shared (epi)genomic features that characterize these complex pathologies. In particular, genetic variants and gene expression profiles associated with T2D and AD/PD will be discussed as possible contributors to determine the susceptibility and progression to these disorders. Moreover, potential shared epigenetic modifications and factors among T2D, AD and PD will also be illustrated. Overall, this review shows that findings from genomic studies still deserves further research to evaluate and identify genetic factors that directly contribute to the shared etiopathogenesis. Moreover, a common epigenetic background still needs to be investigated and characterized. The evidences discussed in this review underline the importance of integrating large-scale (epi)genomic data with additional molecular information and clinical and social background in order to finely dissect the complex etiopathogenic networks that build up the "disease interactome" characterizing T2D, AD and PD.


Pharmacological and functional comparison of the polo-like kinase family: insight into inhibitor and substrate specificity.
PLK1 (polo-like kinase 1) is a key mitotic kinase and a therapeutic target in the treatment of proliferative diseases. Here we investigate the relative substrate specificity and pharmacological relatedness of PLK1, -2, -3, and -4 that together comprise a conserved family of Ser/Thr kinases (PLK family). We report consensus substrate sequences for PLK2, -3, and -4 and an expanded consensus sequence for PLK1, which we use to design an optimal peptide substrate, PLKtide. We report inhibitory activity for the entire PLK family across a diverse set of small-molecule ATP-competitive inhibitors including several clinical compounds. With respect to both substrate and ATP-site specificity, highest similarity is observed between PLK2 and PLK3, PLK1 is next most similar, and PLK4 is least similar. Further, we have identified and report time-dependent inhibition by two potent and selective PLK inhibitors.


Low-level vibrations retain bone marrow's osteogenic potential and augment recovery of trabecular bone during reambulation.
Mechanical disuse will bias bone marrow stromal cells towards adipogenesis, ultimately compromising the regenerative capacity of the stem cell pool and impeding the rapid and full recovery of bone morphology. Here, it was tested whether brief daily exposure to high-frequency, low-magnitude vibrations can preserve the marrow environment during disuse and enhance the initiation of tissue recovery upon reambulation. Male C57BL/6J mice were subjected to hindlimb unloading (HU, n = 24), HU interrupted by weight-bearing for 15 min/d (HU+SHAM, n = 24), HU interrupted by low-level whole body vibrations (0.2 g, 90 Hz) for 15 min/d (HU+VIB, n = 24), or served as age-matched controls (AC, n = 24). Following 3 w of disuse, half of the mice in each group were released for 3 w of reambulation (RA), while the others were sacrificed. RA+VIB mice continued to receive vibrations for 15 min/d while RA+SHAM continued to receive sham loading. After disuse, HU+VIB mice had a 30% greater osteogenic marrow stromal cell population, 30% smaller osteoclast surface, 76% greater osteoblast surface but similar trabecular bone volume fraction compared to HU. After 3 w of reambulation, trabecular bone of RA+VIB mice had a 30% greater bone volume fraction, 51% greater marrow osteoprogenitor population, 83% greater osteoblast surfaces, 59% greater bone formation rates, and a 235% greater ratio of bone lining osteoblasts to marrow adipocytes than RA mice. A subsequent experiment indicated that receiving the mechanical intervention only during disuse, rather than only during reambulation, was more effective in altering trabecular morphology. These data indicate that the osteogenic potential of bone marrow cells is retained by low-magnitude vibrations during disuse, an attribute which may have contributed to an enhanced recovery of bone morphology during reambulation.


Revaluing donor and recipient bodies in the globalised blood economy: transitions in public policy on blood safety in the United Kingdom.
The clinical use of blood has a long history, but its apparent stability belies the complexity of contemporary practices in this field. In this article, we explore how the production, supply and deployment of blood products are socially mediated, drawing on theoretical perspectives from recent work on 'tissue economies'. We highlight the ways in which safety threats in the form of infections that might be transmitted through blood and plasma impact on this tissue economy and how these have led to a revaluation of donor bodies and restructuring of blood economies. Specifically, we consider these themes in relation to the management of recent threats to blood safety in the United Kingdom. We show that the tension between securing the supply of blood and its products and ensuring its safety may give rise to ethical concerns and reshape relations between donor and recipient bodies.


