Role of fibronectin in collagen deposition: Fab' to the gelatin-binding domain of fibronectin inhibits both fibronectin and collagen organization in fibroblast extracellular matrix.
We report the effect of Fab' (anti-60k) to a 60,000 mol wt gelatin binding domain of fibronectin (1981, J. Biol. Chem. 256:5583) on diploid fibroblast (IMR-90) extracellular fibronectin and collagen organization. Anti-60k Fab' did not inhibit IMR-90 attachment or proliferation in fibronectin-depleted medium. Fibroblasts cultured with preimmune Fab' deposited a dense extracellular network of fibronectin and collagen detectable by immunofluorescence, while anti-60k Fab' prevented extracellular collagen and fibronectin fibril deposition. Matrix fibronectin and collagen deposition remained decreased in cultures containing anti-60k Fab' until cells became bilayered or more dense, when fibronectin and collagen began to appear in lower cell layers. Anti-60k Fab' added to confluent cultures 24 h before fixation and staining had no effect on matrix fibronectin or collagen, so anti-60k Fab' did not simply block immunostaining. Confluent cultures grown in anti-60k Fab' and labeled for 24 h with [3H]proline incorporated identical amounts of [3H]proline and [3H]hydroxyproline, but [3H]hydroxyproline deposition in the cell layer was significantly decreased by anti-60k Fab' (P less than 0.01). Extracellular matrix collagen does not appear to form a scaffold for fibronectin deposition, as neither gelatin nor a gelatin-binding fragment of plasma fibronectin inhibited deposition of matrix fibronectin. Our results suggest that interstitial collagens and fibronectin interact to form a fibrillar component of the extracellular matrix, and that fibronectin is required for normal collagen organization and deposition by fibroblasts in vitro. Domain-specific antibodies to fibronectin are powerful tools to study the biological role of fibronectin in extracellular matrix organization and other processes.


Endograft Infection After Endovascular Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis.
To report a meta-analysis of the published evidence on the outcomes of aortic endograft infection after endovascular aneurysm repair (EVAR). A search of electronic information sources (PubMed/MEDLINE, SCOPUS, CENTRAL) and bibliographic reference lists identified 12 studies reporting on 362 patients (mean age 72 years; 279 men). The methodological quality of the selected studies was assessed using the Newcastle-Ottawa scale. Endpoints were 30-day/in-hospital mortality and follow-up mortality. Pooled estimates are reported with the 95% confidence interval (CI). The review was registered at the International Prospective Register of Systematic Reviews in Health and Social Care (CRD42016034166). The incidence of graft infection after EVAR was 0.6% (95% CI 0.4% to 0.8%). The time from implantation to diagnosis ranged from 1 to 128 months (mean 25). The majority of patients (293, 81%) underwent surgical treatment (95% CI 77% to 83%); 9 (2.5%) patients (95% CI 21% to 43%) received conservative treatment. Aortic replacement with a prosthetic graft was performed in 58% (95% CI 52% to 62%), whereas cryopreserved allografts and autologous grafts were used in 31% (95% CI 28% to 33%) and 11% (95% CI% 8 to 14%), respectively. Less than half of the patients (40%) had emergency surgery. The pooled estimate of 30-day/in-hospital mortality was 26.6% (95% CI 16.9% to 39.2%). The pooled 30-day/in-hospital mortality for 9 patients treated conservatively was 63.3% (95% CI 30.7% to 87.0%). The pooled overall follow-up mortality was 45.7% (95% CI 36.4% to 55.4%) vs 58.6% (95% CI 28.8% to 83.3%) for the 9 patients receiving conservative treatment. Aortic endograft infection is a rare complication after EVAR. Surgical treatment with complete explantation of the infected endograft seems to be the optimal management in selected patients. Supportive medical treatment without surgical intervention has a significant associated mortality.


Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection.
This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS-CoV-2-infected patients. A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse-transcription polymerase chain reaction (RT-PCR) assay. Twenty-one common-type and nine severe-type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT-PCR results. Fifty-eight samples from other patents were all negative. We speculate that SARS-CoV-2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.


Intranasal sphenopalatine ganglion block by lignocaine spray for postdural puncture headache following spinal anesthesia: a randomized clinical trial.
In a randomized clinical study, we investigated the effectiveness of nasal lignocaine spray and swabs in treating postdural puncture headache (PDPH) after spinal anesthesia. Group S patients received two puffs of lignocaine 10% spray in both nostrils followed by cotton soaked in normal saline, and group B patients received two puffs of saline spray in both nostrils followed by a cotton swab soaked in lignocaine 2%. Patients were assessed before the procedure and 30 minutes, 60 minutes, 2 h, 24 h, 48 h, and 72 h after the procedure for pain relief with the help of a visual analogue scale (VAS). Hemodynamic parameters and adverse effects were also recorded. Normally distributed continuous variables were expressed as mean (95% confidence interval) whereas non-normally distributed variables were expressed as median (IQR). Repeated measures analysis of variance was used to compare the VAS score at different time points between test and control groups. The difference in means between the two groups was compared using the independent sample t -test. The paired t-test was used to compare the changes in clinical and laboratory variables. At each time point, the mean VAS score for pain was substantially different between the two groups. Moreover, until the second hour, the VAS score was significantly lower in group S than in group B. No significant intervention-related adverse effect was observed in either group. Without any noticeable side effects, lignocaine 10% spray is more successful in treating PDPH after spinal anesthesia, particularly in the first two hours.


Methylphenidate treatment for bulimia nervosa associated with a cluster B personality disorder.
Psychotherapy and antidepressant medication are helpful to many patients with bulimia nervosa (BN). However, a substantial number of bulimics respond poorly to such treatments. Recent studies suggest that many of the poor responders have cluster B personality disorders. In some ways, the symptomatology of bulimics who have a comorbid cluster B disorder resembles that of patients with attention deficit hyperactivity disorder (ADHD). In particular, individuals in both groups frequently have a high level of impulsivity. Such a resemblance raised the question of whether administration of methylphenidate (MPH), a drug used to treat ADHD, would have therapeutic effects in this subgroup of BN patients. In a pilot study, we administered MPH to 2 patients with BN and cluster B traits and found beneficial effects. These patients had not responded to adequate trials of psychotherapy and selective serotonin reuptake inhibitors (SSRIs). MPH treatment was effective. Both Patients had decreased binging and purging. MPH may be useful for bulimics with cluster B personality disorder who respond poorly to conventional treatment. Further studies of MPH administration may be worthwhile. Due to the potential risks, however, clinical treatment with this agent is not recommended at this time.


Honokiol inhibits osteoclast differentiation and function in vitro.
Honokiol, a neolignan, is a physiologically active component of kouboku (Magnolia obovata), a herb used in traditional Chinese medicine. This study investigated the effects of honokiol on the differentiation and function of osteoclasts induced by receptor activator of nuclear factor-kappaB ligand (RANKL). Honokiol markedly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and the formation of TRAP-positive multinucleated cells in both bone marrow-derived monocytes and RAW264 cells. In experiments to elucidate its mechanism of action, honokiol was found to suppress RANKL-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The RANKL-induced expressions of c-Fos and nuclear factor of activated T cells-c1 (NFATc1), which are crucial transcriptional factors for osteoclastogenesis, were also reduced by treatment with honokiol. Furthermore, honokiol induced disruption of the actin rings in mature osteoclasts (mOCs) without affecting the cell viability and suppressed osteoclastic pit formation on dentin slices. Taken together, these results suggest that honokiol inhibits osteoclast differentiation by suppressing the activation of MAPKs (p38 MAPK, ERK and JNK), decreasing the expressions of c-Fos and NFATc1, and attenuates bone resorption by disrupting the actin rings in mOCs. Therefore, honokiol could prove useful for the treatment of bone diseases associated with excessive bone resorption.


Emotional responses to music: the need to consider underlying mechanisms.
Research indicates that people value music primarily because of the emotions it evokes. Yet, the notion of musical emotions remains controversial, and researchers have so far been unable to offer a satisfactory account of such emotions. We argue that the study of musical emotions has suffered from a neglect of underlying mechanisms. Specifically, researchers have studied musical emotions without regard to how they were evoked, or have assumed that the emotions must be based on the "default" mechanism for emotion induction, a cognitive appraisal. Here, we present a novel theoretical framework featuring six additional mechanisms through which music listening may induce emotions: (1) brain stem reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual imagery, (5) episodic memory, and (6) musical expectancy. We propose that these mechanisms differ regarding such characteristics as their information focus, ontogenetic development, key brain regions, cultural impact, induction speed, degree of volitional influence, modularity, and dependence on musical structure. By synthesizing theory and findings from different domains, we are able to provide the first set of hypotheses that can help researchers to distinguish among the mechanisms. We show that failure to control for the underlying mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue that the new framework may guide future research and help to resolve previous disagreements in the field. We conclude that music evokes emotions through mechanisms that are not unique to music, and that the study of musical emotions could benefit the emotion field as a whole by providing novel paradigms for emotion induction.


A compartmentalized signaling network mediates crossover control in meiosis.
During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation.


