Flexor tendon healing and adhesion formation after Sterispon wrapping: a study in the rabbit.
The influence of Sterispon (Allen & Hanbury) wrapping on the healing of the rabbit flexor digitorum profundus tendon sutured within the digital sheath was studied. Control tendons healed in 2 weeks in association with thick adhesions. The wrapped tendons were surrounded with fewer adhesions, but 50% separated. Healing was delayed until adhesions reached the suture site. A sheath of a single layer of mesothelial cells formed on the surface of the Sterispon opposite the tendon and this markedly reduced adhesions at the suture site. The cellular reaction was bland. Sterispon wrapping had a similar effect on tendon healing and adhesion formation as wrapping with other non-absorbable substances and the results support the theory that healing in the digital sheath is necessarily mediated through the formation of adhesions. Sterispon wrapping has been helpful after tenolysis operations.


Surviving glioblastoma and a sense of disconnection.
Given the poor prognosis of glioblastoma, little focus has been placed on the needs of long-term survivors (those alive at least two years following diagnosis). The aim of this project was to explore the lived experience of long-term survivors of glioblastoma using a qualitative approach. Long-term survivors of glioblastoma diagnosed between 1/1/2006-31/12/2016 were identified at the tertiary centre involved. Participants underwent a semi-structured qualitative interview and caregiver dyads were collected if available. Thematic analysis was undertaken where themes were gradually generated from the data alongside data collection and confirmed or contrasted as data collection proceeded. Participants were selected and interviewed until data saturation was reached at 10 interviews. The overarching theme explaining the data was a sense of disconnection, beginning with the shock of diagnosis, and evolving over time, leading survivors to feel disconnected from (1) 'who I was', redefining their work, independence and social self; (2) 'who I am', contributing to social isolation, disavowal, and anxiety and depression; and (3) 'who I could be', reassessing their future. This unique study highlights the acute emotional distress and disconnection that begins with diagnosis and its evolving impact on the lived experience. Clinicians need to consider the emotional impact of survival when managing these patients and adopt a holistic approach, including the early introduction of psychosocial support to patients and their caregivers. Further validation of these findings in a larger cohort is desirable.


Prevalence of root dilaceration in adult patients referred to shiraz dental school (2005-2010).
Dilaceration is defined as a sudden change in the axial inclination of root or between the crown and the root of a tooth. There is no previous study evaluating its prevalence in south of Iran. This study evaluates the prevalence of root dilaceration on the basis of its location in dental arch in a sample of dental patients referring to Shiraz dental school, Iran. This retrospective study was performed using full mouth periapical radiographs of 250 patients who were referred to Shiraz dental school. Buccal and lingual dilaceration was determined by its known" bull's eye" appearance in the radiographs or if the deviation was in the mesial or distal directions; the angle of 90 degree or greater between the deviation and the axis of root was the inclusion criteria. Root dilaceration was detected in 0.3% of teeth and 7.2% of patients. It was distributed equally between the maxilla and mandible. Mandibular second molar was the most frequent dilacerated tooth (1.6%) followed by maxillary first molar (1.3%) and mandibular first molar (0.6%). The alveolar nerve was the most common anatomic structure near dilacerated teeth. According to this study, root dilaceration is an uncommon developmental anomaly which occurs mostly in the posterior teeth.


The transcriptome of Icerya aegyptiaca (Hemiptera: Monophlebidae) and comparison with neococcoids reveal genetic clues of evolution in the scale insects.
Scale insects are worldwide sap-sucking parasites, which can be distinguished into neococcoids and non-neococcoids. Neococcoids are monophyletic with a peculiar reproductive system, paternal genome elimination (PGE). Different with neococcoids, Iceryini, a tribe in non-neococcoids including several damaging pests, has abdominal spiracles, compound eyes in males, relatively abundant wax, unique hermaphrodite system, and specific symbionts. However, the current studies on the gene resources and genomic mechanism of scale insects are mainly limited in the neococcoids, and lacked of comparison in an evolution frame. We sequenced and de novo assembled a transcriptome of Icerya aegyptiaca (Douglas), a worldwide pest of Iceryini, and used it as representative of non-neococcoids to compare with the genomes or transcriptomes of other six species from different families of neococcoids. We found that the genes under positive selection or negative selection intensification (simplified as "selected genes" below) in I. aegyptiaca included those related to neurogenesis and development, especially eye development. Some genes related to fatty acid biosynthesis were unique in its transcriptome with relatively high expression and not detected in neococcoids. These results may indicate a potential link to the unique structures and abundant wax of I. aegyptiaca compared with neococcoids. Meanwhile, genes related to DNA repair, mitosis, spindle, cytokinesis and oogenesis, were included in the selected genes in I. aegyptiaca, which is possibly associated with cell division and germ cell formation of the hermaphrodite system. Chromatin-related process were enriched from selected genes in neococcoids, along with some mitosis-related genes also detected, which may be related to their unique PGE system. Moreover, in neococcoid species, male-biased genes tend to undergo negative selection relaxation under the PGE system. We also found that the candidate horizontally transferred genes (HTGs) in the scale insects mainly derived from bacteria and fungi. bioD and bioB, the two biotin-synthesizing HTGs were exclusively found in the scale insects and neococcoids, respectively, which possibly show potential demand changes in the symbiotic relationships. Our study reports the first I. aegyptiaca transcriptome and provides preliminary insights for the genetic change of structures, reproductive systems and symbiont relationships at an evolutionary aspect. This will provide a basis for further research and control of scale insects.