A prevention strategy to reduce the incidence of injury in high school basketball: a cluster randomized controlled trial.
To examine the effectiveness of a sport-specific balance training program in reducing injury in adolescent basketball. Cluster randomized controlled trial. Twenty-five high schools in Calgary and surrounding area. Nine hundred and twenty high school basketball players (ages 12-18). Subjects were randomly allocated by school to the control (n = 426) and training group (n = 494). Both groups were taught a standardized warm-up program. The training group was also taught an additional warm-up component and a home-based balance training program using a wobble board. All injuries occurring during basketball that required medical attention and/or caused a player to be removed from that current session and/or miss a subsequent session were then recorded and assessed by a team therapist who was blinded to training group allocation. A basketball-specific balance training program was protective of acute-onset injuries in high school basketball [RR = 0.71 (95% CI; 0.5-0.99)]. The protective effect found with respect to all injury [RR = 0.8 (95% CI; 0.57-1.11)], lower-extremity injury [RR = 0.83 (95% CI; 0.57-1.19)], and ankle sprain injury [RR = 0.71 (95% CI; 0.45-1.13)] were not statistically significant. Self-reported compliance to the intended home-based training program was poor (298/494 or 60.3%). A basketball-specific balance training program was effective in reducing acute-onset injuries in high school basketball. There was also a clinically relevant trend found with respect to the reduction of all, lower-extremity, and ankle sprain injury. Future research should include further development of neuromuscular prevention strategies in addition to further evaluation of methods to increase compliance to an injury-prevention training program in adolescents.


The effect of different chemical intra-oral prostheses cleansers on the surface properties of Parylene-coated PMMA.
The purpose of this study was to investigate the effect of different chemical intra-oral prosthesis cleansers on the surface properties of Parylene-C coated and non-coated polymethyl methacrylate (PMMA). A total of 120 PMMA samples were prepared. Half of the samples were coated with 10 µm of Parylene-C. Samples were exposed to either air (control) or one of two types of denture cleansers, an alkaline peroxide cleanser (Steradent) or a neutral peroxide cleanser with enzyme (Poligrip). Surface roughness (Ra) and surface free energy (SFE) values were measured and compared between groups. Scanning electron microscopy was used for visual analysis. The samples coated with Parylene exhibited significantly lower mean Ra values compared to the non-coated samples (p<0.001). Immersion in Steradent increased the roughness of non-coated PMMA, but its effect was minimized on the coated surfaces. SFE increased for the samples exposed to air and Poligrip, but decreased for the samples exposed to Steradent.


A model-based approach to limb apraxia in Alzheimer's disease.
Limb apraxia is a neurological deficit characterized by an inability to pantomime and/or imitate gestures, which can result from neurodegenerative disorders such as Alzheimer's disease (AD). The major goal of the study was to describe comprehensively the apraxia deficits observed in AD patients and to relate those deficits to general cognitive status, measures of daily activity, and other neuropsychological measures. Limb apraxia was assessed on a variety of conceptual and gesture production tasks in 30 AD patients. As a group, AD patients were impaired across gesture production tasks: of note was the greater impairment in imitation, as opposed to pantomime, which was especially pronounced when patients were imitating with a delay. Imitation performance was best predicted by measures of visuospatial processing, while imitation with delay was best predicted by measures of working memory. In addition, pantomime in response to pictures of tools was less accurate than Pantomime to Verbal Command and holding the tool during performance did not decrease the participants' impairment, while introducing a verbal cue during imitation increased the severity of deficits. Furthermore, investigation into patterns of deficits clearly demonstrated that the nature of limb apraxia deficits observed in AD can be quite heterogeneous and that dissociations between the conceptual and the production system exist. Finally, we also report on significant correlations between general cognitive status and limb apraxia.


[Macroscopic and microscopic lesions in bronchial asthma].
Bronchial asthma is a chronic inflammatory disease characterized by reversible airways obstruction, inflammation, and increased bronchial hyperresponsivennes. The aim of this study was to evaluate the macroscopic and microscopic airways lesions, using bronhoscopy followed by biopsy in 38 cases of Outpatient Department from Clinic of Pulmonary Diseases Iaşi, investigated between January 2005 - June 2008. Patients distribution according to the degree of severity was performed, using the international recommendations for asthma management of the Global Initiative for Asthma (GINA): intermittent (n=7 patients), mild persistent (n=10 patients), moderate persistent (n=16 patients), and severe persistent (n=5 patients). 23,68% of patients had a chronic disease of more than 15 years. The endoscopic changes of the peripheral airways were represented by edema, congestion, bronchial stenosis and mucus hypersecretion. Microscopic routine exam showed epithelial lesions (epithelial desquamation, goblet cell hyperplasia, squamous metaplasia), basement membrane thickening, edema, increased vascularisation, glandular and muscular hypertrophy and bronchial inflammatory infiltrate. Although bronhoscopy exam offers important information regarding changes of the airway mucosa in bronchial asthma, it concomitantly provide bioptic control, as microscopic examination still represents the "gold standard" assessment of bronchial wall remodeling process.