Combined Distributed Shared-Buffered and Diagonally-Linked Mesh Topology for High-Performance Interconnect.
Networks-on-Chip (NoCs) have become the de-facto on-chip interconnect for multi/manycore systems. A typical NoC router is made up of buffers used to store packets that are unable to advance to their desired destination. However, buffers consume significant power/area and are often underutilized, especially in cases of applications with non-uniform traffic patterns thus leading to performance degradation for such applications. To improve network performance, the Roundabout NoC (R-NoC) concept is considered. R-NoC is inspired by real-life multi-lane traffic roundabouts and consists of lanes that are shared by multiple input/output ports to maximize buffering resource utilization. R-NoC relies on router-internal adaptive routing that decides the lane path based on back pressure. Back pressure makes it possible to assess lane utilization and route packets accordingly. This is made possible thanks to the use of elastic buffers for control flow, a clever type of handshaking in a way similar to asynchronous circuits. Another prominent feature of R-NoC is that internal routing and arbitration are completely distributed which allows for significant freedom in deciding internal router topology and parameters. This work leverages this property and proposes novel yet unexplored configurations for which an in-depth evaluation of corresponding implementations on 45 nm CMOS technology is given. Each configuration is evaluated performance and power-wise on both synthetic and real application traffic. Several R-NoC configurations are identified and demonstrated to provide very significant performance improvements over standard mesh configurations and a typical input-buffered router, without compromising area and power consumption. Exploiting the distributed nature of R-NoC routers, a diagonally-linked configuration is then proposed which incurs moderate area overhead and features yet better performance and energy efficiency.


Induction of type I IFN is a physiological immune reaction to apoptotic cell-derived membrane microparticles.
Membrane microparticles (MMP) released from apoptotic cells deliver signals that secure the anti-inflammatory response beyond the nearest proximity of the apoptotic cell. Plasmacytoid dendritic cells (pDC) are sentinels prepared to detect cellular processes that endanger the organism. They play a key role in the regulation of both pro- and anti-inflammatory immune responses. Based on the assumption that pDC could participate in the initiation of the anti-inflammatory response to apoptotic cells, we investigated the effects of apoptotic cell-derived MMP on human pDC. The results obtained in our experiments confirmed that MMP released from apoptotic cells trigger IFN-α secretion from human pDC. They further suggest that pDC activation results from sensing of DNA contained in MMP. MMP-DNA displays a particularly strong stimulatory activity compared with MMP-RNA and other sources of DNA. Inhibition of MMP-induced IFN-α secretion by cytochalasin D, chloroquine, and an inhibitory G-rich oligodeoxynucleotide identify TLR9 as the receptor for MMP-DNA. In marked contrast to the pDC response in autoimmune patients, in healthy subjects MMP-mediated stimulation of pDC-derived IFN-α was found to be independent of FcγRIIA (CD32A). Based on our findings, we conclude that induction of pDC-derived IFN-α by MMP is a physiological event; future investigations are necessary to elucidate whether pDC activation promotes inflammation or propagates tolerance in the context of apoptotic cell clearance.


Bromide ion effect on N-nitrosodimethylamine formation by monochloramine.
N-Nitrosodimethylamine (NDMA) formation experiments conducted in phosphate buffer demonstrated that in waters containing monochloramine, the presence of bromide ion enhanced NDMA formation at the relatively high pH values of 8 and 9 after 24 h of reaction time, which was consistent with literature results. However, at relatively low to neutral pH (6 to 7), the presence of bromide resulted in lower NDMA formation as compared to results obtained in the absence of bromide. The hypothesis that bromamines were the species directly responsible for enhanced NDMA formation at high pH was tested and was shown not to be valid. Additional active bromine species were also tested, including hypobromous acid, hypobromite ion, and tribromide ion, with no species showing an ability to directly enhance NDMA formation. Analysis of the UV spectral data corresponding to the NDMA experiments suggest that the mechanism by which bromide enhances NDMA formation lies in the formation of a haloamine compound, possibly the mixed dihaloamine bromochloramine.


A comparative QSAR analysis of quinazoline analogues as tyrosine kinase (erbB-2) inhibitors.
In this paper, an attempt was made to develop a Quantitative Structure Activity Relationship (QSAR) model on a series of quinazoline derivatives acting as Protein tyrosine kinases (erbB-2) inhibitors using Multiple Linear Regression, Principal Component Regression and Partial Least Squares Regression methods. Among these three methods, Multiple Linear Regression (MLR) method has come out with a very promising result as compared to other two methods. Various 2D descriptors were calculated and used in the present analysis. For model validation, the dataset was divided into training and test sets using spherical exclusion method. The developed MLR- QSAR model was found to be statistically significant with respect to training (r2 =0.956), cross-validation (q2 = 0.915), and external validation (pred_r2= 0.6170). The developed MLR model suggests that Estate Contribution descriptors SaaOE-Index (30.07%) and SsCIE-index (15.79%) are the most important descriptors in predicting Tyrosine kinase (erbB-2) inhibitory activity. Electron withdrawing group at 4th position of quinazoline enhances the activity as evident by positive value of SsClE-index (15.79). In addition, for quinazoline substituents, estate contribution descriptors SsCH3E -index has a large deactivating effect.


Autoantibodies to bullous pemphigoid and epidermolysis bullosa acquisita antigens in an infant.
We describe a 1-year-old boy with multiple tense blisters on the skin, who showed circulating autoantibodies directed to both bullous pemphigoid and epidermolysis bullosa acquisita antigens. The patient's serum IgG antibodies bound to the 290-kDa epidermolysis bullosa acquisita antigen with immunoblot analysis of human dermal extracts. Immunoblot analysis also demonstrated that the patient's serum autoantibodies were reactive with recombinant NC16a domain of the 180-kDa bullous pemphigoid antigen. This study confirmed the presence of circulating autoantibodies directed to both bullous pemphigoid antigen and epidermolysis bullosa acquisita antigen.


Sex-linked retinitis pigmentosa: ultrastructure of photoreceptors and pigment epithelium.
An ultrastructural study of a postmortem donor eye from a 24-year-old male patient with sex-linked retinitis pigmentosa showed abnormalities in all remaining cones and rods. Central foveal cones were reduced in number by about 50% and had shortened and severely distorted outer segments. Cones from the parafovea through the midperiphery gradually decreased in density and had no organized outer segments. In the far periphery, cones and rods had only slightly shortened outer segments. Photoreceptors equidistant from the fovea in all quadrants showed similar changes. The virtual absence of organized cone outer segments from the parafovea through the midperiphery was conspicuous in that this patient had full visual fields with large test lights 3 weeks prior to death. The pigment epithelium contained abnormally large numbers of melanolysosomes and few free melanin granules from the fovea through the midperiphery and few melanolysosomes and many free melanin granules in the far periphery. Whether or not these observations in the pigment epithelial cells represent a primary defect in this disease or reflect changes secondary to a defect in the photoreceptor cells remains to be defined.


Increasing Patient Acceptance and Adherence Toward Insulin.
Because of the progressive nature of type 2 diabetes mellitus (T2DM), the majority of patients will need insulin to achieve and maintain glycemic control. By maintaining glycemic control, patients will avoid acute osmotic symptoms of hyperglycemia, instability in plasma glucose (PG) over time, and prevent or delay the development of diabetes complications without adversely affecting quality of life. Despite recommendations for initiating insulin therapy, both patient and health system barriers stand in the way. To develop confidence in individualizing patient therapy and maximize outcomes for patients with T2DM, healthcare practitioners (HCPs) were updated on recommendations and clinical evidence supporting when to initiate insulin therapy, strategies for overcoming provider and patient barriers for initiating insulin therapy, and the safety and efficacy of current and emerging insulin therapy and delivery technology for patients with T2DM.


Long-term toxicity and survival outcomes after stereotactic ablative radiotherapy for patients with centrally located thoracic tumors.
Background Stereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastases; however, adverse effects are greater for central tumors. We evaluated factors affecting outcomes and toxicities after SABR for patients with primary lung and oligometastatic tumors. Patients and methods We retrospectively identified consecutive patients with centrally located lung tumors that were treated at our hospital from 2009-2016. The effects of patient, disease, and treatment-related parameters on local control (LC), overall survival (OS), and toxicity-free survival (TFS) were evaluated with multivariate analyses. Results Among 65 consecutive patients identified with 70 centrally located tumors, 20 tumors (28%) were reirradiated. Median (range) total dose for all tumors was 55 (30-60) Gy in 5 (3-10) fractions. Radiographic complete response was obtained in 43 lesions (61%). None of the analyzed factors were correlated with complete response. After a median follow-up of 57 (95% CI, 48-65) months, 10 tumors (14%) relapsed and 37 patients (57%) died; the actuarial 2- and 5-year OS rates were 52% and 28%, respectively. Median OS was significantly lower in patients with grade 3 or higher toxicity vs. lower toxicity (5 vs. 39 months; P < 0.001). Among 17 severe toxicities, 5 were grade 5, and 3 of them were reirradiated to the same field. Grade 3 to 5 TFS was lower with vs. without reirradiation (2-year TFS, 63% vs. 96%; P = 0.02). Conclusions Our study showed that modern SABR is effective for central lung tumors, and toxicities are acceptable. SABR for reirradiated central lung lesions and possibly for lesions abutting the tracheobronchial tree may result in higher risk of serious toxicities.


Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response.
Human p29 is a putative component of spliceosomes, but its role in pre-mRNA is elusive. By siRNA knockdown and stable overexpression, we demonstrated that human p29 is involved in DNA damage response and Fanconi anemia pathway in cultured cells. In this study, we generated p29 knockout mice (mp29(GT/GT)) using the mp29 gene trap embryonic stem cells to study the role of mp29 in DNA damage response in vivo. Interruption of mp29 at both alleles resulted in embryonic lethality. Embryonic abnormality occurred as early as E6.5 in mp29(GT/GT) mice accompanied with decreased mRNA levels of α-tubulin and Chk1. The reduction of α-tubulin and Chk1 mRNAs is likely due to an impaired post-transcriptional event. An aberrant G2/M checkpoint was found in mp29 gene trap embryos when exposed to aphidicolin and UV light. This embryonic lethality was rescued by crossing with mp29 transgenic mice. Additionally, the knockdown of zfp29 in zebrafish resulted in embryonic death at 72 hours of development postfertilization (hpf). A lower level of acetylated α-tubulin was also observed in zfp29 morphants. Together, these results illustrate an indispensable role of mp29 in DNA checkpoint response during embryonic development.