Bf polymorphism: another variant (S0.8).
A "new" variant band in the Bf system has been found in the serum of three individuals belonging to a tribe of Brazilian Indians (Karaja--Bananal--Goias) and in the serum of a Caucasian individual from the area of Strasbourg. It is highly probable that the band represents another allele at the Bf locus BfS0.8.


The convergent synthesis and anticancer activity of broussonetinines related analogues.
The convergent synthesis of broussonetinines related congeners 3 and 4 with the simple C13 alkyl side chain and differently configured pyrrolidine skeleton has been achieved. Our approach relied on the [3,3]-sigmatropic rearrangements of chiral allylic substrates derived from d-xylose. Cross metathesis of the common oxazolidinone intermediates 7 and 8 with tridec-1-ene followed by alkylative cyclization completed the construction of both C-alkyl iminosugars. The targeted compounds 3 and 4 were screened for antiproliferative/cytotoxic activities against multiple cancer cell lines by MTT assay. Compound 3 exhibited very good in vitro potency on Caco-2 and Jurkat cell lines with IC50 value of 5.1 μM and 5.8 μM, respectively.


Masculinizing sclerosing stromal cell tumor in pregnancy: report of a case and review of the literature.
To report a case of sclerosing stromal cell tumor of the ovary in pregnancy and to review the literature of this rare ovarian tumor. The patient's office record and hospital record were reviewed. Gross and microscopic pathology were reviewed by one gynecologic pathologist. A Medline literature search and literature review were performed. Over eighty cases of sclerosing stromal cell tumor of the ovary have been reported in the literature since the definition of this pathologic condition in 1973. Only five cases have been reported during pregnancy and only two of these resulted in maternal virilization. This report describes severe maternal virilization with birth of a non-virilized female infant. Sclerosing stromal cell tumor of the ovary can result in severe virilization via androgen production. Surgery with removal of the involved ovary is required for diagnosis and cure. Prognosis is excellent.


Lineage switch with t(6;11)(q27;q23) from T-cell lymphoblastic lymphoma to acute monoblastic leukemia at relapse.
We present a patient with T-cell lymphoblastic lymphoma (T-LBL) harboring t(6;11)(q27;q23) that converted to acute monoblastic leukemia at relapse. A 27-year-old man developed T-LBL with a mediastinal mass. He exhibited several recurrences in the central nervous system and marrow. A fifth relapse occurred in the marrow, with 42.8% blasts with CD4, CD5, CD7, CD10, CD33, CD34, HLA-DR and cytoplasmic (cy) CD3. While achieving complete remission with nelarabine, sixth relapse occurred in the marrow with 6.8% blasts, which had characteristics of monoblastic features, 2 months later. Marrow blasts were positive for myeloperoxidase, CD4, CD33, CD56, CD64, and HLA-DR, but were negative for cyCD3, CD5, CD7, CD10, and CD34. Marrow cells at both the 5th lymphoid and 6th myeloid relapses had t(6;11)(q27;q23) and the same MLL-MLLT4 fusion transcript. In addition, the MLL-MLLT4 fusion sequences documented in the initial mediastinal cells were the same as seen in peripheral blood cells at the 6th relapse. The patient continues 7th remission after one course of gemtuzumab ozogamicin therapy followed by cord blood transplantation for more than 3 years. Sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanism of leukemic recurrence and possible implications for treatment selection.


Synthesis and in vivo activity of some porphyrindione derivatives with potential in photodynamic therapy.
A number of synthetic bacteriochlorins were prepared from porphyrindiones. The potential of these compounds as sensitizers for photodynamic therapy was examined using the FANFT-induced urothelial cell carcinoma (AY-27) transplanted into rats. In a number of cases, tumor regression was significant following treatment with both drug and light.


