Compliance to donning and doffing of personal protective equipment among dental healthcare practitioners during the coronavirus pandemic: a quality improvement plan, do, study and act (PDSA) Initiative.
With the emergence of SARS-Cov-2, the Centers for Disease Control and Prevention (CDC) defined mandatory guidelines for donning and doffing personal protective equipment (PPE) among dental healthcare professionals. The study's objective was to improve the compliance of the donning and doffing protocols for PPE among dental practitioners by the Plan, Do, Study, and Act (PDSA) cycle. A quasi-experimental study was conducted on a sample of dental healthcare professionals using the non-probability purposive technique. In the first planning stage, compliance with CDC-approved donning and doffing was assessed on the clinical premises. In the second stage, an educational session was arranged with all the healthcare professionals to explain stepwise guidelines of donning and doffing to improve the quality of donning and doffing compliance. In the third stage, improvement in the quality outcome was then assessed after the session. Data were normally distributed. Qualitative variables for all the steps of donning and doffing are reported as frequency and percentages. Pareto charts were made to assess the non-compliance rate for donning and doffing protocols among dental healthcare professionals. There was an improvement of 44.55% in the hand hygiene practices before wearing the PPE after the second step of the PDSA cycle. A percentage improvement of 7.4% was recorded for removing jewellery, wearing the gown and wearing a surgical cap. No improvement was seen in securing the mask/ respirator ties, washing hands after wearing the respirator, placing the goggles or face shield practices. PDSA cycle improved the overall compliance to PPE donning and doffing practices. Most of the protocols were followed by the dental healthcare professionals; however, some of them remained the same or worsened due to ease in SARS-CoV 2 restrictions.


Graph Trilateration for Indoor Localization in Sparsely Distributed Edge Computing Devices in Complex Environments Using Bluetooth Technology.
Spatial navigation patterns in indoor space usage can reveal important cues about the cognitive health of participants. In this work, we present a low-cost, scalable, open-source edge computing system using Bluetooth low energy (BLE) beacons for tracking indoor movements in a large, 1700 m2 facility used to carry out therapeutic activities for participants with mild cognitive impairment (MCI). The facility is instrumented with 39 edge computing systems, along with an on-premise fog server. The participants carry a BLE beacon, in which BLE signals are received and analyzed by the edge computing systems. Edge computing systems are sparsely distributed in the wide, complex indoor space, challenging the standard trilateration technique for localizing subjects, which assumes a dense installation of BLE beacons. We propose a graph trilateration approach that considers the temporal density of hits from the BLE beacon to surrounding edge devices to handle the inconsistent coverage of edge devices. This proposed method helps us tackle the varying signal strength, which leads to intermittent detection of beacons. The proposed method can pinpoint the positions of multiple participants with an average error of 4.4 m and over 85% accuracy in region-level localization across the entire study area. Our experimental results, evaluated in a clinical environment, suggest that an ordinary medical facility can be transformed into a smart space that enables automatic assessment of individuals' movements, which may reflect health status or response to treatment.


Critical issues in transition and survivorship for adolescents and young adults with cancers.
The majority of children, adolescents, and young adults diagnosed with cancer will become long-term survivors with many potential years of life ahead of them. Their journey from health through diagnosis and treatment to survivorship involves multiple transitions. Transitional services that should be available throughout this journey include health-related education, health surveillance and screening, management of cancer-related complications, and psychosocial support relevant to their developmental needs. Survivors require lifelong care that focuses not only on the medical risks arising from their cancer therapy, but also the psychosocial, educational, and vocational implications of surviving cancer. Because many community health care providers lack familiarity with the health risks associated with childhood or adolescent/young adult cancer, survivors must have sufficient health knowledge to advocate for risk-based cancer-related follow-up; the provision of a treatment summary and care plan at the conclusion of their cancer therapy is an important tool for facilitating this process. The availability of resources for survivors varies by geography, health care system, and survivor characteristics. Adolescents and young adults who receive their care outside of a pediatric cancer center have particularly limited access. The limitations in cancer center resources (along with survivor preference) strongly suggest that the long-term care of survivors will need to be shared between the cancer centers and primary care providers in survivors' communities.


Equal-Volume Strength Training With Different Training Frequencies Induces Similar Muscle Hypertrophy and Strength Improvement in Trained Participants.
The main goal of the current study was to compare the effects of volume-equated training frequency on gains in muscle mass and strength. In addition, we aimed to investigate whether the effect of training frequency was affected by the complexity, concerning the degrees of freedom, of an exercise. Participants were randomized to a moderate training frequency group (two weekly sessions) or high training frequency group (four weekly sessions). Twenty-one participants (male: 11, female: 10, age: 25.9 ± 4.0) completed the 9-week whole-body progressive heavy resistance training intervention with moderate (n = 13) or high (n = 8) training frequency. Whole-body and regional changes in lean mass were measured using dual-energy x-ray absorptiometry, while the vastus lateralis thickness was measured by ultrasound. Changes in muscle strength were measured as one repetition maximum for squat, hack squat, bench press, and chest press. No differences between groups were observed for any of the measures of muscle growth or muscle strength. Muscle strength increased to a greater extent in hack squat and chest press than squat and bench press for both moderate (50 and 21% vs. 19 and 14%, respectively) and high-frequency groups (63 and 31% vs. 19 and 16%, respectively), with no differences between groups. These results suggest that training frequency is less decisive when weekly training volume is equated. Further, familiarity with an exercise seems to be of greater importance for strength adaptations than the complexity of the exercise.


Signaling mechanisms of HAMP domains in chemoreceptors and sensor kinases.
HAMP domains mediate input-output signaling in histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis proteins, and some phosphatases. HAMP subunits have two 16-residue amphiphilic helices (AS1, AS2) joined by a 14- to 15-residue connector segment. Two alternative HAMP structures in these homodimeric signaling proteins have been described: HAMP(A), a tightly packed, parallel, four-helix bundle; and HAMP(B), a more loosely packed bundle with an altered AS2/AS2' packing arrangement. Stimulus-induced conformational changes probably modulate HAMP signaling by shifting the relative stabilities of these opposing structural states. Changes in AS2/AS2' packing, in turn, modulate output signals by altering structural interactions between output helices through heptad repeat stutters that produce packing phase clashes. Output helices that are too tightly or too loosely packed most likely produce kinase-off output states, whereas kinase-on states require an intermediate range of HAMP stabilities and dynamic behaviors. A three-state, dynamic bundle signaling model best accounts for the signaling properties of chemoreceptor mutants and may apply to other transducers as well.


Genistein and daidzein stimulate hyaluronic acid production in transformed human keratinocyte culture and hairless mouse skin.
We examined the effects of the soy isoflavones genistein (Gen) and daidzein (Dai) on the production of hyaluronic acid (HA) in a transformed human keratinocyte culture and in hairless mouse skin following topical application for 2 weeks. Gen and Dai, but not the glycosides thereof, significantly enhanced the production of HA in vitro and in vivo. Histochemistry using an HA-binding protein revealed that topical Gen and estradiol raised both the density and intensity of HA staining, which was abundant in the murine dermis. It is suggested that Gen and Dai are not released from their respective glycosides in culture or murine skin. Moreover, topical Gen and Dai may prevent and improve the cutaneous alterations caused by the loss of HA in skin.


Physical properties of mixed Langmuir monolayers of polystyrene particles with poly(N,N-dimethylaminoethylmethacrylate) hairs and a poly(2-hydroxyethyl methacrylate) polymer at an air/water interface.
The effect of adding a poly(2-hydroxyethyl methacrylate) (PHEMA) polymer to a Langmuir monolayer of polystyrene particles carrying poly(N,N-dimethylaminoethylmethacrylate) hair (PDMA-PS particles) at air/water interfaces on the physical properties of the monolayer was studied. The addition of PHEMA to a PDMA-PS particle monolayer at an air/water interface gave a polymer-like monolayer at low surface pressures and a particle-like monolayer at high surface pressures. The PDMA-PS particles formed small aggregates that were dispersed throughout the PHEMA monolayer at low surface pressures, a result suggesting that the particles were trapped in the PHEMA network. Monolayers of closely packed particles were observed at higher surface pressures, suggesting that PHEMA was squeezed-out at higher surface pressures. The stiffness of the mixed monolayer was independent of the surface pressure, but increased as the ratio of PHEMA in the mixed monolayer increased. This increased stiffness was explained by the immobilization of the PDMA-PS particles by PHEMA.


Role of exonuclease and beta protein of phage lambda in genetic recombination. V. Recombination of lambda DNA in vitro.
The sequential action of lambda exonuclease and polynucleotide ligase upon redundant joint molecules is sufficient to produce intact polynucleotide chains and heat-stable, biologically active molecules of lambda DNA, whereas the action of ligase alone is insufficient. These results (a) confirm the previously described mechanism of single-strand assimilation, including a subsidiary mechanism by which the further action of lambda exonuclease is arrested when a redundant strand is completely assimilated, and (b) represent a simulation of the steps in genetic recombination that follow the formation of biparental complexes (synapsis). lambda exonuclease is postulated to catalyze a concerted reaction that includes exposure of complementary sequences, formation of heteroduplex regions, and elimination of redundant branches.


Sequence and analysis of the Arabidopsis genome.
The comprehensive analysis of the genome sequence of the plant Arabidopsis thaliana has been completed recently. The genome sequence and associated analyses provide the foundations for rapid progress in many fields of plant research, such as the exploitation of genetic variation in Arabidopsis ecotypes, the assessment of the transcriptome and proteome, and the association of genome changes at the sequence level with evolutionary processes. Nevertheless, genome sequencing and analysis are only the first steps towards a new plant biology. Much remains to be done to refine the analysis of encoded genes, to define the functions of encoded proteins systematically, and to establish new generations of databases to capture and relate diverse data sets generated in widely distributed laboratories.