Musculoskeletal Infection in Orthopaedic Oncology: Assessment of the 2018 International Consensus Meeting on Musculoskeletal Infection.
The first International Consensus Meeting (ICM) on Musculoskeletal Infection convened in 2013 in order to provide agreement on the prevention, the diagnosis, and the treatment of surgical site infection (SSI) and periprosthetic joint infection (PJI). Recognizing the added susceptibility of orthopaedic oncology patients to SSI and PJI, the second ICM in 2018 included questions and corresponding recommendations from this subspecialty of orthopaedics. The 13 steps of the Delphi method were followed over the course of 26 months, starting in June 2016. From July 25 to 27, 2018, delegates from 93 countries convened at Thomas Jefferson University in Philadelphia, Pennsylvania. Delegates were divided into their subspecialty workgroups, where questions and recommendations were discussed, modified, and subsequently voted upon. The level of consensus measured the agreement among the delegates on the basis of the voting results. The level of evidence that accompanied each question and recommendation was dependent on the types of studies that were reviewed for each question and the number of flaws that were present in those studies. There were 30 orthopaedic oncology questions and recommendations that were voted on by 14 delegates with expertise in either orthopaedic oncology or infectious disease. Twenty-six (87%) of the questions were unanimous among the delegates. The remaining 13% (n = 4) were agreed upon by 93% of the delegates, with 7% of the delegates abstaining from the vote. The inclusion of orthopaedic oncology in the 2018 ICM on Musculoskeletal Infection was particularly important because of the high rate of SSI and PJI following these procedures. Despite there being strong consensus among voting delegates, these recommendations are based on limited levels of evidence and tend to reflect the recommendations from hip and knee arthroplasty. We hope that high-quality prospective studies in the field of orthopaedic oncology are available for the third ICM.


[Fixed lupus erythematosus (its treatment with thalidomide)].
The results obtained from the first 20 cases of Discoid Lupus Erithematosus treated with Thalidomide showed evidence of its great efficacy, evident from the first 15 days of treatment. In the incipient cases the results were even spectacular. 2. The minimum dosage used by the authors seems to be adequate on the basis of the results obtained. 3. The precise mode of action of thalidomide but it is thought that in acts on the hypothalamus. 4. The intolerance to Thalidomide and its undesireable side effects consisted slight somnolence; only one case had fever, cephalea, arthralgia, vertigo, nausea and urticaria which is unknown made it necessary to discontinue the medication. 5. The teratogenic effect of thalidomide obliges us to redouble the vigilance in women in age of reproduction by using of parenteral contraceptives applied by or in presence of the investigator. This study included one case that started treatment during the 7th month of pregnancy, without any problem and with an excellent result. The patient gave birth to a healthy full term infant. 6. It is recognized that this preliminary study should be continued with a greater number of cases and that these should be continued for a longer follow-up evaluation. At the present time, the authors believe that thalidomide is the best treatment for Discoid Lupus Erythematosus.


Pancreatic index: A prognostic factor of upfront surgery for body or tail pancreatic ductal adenocarcinoma with vascular involvement-A retrospective study.
The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty-five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301-0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA-PBTC (OR = 0.272, 95% CI: 0.077-0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285-0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206-6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140-0.763, p = 0.010) were independent factors. This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long-term prognosis comparable to that of resectable PBTC patients.


Nitric oxide is involved in the brassinolide-induced adventitious root development in cucumber.
Brassinolide (BR), as a new type of plant hormones, is involved in the processes of plant growth and stress response. Previous studies have reported the roles of BR in regulating plant developmental processes and also response tolerance to abiotic stresses in plants. The main purpose of our study was to explore whether nitric oxide (NO) plays a role in the process of BR-induced adventitious root formation in cucumber (Cucumis sativus L.). Exogenous application of 1 μM BR significantly promoted adventitious rooting, while high concentrations of BR (2-8 μM) effectively inhibited adventitious rooting. NO donor (S-nitroso-N-acerylpenicillamine, SNAP) promoted the occurrence of adventitious roots. Simultaneously, BR and SNAP applied together significantly promoted adventitious rooting and the combined effect was superior to the application of BR or SNAP alone. Moreover, NO scavenger (c-PTIO) and inhibitors (L-NAME and Tungstate) inhibited the positive effects of BR on adventitious rooting. BR at 1 μM also increased endogenous NO content, NO synthase (NOS-like) and Nitrate reductase (NR) activities, while BRz (a specific BR biosynthesis inhibitor) decreased these effects. In addition, the relative expression level of NR was up-regulated by BR and SNAP, whereas BRz down-regulated it. The application of NO inhibitor (Tungstate) in BR also inhibited the up-regulation of NR. BR promoted the formation of adventitious roots by inducing the production of endogenous NO in cucumber.


Follow up for emergency department patients after intravenous contrast and risk of nephropathy.
Contrast-induced nephropathy (CIN), defined as an increase in serum creatinine (SCr) greater than 25% or ≥0.5 mg/dL within 3 days of intravenous (IV) contrast administration in the absence of an alternative cause, is the third most common cause of new acute renal failure in hospitalized patients. It is known to increase in-hospital mortality up to 27%. The purpose of this study was to investigate the rate of outpatient follow up and the occurrence of CIN in patients who presented to the emergency department (ED) and were discharged home after computed tomography (CT) of the abdomen and pelvis (AP) with IV contrast. We conducted a single center retrospective review of charts for patients who required CT of AP with IV contrast and who were discharged home. Patients' clinical data included the presence of diabetes mellitus, hypertension, chronic kidney disease (CKD) and congestive heart failure (CHF). Five hundred and thirty six patients underwent CT of AP with IV contrast in 2011 and were discharged home. Diabetes mellitus was documented in 96 patients (18%). Hypertension was present in 141 patients (26.3%), and 82 patients (15.3%) were on angiotensin-converting-enzyme inhibitors (ACEI). Five patients (0.9%) had documented CHF and all of them were taking furosemide. Seventy patients (13%) had a baseline SCr >1.2 mg/dL. One hundred fifty patients (28%) followed up in one of the clinics or the ED within one week after discharge, but only 40 patients (7.5%) had laboratory workup. Out of 40 patients who followed up within 1 week after discharge, 9 patients (22.5%) developed CIN. One hundred ninety patients (35.4%) followed up in one of the clinics or the ED after 7 days and within 1 month after discharge, but only 71 patients (13.2%) had laboratory workup completed. Out of 71 patients who followed up within 1 month, 11 patients (15%) developed CIN. The overall incidence of CIN was 15.3% (17 out of 111 patients). There was a poor outpatient follow up after CT of AP with IV contrast and biochemically CIN appears to be present in some patients. Unlike previous reports that CKD is the major risk factor for CIN, our results demonstrated that risk factors such as advanced age, DM and hypertension seem to predispose patients to CIN rather than abnormal baseline SCr. [West J Emerg Med. 2014;15(3):276-281.].


Use of sleeve nets to improve survival of the Boisduval silkworm, Anaphe panda, in the Kakamega forest of western Kenya.
Prospects for development of a wild silk industry in Africa would be improved if silkworm survival during mass production could be improved. A study on the survival of the Boisduval silkworm, Anaphe panda (Boisduval) (Lepidoptera: Thaumetopoeidae) was conducted with and without protection by net sleeves in two different forest habitats (natural and modified) in the Kakamega forest of western Kenya. Overall, cohort survival was significantly higher (P < 0.001) in the natural than in the modified forest, but larval survival was improved over three-fold by protection with net sleeves in both habitat types. In the modified forest, only 16.8% of unprotected larvae survived to the pupal stage and formed cocoons, whereas 62.3% survived in the same environment when they were protected with net sleeves. In the natural forest, 20.4% of unprotected larvae survived, whereas 67.7% survived in net sleeves. There was also a significant effect of season; cohorts of larvae that eclosed in the wet season had significantly lower survival than those eclosing in the dry season (P = 0.02). Sources of mortality appeared to be natural enemies (parasites, predators and diseases) and climatic factors.


Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.
Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.


Effect of storage time of extended-pour and conventional alginate impressions on dimensional accuracy of casts.
Some manufacturers claim to have produced new irreversible hydro-colloids that are able to maintain their dimensional stability during storage. The present study evaluated the effect of storage time on dimensional stability of three alginates: Hydrogum 5, Tropicalgin and Alginoplast. In this experimental in-vitro trial, a total of 90 alginate impressions were made from a Dentoform model using Hydrogum 5, Tropicalgin and Alginoplast alginates. The impressions were stored in a sealed plastic bag without a damp paper towel for 0, 24, 48, 72 and 120 hours and then poured with type III dental stone. Cross-arch (facial of 6 to facial of 6 on the opposite side) and antero-posterior (distal of right first molar to the ipsilateral central incisor) measurements were made with a digital caliper on the casts. Data were analyzed by two-way and one-way ANOVA and Tukey's post-hoc test (P<0.05). Alginate type and the pouring time significantly affected the dimensional stability of alginate impressions (both Ps<0.001). Pouring of Hydrogum 5 impressions can be delayed for up to 120 hours without significant dimensional changes. Alginoplast impressions may be poured after 72 hours, but Tropicalgin should be poured immediately and the storage time should not be more than 24 hours. Immediate pouring of alginate impressions provides the highest accuracy in reproducing the teeth and adjacent tissues; however, this study demonstrated that pouring may be delayed for up to five days using extended-pour (Hydrogum 5) alginates.