Obesity is associated with Henoch-Schönlein Purpura Nephritis and development of end-stage renal disease in children.
Objectives: To explore the association of obesity with the occurrence of Henoch-Schönlein Purpura Nephritis (HSPN) and development of end-stage renal disease (ESRD) in children with Henoch-Schönlein Purpura (HSP).Methods: This was a retrospective study of 446 pediatric patients with diagnosed HSP. All patients' demographic characteristics, clinical features, and laboratory data were collected from the electronic medical records in hospitals from January 2008 to December 2014, and the prognosis was followed up till December 2018. Multivariate logistic regression and the Cox proportional hazard regression were employed for exploring the potential risk factors for occurrence of HSPN and development of ESRD, respectively.Results: It is reported that 35.2% (n = 157) of HSP patients had HSPN. The multivariate logistic regression showed that obesity (OR = 3.82; 95% CI: 1.92-7.49; p < .01), age over 6 years old at onset (OR = 2.24; 95% CI: 1.32-4.87; p < .01) and angioedema (OR = 1.72; 95% CI: 1.25-4.02; p < .01) were significantly associated with the occurrence of HSPN. During a median follow-up of 52.0 months, 5.2% (n = 23) of HSP patients developed ESRD. The Cox proportional hazard regression indicated that obesity (HR = 3.27; 95% CI: 2.01-6.37; p < .01) and International Study of Kidney Disease of Children (ISKDC) III (HR= 2.88; 95% CI: 1.96-3.80; p < .01) were predictors for the development of ESRD in patients with HSP.Conclusions: Obesity is associated with an increased risk of renal involvement and contributes to the development of ESRD in pediatric patients with HSP.


Setup and characterization of a multiphoton FLIM instrument for protein-protein interaction measurements in living cells.
Fluorescence lifetime microscopy (FLIM) is currently one of the best techniques to perform accurate measurements of interactions in living cells. It is independent of the fluorophore concentration, thus avoiding several common artifacts found in Förster Resonance Energy Transfer (FRET) imaging. However, for FLIM to achieve high performance, a rigorous instrumental setup and characterization is needed. We use known fluorophores to perform characterization experiments in our instrumental setup. This allows us to verify the accuracy of the fluorescence lifetime determination, and test the linearity of the instrument by fluorescence quenching. We develop and validate here a protocol for rigorous characterization of time-domain FLIM instruments. Following this protocol, we show that our system provides accurate and reproducible measurements. We also used HeLa cells expressing proteins fused to Green Fluorescent Proteins variants (CFP and YFP) to confirm its ability to detect interactions in living cells by FRET. We report a well-designed protocol in which precise and reproducible lifetime measurements can be performed. It is usable for all confocal-based FLIM instruments and is a useful tool for anyone who wants to perform quantitative lifetime measurements, especially when studying interactions in living cells using FRET.


Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors.
5-(Trifluoroacetyl)thiophene-2-carboxamides were found to be potent and selective class II HDAC inhibitors. This paper describes their further development and the investigation on the cause for the lack of cell-based activity. A rapid screening assay was set up which enabled the identification of more metabolic stable compounds as potent and selective class II HDAC inhibitors.


Use Motives of Patients with Amphetamine-Type Stimulants Use Disorder and Attention-Deficit/Hyperactivity Disorder.
There is a frequent comorbidity of amphetamine-type stimulants (ATS) use disorders and attention-deficit/hyperactivity disorder (ADHD). The assumption that this patient group "self-medicate" suggests that there are different use motives for ATS addicted patients with and without ADHD. Our study investigates these potential differences in use motives. Within a mixed-method approach, we examined the use motives of adults with ATS use disorder with and without ADHD in the first and latest month of their use. For this purpose, we used the 12-item Amphetamine-Type Stimulants Motive Questionnaire (AMQ) and a mind mapping technique after verifying that these tools are applicable to adults with ADHD. The mixed-method approach showed that enhancement motives were the most important motives in the first month of use (e.g., fun/kick/rush/desire, and curiosity/interest in the drug/appeal), and over time, the incidence of coping motives increased (e.g., repression and freeing the mind/not having to think/switching off). There were no differences between adults with and without ADHD in the AMQ data, while the qualitative data showed that adults with ADHD used ATS less often out of social motives. In particular, the results showed no differences in the coping dimension and, thus, did not suggest that self-medication is an important factor for patients with ADHD. Patients with and without ADHD show very similar motive patterns for ATS use. This indicates that ATS treatment programs addressing use motives do not necessarily have to be different for patients with and without ADHD.


[The isolation of monoclonal antibodies to hepatoma-associated nonhistone chromosomal proteins from rat kidneys].
A monoclonal antibody (5D2) has been produced to a fraction of nonhistone proteins of kidney origin, associated with the rat hepatoma 27 and not obtained in normal liver. The 5D2 antibody was found to precipitate three proteins with molecular weights of 22-23 kDa. Indirect immunofluorescence studies on fixed hepatoma cell-preparations showed speckled nuclear staining patterns. In contrast, the 5D2 antibody was unreactive with intact hepatocytes.


Group consultations for menopause: A way forward if we can encourage women to join?
The number of patients presenting to primary care requiring support with menopause symptoms is increasing and the number of available appointments in general practice is reducing. In attempt to improve access new ways of engaging with these patients may be beneficial. Group consultations could be a solution. Here I describe my experience of setting up group consultations in a GP practice.