[Pharmacotherapy of portal hypertension and its complications: analysis of efficacy of preparations for clinical practice and discussion of promising methods of treatment].
Bleeding from oesophageal varicose veins is the terminal stage of a sequence of complications of liver cirrhosis caused by progressive fibrosis, circulation blockade, and development of portal hypertension syndrome followed by collateral shunt. It leads to progressive vein dilation and their rupture. The main issue of today is to prevent the development of successive stages of portal hypertension, to search for therapeutic and surgical methods for marked reduction of pressure in the portal system, and to prevent the risk of hemorrhage from varicose veins. Another approach is to use local endoscopic treatment of varicose veins for prevention of their rupture. The authors analyse the efficacy of pharmacotherapy in patients with liver cirrhosis and portal hypertension and discuss the existing recommendations on the prevention of hemorrhage with special reference to the yet unsolved problems and prospects for the improvement of therapy.


Identity and ranking of colonic mesenchymal stromal cells.
Although ongoing clinical trials utilize systemic administration of bone-marrow mesenchymal stromal cells (BM-MSCs) in Crohn's disease (CD), nothing is known about the presence and the function of mesenchymal stromal cells (MSCs) in the normal human bowel. MSCs are bone marrow (BM) multipotent cells supporting hematopoiesis with the potential to differentiate into multiple skeletal phenotypes. A recently identified new marker, CD146, allowing to prospectively isolate MSCs from BM, renders also possible their identification in different tissues. In order to elucidate the presence and functional role of MSCs in human bowel we analyzed normal adult colon sections and isolated MSCs from them. In colon (C) sections, resident MSCs form a net enveloping crypts in lamina propria, coinciding with structural myofibroblasts or interstitial stromal cells. Nine sub-clonal CD146(+) MSC lines were derived and characterized from colon biopsies, in addition to MSC lines from five other human tissues. In spite of a phenotype qualitative identity between the BM- and C-MSC populations, they were discriminated and categorized. Similarities between C-MSC and BM-MSCs are represented by: Osteogenic differentiation, hematopoietic supporting activity, immune-modulation, and surface-antigen qualitative expression. The differences between these populations are: C-MSCs mean intensity expression is lower for CD13, CD29, and CD49c surface-antigens, proliferative rate faster, life-span shorter, chondrogenic differentiation rare, and adipogenic differentiation completely blocked. Briefly, BM-MSCs, deserve the rank of progenitors, whereas C-MSCs belong to the restricted precursor hierarchy. The presence and functional role of MSCs in human colon provide a rationale for BM-MSC replacement therapy in CD, where resident bowel MSCs might be exhausted or diverted from their physiological functions.


Association study between antipsychotics- induced restless legs syndrome and polymorphisms of dopamine D1, D2, D3, and D4 receptor genes in schizophrenia.
The cause of restless legs syndrome (RLS) is not yet clear, but more promising theories involve dopaminergic deficiency and genetic causes. This study investigated whether single-nucleotide polymorphisms in the genes of dopamine receptors DRD1, DRD2, DRD3 and DRD4 are associated with antipsychotics-induced RLS in schizophrenia. We evaluated 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group and its rating scale for RLS. Genotyping was performed for the DRD1 gene -48A/G, DRD2 gene TaqI A, DRD3 gene Ser9Gly and DRD4 gene -521C/T single-nucleotide polymorphisms. The method of multifactor dimensionality reduction was used to analyze gene-gene interactions. We classified the schizophrenic patients into 96 with and 94 without RLS symptoms. The genotype frequencies of all polymorphisms investigated did not differ significantly between these 2 groups. MDR analysis did not show a significant effect of the 4 dopamine receptor gene variants on susceptibility to antipsychotic-induced RLS symptoms (p > 0.05). These genetics data suggest that the analyzed polymorphisms of the dopamine genes may not be associated with RLS symptoms in schizophrenia. Confirming the results reported here requires a larger-scale study involving patients taking specific antipsychotics.


[Experiences with the Port-A-Cath system, a fully implantable central venous access system, in children].
The Port-A-Cath-system is a totally implantable catheter system for central venous access. It consists of a subcutaneous injection port, fixed on the pectoral fascia, and a silicone catheter, positioned via a jugular vein into the right atrium. This system was utilised in 14 children (between 10 weeks and 14 years of age) for administration of chemotherapy, total parenteral nutrition, delivery of drugs or blood products, and venous blood sampling over a 15 months period. The device presents only few problems in respect of biocompatibility. Three complications occurred: one case of sepsis, one of catheter dislocation and one of catheter occlusion. The advantage of the total implantability of the system and the low complication rate are attractive alternatives to other methods of prolonged central venous access.