[Assessing quality of life in older adults living at home: Overview and justification of fourteen relevant domains].
An increasing group of older adults living at home in the Netherlands requires proper support through the use of services. Determining important outcomes is crucial in this respect. For this specific group, broad outcomes in terms of quality of life (QoL) are relevant, focusing on the influence of services on capabilities. This article describes the development and content of the ASCOT-NL (Adult Social Care Outcomes Toolkit, Dutch version) and the EQLT (Extended Quality of Life Tool), and highlights application possibilities in the evaluation of care. Both instruments aim to measure effects of care on QoL of elderly people living at home in multiple relevant domains. The ASCOT-NL has eight domains, the EQLT includes these eight domains and adds six domains, resulting in a total of fourteen domains. The domains of the ASCOT-NL are based on the goals of social support and care; the additional domains of the EQLT are based on empirical research on QoL from the perspective of older people living at home and how care can contribute to QoL.


Bet hedging in a warming ocean: predictability of maternal environment shapes offspring size variation in marine sticklebacks.
Bet hedging at reproduction is expected to evolve when mothers are exposed to unpredictable cues for future environmental conditions, whereas transgenerational plasticity (TGP) should be favoured when cues reliably predict the environment offspring will experience. Since climate predictions forecast an increase in both temperature and climate variability, both TGP and bet hedging are likely to become important strategies to mediate climate change effects. Here, the potential to produce variably sized offspring in both warming and unpredictable environments was tested by investigating whether stickleback (Gasterosteus aculeatus) mothers adjusted mean offspring size and within-clutch variation in offspring size in response to experimental manipulation of maternal thermal environment and predictability (alternating between ambient and elevated water temperatures). Reproductive output traits of F1 females were influenced by both temperature and environmental predictability. Mothers that developed at ambient temperature (17 °C) produced larger, but fewer eggs than mothers that developed at elevated temperature (21 °C), implying selection for different-sized offspring in different environments. Mothers in unpredictable environments had smaller mean egg sizes and tended to have greater within-female egg size variability, especially at 21 °C, suggesting that mothers may have dynamically modified the variance in offspring size to spread the risk of incorrectly predicting future environmental conditions. Both TGP and diversification influenced F2 offspring body size. F2 offspring reared at 21 °C had larger mean body sizes if their mother developed at 21 °C, but this TGP benefit was not present for offspring of 17 °C mothers reared at 17 °C, indicating that maternal TGP will be highly relevant for ocean warming scenarios in this system. Offspring of variable environment mothers were smaller but more variable in size than offspring from constant environment mothers, particularly at 21 °C. In summary, stickleback mothers may have used both TGP and diversified bet-hedging strategies to cope with the dual stress of ocean warming and environmental uncertainty.


Long Noncoding RNA H19 Acts as a Competing Endogenous RNA to Mediate CTGF Expression by Sponging miR-455 in Cardiac Fibrosis.
Cardiac fibrosis is closely related to multiple cardiovascular system diseases, and noncoding RNAs (ncRNAs), including long noncoding RNA (lncRNA) and microRNA (miRNA), have been reported to play a vital role in fibrogenesis. The present study aims to investigate the potential regulatory mechanism of lncRNA H19 and miR-455 on fibrosis-associated protein synthesis in cardiac fibroblasts (CFs). miRNA microarray assay revealed 34 significantly dysregulated miRNAs, including 13 upregulated miRNAs and 21 downregulated miRNAs. Among these aberrantly expressed miRNAs, we paid attention to miR-455, which was significantly downregulated in diabetic mouse myocardium and Ang II-induced CFs. Loss- and gain-of-function experiments showed that miR-455 expression levels were negatively correlated with collagen I and III expression in Ang II-induced CFs. Bioinformatic prediction programs (TargetScan, miRanda, starBase) predicted that miR-455 targeted connective tissue growth factor (CTGF) and H19 with complementary binding sites at the 3'-untranslated region, which was validated by luciferase reporter assay. Functional validation assay demonstrated that H19 knockdown could enhance the antifibrotic role of miR-455 and attenuate the CTGF expression and further decrease fibrosis-associated protein synthesis (collagen I, III, and α-SMA). The present study reveals a novel function of the H19/miR-455 axis targeting CTGF in cardiac fibrosis, suggesting its potential therapeutic role in cardiac diseases.


Spinal manipulation and beta-endorphin: a controlled study of the effect of a spinal manipulation on plasma beta-endorphin levels in normal males.
The role of spinal manipulation in the relief of pain is becoming clearer and more demonstrable as time passes. One approach to this study is the effect of manipulation on the neurochemical mechanisms of antinociception. Chief among these is beta-endorphin, which has been found to produce a wide range of beneficial effects, especially analgesia. The intent of our study was to demonstrate the effect of spinal manipulation on plasma beta-endorphin levels. Three groups of male subjects were randomly created: the experimental, sham and control groups. All three groups were screened for symptomatology, present use of medications and the present use of innocuous stimulants, such as nicotine and caffeine. A standard protocol involving a 20-min pretest resting period, an intervention and a 40-min test period ensued. The experimental group received a manipulation in the region of the cervical spine; the placebo group received a sham maneuver with no dynamic thrust; the control group received no intervention. Samples were taken by venipuncture at -20, -5, +5, +10 and +30 min. The data were analyzed by repeated measures analysis of variance and by Scheffe's post-hoc multiple comparison tests. Plasma beta-endorphin levels were assessed by radioimmune assay technique (according to the method described by Harber and Sutton in 1984). The results of our study demonstrated a small, but statistically significant, increase in serum beta-endorphin levels in the experimental group at the 5-min postintervention point. The levels in the placebo and control groups demonstrated a steady decrease that was distinct from the response in the experimental group.(ABSTRACT TRUNCATED AT 250 WORDS)


Effective piezoelectric response of substrate-integrated ZnO nanowire array devices on galvanized steel.
Harvesting waste energy through electromechanical coupling in practical devices requires combining device design with the development of synthetic strategies for large-area controlled fabrication of active piezoelectric materials. Here, we show a facile route to the large-area fabrication of ZnO nanostructured arrays using commodity galvanized steel as the Zn precursor as well as the substrate. The ZnO nanowires are further integrated within a device construct and the effective piezoelectric response is deduced based on a novel experimental approach involving induction of stress in the nanowires through pressure wave propagation along with phase-selective lock-in detection of the induced current. The robust methodology for measurement of the effective piezoelectric coefficient developed here allows for interrogation of piezoelectric functionality for the entire substrate under bending-type deformation of the ZnO nanowires.


Idiopathic systemic granulomatous disease with encephalitis in a horse.
A 14-year-old standardbred mare with clinically suspected acute bronchitis was killed because of rapidly progressing central nervous disturbances. Necropsy revealed systemic granulomatous inflammation and vasculitis involving the lungs, thoracic lymph nodes, ribs, and liver. In the cerebrum there was a severe subacute bilateral encephalitis and malacia predominately affecting the white matter, and vasculitis with perivascular infiltration of lymphocytes, macrophages, and giant cells. A causative infectious agent could not be detected by Ziehl-Neelsen, Grocott, or Giemsa stains, by periodic acid-Schiff reaction of tissue sections, nor by bacterial and fungal cultures. Therefore, idiopathic systemic granulomatous disease (ISGD) was diagnosed and an immune-mediated pathogenesis was suspected. Inflammatory involvement of the brain has hitherto not been reported in cases of equine ISGD. This case seems to be an uncommon variant of ISGD with encephalitis and lack of dermal involvement.


Korean fermented soybean paste (Doenjang) has anti-obesity and anti-hypertensive effects via the renin-angiotensin system (RAS) in high-fat diet-induced obese rats.
The health-beneficial outcomes of doenjang, a Korean fermented food have been questioned due to its high salt content; moreover, the detailed underlying mechanisms of its health beneficial effects are not fully investigated. Thus, this study aimed to investigate doenjang's anti-obesity effects, anti-hypertensive effects, and its underlying mechanisms in high-fat diet -induced obesity. Sprague-Dawley rats fed with normal diet (ND), high-fat diet (HD), HD with 8% additive salt (HDS), or HD with doenjang containing 8% salt (HDJ) for 13 weeks. Compared to HD and HDS groups, the HDJ group had lower body and epididymal fat tissue weight gain and showed hypotrophy and hypoplasia. The RAS-related mRNA levels in the adipose tissue, including Renin and Ace were downregulated in the HDJ group compared to HD and HDS groups. Additionally, HDJ groups had significant improvements in systolic blood pressure, serum RAS-associated parameters (e.g., angiotensin II and aldosterone), renal mRNA levels related to RAS (e.g., angiotensin II receptor type 1 and 2), and aldosterone-associated mRNA expressions (e.g., mineralocorticoid receptor) in the kidney of HD-induced obese rats. Most importantly, HDS and HDJ groups showed distinct outcomes regarding adipogenesis and electrolytes metabolism, even though both diets contain a high level of salt. HDS group showed a higher epididymal fat tissue weight, mass, and adipocyte size than HDJ group. In addition, compared with HDJ group, HDS group significantly decreased the release of Na+ and K+ throughout the urine and feces. The present study addresses that doenjang has anti-obesity effects and anti-hypertensive effects by activating RAS in the adipose tissue and kidney, respectively. Additionally, this study also demonstrates that salt in doenjang and the additive salt differently influences adipogenesis and electrolytes metabolism, supporting doenjang has health advantageous effects regardless of its high salt contents.


Genomic variations in paired normal controls for lung adenocarcinomas.
Somatic genomic mutations in lung adenocarcinomas (LUADs) have been extensively dissected, but whether the counterpart normal lung tissues that are exposed to ambient air or tobacco smoke as the tumor tissues do, harbor genomic variations, remains unclear. Here, the genome of normal lung tissues and paired tumors of 11 patients with LUAD were sequenced, the genome sequences of counterpart normal controls (CNCs) and tumor tissues of 513 patients were downloaded from TCGA database and analyzed. In the initial screening, genomic alterations were identified in the "normal" lung tissues and verified by Sanger capillary sequencing. In CNCs of TCGA datasets, a mean of 0.2721 exonic variations/Mb and 5.2885 altered genes per sample were uncovered. The C:G→T:A transitions, a signature of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes in CNCs. 16 genes had a variant rate of more than 2%, and CNC variations in MUC5B, ZXDB, PLIN4, CCDC144NL, CNTNAP3B, and CCDC180 were associated with poor prognosis whereas alterations in CHD3 and KRTAP5-5 were associated with favorable clinical outcome of the patients. This study identified the genomic alterations in CNC samples of LUADs, and further highlighted the DNA damage effect of tobacco on lung epithelial cells.