Commercial considerations for immunoproteomics.
The underlying drivers of scientific processes have been rapidly evolving, but the ever-present need for research funding is typically foremost amongst these. Successful laboratories are embracing this reality by making certain that their projects have commercial value right from the beginning of the project conception. Which factors to be considered for commercial success need to be well thought out and incorporated into a project plan with similar levels of detail as would be the technical elements. Specific examples of commercial outcomes in the field of Immunoproteomics are exemplified in this discussion.


Embolization of a thoracic aortic aneurysm; the straddling coil technique: technical note.
Occlusion of a patent postligated aortic aneurysm was performed percutaneously with modified use of giant steel coils in a 50-year-old man. Steel coils were placed across the short, narrowed segment of the aorta. Successful thrombosis of entire aortic aneurysm was accomplished. No complications occurred.


The prevalence of and major risk factors associated with diabetic retinopathy in Gegharkunik province of Armenia: cross-sectional study.
Diabetic retinopathy (DR) is one of the leading causes of blindness in adults in industrialized countries and the emerging cause of blindness in developing countries. The objective of this study was to describe the prevalence of DR and risk factors associated with it among diabetic patients. The analytical cross-sectional survey and eye screenings were carried out among 625 diabetic patients from urban and rural areas of Gegharkunik region. DR was assessed by dilated ophthalmoscopy and defined based on the WHO International Classification of Diseases. The survey instrument, included questions about demographics, disease history, health status, medication use and healthy lifestyle. Descriptive statistics and logistic regression were used to analyze the data. The prevalence of DR in the sample was 36.2%. A total of 90.2% of patients with DR had non-proliferative, while 9.8% had proliferative DR. In bivariate analysis, age, diabetes duration, being under insulin treatment, blood glucose level, having non-communicable diseases were significantly associated with DR. In the adjusted analysis being under insulin treatment (OR = 3.24; 95% CI: 1.56-6.75), diabetes duration (OR = 1.23; 95% CI: 1.16-1.31) and age (OR = 1.05; 95% CI: 1.02-1.08) were independently associated with DR. Earlier diagnosis of diabetes and DR can help to control some of these factors and prevent further complications and vision loss. Population-based educational programs on diabetes and diabetic retinopathy and continuous medical education on diabetes management can improve diabetes care and self-management and prevent eye complications.


Facile synthesis and functionalization of manganese oxide nanoparticles for targeted T1-weighted tumor MR imaging.
We report the polyethyleneimine (PEI)-enabled synthesis and functionalization of manganese oxide (Mn3O4) nanoparticles (NPs) for targeted tumor magnetic resonance (MR) imaging in vivo. In this work, monodispersed PEI-coated Mn3O4 NPs were formed by decomposition of acetylacetone manganese via a solvothermal approach. The Mn3O4 NPs with PEI coating were sequentially conjugated with fluorescein isothiocyanate, folic acid (FA)-linked polyethylene glycol (PEG), and PEG monomethyl ether. Followed by final acetylation of the remaining PEI surface amines, multifunctional Mn3O4 NPs were formed and well characterized. We show that the formed multifunctional Mn3O4 NPs with a mean diameter of 8.0 nm possess good water-dispersibility, colloidal stability, and cytocompatibility and hemocompatibility in the given concentration range. Flow cytometry and confocal microscopic observation reveal that the multifunctional Mn3O4 NPs are able to target FA receptor-overexpressing cancer cells in vitro. Importantly, the FA-targeted Mn3O4 NPs can be used as a nanoprobe for efficient T1-weighted MR imaging of cancer cells in vitro and the xenografted tumor model in vivo via an active FA-mediated targeting pathway. With the facile PEI-enabled formation and functionalization, the developed PEI-coated Mn3O4 NPs may be modified with other biomolecules for different biomedical imaging applications.


Primary localized stages I and II non-Hodgkin's lymphoma of the nasopharynx: a retrospective 17-year single institutional experience.
The aim of this retrospective study was to define the natural history, clinicopathological findings, prognostic factors, and treatment outcome of 43 patients with localized stages I and II primary non-Hodgkin's lymphoma (NHL) of the nasopharynx, followed up in a single institution over a 17-year period. Forty-three (13 women and 30 men) consecutive patients with localized stages I (N = 12) and II (N = 31) primary nasopharyngeal NHL were treated in our institution between 1990 and 2007. The pathologic reports were classified according to the International Working Formulation (N = 22) or Revised European-American Lymphoma classification (N = 21). The vast majority of patients (88%) were managed with a sequential combination of chemotherapy and radiation therapy. Chemotherapy mainly consisted of 4-8 (median 6) cycles of CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisolone). Involved-field radiation therapy with a median dose of 44 Gy was delivered to the primary site and entire cervical lymph nodes. The median age of the patients was 53 years (range, 6 to 86 years). The majority of the patients (70%) had high-grade histology. B-cell types represented 67% of the cases, among which diffuse large B cell was the most common histological subtype. After a median follow-up of 70 months, the 5-year disease-free survival and overall survival were 58.8% and 70.6%, respectively. In multivariate analysis, age less than or equal to 30 years (hazard ratio (HR) = 5.32, 95% confidence interval (CI) = 1.69-16.76), elevated serum lactate dehydrogenase level (HR = 3.69, 95% CI = 1.43-9.51), and modified International Prognostic Index with more than or equal to two risk factors (HR = 17.99, 95% CI = 2.32-139.30) retained statistical significance. Our limited data suggest that primary nasopharyngeal NHL tends to have aggressive histology and unfavorable clinical course with poor outcome, despite a considerably localized disease at the time of presentation and high frequency of complete initial response rates. Combined modality therapy should be considered for the majority of patients with primary localized nasopharyngeal NHL.