Electronic health record alerts for management of heart failure with reduced ejection fraction in hospitalized patients: the PROMPT-AHF trial.
Patients hospitalized for acute heart failure (AHF) continue to be discharged on an inadequate number of guideline-directed medical therapies (GDMT) despite evidence that inpatient initiation is beneficial. This study aimed to examine whether a tailored electronic health record (EHR) alert increased rates of GDMT prescription at discharge in eligible patients hospitalized for AHF. Pragmatic trial of messaging to providers about treatment of acute heart failure (PROMPT-AHF) was a pragmatic, multicenter, EHR-based, and randomized clinical trial. Patients were automatically enrolled 48 h after admission if they met pre-specified criteria for an AHF hospitalization. Providers of patients in the intervention arm received an alert during order entry with relevant patient characteristics along with individualized GDMT recommendations with links to an order set. The primary outcome was an increase in the number of GDMT prescriptions at discharge. Thousand and twelve patients were enrolled between May 2021 and November 2022. The median age was 74 years; 26% were female, and 24% were Black. At the time of the alert, 85% of patients were on β-blockers, 55% on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 20% on mineralocorticoid receptor antagonist (MRA) and 17% on sodium-glucose cotransporter 2 inhibitor. The primary outcome occurred in 34% of both the alert and no alert groups [adjusted risk ratio (RR): 0.95 (0.81, 1.12), P = .99]. Patients randomized to the alert arm were more likely to have an increase in MRA [adjusted RR: 1.54 (1.10, 2.16), P = .01]. At the time of discharge, 11.2% of patients were on all four pillars of GDMT. A real-time, targeted, and tailored EHR-based alert system for AHF did not lead to a higher number of overall GDMT prescriptions at discharge. Further refinement and improvement of such alerts and changes to clinician incentives are needed to overcome barriers to the implementation of GDMT during hospitalizations for AHF. GDMT remains suboptimal in this setting, with only one in nine patients being discharged on a comprehensive evidence-based regimen for heart failure.


The natural Disc1-deletion present in several inbred mouse strains does not affect sleep.
The gene Disrupted in Schizophrenia-1 (DISC1) is linked to a range of psychiatric disorders. Two recent transgenic studies suggest DISC1 is also involved in homeostatic sleep regulation. Several strains of inbred mice commonly used for genome manipulation experiments, including several Swiss and likely all 129 substrains, carry a natural deletion mutation of Disc1. This constitutes a potential confound for studying sleep in genetically modified mice. Since disturbed sleep can also influence psychiatric and neurodegenerative disease models, this putative confound might affect a wide range of studies in several fields. Therefore, we asked to what extent the natural Disc1 deletion affects sleep. To this end, we first compared sleep and electroencephalogram (EEG) phenotypes of 129S4 mice carrying the Disc1 deletion and C57BL/6N mice carrying the full-length version. We then bred Disc1 from C57BL/6N into the 129S4 background, resulting in S4-Disc1 mice. The differences between 129S4 and C57BL/6N were not detected in the 129S4 to S4-Disc1 comparison. We conclude that the mutation has no effect on the measured sleep and EEG characteristics. Thus, it is unlikely the widespread Disc1 deletion has led to spurious results in previous sleep studies or that it alters sleep in mouse models of psychiatric or neurodegenerative diseases.


Pilot study of minocycline in relapsing-remitting multiple sclerosis.
Current multiple sclerosis (MS) treatment is only partially effective and not all patients respond well. The goal in this study was to evaluate minocycline for its safety, tolerability, and MRI impact as a potential therapy over 36 months after a three month run-in in ten relapsing-remitting (RR) MS patients. Clinical assessments were at three month intervals until six months, then at six month intervals. Three Tesla MRI was performed monthly during the run-in and first six months of treatment, then at 12, 24, and 36 months. Treatment was safe and well tolerated. Annualized relapse rate was 1.2 during the run-in and 0.25 during treatment. The proportion of active scans was lower during the first six months of treatment (5.6%, p < 0.001) and during the extension (8.7%, p = 0.002) than during the run-in (47.5%). Consistent with these outcomes, mean T2 lesion volume remained stable over three years and percent brain volume change was reduced during year three (-0.37%) of minocycline treatment. This trial is limited by small sample and no control group but suggests that minocycline is safe and potentially beneficial in RRMS. This supports further investigation of its efficacy.


PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice.
PPARalpha is a ligand-dependent transcription factor expressed at high levels in the liver. Its activation by the drug gemfibrozil reduces clinical events in humans with established atherosclerosis, but the underlying mechanisms are incompletely defined. To clarify the role of PPARalpha in vascular disease, we crossed PPARalpha-null mice with apoE-null mice to determine if the genetic absence of PPARalpha affects vascular disease in a robust atherosclerosis model. On a high-fat diet, concentrations of atherogenic lipoproteins were higher in PPARalpha(-/-)apoE(-/-) than in PPARalpha(+/+)apoE(-/-) mice, due to increased VLDL production. However, en face atherosclerotic lesion areas at the aortic arch, thoracic aorta, and abdominal aorta were less in PPARalpha-null animals of both sexes after 6 and 10 weeks of high-fat feeding. Despite gaining as much or more weight than their PPARalpha(+/+)apoE(-/-) littermates, PPARalpha(-/-)apoE(-/-) mice had lower fasting levels of glucose and insulin. PPARalpha-null animals had greater suppression of endogenous glucose production in hyperinsulinemic clamp experiments, reflecting less insulin resistance in the absence of PPARalpha. PPARalpha(-/-)apoE(-/-) mice also had lower blood pressures than their PPARalpha(+/+)apoE(-/-) littermates after high-fat feeding. These results suggest that PPARalpha may participate in the pathogenesis of diet-induced insulin resistance and atherosclerosis.


A simple way to achieve bioinspired hybrid wettability surface with micro/nanopatterns for efficient fog collection.
Fog collection is receiving increasing attention for providing water in semi-arid deserts and inland areas. Inspired by the fog harvesting ability of the hydrophobic-hydrophilic surface of Namib desert beetles, we present a simple, low-cost method to prepare a hybrid superhydrophobic-hydrophilic surface. The surface contains micro/nanopatterns, and is prepared by incorporating femtosecond-laser fabricated polytetrafluoroethylene nanoparticles deposited on superhydrophobic copper mesh with a pristine hydrophilic copper sheet. The as-prepared surface exhibits enhanced fog collection efficiency compared with uniform (super)hydrophobic or (super)hydrophilic surfaces. This enhancement can be tuned by controlling the mesh number, inclination angle, and fabrication structure. Moreover, the surface shows excellent anti-corrosion ability after immersing in 1 M HCl, 1 M NaOH, and 10 wt% NaCl solutions for 2 hours. This work may provide insight into fabricating hybrid superhydrophobic-hydrophilic surfaces for efficient atmospheric water collection.


Superior vena cava syndrome in chronic intestinal failure patients: When the going gets tough.
Catheter-related venous thrombosis is a severe complication of home parenteral nutrition (HPN) with potentially devastating consequences such as superior vena cava syndrome (SVCS). Early recognition and awareness of factors leading to its development are of paramount importance. However, studies are lacking in HPN patients focusing on this topic. In this study, we aimed to determine the incidence of SVCS in HPN patients and describe SVCS-related outcomes. This retrospective cohort study comprised all adult HPN patients who developed SVCS between 2000 and 2022 at our national HPN referral center. Primary outcome was the incidence of SVCS. Secondary outcomes include SVCS-related symptoms, tip location of central venous access device (CVAD) post-insertion and at time of SVCS, diagnostics and treatment. SVCS was diagnosed in 38 of 616 patients (6%), with an annual cumulative incidence rate ranging between 0 and 4.2%. Most common presenting symptoms were facial edema (82%) and arm edema (50%). Post-insertion, 17% (6/36) of patients had a correct position of the CVAD tip and 11% (4/36) during SVCS diagnosis. Computed tomography was the most used diagnostic imaging technique (66%). Sixty-three percent of patients started, 11% switched, and 21% continued anticoagulant treatment. The incidence of SVCS is relatively high in our vulnerable HPN population. It is key to recognize whenever such patients present with vascular obstruction-related symptoms and treat them in an early stage by a multidisciplinary team.