Cisplatin combination chemotherapy in advanced seminoma.
Thirty-one patients were treated with cisplatin combination chemotherapy for advanced seminoma (26 Stage III or bulky Stage II testicular, and five disseminated extragonadal). Seventeen (89%) of 19 patients not previously pretreated and four (80%) of five who had received only abdominal irradiation entered continuous complete remission (CR), versus only two (28%) of seven patients who had received extensive infra- and supradiaphragmatic radiotherapy. Results were not significantly influenced by stage, human chorionic gonadotropin (HCG) titers and histologic subgroups, whereas patients with lactic dehydrogenase (LDH) values exceeding 500 mIU/ml did worse (50% continuous CR rate in 12 cases) than those with normal or less elevated titers (89% continuous CR rate in 19 cases). After a median follow-up period of 34 months (range, 12+ to 77+ months), 23 patients (74.5%) remain alive in continuous CR, two (6%) died in CR and another one (3%) entered CR after deferred treatment of residual disease. Five patients (16%) died of cancer. Toxicity was severe in extensively irradiated patients, but it was acceptable in those not pretreated and in those who had received only subdiaphragmatic radiotherapy. Cisplatin combination chemotherapy can be successfully and safely used as the primary treatment of choice in patients with advanced seminoma. It is also an excellent salvage therapy for patients who had received subdiaphragmatic irradiation only. On the contrary, it is very difficult to treat with chemotherapy extensively irradiated patients.


Search for the genes involved in oocyte maturation and early embryo development in the hen.
The initial stages of development depend on mRNA and proteins accumulated in the oocyte, and during these stages, certain genes are essential for fertilization, first cleavage and embryonic genome activation. The aim of this study was first to search for avian oocyte-specific genes using an in silico and a microarray approaches, then to investigate the temporal and spatial dynamics of the expression of some of these genes during follicular maturation and early embryogenesis. The in silico approach allowed us to identify 18 chicken homologs of mouse potential oocyte genes found by digital differential display. Using the chicken Affymetrix microarray, we identified 461 genes overexpressed in granulosa cells (GCs) and 250 genes overexpressed in the germinal disc (GD) of the hen oocyte. Six genes were identified using both in silico and microarray approaches. Based on GO annotations, GC and GD genes were differentially involved in biological processes, reflecting different physiological destinations of these two cell layers. Finally we studied the spatial and temporal dynamics of the expression of 21 chicken genes. According to their expression patterns all these genes are involved in different stages of final follicular maturation and/or early embryogenesis in the chicken. Among them, 8 genes (btg4, chkmos, wee, zpA, dazL, cvh, zar1 and ktfn) were preferentially expressed in the maturing occyte and cvh, zar1 and ktfn were also highly expressed in the early embryo. We showed that in silico and Affymetrix microarray approaches were relevant and complementary in order to find new avian genes potentially involved in oocyte maturation and/or early embryo development, and allowed the discovery of new potential chicken mature oocyte and chicken granulosa cell markers for future studies. Moreover, detailed study of the expression of some of these genes revealed promising candidates for maternal effect genes in the chicken. Finally, the finding concerning the different state of rRNA compared to that of mRNA during the postovulatory period shed light on some mechanisms through which oocyte to embryo transition occurs in the hen.


Electrochemotherapy - A locoregional therapy with well-established palliative effect in patient with large recurrent lesion of head and neck.
Electrochemotherapy (ECT) is a well established treatment strategy for skin tumors of different histology. The aim of this study was to evaluate the feasibility and efficacy of electrochemotherapy in the palliative setting in patients with head and neck malignancies, already treated with surgery and/or radio-chemotherapy with no other therapeutic option. Thirty-six patients with a loco-regional M0/M1 relapse with no other therapeutic option not suitable for a cure with a radical intent by surgery or RT and not suitable for systemic therapy and/or already treated with it, were admitted to electrochemotherapy (ECT) protocol treatment. ECT was performed according ESOPE guidelines. Clinical features, treatment response, and adverse effects were evaluated 15, 30 days and then every months after the treatment. An overall response of 100% was observed. Only 3 patients out 36 showed a CR. Overall survival probability at 12 months was 41.6% (median OS: 9 months). In all patient, an improvement of quality of life in terms of pain, bleeding events were observed, while need for medical assistance or dressing was significantly reduced 1 month after electrochemotherapy (p < 0.001). Electrochemotherapy is an effective palliative treatment of non-resectable head and neck malignancies able. Due to the ECT limited side effects, its early use would be desirable to obtain a better local control of the disease and improve quality of life of patients.


Vapocoolant spray vs subcutaneous lidocaine injection for reducing the pain of intravenous cannulation: a randomized, controlled, clinical trial.
We compared the efficacy, acceptability, and safety of a topical vapocoolant alkane spray and 1% plain s.c. lidocaine in reducing pain from i.v. cannulation. This was a non-blinded, randomized, controlled trial, in a large emergency department. Adult patients requiring i.v. cannulation were enrolled. The vapocoolant was administered from a pressure pack, at a distance of 12 cm for 2 s, and cannulation was undertaken within 15 s. Alternatively, 1% plain lidocaine 0.2 ml was administered s.c. using a 27 G needle, and cannulation was undertaken after a minimum of 30 s. The primary outcomes were anaesthetic administration and cannulation pain (0-100 mm visual analogue scale). Convenience of anaesthetic use and patient satisfaction were measured using a five-point Likert scale. One hundred and ten patients were enrolled in each group. The groups did not differ in age, gender, cannulation anxiety, cannulator experience, cannulation indication or site, or cannula size. Median anaesthetic administration pain scores were 0 and 11 mm in the vapocoolant and lidocaine groups, respectively (P<0.001). Median cannulation pain scores were 9 and 0 mm, respectively (P<0.001). Vapocoolant was associated with greater cannulation success (83.6% vs 67.3%, P=0.005), less time to administer (median 9.0 vs 84.5 s, P<0.001), and more staff convenience (median 5 vs 4, P<0.001). Median patient satisfaction was 4 in both groups. Unexpected events were rare and minor. Although vapocoolant reduces cannulation pain less than lidocaine, it has a number of important advantages. Vapocoolant offers a useful alternative in the emergency department setting.


Effect of the Distillation Time on the Chemical Composition, Antioxidant Potential and Antimicrobial Activity of Essential Oils from Different Cannabis sativa L. Cultivars.
Within the unavoidable variability of various origins in the characteristics of essential oils, the aim of this study was to evaluate the effect of the distillation time on the chemical composition and biological activity of Cannabis sativa essential oils (EOs). The dry inflorescences came from Carmagnola, Kompolti, Futura 75, Gran Sasso Kush and Carmagnola Lemon varieties from Abruzzo region (Central Italy), the last two being new cultivar here described for the first time. EOs were collected at 2 h and 4 h of distillation; GC/MS technique was applied to characterize their volatile fraction. The EOs were evaluated for total polyphenol content (TPC), antioxidant capacity (AOC) and antimicrobial activity against food-borne pathogens and spoilage bacteria. The time of distillation particularly influenced EOs chemical composition, extracting more or less terpenic components, but generally enriching with minor sesquiterpenes and cannabidiol. A logical response in ratio of time was observed for antioxidant potential, being the essential oils at 4 h of distillation more active than those distilled for 2 h, and particularly Futura 75. Conversely, except for Futura 75, the effect of time on the antimicrobial activity was variable and requires further investigations; nevertheless, the inhibitory activity of all EOs against Pseudomonas fluorescens P34 was an interesting result.


Mirenas against malignancy: an alternative to operative management.
Complex atypical hyperplasia is a recognised precursor to endometrial cancer, the most common gynaecological cancer of the Western World, with hysterectomy being the first line of management. With the increasing elderly population size and BMI, optimal surgical management can be challenging in a sub-set of patients. Levonorgestrol releasing IUS system (Mirena coil) has been identified as a treatment for those unsuitable for surgical management. To assess the efficacy of Mirena coils in the treatment of endometrial cancers and complex atypical hyperplasia in our patient population. Retrospective analysis of all type 1 endometrial cancers and CAH diagnosed in Tayside from April 2011 to March 2016 (duration 5 years) managed by a Mirena coil. Primary outcome was resolution of malignancy on biopsy. Secondary outcome was continuation of treatment. Two hundred nineteen out of 245 eligible endometrial cancers and 38 of 41 CAH case notes were available for assessment. A Mirena coil was the primary mode of treatment in eight endometrial cancers (3.6%) and 18 cases of CAH (47.4%). Of the eight endometrial cancers treated, five (62%) continued with the Mirena coil as the primary mode of treatment. Two patients died during their follow-up due to unrelated illnesses and one patient proceeded to hysterectomy due to the absence of progestogenic effect on repeat Pipelle biopsy at six months (12.5%). Four patients have been followed for one year and of those; two showed no evidence of malignancy, one was unable to be biopsied and the last showed persistent disease but was too frail for intervention. At two-year follow-up, two patients remain with one showing disease recurrence. Thirteen patients (87%) have continued to use the Mirena as management of CAH out of 18 treatments. Of the five patients who did not continue with the IUS; two patients had progressive disease, despite the coil (11%), two patients lost enough weight to proceed to hysterectomy and one patient died unexpectedly. Medical co-morbidities and BMI were the main cited reasons for proceeding with the IUS as the primary treatment. Average BMI of endometrial cancer cases was 43.9 and 45.1 for CAH. Mirena coil is effective in treating or controlling the progression of endometrial malignancy in the subgroup of patients where there is an increased risk associated with definitive surgery. The treatment failure rate appears to be consistent at about one-tenth of the cohort of women with both endometrial cancers and complex atypical hyperplasia.


Microtubules in root hairs.
The microtubules of root hairs of Raphanus sativus, Lepidium sativum, Equisetum hyemale, Limnobium stoloniferum, Ceratopteris thalictroides, Allium sativum and Urtica dioica were investigated using immunofluorescence and electron microscopy. Arrays of cortical microtubules were observed in all hairs. The microtubules in the hairs show net axial orientations, but in Allium and Urtica helical microtubule patterns are also present. Numerical parameters of microtubules in Raphanus, Equisetum and Limnobium were determined from dry-cleave preparations. The results are discussed with respect to cell wall deposition and cell morphogenesis.