Biomarkers are associated with clinical and endoscopic outcomes with vedolizumab treatment in Crohn's disease.
Vedolizumab, an α4β7 integrin antagonist, is an effective therapy for Crohn's disease (CD). Biomarkers are needed to guide therapy and predict outcomes. This study evaluated biomarker concentrations and outcomes in patients with CD undergoing vedolizumab treatment. Sera at weeks 0, 2, 6, 14, and ⩾26 were collected from vedolizumab-treated, refractory CD patients. Concentrations of soluble (s)-Vascular Cell Adhesion Molecule (VCAM)-1, s-Intercellular Cell Adhesion Molecule (ICAM)-1, s-Mucosal Addressin Cell Adhesion Molecule (MAdCAM)-1, and s-α4β7 integrin were evaluated for associations with achieving endoscopic remission. A total of 22 patients with CD were included. In all patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased compared with baseline. s-VCAM-1 and s-ICAM-1 changed differentially in patients who achieved remission. At week 6, median s-VCAM-1 (859.6 ng/ml versus 460.3 ng/ml, p = 0.03) and s-ICAM-1 (545.7 ng/ml versus 286.2 ng/ml, p = 0.03) concentrations were higher in patients who achieved endoscopic remission compared with those who did not, and similar differences were observed for s-ICAM-1 concentrations in patients who achieved clinical remission, compared with those who did not (669.1 ng/ml versus 291.0 ng/ml, p = 0.04). Week 14 s-α4β7 concentrations were lower in patients who achieved endoscopic remission, compared with those who did not (7.5 ng/ml versus 17.6 ng/ml, p = 0.020). In all vedolizumab-treated CD patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased. However, higher concentrations of s-ICAM-1 and s-VCAM-1 at week 6 and lower concentrations of s-α4β7 at week 14 differentiated patients who achieved endoscopic remission. These findings may help identify early predictors of response to vedolizumab treatment in patients with CD. Further validation in less refractory CD patients is needed.


Prognostic factors for upper tract transitional cell carcinoma: a retrospective review of 66 patients.
We assessed the prognostic factors on recurrence and disease-specific survival of patients treated for upper tract transitional cell carcinoma (TCC). Data on 66 patients who were treated for upper tract TCC in a single centre over a 13-year period were analysed. Mean follow-up time was 49.2 months. Fifty-five out of 66 (83.3%) underwent nephroureterectomy with excision of a bladder cuff. Four (6.1%) patients had nephrectomy alone while three (4.5%) had renal-sparing surgery. Four patients did not receive surgery due to advanced age and other comorbidities. Age, sex, tumour location, stage and grade were analysed as prognostic factors for disease recurrence and disease-specific survival using log rank univariate analysis. Disease recurrence occurred in 45 (68.2%) patients at a median time of 11.0 months. Recurrences were found in the bladder in 27.3%, the contralateral renal pelvis in 4.5%, local retroperitoneum in 19.7%, distant sites in 13.6%, with simultaneous local and distant metastases occurring in 3.0%. Tumour stage was the only significant prognostic factor for recurrence. Presence of extraurothelial recurrence, stage and grade were significant prognostic factors for disease-specific survival. Tumour stage was the most consistent predictor of both disease recurrence and survival. These findings would guide the need for any adjuvant chemoradiotherapy.


External iliac vein aneurysm treated via balloon-assisted aneurysmorrhaphy with a contemporary review of the literature.
Isolated external iliac vein aneurysm is exceedingly rare, not well-described in the literature, and presents several potential surgical approaches. Herein, we describe the case of a 72-year-old woman who presented with incidentally found 4.3 cm × 3.4 cm × 5.6 cm right external iliac vein aneurysm after undergoing magnetic resonance imaging for orthopedic work-up. She was treated via parallel supra- and infra-inguinal incisions and novel combination of primary aneurysmorrhaphy with intraluminal balloon mandrel-assisted closure. The patient was discharged on postoperative day two, and 6-month follow-up ultrasound showed a normal caliber vessel with normal compressibility, suggesting this technique is safe and effective for appropriately selected patients.