Diluted hydrochloric acid generates larger radiofrequency ablation lesions in excised porcine livers.
This study evaluated the influence of continuous infusion of diluted hydrochloric acid during radiofrequency ablation (RFA) on the size of ablated lesions. Experiments were performed in 20 excised porcine livers using three different treatment modalities: (1) normal saline-enhanced RFA (NS-RFA), which was normal saline pumped into ablated tissue during RFA; (2) diluted hydrochloric acid ablation (DHAA), which was 3 mol/L diluted hydrochloric acid (HCl) injected into hepatic tissue without RFA; and (3) HCl-enhanced RFA (HCl-RFA), which was 3 mol/L diluted HCl continuously infused into ablated tissue during RFA. We produced 20 HCl-RFA and NS-RFA lesions, respectively, using a monopolar perfusion electrode connected to a commercially available radiofrequency generator, and 20 DHAA lesions using an 18-gauge Chiba needle. The ablated lesions were evaluated both macroscopically and histologically. Dimensions of lesions were compared among HCl-RFA, NS-RFA, and DHAA. The ablated lesions had an elliptical-like shape and were well-demarcated with normal liver tissue. The mean volume, longitudinal diameter, and transverse diameter of NS-RFA lesions were 11.24±0.29 cm(3), 3.4±0.07 cm, and 2.48±0.03 cm, those of HCl-RFA lesions were 58.14±3.05 cm(3), 5.51±0.05 cm, and 4.49±0.11 cm, and those of DHAA lesions were 4.41±0.16 cm(3), 2.43±0.08 cm, and 1.8±0.03 cm, respectively. The mean dimensions of HCl-RFA lesions were the largest among the three types of ablation (P < 0.001). Under the present experimental conditions, the continuous infusion of diluted HCl during RFA can generate larger ablated lesions than NS-RFA or DHAA in excised porcine livers.


Controlling solubility and modulating peripheral function in dendrimer encapsulated dyes.
The synthesis of large dendrons and dendrimers with site-isolated dyes at their core has been explored. The dyes selected for this work were coumarin 343 and pentathiophene, as energy transfer processes prevail when the two dyes are intimately mixed but each should behave independently of the other if site-isolation is achieved. Because the two dyes have very different functional characteristics, a protocol involving orthogonal protecting groups and allowing the use of a single family of electroactive dendrons for their encapsulation had to be developed. The synthetic protocol must balance the need to incorporate electroactive groups at the periphery of the dendrons with the requirement for high solubility and a size sufficient to fully encapsulate the central dye. Because of their poor solubility and tendency to crystallize, dendrons with uniform triarylamine substitution proved unsatisfactory leading to the development of new unsymmetrical dendrons with alternating branched alkyl groups and triarylamine moieties at their periphery. These dendrons, which show excellent solubility and no tendency to crystallize, were assembled into large dendrimers using a modular protocol with the light emitting dye at their core. It is expected that the large size of the dendritic shell will provide effective site-isolation for the encapsulated central dyes enabling them to exhibit their intrinsic emission properties with minimal energy transfer between neighboring core fluorophores when processed in bulk thin films.


HPLC-DAD-MS Characterization, Antioxidant Activity, α-amylase Inhibition, Molecular Docking, and ADMET of Flavonoids from Fenugreek Seeds.
Fenugreek (Trigonella foenum-graecum) has a great beneficial health effect; it has been used in traditional medicine by many cultures. Likewise, the α-amylase inhibitors are potential compounds in the development of drugs for the treatment of diabetes. The beneficial health effects of fenugreek lead us to explore the chemical composition of the seeds and their antioxidant and α-amylase inhibition activities. The flavonoid extraction from fenugreek seeds was achieved with methanol through a Soxhlet apparatus. Then, the flavonoid glycosides were characterized using HPLC-DAD-ESI-MS analysis. The antioxidant capacity of fenugreek seed was measured using DPPH, FRAP, ABTS, and CUPRAC assays. Finally, the α-amylase inhibition activity was carried out using in vitro and in silico methods. The methanolic extract was found to contain high amounts of total phenolics (154.68 ± 1.50 μg GAE/mg E), flavonoids (37.69 ± 0.73 μg QE/mg E). The highest radical-scavenging ability was recorded for the methanolic extract against DPPH (IC50 = 556.6 ± 9.87 μg/mL), ABTS (IC50 = 593.62 ± 9.35 μg/mL). The ME had the best reducing power according to the CUPRAC (A 0.5 = 451.90 ± 9.07 μg/mL). The results indicate that the methanolic extracts of fenugreek seed best α-amylase inhibition activities IC50 = 653.52 ± 3.24 μg/mL. Twenty-seven flavonoids were detected, and all studied flavonoids selected have good affinity and stabilize very well in the pocket of α-amylase. The interactions between the studied flavonoids with α-amylase were investigated. The flavonoids from fenugreek seed present a good inhibitory effect against α-amylase, which is beneficial for the prevention of diabetes and its complications.