[Properties of urease immobilized on the functional organic silica surface].
The paper deals with kinetics of the urea hydrolysis by microbial-origin urease dissolved and immobilized on the organic silica surface. It is shown that hydrolysis kinetics for soluble urease is described by the Michaelis-Menten equation until the concentration of urea reaches 1 M. Two fractions differing in the Michaelis constant are revealed for silochrome immobilized urease. The rate of urea hydrolysis by native and immobilized urease was studied depending on the pH value in presence of the substrate in the 1 M and 5 mM concentration. The hydrolysis rate of 1 M urea in the buffer-free solution by silochrome-immobilized urease is practically independent of pH within 4.5-6.5. Application of a 2.5 mM phosphate-citrate buffer as a solvent causes an increase in the hydrolysis rate within this pH range. For a soluble urease the 1 M urea hydrolysis rate dependence on pH is ordinary at pH 5.8-6.0. If the substrate concentration is 5 mM, the pH-dependences for the rate of the urea hydrolysis by silochrome- and aerosil-immobilized urease are close and at pH above 6.0 coincide with those for a soluble enzyme. The found differences in the properties of soluble and immobilized ureases are explained by the substrate and reaction products diffusion.


Measuring b-galactosidase activity in opaque dairy solutions under optimum conditions for galactooligosaccharide synthesis by isothermal titration calorimetry.
The dairy industry uses enzymes to make cheese, alter product flavor, and eliminate lactose. The activities of these enzymes have been measured in clear buffered solutions, but because of the limitations of spectrophotometric methods, enzyme activities have not been measured in opaque or colored dairy products where they are used. Isothermal titration calorimetry (ITC) can be used to determine reaction kinetics in opaque and colored solutions by measuring the heat rate (thermal power) from enzyme-catalyzed reactions as a function of time. This study used ITC to measure β-galactosidase activity in opaque solutions of milk, sweet whey, sweet whey permeate, acid whey, and acid whey permeate with 2 β-galactosidase (EC 126.96.36.199) isozymes derived from A. oryzae and K. lactis. The components of the dairy fluids alter the enzyme kinetics and reaction thermodynamics, and the reactions catalyzed by the 2 homologs differ as shown by differing thermodynamic profiles. The study demonstrates that ITC can be used to measure enzyme activity in opaque and colored dairy fluids and identify reactions by their thermodynamic properties.


CORAL: Monte Carlo Method to Predict Endpoints for Medical Chemistry.
The applications of optimal molecular descriptors as a tool to predict endpoints related to medicinal chemistry are listed. The general scheme of building up of the optimal descriptors is represented in detail. Simplified molecular input-line entry system (SMILES) is being used to represent the molecular architecture. The optimal descriptor is the sum of correlation weights of molecular fragments extracted from SMILES. The numerical data on the correlation weights are calculated by the Monte Carlo method. The data should provide maximal correlation coefficient between experimental values of endpoint and corresponding values of the optimal descriptor. The scheme contains two phases: (i) selection of reliable parameters of the Monte Carlo optimization; and (ii) building up a model. The mechanistic interpretation for models based on the optimal descriptors is suggested. The interpretation is calculated on results of several runs of the Monte Carlo optimization. The domain of applicability for these models is defined according to the prevalence of molecular fragments in the training and calibration sets.


Integrated Low-Rank-Based Discriminative Feature Learning for Recognition.
Feature learning plays a central role in pattern recognition. In recent years, many representation-based feature learning methods have been proposed and have achieved great success in many applications. However, these methods perform feature learning and subsequent classification in two separate steps, which may not be optimal for recognition tasks. In this paper, we present a supervised low-rank-based approach for learning discriminative features. By integrating latent low-rank representation (LatLRR) with a ridge regression-based classifier, our approach combines feature learning with classification, so that the regulated classification error is minimized. In this way, the extracted features are more discriminative for the recognition tasks. Our approach benefits from a recent discovery on the closed-form solutions to noiseless LatLRR. When there is noise, a robust Principal Component Analysis (PCA)-based denoising step can be added as preprocessing. When the scale of a problem is large, we utilize a fast randomized algorithm to speed up the computation of robust PCA. Extensive experimental results demonstrate the effectiveness and robustness of our method.


Estrogen receptor β expression in the mouse forebrain: age and sex differences.
Estrogen receptors regulate multiple brain functions, including stress, sexual, and memory-associated behaviors as well as controlling neuroendocrine and autonomic function. During development, estrogen signaling is involved in programming adult sex differences in physiology and behavior. Expression of estrogen receptor α changes across development in a region-specific fashion. By contrast, estrogen receptor β (ERβ) is expressed in many brain regions, yet few studies have explored sex and developmental differences in its expression, largely because of the absence of selective reagents for anatomical localization of the protein. This study utilized bacterial artificial chromosome transgenic mice expressing ERβ identified by enhanced green fluorescent protein (EGFP) to compare expression levels and distribution of ERβ in the male and female mouse forebrain on the day of birth (P0), on postnatal day 4 (P4), and on P21. By using qualitative analysis, we mapped the distribution of ERβ-EGFP and found developmental alterations in ERβ expression within the cortex, hippocampus, and hypothalamic regions including the arcuate, ventromedial, and paraventricular nuclei. We also report a sex difference in ERβ in the bed nucleus of the stria terminalis, with males showing greater expression at P4 and P21. Another sex difference was found in the anteroventral periventricular nucleus of P21, but not P0 or P4, mice, in which ERβ-EGFP-immunoreactive cells were densely clustered near the third ventricle in females but not males. These developmental changes and sex differences in ERβ indicate a mechanism through which estrogens might differentially affect brain functions or program adult physiology at select times during development.


The prominent proteins expressed in healthy gingiva: a pilot exploratory tissue proteomics study.
Gingiva is a unique tissue which protects the underlying periodontal tissues from consistent mechanical and bacterial aggressions. Molecular analysis of gingiva is likely to improve our understanding of the underlying biological processes at work. The aim of this preliminary exploratory study is to analyze the proteomic profile of healthy gingiva and to detect prominently expressed proteins. Gingival tissue samples were obtained from periodontally healthy individuals who underwent surgical crown lengthening procedure. After protein isolation, two dimensional gel electrophoresis (2DE) gels were prepared for each sample and only protein spots common to all gels were selected to eliminate the bias caused by the effect of individuals on proteomic profile. Following the 2DE; in-gel tryptic digestion and MALDI-TOF/TOF steps were performed for protein identifications. Forty-seven proteins were successfully identified. The identified proteins were classified based on their classes, molecular functions and involvements in biological processes and metabolic pathways. Among them, 14-3-3 protein sigma, Protein DJ-1, Alpha-enolase, Triosephosphate isomerase, Superoxide dismutase, Peroxiredoxin-1, Protein S100-A9, Galectin-7, Annexin A2/A4, Carbonic anhydrase 1 and chaperone proteins are worthy of attention. The proteomic profile of the gingiva reflected its highly dynamic characteristics. Despite complexity of the gingival tissue proteome, 2DE was an effective approach in studying the common protein expression profile of the gingiva. Considering the significance of gingiva in the formation of periodontal diseases, it is important to generate a detailed proteome map of gingival tissue to set up a bridge between molecular events and the disease formation. This study established an initial proteome map of the gingival tissue from healthy individuals.


Stress-induced aberrations in sensory processing predict worse cognitive outcomes in healthy aging adults.
It is well recognized that not all individuals age equivalently, with functional dependence attributable, at least in part, to stress accumulated across the lifespan. Amongst these dependencies are age-related declines in cognitive function, which may be the result of impaired inhibitory processing (e.g., sensory gating). Herein, we examined the unique roles of life and biological stress on somatosensory gating dynamics in 74 adults (22-72 years old). Participants completed a sensory gating paired-pulse electrical stimulation paradigm of the right median nerve during magnetoencephalography (MEG) and data were subjected to advanced oscillatory and time-domain analysis methods. We observed separable mechanisms by which increasing levels of life and biological stress predicted higher oscillatory gating ratios, indicative of age-related impairments in inhibitory function. Specifically, elevations in life stress significantly modulated the neural response to the first stimulation in the pair, while elevations in biological stress significantly modulated the neural response to the second stimulation in the pair. In contrast, neither elevations in life nor biological stress significantly predicted the gating of time-domain neural activity in the somatosensory cortex. Finally, our study is the first to link stress-induced decline in sensory gating to cognitive dysfunction, suggesting that gating paradigms may hold promise for detecting discrepant functional trajectories in age-related pathologies in the future.


Deodorization of Garlic Breath by Foods, and the Role of Polyphenol Oxidase and Phenolic Compounds.
Garlic causes a strong garlic breath that may persist for almost a day. Therefore, it is important to study deodorization techniques for garlic breath. The volatiles responsible for garlic breath include diallyl disulfide, allyl mercaptan, allyl methyl disulfide, and allyl methyl sulfide. After eating garlic, water (control), raw, juiced or heated apple, raw or heated lettuce, raw or juiced mint leaves, or green tea were consumed immediately. The levels of the garlic volatiles on the breath were analyzed from 1 to 60 min by selected ion flow tube mass spectrometry (SIFT-MS). Garlic was also blended with water (control), polyphenol oxidase (PPO), rosemarinic acid, quercetin or catechin, and the volatiles in the headspace analyzed from 3 to 40 min by SIFT-MS. Raw apple, raw lettuce, and mint leaves significantly decreased all of the garlic breath volatiles in vivo. The proposed mechanism is enzymatic deodorization where volatiles react with phenolic compounds. Apple juice and mint juice also had a deodorizing effect on most of the garlic volatiles but were generally not as effective as the raw food, probably because the juice had enzymatic activity but the phenolic compounds had already polymerized. Both heated apple and heated lettuce produced a significant reduction of diallyl disulfide and allyl mercaptan. The presence of phenolic compounds that react with the volatile compounds even in the absence of enzymes is the most likely mechanism. Green tea had no deodorizing effect on the garlic volatile compounds. Rosmarinic acid, catechin, quercetin, and PPO significantly decreased all garlic breath volatiles in vitro. Rosmarinic acid was the most effective at deodorization.