Are you paying attention to me? The effect of social presence on spatial attention to gaze and arrows.
Prior research has shown that the presence of another individual and type of attention cue (social gaze vs. nonsocial arrow) can modulate attention, with little done to integrate the two. We thus investigate the role of two social presence factors when completing a joint cueing task with either social (gaze) or nonsocial (arrow) cues. Familiarity was operationalized as participants engaged in a prompted conversation either before (n = 60 dyads) or after (n = 59 dyads) the task. To determine the effect of previous responder identity on attention, we contrasted trials where participants responded twice in a row (same responder) with switch trials (different responder), along with whether the previous target was in the same or a different location. Although familiarity only affected global speed and not magnitudes of cueing, we did find that attention to gaze and arrows was differentially affected by previous responder and previous target location. Specifically, for gaze cues muted cueing effects occurred for trials where the previous responder was different, while for arrow cues there was less muting of the cueing effect regardless of previous responder. Taken together, previous responder and previous target location both modulated attention, with the effect on attention dependent on the type of cue, gaze, or arrow.


Endoscopy in the management of patients after ileal pouch surgery for ulcerative colitis.
Pouchitis is the most common complication following ileal pouch-anal anastomosis in patients with ulcerative colitis. However, there are several other inflammatory and noninflammatory conditions that can mimic pouchitis, and endoscopy with biopsies is essential for distinguishing these various conditions. This paper will review the differential diagnosis of pouchitis and the role of endoscopy in the diagnosis and management of disorders of the ileal pouch.


Suspected clinical toxoplasmosis in a 12-week-old puppy in Singapore.
Toxoplasma gondii is traditionally known as a parasite of felids, with possible infection in intermediate hosts such as dogs and humans, and thus a disease of public health significance. Published data on the prevalence of toxoplasmosis in dogs and cats in Singapore is scanty, and this paper documents a suspect clinical case of toxoplasmosis in a free-roaming puppy trapped from an offshore island of Singapore. A 12-week-old puppy presented with hindlimb weakness and sarcopenia, with rapidly progressing ascending paralysis and respiratory distress, one week after trapping. Toxoplasmosis was suspected after indirect fluorescence antibody testing (IFAT) revealed anti-T. gondii antibodies. The puppy responded quickly to clindamycin treatment and was discharged from hospital after 10 days. While rare and undocumented, veterinary clinicians in Singapore are advised to also include toxoplasmosis infection as a differential diagnosis in dogs presenting with similar clinical signs. This is especially so for dogs which have access to the outdoors.


Uniting Experiments and Big Data to advance ecology and conservation.
Many ecologists increasingly advocate for research frameworks centered on the use of 'big data' to address anthropogenic impacts on ecosystems. Yet, experiments are often considered essential for identifying mechanisms and informing conservation interventions. We highlight the complementarity of these research frameworks and expose largely untapped opportunities for combining them to speed advancements in ecology and conservation. With nascent but increasing application of model integration, we argue that there is an urgent need to unite experimental and big data frameworks throughout the scientific process. Such an integrated framework offers potential for capitalizing on the benefits of both frameworks to gain rapid and reliable answers to ecological challenges.


The in-practice prevention programme: an example of flexible commissioning from Yorkshire and the Humber.
Introduction An In-Practice Prevention (IPP) programme was developed by the Local Dental Network in the North Yorkshire and the Humber area in England in response to an oral health needs assessment. The underpinning logic model drew on a flexible commissioning approach and aimed to incentivise dental teams with NHS contracts to promote the delivery of prevention. This used care pathways that involved the whole dental team and was cost-neutral.Aim The programme was evaluated using realist methodology to identify 'what works, in which circumstances, how and for who?'.Design Realist evaluations are explanatory in nature and attempt to understand the factors that appear to influence the success (or not) of an intervention, rather than demonstrating causality.Methods and results Following a review of the pertinent literature, semi-structured interviews and focus groups, five theory areas were considered to be critical to the delivery of IPP. In order of stated priority, these were: 1) clinical leadership; 2) 'skill mix'; 3) financial incentives; 4) institutional logic/practice culture; and 5) behaviour change.Conclusion The results appear to show that clinically-led programmes could offer value to dental commissioners within a flexible commissioning model, although this would need to be further tested using an experiment design.


High intensity focused ultrasound responsive release behavior of metallo-supramolecular block PPG-PEG copolymer micelles.
An amphiphilic metallo-supramolecular poly(propylene glycol)-block-poly(ethylene glycol) block copolymer containing a bis(2,2':6',2″-terpyridine) ruthenium (II) complex as a supramolecular connection between the two constituting blocks was used to prepare stable aqueous micelles which displayed a high intensity focused ultrasound (HIFU) triggered release behavior. By adjusting the HIFU time and intensity, the novel modality of HIFU triggered release allows for fine-tuning of the release kinetics of the encapsulants from the micelles in a remote and controlled way. Nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry confirmed that the degradation of the micelles was due to the cleavage of the ether bond connected to the pyridine ring. This well controlled HIFU-copolymer micelle drug delivery system has considerable potential in targeted therapy.