Functional interactions between starch synthase III and isoamylase-type starch-debranching enzyme in maize endosperm.
This study characterized genetic interactions between the maize (Zea mays) genes dull1 (du1), encoding starch synthase III (SSIII), and isa2, encoding a noncatalytic subunit of heteromeric isoamylase-type starch-debranching enzyme (ISA1/ISA2 heteromer). Mutants lacking ISA2 still possess the ISA1 homomeric enzyme. Eight du1(-) mutations were characterized, and structural changes in amylopectin resulting from each were measured. In every instance, the same complex pattern of alterations in discontinuous spans of chain lengths was observed, which cannot be explained solely by a discrete range of substrates preferred by SSIII. Homozygous double mutants were constructed containing the null mutation isa2-339 and either du1-Ref, encoding a truncated SSIII protein lacking the catalytic domain, or the null allele du1-R4059. In contrast to the single mutant parents, double mutant endosperms affected in both SSIII and ISA2 were starch deficient and accumulated phytoglycogen. This phenotype was previously observed only in maize sugary1 mutants impaired for the catalytic subunit ISA1. ISA1 homomeric enzyme complexes assembled in both double mutants and were enzymatically active in vitro. Thus, SSIII is required for normal starch crystallization and the prevention of phytoglycogen accumulation when the only isoamylase-type debranching activity present is ISA1 homomer, but not in the wild-type condition, when both ISA1 homomer and ISA1/ISA2 heteromer are present. Previous genetic and biochemical analyses showed that SSIII also is required for normal glucan accumulation when the only isoamylase-type debranching enzyme activity present is ISA1/ISA heteromer. These data indicate that isoamylase-type debranching enzyme and SSIII work in a coordinated fashion to repress phytoglycogen accumulation.


The subunit structure of beta-glucosidase from Botryodiplodia theobromae Pat.
1. A homologous series of beta-glcosidase (beta-D-glcoside glcohydrolase, EC 18.104.22.168), which varied in relative amounts in different preparations from cultures of similar and different age, was observed in cultures od Botryodiplodia theobromae Pat grown for 4-8 week on cotton flock (cellulose) as carbon source. 2. Aging of the purified high-molecular-weight species led to some amount of siddociation into a homolous series of lower-molecular-weight speices. 3. Rough molecular-weight estimates, by gel filtration, of the various species derived from the purifeid high-molecular-weight enzyme were 350000-3800000, 170000, 180000, 83000-87000 and 45000-47000. 4. Electron micrographs of the negatively stained 350000-380000-molecular-weight enzyme showed that the molecule is an octamer in which each roughly spherical monomer occupies a corner of a cube with each side about 7.14nm long. 5. Carboxamidomethylation of the reduced form of each molecular-weight species of the enzyme led to irreversible dissociation of the molecules into electrophoretically identical polypeptides with a moleclar weight of 10000-12000. 6. These results suggest a slow association-dissociation of the type (8n)in equilibrium 2 (4n) in equilibrium 4(2n) in equilibrium 8(n), where n is defined as the monomer. The monomer is in turn made up of four polypeptide a subunits whi-ch are non-catalytic. 7. The Michaelis constants (Km) and heat stability of the four wnzymically active molecular species derived from the purified enzyme increased with molecular complexity, whereas all four species were inhibited by glycerol (100nM) at low concentrations of substrate (o-nitrophenyl beta-D-glucopyranoside) but activated at high substrat concentrations. 8. Only the lowest-molecular-weight species (45species (45,000-47000 mol. wt.) showed substrate inhibition.


Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action.
ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose overexpression has been linked to the progress of various cancer types. Here, we report a DNA-encoded library screen leading to the discovery of BAY-850, a potent and isoform selective inhibitor that specifically induces ATAD2 bromodomain dimerization and prevents interactions with acetylated histones in vitro, as well as with chromatin in cells. These features qualify BAY-850 as a chemical probe to explore ATAD2 biology.


Is UV-B radiation affecting charophycean algae in shallow freshwater systems?
The objective of this study was to determine the effects of UV-B radiation on charophycean algae under natural conditions, since charophytes enhance water transparency in freshwater systems and levels of UV-B radiation have increased by ozone depletion. Potential and actual UV-B effects were studied by combining a glasshouse experiment in which plants were exposed to various levels of UV-B radiation and field measurements in two freshwater systems dominated by charophytes in the Netherlands. The glasshouse experiment showed that charophytes were sensitive to UV-B radiation. UV-B radiation negatively affected growth, while it increased levels of DNA damage in Chara aspera. Moreover, the charophytes did not seem to develop UV-B screens to protect against UV-B radiation since no increase in UV-B absorbing compounds was found. At field conditions, both spectroradiometrical measurements and DNA dosimeters showed that UV-B radiation was attenuated quickly in both freshwater systems, indicating that UV-B does not reach the submerged charophyte vegetation. However, specific conditions, like fluctuating water tables, may result in UV-B exposure to charophytes for certain periods annually.


Consistent visual analyses of intrasubject data.
Visual inspection of single-case data is the primary method of interpretation of the effects of an independent variable on a dependent variable in applied behavior analysis. The purpose of the current study was to replicate and extend the results of DeProspero and Cohen (1979) by reexamining the consistency of visual analysis across raters. We recruited members of the board of editors and associate editors for the Journal of Applied Behavior Analysis to judge graphs on a 100-point scale of experimental control and by providing a dichotomous response (i.e., "yes" or "no" for experimental control). Results showed high interrater agreement across the three types of graphs, suggesting that visual inspection can lead to consistent interpretation of single-case data among well-trained raters.


Natural adaptation and human selection of northeast African sheep genomes.
African sheep manifest diverse but distinct physio-anatomical traits, which are the outcomes of natural- and human-driven selection. Here, we generated 34.8 million variants from 150 indigenous northeast African sheep genomes sequenced at an average depth of ∼54× for 130 samples (Ethiopia, Libya) and ∼20× for 20 samples (Sudan). These represented sheep from diverse environments, tail morphology and post-Neolithic introductions to Africa. Phylogenetic and model-based admixture analysis provided evidence of four genetic groups corresponding to altitudinal geographic origins, tail morphotypes and possible historical introduction and dispersal of the species into and across the continent. Running admixture at higher levels of K (6 ≤ K ≤ 25), revealed cryptic levels of genome intermixing as well as distinct genetic backgrounds in some populations. Comparative genomic analysis identified targets of selection that spanned conserved haplotype structures overlapping clusters of genes and gene families. These were related to hypoxia responses, ear morphology, caudal vertebrae and tail skeleton length, and tail fat-depot structures. Our findings provide novel insights underpinning morphological variation and response to human-driven selection and environmental adaptation in African indigenous sheep.


Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion.
Nuclear factor-kappa B (NF-kappaB)/Rel transcription factors play an important role in the inducible regulation of a variety of genes involved in the inflammatory and proliferative responses of cells. The present study was designed to elucidate the implication of NF-kappaB/Rel in the pathogenesis of atherosclerosis. Activation of the dimeric NF-kappaB complex is regulated at a posttranslational level and requires the release of the inhibitor protein IkappaB. The newly developed mAb alpha-p65mAb recognizes the IkappaB binding region on the p65 (RelA) DNA binding subunit and therefore selectively reacts with p65 in activated NF-kappaB. Using immunofluorescence and immunohistochemical techniques, activated NF-kappaB was detected in the fibrotic-thickened intima/media and atheromatous areas of the atherosclerotic lesion. Activation of NF-kappaB was identified in smooth muscle cells, macrophages, and endothelial cells. Little or no activated NF-kappaB was detected in vessels lacking atherosclerosis. Electrophoretic mobility shift assays and colocalization of activated NF-kappaB with NF-kappaB target gene expression suggest functional implications for this transcription factor in the atherosclerotic lesion. This study demonstrates the presence of activated NF-kappaB in human atherosclerotic tissue for the first time. Atherosclerosis, characterized by features of chronic inflammation and proliferative processes, may be a paradigm for the involvement of NF-kappaB/Rel in chronic inflammatory disease.


Lipid peroxidation biomarkers for evaluating oxidative stress and assessing antioxidant capacity in vivo.
Recently, the biological roles of lipid peroxidation products have received a great deal of attention not only for elucidating pathological mechanisms but also for practical clinical applications as biomarkers. In the last 50 years, lipid peroxidation has been the subject of extensive studies from the viewpoints of mechanisms, dynamics, product analysis, involvement in diseases, inhibition, and biological signaling. Lipid hydroperoxides are formed as major primary products, but they are substrates for various enzymes and they also undergo various secondary reactions. During this decade, hydroxyoctadecadienoic acid from linoleates, F(2)-isoprostanes from arachidonates, and neuroprostanes from docosahexanoates have been proposed as biomarkers for evaluating oxidative stress in vivo and its related diseases. The implications of lipid peroxidation products in vivo will be briefly reviewed and their practical applications will be discussed.


Venous graft surgery in treatment of coronary heart disease.
Sixty-seven patients have had aortocoronary venous graft bypass surgery by one surgeon for the relief of symptoms of severe coronary heart disease, including eight emergency operations. The overall operative, hospital, and late mortality was low in patients with favourable myocardial function and no previous myocardial infarction. There was a 7% mortality in patients with a normal preoperative chest radiogram, 8% mortality when the left ventricular end-diastolic pressure was normal preoperatively, and a 5% mortality in patients who had normal left ventricular angiograms. The overall mortality in all elective operations for cardiac pain resistant to medical treatment was 15.8%. 89% of survivors improved; 67% are pain-free. Exercise tolerance in survivors is increased by 135%, atrial pacing results are improved by 10%. Left ventricular end-diastolic pressure is unchanged. Left ventricular function on angiography is improved. The improvement in left ventricular function assessed objectively correlates positively with vein-graft patency, as does freedom from angina pectoris.