Improving P-gp expression in human mononuclear cells in vitro transfected by multidrug resistance-1 mRNA.
To evaluate the expression and function activity of P-glycoprotein (P-gp) in human mononuclear cells (MNCs) in vitro transfected by multidrug resistance-1 (MDR1) mRNA. Two MDR1 cDNA vectors, pT7TS_MDR1 and pGEM5Zf(+)_MDR1, were constructed and transcripted in vitro. Vector pGEM5Zf(+)_MDR1 only contained the coding region of mdr1 cDNA, and pT7TS_MDR1 also included Xeponus beta-globin 5' and 3' untranslated region. MNCs were prepared from peripheral blood of parvicellular lung cancer patient. The two human mdrl mRNAs were then transferred into human MNCs in vitro by DOTAP. And the expression efficiency and pump function of P-gp were measured with flow cytometry. Expression of P-gp significantly elevated in both transferred cells compared with untransferred cells (P < 0.01). And pT7TS_MDR1 showed higher capability in elevating the expression of P-gp than pGEM5Zf(+)_MDR1 (P < 0.01). The P-gp function was elevated in both pT7TS_MDR1 and pGEM5Zf(+) MDR1 groups. The survival ratio of MNCs in erythrocyte-lysis-solution (ELS, 86.07%) and lymphocyte-isolation-solution (LIS, 83.67%) had no significant difference. The CD34+ cells content of the MNCs used for transfection was 2.65% and 1.01% in ELS and LIS group, respectively (P < 0.01). It is a feasible approach to improve P-gp expression in human MNCs by transfection of MDR-1 mRNA. And the ELS may be more suitable for purifing MNCs for mRNA transfection than LIS.


Molecular dynamics simulations of the bacterial UraA H+-uracil symporter in lipid bilayers reveal a closed state and a selective interaction with cardiolipin.
The Escherichia coli UraA H+-uracil symporter is a member of the nucleobase/ascorbate transporter (NAT) family of proteins, and is responsible for the proton-driven uptake of uracil. Multiscale molecular dynamics simulations of the UraA symporter in phospholipid bilayers consisting of: 1) 1-palmitoyl 2-oleoyl-phosphatidylcholine (POPC); 2) 1-palmitoyl 2-oleoyl-phosphatidylethanolamine (POPE); and 3) a mixture of 75% POPE, 20% 1-palmitoyl 2-oleoyl-phosphatidylglycerol (POPG); and 5% 1-palmitoyl 2-oleoyl-diphosphatidylglycerol/cardiolipin (CL) to mimic the lipid composition of the bacterial inner membrane, were performed using the MARTINI coarse-grained force field to self-assemble lipids around the crystal structure of this membrane transport protein, followed by atomistic simulations. The overall fold of the protein in lipid bilayers remained similar to the crystal structure in detergent on the timescale of our simulations. Simulations were performed in the absence of uracil, and resulted in a closed state of the transporter, due to relative movement of the gate and core domains. Anionic lipids, including POPG and especially CL, were found to associate with UraA, involving interactions between specific basic residues in loop regions and phosphate oxygens of the CL head group. In particular, three CL binding sites were identified on UraA: two in the inner leaflet and a single site in the outer leaflet. Mutation of basic residues in the binding sites resulted in the loss of CL binding in the simulations. CL may play a role as a "proton trap" that channels protons to and from this transporter within CL-enriched areas of the inner bacterial membrane.


A Tailored Advice Tool to Prevent Injuries Among Novice Runners: Protocol for a Randomized Controlled Trial.
Besides the beneficial health effects of being active, running is associated with a risk of sustaining injuries. Runners need to change their behavior to increase the use of effective measures and subsequently reduce the number of running-related injuries. The RunFitCheck intervention was developed according to an evidence- and practice-based approach to stimulate injury-preventive behavior among novice runners. This paper describes the study design in detail. A randomized controlled trial with a follow-up period of 5 months will be conducted. The participants will be novice runners. At enrollment, participants will be asked to report injury-preventive measures they usually take during their running activities. After completing the enrollment questionnaire, participants will be randomized to intervention and control groups. The intervention group will have access to the RunFitCheck intervention; the control group will perform their running activities as usual. Participants will be asked to report retrospectively in detail what they have done regarding injury prevention during their running activities at 1, 3, and 5 months after enrollment. Descriptive analyses will be conducted for different baseline variables in the intervention and control group. Relative risks and 95% CIs will be used to analyze behavioral changes according to the intention-to-treat principle. The project was funded in 2016 and enrollment was completed in 2017. Data analysis is currently under way and the results are expected to be submitted for publication in 2019. To nullify the negative side effects of running, prevention of training errors is desirable. As the use of injury prevention measures is not compulsory in running, a behavioral change is necessary to increase the use of effective injury-preventive measures and to prevent running-related injuries. Netherlands Trial Register NTR6381; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6381 (Archived by WebCite at http://www.webcitation.org/736Xjm5jv). RR1-10.2196/9708.


Subcuticular suture compared with staples for skin closure after cesarean delivery: a randomized controlled trial.
To compare subcuticular sutures with staples for skin closure after cesarean delivery in a randomized trial in which each woman was her own control. Women undergoing cesarean delivery (primary, n=32; repeat, n=31) were randomized to side distribution of skin closure methods with one side of the skin incision closed with staples and the other side closed with subcuticular suture. The primary outcome was the overall preferred side of the scar 6 months postoperatively. Additional outcomes were women's preferred method of closure and cosmetically preferred side of the scar, difference in objective cosmetic scores (assessed by two plastic surgeons), and pain between the two sides of the scar and infection rate. Significantly more women preferred the stapled side, both overall (odds ratio [OR] 2.55; 95% confidence interval [CI] 1.18-5.52) and cosmetically (OR 2.67; 95% CI 1.24-5.74), and reported staples as their preferred technique (OR 2.00; 95% CI 1.10-3.64). There were no significant differences in pain scores at any time. One plastic surgeon preferred the stapled side (OR 2.8; 95% CI 1.01-7.78) and scored it significantly higher on a cosmetic visual analog scale (P=.031); the other found no significant difference. There were four (6.8%) cases of infection-three on the sutured side and one bilateral. Staples were preferred to subcuticular suture for skin closure by women after cesarean delivery. ClinicalTrials.gov; www.clinicaltrials.gov; NCT01217567. : I.


The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein.
Saccharomyces telomeres consist of approximately 350 bp of C(1-3)A/TG(1-3) DNA. Most of this approximately 350 bp is replicated by standard, semiconservative DNA replication. After conventional replication, the C(1-3)A strand is degraded to generate a long single strand TG(1-3) tail that can serve as a substrate for telomerase. Cdc13p is a single strand TG(1-3) DNA-binding protein that localizes to telomeres in vivo. Genetic data suggest that the Cdc13p has multiple roles in telomere replication. We used two hybrid analysis to demonstrate that Cdc13p interacted with both the catalytic subunit of DNA polymerase alpha, Pol1p, and the telomerase RNA-associated protein, Est1p. The association of these proteins was confirmed by biochemical analysis using full-length or nearly full-length proteins. Point mutations in either CDC13 or POL1 that reduced the Cdc13p-Pol1p interaction resulted in telomerase mediated telomere lengthening. Over-expression of the carboxyl terminus of Est1p partially suppressed the temperature sensitive lethality of a cdc13-1 strain. We propose that Cdc13p's interaction with Est1p promotes TG(1-3) strand lengthening by telomerase and its interaction with Pol1p promotes C(1-3)A strand resynthesis by DNA polymerase alpha.


Do physician-payment mechanisms affect hospital utilization? A study of Health Service Organizations in Ontario.
To determine whether payment of primary care physicians based on capitation, with an additional incentive payment for low hospital-utilization rates, resulted in lower hospital-utilization rates among patients of these physicians than among patients of physicians still paid on a fee-for-service basis. Retrospective cohort study. Capitation-based and fee-for-service primary care practices in Ontario. Thirty-nine physicians whose method of payment was converted from fee-for-service to capitation during the period from June 1985 to January 1989 and 7 physicians who remained in fee-for-service practice, two of whom were matched with one physician in capitation-based practice on the basis of practice location, type of practice (academic v. community), hours of practice (part-time v. full-time), years since graduation, physician group size, practice size (number of patients), type of group (primary care v. multispecialty), sex, certification in family medicine, country of graduation (Canada v. other) and age. One physician in capitation-based practice was matched with only one physician in fee-for-service practice. Annual hospital-utilization rates (hospital separations or hospital days per 1000 patients in each practice) for the physicians paid on a capitation basis 3 years before, 1 year before and 3 years after they converted from fee-for-service payment and at corresponding periods for the matched physicians still paid on a fee-for-service basis. The mean annual rate of hospital days used, adjusted for the age and sex of patients as well as for their social-program-recipient status, fell from 1085 per 1000 patients (3 years before the conversion date) to 1030 (1 year before conversion) and to 954 (3 years after conversion) in capitation-based practices. For the matched physicians in fee-for-service practice, the rates during the corresponding periods were 1085, 1035 and 956 hospital days per 1000 patients. The pattern was similar for rates of hospital separations, adjusted for patient's age, sex and social-program-recipient status. There were no statistically significant differences between the rates of hospital utilization among patients of physicians in capitation-based practices and the rates among those of physicians in fee-for-service practices during each of the three periods, nor were there significant differences in the changes in rates. Capitation payment, with an additional incentive payment to encourage low hospital-utilization rates, did not reduce hospital use. Factors other than the method of physician payment appear to be responsible for the variations in hospital utilization among practices.