Development and evaluation of monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay for the diagnosis of acute leptospirosis in humans.
Monoclonal antibody (MAb)-based ELISA was developed to detect leptospiral antigens from the plasma of febrile patients. The MAb reacts specifically with pathogenic leptospires and the assay possesses excellent diagnostic test parameters compared to PCR, indicating that this new ELISA is useful for the early diagnosis of leptospirosis with low operational cost.


Phosphorus in the soil-plant-animal ecosystem : An introduction to a model.
A compartmental model of phosphorus in soil-plant-animal ecosystem is described. It consists of 17 compartments, five in soil, six in plant, three in above ground fauna and three in soil organisms and microorganisms. Common amounts and rates of turnover in each of these compartments is presented. Though the total amount of P in the ecosystem is large, only a very small part of it is being cycled, and presented data show that removal of P from an agricultural pastoral ecosystem is very slight. Most of the available phosphorus which is absorbed by plant roots is gradually fixed in forms of long-range unavailability, both by plants and by animals. This process of biological fixation is counterbalanced mainly by the activity of soil microorganisms. Quantities of input-output of P in intensive pastoral ecosystems are also presented, and some agronomical and ecological implications are considered. The manipulation of soil microorganisms and change towards more desirable P releasing strains or species may decrease need of fertilization, lower the risk of eutrophication and enhance productivity of such ecosystems. Such manipulations, however, can be achieved only after appropriate research.


Early phylogenetic value of the major GABA(A) receptor subunit mRNAs in the telencephalon.
In an effort to establish distinct phylogenetic values for the major GABA(A) receptor subunit mRNAs (alpha(1), beta(2) and gamma(2)) in the telencephalon, the cellular expression capacity of these mRNAs was evaluated in this brain region of two distantly related mammals (hedgehog and rat). Application of emulsion hybridization histochemistry and quantitative film autoradiography approaches allowed us to detect elevated ( P<0.01) beta(2) mRNA levels in primitive telencephalic neuronal populations such as those of the glomerular olfactory layer of the hedgehog. Conversely, notable levels of the alpha(1)-subunit mRNA were also registered for the higher telencephalic regions such as the oriens-pyramidalis layer of the hippocampus although elevated levels were mostly obtained for the rat. Interestingly, it was the high number of giant pyramidal neurons that were actively involved in the expression of this subunit. A similar pattern was also detected for pyramidal-like cells of the rat lateral amygdala region expressing the gamma(2)-subunit mRNA. Taken together, these results suggest an early phylogenetic success of GABAergic neuronal mechanisms relying mainly on elevated beta(2)-subunit levels. On the other hand, elevated quantities of gamma(2)- and, above all, of alpha(1)-subunit mRNAs in the rat seem instead to be related to the highly advanced behavioral and mnemonic strategies that are under the control of these telencephalic regions.


Evidence for the de novo regeneration of the pattern of the length heteroplasmy associated with the T16189C variant in the control (D-loop) region of mitochondrial DNA.
We have investigated the genetics of the length heteroplasmy associated with the T16189C variant of mitochondrial DNA (mtDNA), and report here definitive evidence that the pattern of the length heteroplasmy is not simply the outcome of drift related to the random segregation of the mtDNA population during cell division, but is actively maintained and regenerated de novo following each cell division. The pattern of the length heteroplasmy was maintained in a fibroblast cell line during an extensive mtDNA depletion experiment by ethidium bromide treatment, and following the subsequent repopulation of the cells with mtDNA. The investigation of the pattern of the length heteroplasmy by single cell pick up shows a similar pattern in sister cells despite the evidence of the randomness of mtDNA segregation, providing definitive evidence for the de novo regeneration of the pattern following cell division. Consistent with this conclusion is the observation that similar patterns of length heteroplasmy are found in tissues of single individuals.


The effects of 1,6-dinitropyrene on spindle morphology in transformed human cells.
The effects of 1,6-dinitropyrene (1,6-DNP) on the fidelity of cell division were studied in the transformed human fibroblast cell line MRC5VA. Over a dose range of 0.1-10 micrograms/ml of 1.6-DNP, we observed significant increases in the levels of abnormal division stages, associated with damage to the spindle apparatus of the cell. Qualitative changes in spindle morphology and a quantitative decrease in pole-to-pole spindle length were also observed with increasing doses of 1.6-DNP. Such changes in the size and morphology of the spindle corresponded with an accumulation of cells blocked at metaphase. The presence of catalase did not modify the response, suggesting that the effects on the spindle apparatus and cell division were not caused by the generation of radicals but by the direct action of 1.6-DNP.