Influences of spinal decompression therapy and general traction therapy on the pain, disability, and straight leg raising of patients with intervertebral disc herniation.
[Purpose] The purpose of this study was to identify how spinal decompression therapy and general traction therapy influence the pain, disability, and straight leg raise (SLR) ability of patients with intervertebral disc herniation. [Subjects] The subjects were 30 patients with chronic lumbar pain who were divided into a spinal decompression therapy group (SDTG, n=15), and a general traction therapy group (GTTG, n=15). [Methods] The SDTG used a spinal decompression device, and the GTTG used a lumbar traction device. Both groups received conservative physical therapy three times a week for four weeks. A visual analog scale (VAS) was used to measure the degree of pain the patients with chronic lumbar pain. The Oswestry Disability Index (ODI) was used to measure the degree of functional disability. A goniometer was used to measure the patients' SLR ability. [Results] Both SDTG and GTTG showed statistically significant decreases in VAS and ODI scores and a statistically significant increase in SLR angle. A comparison of the two groups found no statistically significant differences. [Conclusion] Spinal decompression therapy and general traction therapy are effective at improving the pain, disability, and SLR of patients with intervertebral disc herniation. Thus, selective treatment may be required.


Clinicopathological analysis of patients operated for appendiceal mucocele.
The term mucocele refers to the dilatation of the appendix due to mucus, and it is an uncommon disorder with an estimated incidence of 0.2%-0.3% of all appendectomies performed and 8%-10% of all appendiceal tumors. It is often asymptomatic, but may manifest appendicitis-like symptoms. Twenty-six patients (14 females and 12 males) were operated on due to mucocele of the appendix. Sixteen patients exhibiting the characteristics of clinically acute appendicitis required an emergency operation. Appendectomy was performed on 14 patients, and right hemicolectomy was carried out on 2 patients. Of the remaining 10 patients who received surgery under elective conditions, 4 underwent a right hemicolectomy and 6 underwent an appendectomy. The patients' age ranged from 27 to 81 years. Sixteen open and 4 laparoscopic appendectomies were performed. An incidental appendiceal mucocele was identified in 2 patients who had undergone colonoscopy. According to the histopathological examination, the incidence rate of mucosal hyperplasia, mucinous cystadenoma, and mucinous cystadenocarcinoma was found to be 23.1%, 61.4%, and 15.5%, respectively. In patients with long-term pain in the right lower quadrant of the abdomen, appendiceal mucocele should be considered, and the results of radiological imaging tests should be carefully analyzed before surgery.


Exploring the efficacy of melodic intonation therapy with Broca's aphasia in Arabic.
Even though the efficacy of melodic intonation therapy (MIT) with persons with aphasia (PWA) has been explored in different languages, the efficacy of MIT with Arabic-speaking PWA has never been explored. Aims: To explore the efficacy of MIT, adapted to Arabic, in promoting the expressive abilities of a 70-year-old Jordanian Arabic-speaking male subject with severe Broca's aphasia 3 months post-onset. Methods: An 8-week MIT therapy programme with tapping (1.5 h daily, 6 days a week) was used in a multiple baseline design across two types of trained phrases (i.e. automatic and self-generated phrases). Outcome measures included accuracy of production of trained (at the end of each session) and untrained phrases (at the end of each week). Pre- and post-treatment measures used, were the bilingual aphasia test, the American Speech-Language Hearing Association Functional Assessment of Communicative Skills, the communicative effectiveness index and the American Speech and Hearing Association Quality of Communication Life Scale. Accuracy of production for the trained and untrained phrases was also measured 2 weeks and 4 weeks after the treatment programme was finished. Results: The patient, (MK), improved his expressive productions post-treatment in automatic and self-generated phrases. Automatic phrases exceeded the established 75% accuracy criterion, whereas the self-generated phrases reached criterion and remained constant at follow-up. Moreover, MK gradually started improving on the generalisation stimuli, once the treatment on the self-generated phrases started and maintained the gains 2 weeks and 4 weeks post-treatment. Conclusion: MIT appears to be a viable treatment option for Jordanian Arabic-speaking persons with Broca's aphasia. However, more research is needed with larger groups of Jordanian Arabic-speaking persons with Broca's aphasia to provide more support to the present findings. Moreover, future studies might focus on the efficacy of MIT with persons with Broca's aphasia from different Arab countries and from countries where Arabic is part of the multicultural structure like South Africa and other countries on the African continent.


The rib-vertebra angles on the convexity and concavity of the spinal curve in infantile idiopathic scoliosis.
The components of Mehta's empirical rib-vertebra angle difference (RVAD) were observed as indicators of the prognosis in infantile idiopathic scoliosis (IIS). The following components were investigated in a retrospective study of 169 children with IIS: (1) convex rib-vertebra angle (RVA); (2) concave RVA; (3) RVAD; (4) initial spinal curve angle; and (5) age at diagnosis. The convex RVA, but not the concave RVA, was found to correlate significantly with the initial spinal curve angle. This is consistent with the hypothesis that factors that determine spinal curve progression in IIS are related to those that lead to drooping of the ribs on the convexity of the thoracic spinal curve. In terms of prognosis, the convex RVA, which entailed one measurement, was as accurate as the RVAD, which entailed two measurements and a calculation. A convex RVA of less than 68 degrees on the initial radiograph usually indicates that a spinal curve will progress.


RNAi screening for kinases and phosphatases identifies FoxO regulators.
Forkhead box class O (FoxO) transcription factors are key regulators of growth, metabolism, life span, and stress resistance. FoxOs integrate signals from different pathways and guide the cellular response to varying energy and stress conditions. FoxOs are modulated by several signaling pathways, e.g., the insulin-TOR signaling pathway and the stress induced JNK signaling pathway. Here, we report a genome wide RNAi screen of kinases and phosphatases aiming to find regulators of dFoxO activity in Drosophila S2 cells. By using a combination of transcriptional activity and localization assays we identified several enzymes that modulate dFoxO transcriptional activity, intracellular localization and/or protein stability. Importantly, several currently known dFoxO regulators were found in the screening, confirming the validity of our approach. In addition, several interesting new regulators were identified, including protein kinase C and glycogen synthase kinase 3beta, two proteins with important roles in insulin signaling. Furthermore, several mammalian orthologs of the proteins identified in Drosophila also regulate FOXO activity in mammalian cells. Our results contribute to a comprehensive understanding of FoxO regulatory processes.


Teamwork in community health committees: a case study in two urban informal settlements.
Community health committees (CHCs) are mechanisms for community participation in decision-making and overseeing health services in several low-and middle-income countries (LMICs). There is little research that examines teamwork and internal team relationships between members of these committees in LMICs. We aimed to assess teamwork and factors that affected teamwork of CHCs in an urban slum setting in Nairobi, Kenya. Using a qualitative case-study design, we explored teamwork of two CHCs based in two urban informal settlements in Nairobi. We used semi-structured interviews (n = 16) to explore the factors that influenced teamwork and triangulated responses using three group discussions (n = 14). We assessed the interpersonal and contextual factors that influenced teamwork using a framework for assessing teamwork of teams involved in delivering community health services. Committee members perceived the relationships with each other as trusting and respectful. They had regular interaction with each other as friends, neighbors and lay health workers. CHC members looked to the Community Health Assistants (CHAs) as their supervisor and "boss", despite CHAs being CHC members themselves. The lay-community members in both CHCs expressed different goals for the committee. Some viewed the committee as informal savings group and community-based organization, while others viewed the committee as a structure for supervising Community Health Promoters (CHPs). Some members doubled up as both CHPs and CHC members. Complaints of favoritism arose from CHC members who were not CHPs whenever CHC members who were CHPs received stipends after being assigned health promotion tasks in the community. Underlying factors such as influence by elites, power imbalances and capacity strengthening had an influence on teamwork in CHCs. In the absence of direction and support from the health system, CHCs morph into groups that prioritize the interests of the members. This redirects the teamwork that would have benefited community health services to other common interests of the team. Teamwork can be harnessed by strengthening the capacity of CHC members, CHAs, and health managers in team building and incorporating content on teamwork in the curriculum for training CHCs.


NASA RTLX as a Novel Assessment for Determining Cognitive Load and User Acceptance of Expert and User-Based Evaluation Methods Exemplified Through a mHealth Diabetes Self-Management Application Evaluation.
Many diabetes patients utilize mobile health applications for their personalized self-management needs, but a majority of these systems have deficient usability. To assess the usability, different evaluation methods can be used. Two such methods are the expert-based cognitive walkthrough (CW) and user-based think aloud (TA) which have different advantages and disadvantages and can lead to the detection of many types of usability problems. There is, however, a lack of research on how the evaluators experience performing these different methods; an important aspect to include due to its possible implications for the evaluation overall. In this paper the focus was on assessing the evaluators' cognitive load and method acceptance through an instrument novel for this particular purpose, the NASA RTLX, and through in-depth interviews. Six usability experts and 6 diabetes patients performed the evaluations where 18 usability problems were found with the CW and 20 with the TA and with system usability (SUS) scores of 23.75 and 59.58. Both methods had similarly high cognitive loads: the CW with a RTLX score of 56.11, and the TA of 53.47 and both were experienced as cognitively demanding. The results indicate the potential importance of these dimensions for decision-making purposes between different evaluation methods.