Long-Term Effects of Bevacizumab on Vestibular Schwannoma Volume in Neurofibromatosis Type 2 Patients.
Introduction Bevacizumab offers a medical treatment that may slow the growth of vestibular schwannomas (VS) and possibly preserve hearing in patients with neurofibromatosis type 2 (NF2). This study aims to investigate the effect of long-term bevacizumab treatment on VS progression. Methods Demographic, clinical, audiometric, and radiographic data were collected from the medical records of NF2 patients treated with bevacizumab at a tertiary medical center. Results Eleven tumors from seven NF2 patients treated with bevacizumab were analyzed. The median age was 17 years (range: 12-47 years). Median bevacizumab treatment time was 33 months (range: 12-74 months). Of five patients with serviceable hearing pretreatment, one (20%) maintained serviceable hearing during bevacizumab therapy. Significantly slower growth rates for both tumor diameters and tumor volumes were identified during active bevacizumab treatment. Median tumor diameters and volumes during active bevacizumab treatment were 0 cm/year (range: -0.13-0.17 cm/year) and 0.1 cm 3 /year (range: -0.92-0.41), compared with 0.37 cm/year (range: 0-1.5 cm/year, p = 0.0011) and 1.38 cm 3 /year (range: 0.013-3.74), respectively, without bevacizumab treatment ( p = 0.0263). Reduced tumor progression was noted with bevacizumab treatment utilizing both linear greatest diameter (hazard ratio 0.16, p = 0.006) and segmentation volumes (hazard ratio 0.15, p = 0.023). Complications of bevacizumab treatment included fatigue (43%), nausea/vomiting (43%), hypertension (43%), epistaxis (29%), and proteinuria (29%). One subject had a cerebrovascular accident detected on screening magnetic resonance imaging without symptoms or neurological sequelae. Discussion Bevacizumab may reduce tumor growth rate and the risk of progression based on both volumetric and linear measurements.


Exogenous ghrelin attenuates endotoxin fever in rats.
Ghrelin is a gut-derived peptide that plays a role in energy homeostasis. Recent studies have implicated ghrelin in systemic inflammation, showing increased plasma ghrelin levels after endotoxin (lipopolysaccharide, LPS) administration. The aims of this study were (1) to test the hypothesis that ghrelin administration affects LPS-induced fever; and (2) to assess the putative effects of ghrelin on plasma corticosterone secretion and preoptic region prostaglandin (PG) E(2) levels in euthermic and febrile rats. Rats were implanted with a temperature datalogger capsule in the peritoneal cavity to record body core temperature. One week later, they were challenged with LPS (50 μg/kg, intraperitoneal, i.p.) alone or combined with ghrelin (0.1mg/kg, i.p.). In another group of rats, plasma corticosterone and preoptic region PGE(2) levels were measured 2h after injections. In euthermic animals, systemic administration of ghrelin failed to elicit any thermoregulatory effect, and caused no significant changes in basal plasma corticosterone and preoptic region PGE(2) levels. LPS caused a typical febrile response, accompanied by increased plasma corticosterone and preoptic PGE(2) levels. When LPS administration was combined with ghrelin fever was attenuated, corticosterone secretion further increased, and the elevated preoptic PGE(2) levels were relatively reduced, but a correlation between these two variables (corticosterone and PGE(2)) failed to exist. The present data add ghrelin to the neurochemical milieu controlling the immune/thermoregulatory system acting as an antipyretic molecule. Moreover, our findings also support the notion that ghrelin attenuates fever by means of a direct effect of the peptide reducing PGE(2) production in the preoptic region.


Hand-held Optical Coherence Tomography Monitoring of Submillimeter Retinoblastoma Treated with Indocyanine Green-enhanced Transpupillary Therapy.
Over recent years, hand-held optical coherence tomography (HH-OCT) has become critical for retinoblastoma diagnosis and management. We report precise HH-OCT findings in a case of sub-millimeter retinoblastoma treated with foveal-sparing indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT). A 2-month-old Caucasian female with bilateral Group B retinoblastoma showed two recurrent macular tumors in the right eye, demonstrating 88 μm and 37 μm of growth to 344 μm and 413 μm in thickness, respectively, on HH-OCT. Each was treated with additional intravenous chemotherapy and foveal-sparing ICG-TTT. Tumor regression to 154 μm and 224 μm was documented on HH-OCT and maintained on follow-up. HH-OCT is vital in confirming clinical findings and influencing management decisions in retinoblastoma. In this case, HH-OCT precisely documented submillimeter retinoblastoma recurrence and treatment response.


The Use of Molecular Subtypes for Precision Therapy of Recurrent and Metastatic Gastrointestinal Stromal Tumor.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor in the digestive tract. Tyrosine kinase inhibitors (TKIs), represented by imatinib, sunitinib, and regorafenib, have become the main treatment for recurrent and metastatic GISTs. With the wide application of mutation analysis and the precision medicine, molecular characteristics have been determined that not only predict the prognosis of patients with recurrent and metastatic GISTs, but also are closely related to the efficacy of first-, second- and third-line TKIs for GISTs, as well as other TKIs. Despite the significant effects of TKIs, the emergence of primary and secondary resistance ultimately leads to treatment failure and tumor progression. Currently, due to the signal transmission of KIT/PDGFRA during onset and tumor progression, strategies to counteract drug resistance include the replacement of TKIs and the development of new drugs that are directed towards carcinogenic mutations. In addition, it is also the embodiment of precision medicine for GISTs to explore new carcinogenic mechanisms and develop new drugs relying on new biotechnology. Surgery can benefit specific patients but its major purpose is to diminish the resistant clones. However, the prognosis of recurrent and metastatic patients is still unsatisfactory. Therefore, it is worth paying attention to how to maximize the benefits for patients.


Reduction of antibody response to an 11-valent pneumococcal vaccine coadministered with a vaccine containing acellular pertussis components.
In pneumococcal conjugate vaccines (PCVs), polysaccharide antigens are often conjugated to protein carriers related to other common vaccines. It is therefore important to test PCV interaction with other pediatric vaccines when administered simultaneously. We assessed the immune response to an 11-valent PCV conjugated to diphtheria and tetanus carriers (PncD/T11), administered concomitantly, but in separate sites, with a combined vaccine containing epitopes related antigenically to the carriers: polyribosylribitol phosphate-tetanus tox oid (PRP-T), diphtheria toxoid (DT), and tetanus toxoid (TT). In addition, these combinations contained inactivated poliovirus vaccine (IPV) and either whole-cell pertussis (wP) or acellular pertussis (aP) components. After coadministration of PncD/T11 with the combined vaccine containing wP (DTwP/IPV/PRP-T), the responses to all polysaccharides in the PncD/T11 were satisfactory. In contrast, when coadministered with an aP-containing combination (DTaP/IPV/PRP-T), the response to all seven pneumococcal conjugates to TT was significantly reduced after primary and booster immunization. The pneumococcal conjugates to DT were not significantly reduced after the primary series, but were somewhat reduced after booster. It is likely that some suppression of the tetanus-mediated response occurred even when the PncD/T11 was coadministered with wP, but this suppression was masked by the adjuvant effect of wP. By replacing wP with aP, this adjuvant effect was removed, unmasking the suppression of the tetanus-mediated response. With the increasing use of multiple aP-containing vaccines in infancy, novel approaches to adjuvants and carrier protein technology are likely to be required.


Off-pump myocardial revascularization.
Since 1998, a large body of literature regarding off-pump coronary bypass surgery has been published, although varying techniques and outcomes likely have led to its inconsistent application. One approach has been developed and standardized at KU Leuven. This approach is straightforward and can be replicated without need for conversion toward cardiopulmonary bypass. The patient is 'conditioned' before and during the procedure. Both mammary arteries are harvested through a standard sternotomy. The anterior surface of the heart is exposed with a horizontal line of left-sided pericardial stitches, just above the level of the heart. The anterior coronary vessels are anastomosed after routine shunting. The lateral and inferior aspects of the heart are exposed without deforming the atrio-ventricular axis. This is performed in a stepwise manner. The first step is anchoring a sling into the posterior pericardium under the roof of the left atrium. Second, this sling is gradually pulled upwards, supporting the heart as a cradle. Once the heart is exposed toward the zenith, an apical suction device stabilizes, reformats and exposes the ventricle. The lateral and inferior walls are then revascularized. As a strict no-touch technique is used, free grafts are anastomosed to in-situ arterial grafts.


Identification of a Novel Regulatory Mechanism of Nutrient Transport Controlled by TORC1-Npr1-Amu1/Par32.
Fine-tuning the plasma-membrane permeability to essential nutrients is fundamental to cell growth optimization. Nutritional signals including nitrogen availability are integrated by the TORC1 complex which notably regulates arrestin-mediated endocytosis of amino-acid transporters. Ammonium is a ubiquitous compound playing key physiological roles in many, if not all, organisms. In yeast, it is a preferred nitrogen source transported by three Mep proteins which are orthologues of the mammalian Rhesus factors. By combining genetic, kinetic, biochemical and cell microscopy analyses, the current study reveals a novel mechanism enabling TORC1 to regulate the inherent activity of ammonium transport proteins, independently of arrestin-mediated endocytosis, identifying the still functional orphan Amu1/Par32 as a selective regulator intermediate. We show that, under poor nitrogen supply, the TORC1 effector kinase' Npr1' promotes phosphorylation of Amu1/Par32 which appears mainly cytosolic while ammonium transport proteins are active. Upon preferred nitrogen supplementation, like glutamine or ammonium addition, TORC1 upregulation enables Npr1 inhibition and Amu1/Par32 dephosphorylation. In these conditions, as in Npr1-lacking cells, hypophosphorylated Amu1/Par32 accumulates at the cell surface and mediates the inhibition of specific ammonium transport proteins. We show that the integrity of a conserved repeated motif of Amu1/Par32 is required for the interaction with these transport proteins. This study underscores the diversity of strategies enabling TORC1-Npr1 to selectively monitor cell permeability to nutrients by discriminating between transporters to be degraded or transiently inactivated and kept stable at the plasma membrane. This study further identifies the function of Amu1/Par32 in acute control of ammonium transport in response to variations in nitrogen availability.