Inhibitory effect of L-arginine on growth of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene.
The effect of L-arginine on growth of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene was studied. Growth of induced tumors was inhibited by feeding rats an arginine-enriched diet containing 5% L-arginine in addition to the necessary components for rats, including 15% milk casein. The diet significantly reduced both the rate of tumor induction and the number of tumors induced per rat. Histological examination showed that the tumors induced were more benign in rats fed the arginine-enriched diet than in those fed the control diet. A possible mechanism of the inhibitory effect of L-agrinine id discussed.


Seismic models of the root of the sierra nevada.
Seismic waves generated by earthquakes or explosions show a delay in travel times as they propagate across the Sierra Nevada from all directions except that of the Nevada test site. Early arriving waves from the test site can be explained if they emerge through a rock layer with high seismic velocity from the sharp eastern edge of the Sierran root. Such a layer could be formed by the subducted ophiolite slab that crops out in the western Sierra Nevada foothills. A synthesis of all seismic data indicates that the Sierran root projects downward into the mantle to a depth of about 55 kilometers beneath the high Sierra.


Evaluation of sentinel lymph node biopsy in clinically node-negative breast cancer.
In patients with clinically node-negative breast cancer, diagnosed with palpation and several types of imaging examination, sentinel lymph nodes accurately predict the status of the other axillary nodes, which determine the nature of subsequent adjuvant treatment. In addition, compared with axillary lymph node dissection, sentinel-node biopsy results in less postoperative morbidity, including pain, numbness, swelling, and reduced mobility in the ipsilateral arm. We analyzed the validity of the sentinel node biopsy procedure using dual-agent injection of blue dye and radioactive colloid performed in our hospital from May 2006 through March 2010. A total of 258 breasts of 253 patients were studied. Simultaneous axillary lymph node dissection was performed only if rapid intraoperative diagnosis identified metastasis in sentinel lymph nodes. The identification rate, accuracy, provisional false-negative rate, which was calculated with data from all 65 patients whose sentinel lymph nodes had metastasis, and axillary recurrence rate of sentinel node biopsy were calculated. The sentinel node identification rate was 99.2%, and the accuracy of sentinel lymph node status was 98.0%. The provisional false-negative rate was 7.7%. During an observation period averaging 24 months, axillary recurrence was observed in only 1 of 256 cases (0.4%), and there were no cases of parasternal recurrence. In patients who underwent sentinel-node biopsy without axillary lymph node dissection, there was no obvious morbidity. Our sentinel-node biopsy procedure yielded satisfactory results, which were not inferior to the results of previous clinical trials. Thus, we conclude our sentinel-node biopsy procedure is feasible. If the efficacy and safety of sentinel-node biopsy are confirmed in several large-scale randomized controlled trials in Europe and the United States, sentinel-node biopsy will become a standard surgical technique in the management of clinically node-negative breast cancer.


Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis.
To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and administration of bedaquiline, a novel oral diarylquinoline antimycobacterial agent approved by the Food and Drug Administration for the treatment of adults with pulmonary multidrug-resistant tuberculosis (MDR-TB). A search of PubMed (January 2004-May 2013) and International Pharmaceutical Abstracts (January 2004-May 2013) using the search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included proceedings of the Union World Conference on Lung Health. Preclinical data as well as Phase 1 and 2 studies published in English were evaluated. Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase. Clinical trials have been conducted evaluating the use of bedaquiline in combination with a background regimen for the treatment of adults with pulmonary MDR-TB. Bedaquiline has an excellent in vitro activity against Mycobacterium tuberculosis, including multidrug resistant M tuberculosis; however, its side effect profile limits its use against MDR-TB when no other effective regimen can be provided. Bedaquiline carries Black Box warnings for increased risk of unexplained mortality and QT prolongation. Bedaquiline is metabolized via the CYP3A4 isoenzyme and thus interacts with rifamycins and several antiretrovirals. In an era of emerging resistance and given the suboptimal efficacy and toxicity of currently available regimens for MDR-TB, bedaquiline represents a great addition to the existing armamentarium of anti-TB agents particularly in areas of the world where the disease is endemic.