The effect of fixation technique on graft position in anterior cruciate ligament reconstruction.
The purpose of this paper was to determine the extent to which the technique used in ACL reconstruction and fixation influences graft placement. This is a Comparative Radiographic cohort study. Precise graft placement is one of the most crucial components of a successful anterior cruciate ligament (ACL) reconstruction. Two commonly used techniques of ACL reconstruction are arthroscopic bone-patellar tendon-bone (B-PT-B) autograft with interference screw fixation and semi-tendinosus and gracilis (ST + G) tendon autograft with endobutton femoral and multiple staple belt buckle tibial fixation. Using radiographic measurements of bone tunnel position following ACL reconstruction this study quantified the extent to which these techniques influenced graft placement. Femoral and tibial tunnel position in ACL reconstruction was determined using the post-operative radiographs of 40 male patients who had undergone ACL reconstruction (20 B-PT-B and 20 ST + G). The primary outcome measure was location of bone tunnel position following ACL reconstruction. Measurements were based on the guidelines of Amis et al. Femoral tunnel position of B-PT-B grafts was an average of 9.36% more anterior in the sagittal plane than with ST + G grafts. The mean position of B-PT-B grafts was at 31.11% (SD = 5.45%). The mean position of the ST + G grafts was 21.76% (SD = 6.62%). This difference between the two was found to be significant (p < .001). As demonstrated by this study, placement and orientation may vary to accommodate technique and fixation. Clinical outcomes measured were similar in both groups.


UNC-41/stonin functions with AP2 to recycle synaptic vesicles in Caenorhabditis elegans.
The recycling of synaptic vesicles requires the recovery of vesicle proteins and membrane. Members of the stonin protein family (Drosophila Stoned B, mammalian stonin 2) have been shown to link the synaptic vesicle protein synaptotagmin to the endocytic machinery. Here we characterize the unc-41 gene, which encodes the stonin ortholog in the nematode Caenorhabditis elegans. Transgenic expression of Drosophila stonedB rescues unc-41 mutant phenotypes, demonstrating that UNC-41 is a bona fide member of the stonin family. In unc-41 mutants, synaptotagmin is present in axons, but is mislocalized and diffuse. In contrast, UNC-41 is localized normally in synaptotagmin mutants, demonstrating a unidirectional relationship for localization. The phenotype of snt-1 unc-41 double mutants is stronger than snt-1 mutants, suggesting that UNC-41 may have additional, synaptotagmin-independent functions. We also show that unc-41 mutants have defects in synaptic vesicle membrane endocytosis, including a ∼50% reduction of vesicles in both acetylcholine and GABA motor neurons. These endocytic defects are similar to those observed in apm-2 mutants, which lack the µ2 subunit of the AP2 adaptor complex. However, no further reduction in synaptic vesicles was observed in unc-41 apm-2 double mutants, suggesting that UNC-41 acts in the same endocytic pathway as µ2 adaptin.


Opening the cocaine economy by providing within-session access to a cheaper source of cocaine makes demand for it more elastic.
Previous studies found that opening the cocaine economy by providing postsession access to cocaine had no effect on animals' demand for cocaine, whereas postsession access to saccharin or food made demand for these nondrug reinforcers more elastic. It is possible that there was no effect of economy type on cocaine taking in these earlier studies because of the delay to the postsession cocaine in the open economy. The present experiment tested whether forming an open economy by providing additional within-session cocaine, rather than postsession cocaine, would make rats' demand for cocaine more elastic. Saccharin was used as a nondrug comparison reinforcer. Three groups of rats pressed one lever for cocaine and one for saccharin on an ascending series of fixed ratio (FR) schedules where the number of responses required per reinforcer increased from 1 to 48 over sessions. In the open cocaine and open saccharin economy groups, rats had occasional access during the session to a third lever where cocaine or saccharin reinforcers, respectively, were always available on an FR-1 schedule. The main finding was that demand for cocaine was more elastic in the open cocaine economy group than in either of the other groups. Demand for saccharin was more elastic in the open saccharin economy group than in the open cocaine economy group. This study shows that cocaine taking is sensitive to economy type when the additional source of cocaine in an open economy is available close in time to when rats work for cocaine.


Angiogenesis in cultured and cryopreserved pancreatic islet grafts.
The ability of rat pancreatic islets to revascularize after transplantation was examined via in vitro and in vivo imaging of the microvasculature using laser scanning confocal microscopy (LSCM). Cultured or cryoprocessed islets were transplanted at the renal subcapsular site in rats. At various time intervals after transplantation, three-dimensional imaging of the graft was performed by LSCM. In vitro studies were conducted via microvascular corrosion casting of the grafted kidney in situations where it was difficult to obtain in vivo confocal data due to surgical complications. The vascular morphology of the islet grafts was evaluated quantitatively via digital image analysis algorithms to determine the morphology of the neovascular ingrowth and the rate of revascularization. In cultured islet grafts, the initiation of angiogenesis was observed within 1 week, characterized by the presence of capillary sprouts, tortuous vessels, and blood vessels with blind ends. The revascularization of the graft was typically completed within 2 weeks and could be distinguished as a network of completely perfused blood vessels consisting of intertwining capillaries, with surrounding arterioles and venules. The angiogenesis process in cryopreserved islet grafts required a longer time period to initiate (approximately 2 weeks), and the revascularization was completed in 1 week after the initiation. These results successfully demonstrate the potential of the described in vivo and in vitro LSCM techniques to measure the angiogenesis process in pancreatic islet grafts.


Carriage and community treatment of methicillin-resistant Staphylococcus aureus: what happens to colonized patients after discharge?
During a maternity hospital outbreak of colonization/infection due to methicillin-resistant Staphylococcus aureus (MRSA), mothers and babies from 35 families were known to have been discharged colonized with MRSA. Thirty-two of these families were followed up by screening in the community. After 4 weeks, carriage was still detectable in 22 families. The ten families in which carriage was no longer detectable had MRSA isolated at discharge from enrichment culture only. All of the 11 families who had MRSA isolated on direct culture at discharge continued to carry MRSA. Mothers and babies from the 22 families still carrying MRSA at 4 weeks were offered topical treatment. Carriage persisted in ten of these families despite treatment. The most common site of persistent carriage was the perineum in mothers and the throat in infants.


A new type of vasodilator, HA1077, an isoquinoline derivative, inhibits proliferation of bovine vascular smooth muscle cells in culture.
The effects of a newly developed vasodilator agent, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride], were investigated on the proliferation of cultured bovine aortic vascular smooth muscle cells (VSMC). HA1077 (10-100 microM) inhibited both fetal calf serum-induced proliferation and [3H]thymidine incorporation into DNA of the growth-arrested VSMC in a dose-dependent manner. When quiescent cells were stimulated with platelet-derived growth factor followed by insulin, HA1077 (1-30 microM), administered together with either stimulation, showed dose-dependent inhibition of [3H]thymidine incorporation. Further reduction of [3H]thymidine incorporation was observed when HA1077 was present at both stimulations, suggesting that HA1077 suppresses DNA synthesis acting in both competence and progression stages. After stimulation with fetal calf serum, quiescent VSMC started and ceased DNA synthesis in 15 to 18 hr and 24 hr, respectively. HA1077 inhibited [3H]thymidine incorporation when it was added either from 12 hr to 15 hr or from 21 hr to 24 hr after serum stimulation. In addition, when percent inhibition of [3H]thymidine incorporation by continuous exposure to HA1077 was examined as a function of the time it was added, reductions of the value were observed at 0 to 3 hr, 12 to 18 hr and 21 to 24 hr. Thus, we concluded that HA1077 suppresses DNA synthesis of bovine VSMC acting at the G0/G1 and the G1/S phase transitions and also in the S phase of the cell cycle. It is suggested that this agent may act as a potent inhibitor of VSMC proliferation as well as a vasodilator.


Cognitive reserve as a useful variable to address robotic or conventional upper limb rehabilitation treatment after stroke: a multicentre study of the Fondazione Don Carlo Gnocchi.
Rehabilitation plays a central role in stroke recovery. Besides conventional therapy, technological treatments have become available. The effectiveness and appropriateness of technological rehabilitation are not yet well defined; hence, research focused on different variables impacting recovery is needed. Results from the literature identified cognitive reserve (CR) as a variable impacting on the cognitive outcome. In this paper, the aim was to evaluate whether CR influences the motor outcome in patients after stroke treated with conventional or robotic therapy and whether it may influence one treatment rather than another. Seventy-five stroke patients were enrolled in five Italian neurological rehabilitation centres. Patients were assigned either to a robotic group, rehabilitation by means of robotic devices, or to a conventional group, where a traditional approach was used. Patients were evaluated at baseline and after rehabilitation treatment of 6 weeks through the Action Research Arm Test (ARAT), the Motricity Index (MI) and the Barthel Index (BI). CR was assessed at baseline using the Cognitive Reserve Index (CRI) questionnaire. Considering all patients, a weak correlation was found between the CRI related to leisure time and MI evolution (r = 0.276; P = 0.02). Amongst the patients who performed a robotic rehabilitation, a moderate correlation emerged between the CRI related to working activities and MI evolution (r = 0.422; P = 0.02). Our results suggest that CR may influence the motor outcome. For each patient, CR and its subcategories should be considered in the choice between conventional and robotic treatment.


[Effect of nonionizing microwave radiation on autoimmune reactions and antigenic structure of serum proteins].
The authors discuss the possibility of stimulating the autoimmune reactions of the organism by microwave irradiation. The immunochemical analysis of protein fractions of blood serum has revealed a destabilization of functional activity of the immune system humoral factors at 500 W/cm2 which is manifested by the formation of a new protein with the immunoglobulin G physico-chemical properties.