Sympathetic regulation of cerebral blood flow during reflex hypertension.
The cerebral circulatory effects of physiological stimulation of the sympathetic nervous system have been examined in the present study. In lightly anesthetized rabbits, reflex sympathetic activation was provoked by bilateral sinus deafferentation and vagotomy. Regional cerebral blood flow (CBF) was measured by the [14C]-ethanol technique and compared in paired brain structures following unilateral superior cervical ganglionectomy. Two subgroups of hypertensive rabbits were statistically distinguished. In the first (19 of 28 rabbits), CBF in the innervated hemisphere was little modified by hypertension but there was a significant side-to-side difference in CBF between the hemispheres. In the second group (9 rabbits) CBF was markedly increased by the systemic hypertension, and little difference was noted between innervated and denervated hemispheres. We demonstrate that, during acute hypertension, the superior cervical system contributes to cerebrovascular autoregulation; this contribution varies according to the brain region studied. In a subgroup of animals, little sympathetic activity could be evidenced, and it is hypothesized that in these rabbits a vasodilatory system was activated that counteracted the myogenic, autoregulatory responses.


Constrained Source Space MR Spectroscopy: Multiple Voxels, No Gradient Readout.
Our goal was to develop a novel technique for measuring a small number of localized spectra simultaneously and in a time-efficient manner. Using appropriate radiofrequency pulses, the magnetization from multiple voxels is excited simultaneously and then separated (reconstructed) by using the individual coil-sensitivity profiles from a multichannel receiver coil. Because no gradients are used for k-space encoding, constrained source space MR spectroscopy provides a time advantage over conventional spectroscopic imaging and an improved signal-to-noise ratio per square root of unit time over single-voxel spectroscopy applied at each successive location. In the present work, we considered prototype application of constrained source space MR spectroscopy for 2 voxels. Experimental data from healthy volunteers and simulation results showed that constrained source space MR spectroscopy is effective at extracting 2 independent spectra even in the challenging scenario of the voxels being closely spaced. Also, from 6 patients with various types of brain cancer we obtained 2-voxel constrained source space MR spectroscopy data, which showed spectra of clinical quality in half the time required to perform successive single-voxel MR spectroscopy. Constrained source space MR spectroscopy provides clinical quality spectra and could be used to probe multiple voxels simultaneously in combination with Hadamard encoding for further scan-time reductions.


Specific interactions between human integrin alpha v beta 3 and chimeric hepatitis B virus core particles bearing the receptor-binding epitope of foot-and-mouth disease virus.
Purified integrin alpha v beta 3 was used in solid-phase binding studies with chimeric hepatitis B cores which carry the RGD-containing loop of VP1 protein of the foot-and-mouth disease virus (FMDV). High levels of specific binding between the integrin and the particles were detected by enzyme-linked immunosorbent assays. The binding was Mn2+ cation dependent and could be competed with fibronectin, vitronectin, and the peptide GRGDSPK. Particles in which the RGD motif had been mutated to RGE failed to bind, indicating that the chimeric cores bound specifically to the ligand binding site of integrin alpha v beta 3. Electron micrographs showed several individual alpha v beta 3 molecules bound to the surface of each chimeric particle. Collectively, these data constitute firm evidence that the RGD-containing loop of FMDV is critical for binding to alpha v beta 3 and provide support for identification of alpha v beta 3 as a potential cellular receptor for FMDV.


Anti-platelet-activating factor, antibacterial, and antiradical activities of lipids extract from silver carp brain.
Epidemiological studies have verified the protective role of fish lipids in cardiovascular diseases. However, the effects of fish lipids on health boost remain undefined. Large amounts of by-products, such as fish brain which contains high level of lipids, are produced with silver carp processing. Fish brain is rich in bioactive lipids which are overwhelmingly effective in preventing cardiovascular diseases. The aim of this study was to elucidate the pharmacological activities of silver carp brain lipids against diseases by inhibiting platelet-activating factor (PAF), suppressing bacterial growth and scavenging free radicals. Total lipids (TL) were extracted from silver carp brain and separated into polar lipids (PL) and neutral lipids (NL). The capabilities of the lipid fractions in aggregating washed rabbit platelet or in inhibiting PAF-induced platelet aggregation were tested. Their antibacterial and antiradical activities were studied as well. The lipid fractions exhibited strong inhibitory activities, and the activity of TL was mainly attributed to NL. TL exhibited antibacterial activity towards Staphylococcus aureus, while NL managed to fight against S. aureus and Escherichia coli. PL excelled TL and NL in simultaneously suppressing the growths of Shigella dysenteriae and Salmonella typhi besides those of S. aureus and E. coli. The scavenging effect of PL on 2,2-diphenyl-1-picrylhydrazyl radical was considerably higher than those of TL and NL. The present study may help to explain the protective role of fish lipids against diseases and may be responsible for the effectiveness of fish brain in benefiting health.


[Arthritis in burned persons, caused by Pseudomonas aeruginosa].
The clinical course and morphological changes in 33 limb joints in 20 burnt patients with pyocyanic arthritis have been studied. The latter is characterized by a grave clinical course and not infrequently complicated with sepsis which becomes especially hazardous after destruction of articular cartilages. Destructive changes in the joints would develop in different terms: following 25-45 days in large joints, in smaller one 10-15 days after the appearance of the clinical picture of this complication. Surgical therapy (arthrotomy, amputation of the extremity) associated with conservative measures (antibacterial therapy, blood transfusion, etc) should be considered to be the mostly effective treatment for destructive forms of arthritis.


Aflatoxin awareness and Aflasafe adoption potential of Nigerian smallholder maize farmers: OPEN ACCESS.
Aflatoxin is a potent mycotoxin that can cause cancer and death and is associated with stunted growth. Prevalence of aflatoxin is widespread in Africa negatively impacting health and trade. Aflasafe is a biological control product that can be applied to maize or groundnut fields to reduce aflatoxin contamination. This study examines the levels of aflatoxin and Aflasafe awareness and understanding among smallholder maize farmers in Nigeria. In addition, the factors affecting Aflasafe purchase patterns and sustained usage over multiple growing seasons by farmers were evaluated. In-person surveys of 902 Nigerian smallholder farmers were conducted during October and November of 2016. This work contributes to the existing literature by documenting awareness levels of aflatoxin and use of Aflasafe as a control in Nigeria. Results suggest that the level of awareness of aflatoxin was very high in states where Aflasafe was promoted as an intervention for aflatoxin management. In Kaduna state, the region with the longest intervention, there was a consistent increase in the usage of Aflasafe since its introduction in 2010. Furthermore, farmers who purchase Aflasafe bundled (combined) with other inputs were more likely to persist in using the product. Education was found to significantly and positively impact continued usage of Aflasafe. Continued interventions, promotion and general education of the public are recommended for increased awareness, trial, and adoption of Aflasafe in Nigeria.


How much of the variation in adaptive divergence can be explained by gene flow? An evaluation using lake-stream stickleback pairs.
How much of the variation in adaptive divergence can be explained by gene flow? The answer to this question should objectively reveal whether gene flow generally places a substantial constraint on evolutionary diversification. We studied multiple independent lake-stream population pairs of threespine stickleback (Gasterosteus aculeatus). For each pair, we quantified adaptive divergence based on morphological traits that have a genetic basis and are subject to divergent selection. We then estimated gene flow based on variation at five unlinked microsatellite loci. We found a consistent and significant pattern for morphological divergence to be positively correlated with genetic divergence and negatively correlated with gene flow. Statistical significance and the amount of variation explained varied within and among traits: 36.1-74.1% for body depth and 11.8-51.7% for gill raker number. Variation within each trait was the result of differences among methods for estimating genetic divergence and gene flow. Variation among traits likely reflects different strengths of divergent selection. We conclude that gene flow has a substantial effect on adaptive divergence in nature but that the magnitude of this effect varies among traits. An alternative explanation is that cause and effect are reversed: adaptive divergence is instead constraining gene flow. This effect seems relatively unimportant for our system because genetic divergence and gene flow were not correlated with ecologically relevant habitat features of lakes (surface area) or streams (width, depth, flow, canopy openness).


Automatic high-resolution infarct detection using volumetric multiphase dual-energy CT.
Late contrast enhancement CT (LCE-CT) visualizes the presence of myocardial infarcts. Differentiation of the contrast-enhanced infarct from blood pool is challenging. We developed a novel method using data from first pass CT angiography (CTA) imaging to enable automatic infarct detection. A canine model of myocardial infarction was produced in 11 animals. Two months later, first pass CTA (90 kVp) and LCE-CT (dual energy 90 kVp/150 kVp tin filtered) were performed. Late gadolinium enhancement MRI was used as reference standard. The CTA and LCE-CT were co-registered using a fully automatic non-rigid method based on curved B-splines. The method allowed for limited elastic deformation and the considerable differences in attenuation between first-pass and delayed image. The blood pool was easily identified on the CTA image by high attenuation. Because CTA and LCE-CT were registered, the blood pool segmentation can be directly transferred to the LCE-CT - thereby solving the key problem of infarct/blood pool differentiation. The remaining segmentation of infarcted vs. noninfarcted myocardium was performed using a threshold. Automatic and MRI-guided expert segmentations of LCE-CT infarcts were compared to each other on volume and area basis (intraclass correlation coefficient, ICC) and on voxel basis (dice similarity coefficient, DSC between automatic and expert CT segmentation). CT infarct volumes were compared with the reference standard MRI. The infarcts were mainly subendocardial (81%) and relatively small (median MRI infarct mass 7.4 g). The automatic segmentation showed excellent agreement with expert segmentation on volume and area measurements (ICC = 0.96 and 0.87, respectively). DSC showed moderately good agreement (DSC = 0.47). Compared to MRI there was modest agreement (ICC = 0.62) and excellent correlation (R = 0.9). Manual interaction was less than 1 min per exam. We propose an automatic method for infarct segmentation on LCE-CT using multiphase CT information, which showed excellent agreement with expert readers and favorable correlation with MRI.