Nuclear movement in filamentous fungi.
One of the most striking features of eukaryotic cells is the organization of specific functions into organelles such as nuclei, mitochondria, chloroplasts, the endoplasmic reticulum, vacuoles, peroxisomes or the Golgi apparatus. These membrane-surrounded compartments are not synthesized de novo but are bequeathed to daughter cells during cell division. The successful transmittance of organelles to daughter cells requires the growth, division and separation of these compartments and involves a complex machinery consisting of cytoskeletal components, mechanochemical motor proteins and regulatory factors. Organelles such as nuclei, which are present in most cells in a single copy, must be precisely positioned prior to cytokinesis. In many eukaryotic cells the cleavage plane for cell division is defined by the location of the nucleus prior to mitosis. Nuclear positioning is thus absolutely crucial in the unequal cell divisions that occur during development and embryogenesis. Yeast and filamentous fungi are excellent organisms for the molecular analysis of nuclear migration because of their amenability to a broad variety of powerful analytical methods unavailable in higher eukaryotes. Filamentous fungi are especially attractive models because the longitudinally elongated cells grow by apical tip extension and the organelles are often required to migrate long distances. This review describes nuclear migration in filamentous fungi, the approaches used for and the results of its molecular analysis and the projection of the results to other organisms.


A new documentation standard in the nose examination: SL classification.
The goal of this article is to present a system for standardized documentation of the findings obtained during the examination of the nose. Three levels of data recording have been established for various purposes: (1) First level: Septum-lateral nasal wall (SL) classification, (2) Second level: SL classification including seven drawings, (3) Third level: SL classification including seven drawings and a detailed questionnaire. The first level was found to be a fast, easy, and standard way to document the findings of the nose examination which facilitated follow-up as well. The addition of graphics enhanced its informative power at the second level. The third level helped to describe the proper status of the nose in detail before and after septoplasty which was invaluable for follow-up, statistical analysis, self-education, and self-assessment.


Leaflet Hypomobility After Transcatheter Aortic Valve Replacement: Thrombosis or Mechanical Factors? A Possible Pathophysiological Pattern.
Transcatheter heart valve replacement is an emerging technology in the treatment of valvular disease. During recent years, the opportunity to replace a heart valve via percutaneous access or via a miniinvasive access without the use of cardiopulmonary bypass has revolutionized the approach to this pathology. The different designs of transcatheter valves have also altered the spectrum of possible complications, with the unexpected occurrence of leaflet hypomobility after valve deployment. Here, the pathophysiological pattern of this complication is categorized, and an analysis provided of recently reported clinical evidences.


Text-Based Illness Monitoring for Detection of Novel Influenza A Virus Infections During an Influenza A (H3N2)v Virus Outbreak in Michigan, 2016: Surveillance and Survey.
Rapid reporting of human infections with novel influenza A viruses accelerates detection of viruses with pandemic potential and implementation of an effective public health response. After detection of human infections with influenza A (H3N2) variant (H3N2v) viruses associated with agricultural fairs during August 2016, the Michigan Department of Health and Human Services worked with the US Centers for Disease Control and Prevention (CDC) to identify infections with variant influenza viruses using a text-based illness monitoring system. To enhance detection of influenza infections using text-based monitoring and evaluate the feasibility and acceptability of the system for use in future outbreaks of novel influenza viruses. During an outbreak of H3N2v virus infections among agricultural fair attendees, we deployed a text-illness monitoring (TIM) system to conduct active illness surveillance among households of youth who exhibited swine at fairs. We selected all fairs with suspected H3N2v virus infections. For fairs without suspected infections, we selected only those fairs that met predefined criteria. Eligible respondents were identified and recruited through email outreach and/or on-site meetings at fairs. During the fairs and for 10 days after selected fairs, enrolled households received daily, automated text-messages inquiring about illness; reports of illness were investigated by local health departments. To understand the feasibility and acceptability of the system, we monitored enrollment and trends in participation and distributed a Web-based survey to households of exhibitors from five fairs. Among an estimated 500 households with a member who exhibited swine at one of nine selected fairs, representatives of 87 (17.4%) households were enrolled, representing 392 household members. Among fairs that were ongoing when the TIM system was deployed, the number of respondents peaked at 54 on the third day of the fair and then steadily declined throughout the rest of the monitoring period; 19 out of 87 household representatives (22%) responded through the end of the 10-day monitoring period. We detected 2 H3N2v virus infections using the TIM system, which represents 17% (2/12) of all H3N2v virus infections detected during this outbreak in Michigan. Of the 70 survey respondents, 16 (23%) had participated in the TIM system. A total of 73% (11/15) participated because it was recommended by fair coordinators and 80% (12/15) said they would participate again. Using a text-message system, we monitored for illness among a large number of individuals and households and detected H3N2v virus infections through active surveillance. Text-based illness monitoring systems are useful for detecting novel influenza virus infections when active monitoring is necessary. Participant retention and testing of persons reporting illness are critical elements for system improvement.