Implication of integrins α3β1 and α5β1 in invasion and anoikis of SK-Mel-147 human melanoma cells: non-canonical functions of protein kinase Akt.
Downregulation of integrins α3β1 and α5β1 strongly decreased cell colony formation and in vitro invasion and markedly enhanced anoikis in SK-Mel-147 human melanoma cells. These modifications were accompanied by a marked increase in the levels of active Akt protein kinase, which indicated it played a non-canonical function in the melanoma cells. Pharmacological inhibition of Akt1, an Akt isozyme, in cells depleted of α3β1 or α5β1 restored their invasive activity, while inhibition of the Akt 2 isoform did not cause a visible effect. Similar to our previous results with the α2β1 integrin, this finding suggested that in signaling pathways initiated by α3β1 and α5β1, the Akt1 isoform performs a non-canonical function in regulating invasive phenotype of melanoma cells. In contrast, when the effects of Akt inhibitors on anoikis of the melanoma cells were compared, the Akt2 isoform demonstrated a non-canonical activity in which Akt2 suppression led to a significant attenuation of apoptosis in cells with downregulated α3β1 or α5β1. Our results were the first evidence that, in the same tumor cells, different integrins can control various manifestations of tumor progression through distinct signaling pathways that are both common to various integrins and specific to a particular receptor.


Early and late cranial ultrasonographic appearances and outcome in very low birthweight infants.
Of 798 very low birthweight infants admitted to a regional neonatal intensive care unit over a five year period, 547 were discharged home and 524 available for follow up at two to five years later. Eighty-seven infants had a major impairment. Both early and late cerebral ultrasonographic appearances gave useful prognostic information, but the presence of cystic lesions, particularly if bilateral, was highly significant. There was a close correlation between late parenchymal lesions and previous ipsilateral intraventricular haemorrhage, suggesting a causal relation.


In vivo inhibition of acylpeptide hydrolase by carbapenem antibiotics causes the decrease of plasma concentration of valproic acid in dogs.
1. Our previous in vitro studies suggest that inhibition of the acylpeptide hydrolase (APEH) activity as valproic acid glucuronide (VPA-G) hydrolase by carbapenems in human liver cytosol is a key process for clinical drug-drug interaction (DDI) of valproic acid (VPA) with carbapenems. Here, we investigated whether in vivo DDI of VPA with meropenem (MEPM) was caused via inhibition of APEH in dogs. 2. More rapid decrease of plasma VPA levels and increased urinary excretion of VPA-G were observed after co-administration with MEPM compared with those after without co-administration, whereas the plasma level and bile excretion of VPA-G showed no change. 3. Dog VPA-G hydrolase activity, inhibited by carbapenems, was mainly located in cytosol from both the liver and kidney. APEH-immunodepleted cytosols lacked VPA-G hydrolase activity. Hepatic and renal APEH activity was negligible even at 24 h after dosing of MEPM to a dog. 4. In conclusion, DDI of VPA with carbapenems in dogs is caused by long-lasting inhibition of APEH-mediated VPA-G hydrolysis by carbapenems, which could explain the delayed recovery of plasma VPA levels to the therapeutic window even after discontinuation of carbapenems in humans.


Dialysis facility and patient characteristics associated with utilization of home dialysis.
Nonmedical factors influencing utilization of home dialysis at the facility level are poorly quantified. Home dialysis is comparably effective and safe but less expensive to society and Medicare than in-center hemodialysis. Elimination of modifiable practice variation unrelated to medical factors could contribute to improvements in patient outcomes and use of scarce resources. Prevalent dialysis patient data by facility were collected from the 2007 ESRD Network's annual reports. Facility characteristic data were collected from Medicare's Dialysis Facility Compare file. A multivariate regression model was used to evaluate associations between the use of home dialysis and facility characteristics. The utilization of home dialysis was positively associated with facility size, percent patients employed full- or part-time, younger population, and years a facility was Medicare certified. Variables negatively associated include an increased number of hemodialysis patients per hemodialysis station, chain association, rural location, more densely populated zip code, a late dialysis work shift, and greater percent of black patients within a zip code. Improved understanding of factors affecting the frequency of use of home dialysis may help explain practice variations across the United States that result in an imbalanced use of medical resources within the ESRD population. In turn, this may improve the delivery of healthcare and extend the ability of an increasingly overburdened medical financing system to survive.


Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging.
A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported. This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy. Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging. Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.


Rigidified A3 Adenosine Receptor Agonists: 1-Deazaadenine Modification Maintains High in Vivo Efficacy.
Substitution of rigidified A3 adenosine receptor (AR) agonists with a 2-((5-chlorothiophen-2-yl)ethynyl) or a 2-(4-(5-chlorothiophen-2-yl)-1H-1,2,3-triazol-1-yl) group provides prolonged protection in a model of chronic neuropathic pain. These agonists contain a bicyclo[3.1.0]hexane ((N)-methanocarba) ring system in place of ribose, which adopts a receptor-preferred conformation. N (6)-Small alkyl derivatives were newly optimized for A3AR affinity and the effects of a 1-deaza-adenine modification probed. 1-Deaza-N (6)-ethyl alkyne 20 (MRS7144, K i 1.7 nM) and 1-aza N (6)-propyl alkyne 12 (MRS7154, K i 1.1 nM) were highly efficacious in vivo. Thus, the presence of N1 is not required for nanomolar binding affinity or potent, long-lasting functional activity. Docking of 1-deaza compounds to a receptor homology model confirmed a similar binding mode as previously reported 1-aza derivatives. This is the first demonstration in nonribose adenosine analogues that the 1-deaza modification can maintain high A3AR affinity, selectivity, and efficacy.


The incorporation of focused history in checklist for early recognition and treatment of acute illness and injury.
Diagnostic error and delay are critical impediments to the safety of critically ill patients. Checklist for early recognition and treatment of acute illness and injury (CERTAIN) has been developed as a tool that facilitates timely and error-free evaluation of critically ill patients. While the focused history is an essential part of the CERTAIN framework, it is not clear how best to choreograph this step in the process of evaluation and treatment of the acutely decompensating patient. An un-blinded crossover clinical simulation study was designed in which volunteer critical care clinicians (fellows and attendings) were randomly assigned to start with either obtaining a focused history choreographed in series (after) or in parallel to the primary survey. A focused history was obtained using the standardized SAMPLE model that is incorporated into American College of Trauma Life Support (ATLS) and Pediatric Advanced Life Support (PALS). Clinicians were asked to assess six acutely decompensating patients using pre - determined clinical scenarios (three in series choreography, three in parallel). Once the initial choreography was completed the clinician would crossover to the alternative choreography. The primary outcome was the cognitive burden assessed through the NASA task load index. Secondary outcome was time to completion of a focused history. A total of 84 simulated cases (42 in parallel, 42 in series) were tested on 14 clinicians. Both the overall cognitive load and time to completion improved with each successive practice scenario, however no difference was observed between the series versus parallel choreographies. The median (IQR) overall NASA TLX task load index for series was 39 (17 - 58) and for parallel 43 (27 - 52), p = 0.57. The median (IQR) time to completion of the tasks in series was 125 (112 - 158) seconds and in parallel 122 (108 - 158) seconds, p = 0.92. In this clinical simulation study assessing the incorporation of a focused history into the primary survey of a non-trauma critically ill patient, there was no difference in cognitive burden or time to task completion when using series choreography (after the exam) compared to parallel choreography (concurrent with the primary survey physical exam). However, with repetition of the task both overall task load and time to completion improved in each of the choreographies.


A study of tremor in multiple sclerosis.
One hundred patients with definite multiple sclerosis, who were randomly selected from a multiple sclerosis unit in London, were examined in order to study the prevalence, subtypes, clinical features and associated disability of tremor in this population. There were 35 males and 65 females with an average age of 47 years and an average disease duration of 18.8 years. The mean tremor duration was 13 years, with a median latency of 11 years from disease onset to appearance of tremor. Tremor was reported in 37 patients but was detected in 58. Tremor affected the arms (56%), legs (10%), head (9%) and trunk (7%). There were no examples of face, tongue or jaw tremor. All the patients had action tremor, either postural or kinetic (including intention). Rest, Holmes' ('rubral') and primary orthostatic tremors were not encountered. Tremor severity ranged from minimal in 27%, to mild in 16% and moderate or severe in 15% of cases. Tremor severity correlated with the degree of dysarthria, dysmetria and dysdiadochokinesia but not with grip strength. In order to determine the clinical characteristics of these tremors, the action tremors of the upper limbs were subclassified according to the predominant site and state of tremulous activity. Of the 50 patients with tremor in the right arm, 32% had distal postural tremor, 36% had distal postural and kinetic tremor, 16% had proximal postural and kinetic tremor; 4% had proximal and distal postural and kinetic tremor and 12% isolated intention tremor. Twenty-seven percent of the overall study population had tremor-related disability and 10% had incapacitating tremor. Patients with abnormal tremor (severity grade >1/10) were more likely than those without tremor to be wheelchair dependent and have a worse Expanded Disability Systems Score, but Barthel activities of daily living indices and cognitive scores were comparable in the two groups.


Lipidomic profiling of phosphocholine-containing brain lipids in mice with sensorimotor deficits and anxiety-like features after exposure to Gulf War agents.
The central nervous system (CNS)-based symptoms of Gulf War Illness (GWI) include motor dysfunction, anxiety, and cognitive impairment. Gulf War (GW) agents, such as pyridostigmine bromide (PB), permethrin (PER), N,N-diethyl-meta-toluamide (DEET), and stress, are among the contributory factors to the pathobiology of GWI. This study characterizes disturbances in phosphocholine-containing lipids that accompany neurobehavioral and neuropathological features associated with GW agent exposure. Exposed mice received PB orally, dermal application of PER and DEET and restraint stress daily for 28 days, while controls received vehicle during this period. Neurobehavioral studies included the rotarod, open field, and Morris water maze tests. Histopathological assessments included glial fibrillary acid protein, CD45, and Nissl staining. Liquid chromatography/mass spectrometry with source collision-induced dissociation in negative and positive ionization scanning modes was performed to characterize brain phosphatidylcholine (PC) and sphingomyelin (SM). A significant increase in ether containing PC (ePC34:0, ePC36:2, and ePC36:1) or long-chain fatty acid-containing PC (38:1, 40:4, 40:2) was observed in exposed mice compared with controls. Among differentially expressed PCs, levels of those with monounsaturated fatty acids were more affected than those with saturated and polyunsaturated fatty acids. Sensorimotor deficits and anxiety, together with an increase in astrocytosis, were observed in exposed mice compared with controls. These lipid changes suggest that alterations in peroxisomal pathways and stearoyl-CoA desaturase activity accompany neurobehavioral and neuropathological changes after GW agent exposure and represent possible treatment targets for the CNS symptoms of GWI.