Prognostic Potential of METTL7B in Glioma.
Methyltransferase-like 7B (METTL7B) is a member of methyltransferase-like family. Little is known about the exact role of METTL7B in cancer. This study aims to investigate the role of METTL7B in gliomas. The expression of METTL7B in glioma and adjacent normal tissues were examined by using TCGA, Chinese Glioma Genome Atlas (CGGA) database, and clinical tissues. The results showed that METTL7B was highly expressed in glioma. Patients with high levels of METTL7B usually had poor survival in glioma, especially in low-grade glioma (LGG). Data from CGGA showed that METTL7B was an independent risk factor of glioma and can be used to evaluate the survival time of glioma patients. Hypomethylation in the METTL7B CpG islands was lower in LGG, and all the hypomethylated METTL7B islands were correlated with poor LGG survival. Furthermore, METTL7B levels were correlated with high numbers of tumor infiltrated immune cells in glioma, especially in LGG. ). Gene Set Enrichment Analysis found METTL7B was correlated with leukocyte proliferation, T-cell proliferation, peptidase activity, lymphocyte activation, etc. TCGA and CGGA database analysis showed that there were 1,546 and 1,117 genes that had a synergistic effect with METTL7B in glioma, respectively, and there were 372 genes overlapped between the 2 groups, including PD-L1. Data from clinical tissues also showed PD-L1 was highly expressed in glioma tissues and was positively correlated with METTL7B. Our study suggested that METTL7B was a potential prognostic biomarker for glioma and other cancers, and it may act as an oncogenic driver and may be a potential therapeutic target in human cancer, especially in LGG.


Lower extremity cooling reduces ischemia-reperfusion injury following Zone 3 REBOA in a porcine hemorrhage model.
New strategies to mitigate ischemia during REBOA and to prolong its maximal duration are needed. We hypothesized that simple external cooling of the hind limbs would decrease ischemia-reperfusion injury following prolonged Zone 3 REBOA. Twelve swine were anesthetized, instrumented, splenectomized, and then underwent 15% total blood volume hemorrhage. Animals were randomized to hypothermia or control followed by 4 hours of Zone 3 REBOA, resuscitation with shed blood, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Baseline and end-of-study muscle biopsies were obtained for histologic analysis. There were no significant differences between groups at baseline or after hemorrhage. Maximum creatine kinase was significantly lower in the hypothermia group compared with the normothermia group (median [interquartile range] = 3,445 U/mL [3,380-4,402 U/mL] vs. 22,544 U/mL [17,030-24,981 U/mL]; p < 0.01). Maximum serum myoglobin was also significantly lower in the hypothermia group (1,792 ng/mL [1,250-3,668 ng/mL] vs. 21,186 ng/mL [14,181-24,779 ng/mL]; p < 0.01). Fascial compartment pressures were significantly lower during critical care in the hypothermia group (p = 0.03). No histologic differences were observed in hind limb skeletal muscle. External cooling during prolonged Zone 3 REBOA decreased ischemic muscle injury and resulted in lower compartment pressures following reperfusion. Hypothermia may be a viable option to extend the tolerable duration of Zone 3 occlusion, beyond what is currently achievable. Future survival studies are required to assess functional outcomes.


Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma.
The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL. Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide. No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse. Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.


CD1a is not effective in distinguishing calcifying epithelial odontogenic tumors from amyloid-rich central odontogenic fibroma.
Differential diagnosis between the non-calcifying variant of calcifying epithelial odontogenic tumor (NCLC-CEOT) and amyloid-rich central odontogenic fibroma (AR-COdF) has become a debate, particularly regarding the frequency of CD1a positivity in both entities. This has led to the growing consensus that CD1a-positive staining in AR-NC lesions confirms the diagnosis of AR-COdF. Here, we assess the validity of this consensus. We collected the data of a case series of histopathologically distinct CEOTs, NCLC-CEOTs, and COdFs and stained them for CD1a and amyloid. Of the 9 CEOTs and NCLC-CEOTs, we diagnosed 4 as classic, 3 as associated with a dentigerous cyst, and 2 as combined CEOT/adenomatoid odontogenic tumors. Of the 9 COdFs, we diagnosed 3 as epithelial poor, 3 as epithelial rich (lacking amyloid), 2 as hyalinized with amyloid, and 1 as hyalinized without amyloid and assessed the staining results. Of the 9 CEOTs and NCLC-CEOTs, 7 stained positively for CD1a, 5 diffusely and 2 focally. Notably, 2 classic NCLC-CEOTs stained strongly CD1a positive. All 3 of the epithelial-poor COdFs were predictably CD1a negative. Of the 6 remaining COdFs, 2 were CD1a positive, 1 hyalinized-with-amyloid COdF diffusely and 1 epithelial-rich-without amyloid focally. CD1a positivity, which occurs in classic CEOT and NCLC-CEOT, does not help distinguish between NCLC-CEOT and AR-COdF and is inconsistent in all AR-COdFs. The diagnosis of CEOT and AR-COdF should be guided by appropriate histopathologic criteria irrespective of CD1a staining or the presence of amyloid or calcifications.


Virulence conversion of Legionella pneumophila by conjugal transfer of chromosomal DNA.
In this study, we examined whether virulence conversion occurs in Legionella pneumophila by conjugal transfer of chromosomal DNA. A virulent strain, K6, which has the genes for Kmr and LacZ+ transposed in the chromosome of strain Philadelphia-1, which belongs to serogroup 1, was used as one parent, and an avirulent strain, Chicago-2S, which is a spontaneous streptomycin-resistant derivative of strain Chicago-2 belonging to serogroup 6, was used as the other parent. Experiments in which K6 (approximately 2.6 x 10(9) CFU) and Chicago-2S (approximately 8.9 x 10(9) CFU) were mated typically yielded 10(3) Kmr Smr LacZ+ transconjugants. Thirty-two (about 2.8%) of 1,152 transconjugants belonging to serogroup 6 acquired the ability to grow intracellularly in Acanthamoeba castellanii and guinea pig macrophages. When guinea pigs were infected with sublethal doses of Legionella aerosols generated from one of these transconjugants (HM1011), they developed a severe pneumonia similar to that caused by donor strain K6. These results show that avirulent strain Chicago-2S changed into virulent strain HM1011 through conjugation with virulent strain K6. Furthermore, we showed that Legionella chromosomal virulence genes (icm-dot locus) were horizontally transferred by the conjugation system. The chromosomal conjugation system may play a role(s) in the evolution of L. pneumophila.


A rapid assessment of a community health worker pilot programme to improve the management of hypertension and diabetes in Emfuleni sub-district of Gauteng Province, South Africa.
Non-communicable diseases (NCD) and infectious chronic illnesses are recognised as significant contributing factors to the burden of disease globally, specifically in South Africa, yet clinical management is often poor. The involvement of community health workers (CHWs) in TB and HIV care in South Africa, and other low- and middle-income settings, suggests that they could make an important contribution in the management of NCDs. Using a rapid assessment, this study examines the outcomes of a pilot CHW programme to improve the management of hypertension and diabetes in Gauteng province, South Africa. A record review compared outcomes of patients receiving home visits (n56) with a control group (n168) attending the clinic, matched, as far as possible, on age, gender, and condition. Focus group discussions and semi-structured interviews with CHWs, patients, district, clinic, and NGO staff were used to obtain descriptions of the functioning of the programme and patient experiences. Despite the greater age and co-morbidity among those in the pilot programme, the findings suggest that control of hypertension was improved by CHW home visits in comparison to usual clinic care. However, too few doctor visits, insufficient monitoring of patient outcomes by clinic staff, and a poor procurement process for supplies required by the CHWs hampered the programme's activities. The role of CHWs in the management of hypertension should be given greater consideration, with larger studies being conducted to provide more robust evidence. Adequate training, supervision, and operational support will be required to ensure success of any CHW programme.


Level of Heavy Metals in Two Highly Consumed Fish Species at District Lower Dir, Khyber Pakhtunkhwa, Pakistan.
The current study was designed to assess heavy metals' concentration in muscle tissues of two Chinese carps, common carp (Cyprinus carpio) and silver carp (Hypophthalmichthys molitrix), available to consumers in markets at district Lower Dir, Khyber Pakhtunkhwa, Pakistan. Fish specimens were collected from three main markets in the study area namely; Chakdara, Timergara and Khall. Heavy metals including; manganese (Mn), lead (Pb), iron (Fe), copper (Cu), zinc (Zn), cadmium (Cd) and cobalt (Co) were investigated using atomic absorption spectrophotometer. Cobalt was not detected in any of the fish specimens while the rest of the metals were lying within the permissible limits suggested by FAO/WHO and ITS for food/fish consumption. The results showed a statistically significant (p<0.05) difference between both species with respect to the concentration of the accumulated heavy metals. In common carp, the heavy metal accumulation was in order of Fe>Mn>Zn>Pb>Cu>Cd, while in silver carp the order was Fe>Mn>Zn>Pb>Cd>Cu. Higher concentration of Pb, Mn, Zn, Cu and Cd was recorded in muscle of common carp while the concentration of Fe was higher in silver carp, indicating higher potential of accumulation of heavy metals in common carp. Statistically significant (p<0.05) correlation was observed between Pb and Zn in common carp while between Cu and Cd in silver carp. The concentration of heavy metals was in the suggested permissible limits and poses no threat if consumed. In order to maintain the heavy metals level within permissible limits, proper care should be taken along with regular assessment.


Determination of a broad spectrum of pharmaceuticals and endocrine disruptors in biofilm from a waste water treatment plant-impacted river.
Wastewater treatment plants (WWTPs) are one of the main sources of pharmaceuticals and endocrine disrupting compounds in freshwater ecosystems, and several studies have reported bioaccumulation of these compounds in different organisms in those ecosystems. River biofilms are exceptional indicators of pollution, but very few studies have focused on the accumulation of these emerging contaminants. The objectives of this study were first to develop an efficient analytical methodology for the simultaneous analysis of 44 pharmaceuticals and 13 endocrine disrupting compounds in biofilm, and second, to assess persistence, distribution, and bioaccumulation of these contaminants in natural biofilms inhabiting a WWTP-impacted river. The method is based on pressurized liquid extraction, purification by solid-phase extraction, and analysis by ultra performance liquid chromatography coupled to a mass spectrometer (UPLC-MS/MS) in tandem. Recoveries for pharmaceuticals were 31-137%, and for endocrine disruptors 32-93%. Method detection limits for endocrine disruptors were in the range of 0.2-2.4 ng g(-1), and for pharmaceuticals, 0.07-6.7 ng g(-1). A total of five endocrine disruptors and seven pharmaceuticals were detected in field samples at concentrations up to 100 ng g(-1).