The Radiation Stress Response: Of the People, By the People and For the People.
The radiation stress response can have broad impact. In this Failla Award presentation it is discussed in three components using terms relevant to the current political season as to how the radiation stress response can be applied to the benefit for cancer care and as service to society. Of the people refers to the impact of radiation on cells, tissues and patients. The paradigm our laboratory uses is radiation as a drug, called "focused biology", and physics as "nano-IMRT" because at the nanometer level physics and biology merge. By the people refers to how the general population often reacts to the word "radiation" and how the Radiation Research Society can better enable society to deal with the current realities of radiation in our lives. For the people refers to the potential for radiation oncology and radiation sciences to improve the lives of millions of people globally who are now beyond benefits of cancer treatment and research.


Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats.
The GABAA receptor is implicated in the pathophysiology of schizophrenia and regulated by PKA signalling. Current antipsychotics bind with D2-like receptors, but not the GABAA receptor. The cAMP-responsive element-binding protein 1 (CREB1) is also associated with PKA signalling and may be related to the positive symptoms of schizophrenia. This study investigated the effects of antipsychotics in modulating D2-mediated PKA signalling and its downstream GABAA receptors and CREB1. Rats were treated orally with aripiprazole (0.75 mg/kg, ter in die (t.i.d.)), bifeprunox (0.8 mg/kg, t.i.d.), haloperidol (0.1 mg/kg, t.i.d.) or vehicle for 1 week. The levels of PKA-Cα and p-PKA in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) were detected by Western blots. The mRNA levels of Gabrb1, Gabrb2, Gabrb3 and Creb1, and their protein expression were measured by qRT-PCR and Western blots, respectively. Aripiprazole elevated the levels of p-PKA and the ratio of p-PKA/PKA in the NAc, but not the PFC and CPu. Correlated with this elevated PKA signalling, aripiprazole elevated the mRNA and protein expression of the GABAA (β-1) receptor and CREB1 in the NAc. While haloperidol elevated the levels of p-PKA and the ratio of p-PKA/PKA in both NAc and CPu, it only tended to increase the expression of the GABAA (β-1) receptor and CREB1 in the NAc, but not the CPu. Bifeprunox had no effects on PKA signalling in these brain regions. These results suggest that aripiprazole has selective effects on upregulating the GABAA (β-1) receptor and CREB1 in the NAc, probably via activating PKA signalling.


Poultry waste associated type C botulism in cattle.
Botulism in UK cattle has been confirmed by demonstrating type C botulinum toxin in sera from affected animals. Evidence is presented indicating the source of intoxication to be poultry carcasses containing type C Clostridium botulinum and its toxin. The organism was also found in poultry litter and in alimentary tract samples from slaughtered animals. The implications of these findings are discussed.


Gastrointestinal stromal tumours and other primary gastrointestinal neoplasms. A single-center experience.
In our surgical daily activity, we report the observation of rare tumour as Gastrointestinal Stromal Tumours (GIST). We report the incidence and behaviour of new cases of GIST operated in our Center during the last decade, from 2008 to 2018 and here we also describe the concomitant observation of a second gastroenteric tumor. We have examined all the case files and histological examinations of patients with CD 117-positive GISTs treated in our Institute from 2008 to 2018. We have gathered data regarding clinical symptoms at the time of diagnosis, tumour site, type of surgery performed, tumour size, histopathological data and follow up data. We have analysed 950 cases of patients who underwent surgery for gastrointestinal neoplasia in our department from 2008 to 2018. We have found 12 cases affected by GIST and in 4 cases it was also a second tumour. In two cases GIST were incidentalomas and in the others two patients a second tumour was incidentally observed in primary GIST. Patients with GIST run the risk of developing a second neoplasm, nearly twice as high as the general population with a negative impact on survival; also, incidental GIST is often observed requiring a better molecular characterization for the high risk of developing second neoplasms with the aim of achieving an early diagnosis. Gist, Second neoplasm, Surgery.


Lateral thinkers are not so laterally minded: hemispheric asymmetry, interaction, and creativity.
The biological basis of creativity remains a topic of contention. A long-held view suggests that whereas the left hemisphere is intelligent and analytic, the right hemisphere is the source of all creativity. Consequently, activating the right hemisphere should enhance creative thinking, prompting a plethora of popular books hawking a right hemisphere solution to topics ranging from drawing, to money management, to sex. More recently, an alternate proposal has suggested that creativity is not a lateralised function; instead, creativity is argued to stem from the interaction and integration of information across both the left and right hemispheres. According to this view, individuals with greater interhemispheric communication and/or less-lateralised brains will evidence enhanced creative ability. This paper reviews the neural basis of creativity to determine whether creativity stems from activation of the right hemisphere, or from the interaction of both hemispheres. The relationship between creativity and psychopathology is also examined, evaluating the evidence for a causal link between disorders such as schizophrenia, hemispheric activation, and enhanced creativity. Although the research reviewed indicates greater right hemisphere activity during creative tasks, the interaction between many varied, often distant, cortical regions across both the left and right hemispheres is also a crucial component of creativity. This interaction facilitates the integration of a variety of separate cognitive abilities, fostering creative thinking. As such, creativity is better conceptualised as a distributed, rather than a purely lateralised, function; more lateral thinkers have less lateralised brains.


[Effect of alpha-tocopherol on the respiratory burst of neutrophils, blast transformation of lymphocytes, and activity of human natural killer cells in blood].
The effect of vitamin E on immunological reactions of blood cells was studied. The addition of vitamin E in concentration of 100 microM to neutrophils caused the increase of superoxide production. But this index was decreased when incubation of these cells with A23187 or FMLP was accompanied by alpha-tocopherol in concentration of 100 microM followed by the removal of free ligand or alpha-tocopherol in concentration of 0.5 microM. In the presence of PMA the inhibiting action of alpha-tocopherol was not found (under the 0.5 microM of alpha-tocopherol) or was small (under the concentration of it 100 microM of alpha-tocopherol). The addition of alpha-tocopherol in concentration of 0.5 microM and 50 microM caused the inhibition of blasttransformation of lymphocytes and activity of natural killer cells. This effect was expressed more under the low contents of this vitamin in the incubation medium. The level of blasstransformation of blood in vitamin E-deficient rats was by 20% less than in normal. The exogenous addition of alpha-tocopherol in concentration of 0.5 microM did not affect this value. It was suggested that vitamin E can affect the respiration burst of neutrophils, blasttransformation of lymphocytes and activity of natural killer cells and these actions depend on its concentrations.


Biodegradable poly(ε-caprolactone) as a controlled drug delivery vehicle of vancomycin for the treatment of MRSA infection.
Biodegradable poly(ε-caprolactone) (PCL) is developed as a controlled drug delivery vehicle of vancomycin (VMC) with the advantage of avoiding a second surgery. The PCL-VMC hybrid, prepared through a solution route, is used as a delivery vehicle for vancomycin for controlling MRSA osteomyelitis as well as healing the cavity simultaneously in an experimental study. An in vitro study is conducted to optimize vancomycin impregnation in the PCL-VMC hybrid. An in vitro study on drug release from the hybrid material is investigated in phosphate buffer saline showing steady and sustained release of the drug. The release kinetics is fitted with several models and a non-Fickian nature is established following the Korsmeyer-Peppas model. Spectroscopic techniques and morphology observations reveal the cause of sustained release to be the strong interaction between the drug and the polymer. The results of the antibacterial assay show that the loading of vancomycin into the PCL matrix is able to maintain the activity of the pure drug. For the in vivo study, a unicortical defect is created in the metaphysis of the distal femur in rabbits. After contaminating the defect with MRSA, the 1st group of rabbits were treated with pure polymer, the 2nd group of rabbits were treated with normal saline (PBS), the 3rd group of rabbits were treated with pure VMC and in the last group of rabbits PCL-VMC was placed. Rabbits are assessed by clinical, radiological, histological, gross examination and bacterial load assays. Infection persisted throughout the period of study for both the pure polymer and PBS treated rabbits while rabbits treated with the PCL-VMC hybrid do not show any sign of infection. The VMC treated group rabbits show mild infection for the 1st week of the study; however, the infection becomes gradually more severe with time. Serial histology confirms the formation of new bone without any inflammation and necrosis for the rabbits treated with PCL-VMC. Importantly, the PCL-VMC hybrid bioadsorbs after delivery of the drug and thereby avoids the second surgery to remove the conventional implant.


Obesity Risk Assessment Model Using Wearable Technology with Personalized Activity, Calorie Expenditure and Health Profile.
There is a worldwide increase in the rate of obesity and its related long-term conditions, emphasizing an immediate need to address this modern-age global epidemic of healthy living. Moreover, healthcare spending on long-term or chronic care conditions such as obesity is increasing to the point that requires effective interventions and advancements to reduce the burden of the healthcare. This research focuses on the early risk assessment of overweight/obesity using wearable technology. We establish an individualised health profile that identifies the level of activity and current health status of an individual using real-time activity and vital signs. We developed an algorithm to assess the risk of obesity using the individual's current activity and calorie expenditure. The algorithm was deployed on a smartphone application to collect wearable device data, and user reported data. Based on the collected data, the proposed application assesses the risk of obesity/overweight, measures the current activity level and recommends an optimized calorie plan.