A mind-body technique for symptoms related to fibromyalgia and chronic fatigue.
A novel mind-body approach (amygdala retraining) is hypothesized to improve symptoms related to fibromyalgia and chronic fatigue. To examine the use of a mind-body approach for improving symptoms related to fibromyalgia and chronic fatigue. This was a single-blind, randomized controlled trial. The study was conducted in a tertiary-care fibromyalgia and chronic fatigue clinic. Patients with fibromyalgia, chronic fatigue, or both were included. Patients were randomly assigned to receive amygdala retraining along with standard care or standard care alone. Standard care involved attending a 1.5-day multidisciplinary program. The amygdala retraining group received an additional 2.5-hour training course in which the key tools and techniques adapted from an existing program were taught to the patient. A home-study video course and associated text were provided to supplement the on-site program. Both groups received telephone calls twice a month to answer questions related to technique and to provide support. Validated self-report questionnaires related to general health, well-being, and symptoms, including Short Form-36, Measure Yourself Medical Outcome Profile, Multidimensional Fatigue Inventory, Epworth Sleepiness Scale, and Fibromyalgia Impact Questionnaire. Of the 44 patients randomly assigned who completed baseline assessments, 21 patients completed the study (14 in the standard care group and 7 in the study group). Median age was 48 years (range, 27-56 years), and female subjects comprised 91% of the group. Analyses demonstrated statistically significant improvements in scores for physical health, energy, pain, symptom distress, and fatigue in patients who received the amygdala retraining compared with standard care.


Structural insights on the deformations induced by various mutations on cholesteryl ester transfer protein.
Cholesteryl Ester Transfer Protein (CETP) is a plasma glycoprotein that intervenes the reverse cholesterol transport (RCT) by equimolar exchange of Cholesteryl esters (CE) and Triglycerides (TGs) between anti-atherogenic High-Density Lipoproteins (HDLs) and pro-atherogenic Low-Density Lipoproteins (LDLs) resulting in the increased concentration of CEs in LDL. This is a potential cause for the formation of atherosclerotic plaques in blood vessels leading to fatality. Therefore, blocking the function of CETP has emerged as a novel strategy for suppressing atherosclerotic plaques. The crystal structure of CETP revealed two Cholesteryl esters (CEs) in the hydrophobic tunnel and two phospholipids (PLs) plugged on the concave surface. Previous lipid transfer assay experimental studies have shown a substantial reduction in the neutral lipid transfer in [R201S] and [I443W, V198W] mutants. However, the protein conformational arrangements due to the mutations present in the CETP system leading to a decrease in the transfer rate of neutral lipids is not explored. Thus, I explored the reason behind the decreased transfer rate in mutants using molecular dynamics (MD) simulations and free energy calculations. Resulting evidences show that R201S mutant induces unfavorable bending angle to CETP with a decreased binding efficiency between N-terminal phospholipid of CETP with S201. Also, an unfavorable conformation state of TGs is formed which makes them difficult to transfer across CETP. Likewise, [I443W, V198W] mutant induces unfavorable CE, TG, and bending angle conformation to CETP impeding neutral lipid transfer. Thus, my results provide sufficient insights on the causation for a decreased transfer rate as reported earlier. The detailed understanding obtained here could help in developing a new strategy in preventing the function of CETP by blocking the role of potential hot spot residues.


Isoelectric focusing of some enzymes from Echinococcus granulosus (horse and sheep strains) and E. multilocularis.
Extracts of the horse and sheep strains of Echinococcus granulosus and E. multilocularis were compared on the basis of their isoenzyme patterns for 10 enzymes by means of isoelectric focusing in polyacrylamide gels. The enzymes examined were: acid phosphatase, lactate dehydrogenase, malate dehydrogenase, malic enzyme, phosphoglucoseisomerase, isocitrate dehydrogenase, adenylate kinase, aldolase and alpha-glycerophosphate dehydrogenase. Interspecific and intraspecific differences are apparent in the isoenzyme profiles of all the enzymes except adenylate kinase; the pattern and activity of adenylate kinase are identical for both strains of E. granulosus but this enzyme clearly distinguishes these forms from E. multilocularis. The absence of electromorphic variation in any of the enzymes from either form of E. granulosus may be a result of the self-fertilizing hermaphraditism of these organisms.


Gas chromatographic-mass spectrometric determination of urinary oxoacids using O-(2,3,4,5,6-pentafluorobenzyl)oxime-trimethylsilyl ester derivatization and cation-exchange chromatography.
We introduced a new combined method to isolate, purify and quantify oxoacids in human urine. Preparation of O-(2,3,4,5,6-pentafluorobenzyl) oximes of oxoacids at pH 2 to 3 was followed by cation-exchange column chromatography for removing the biological interferences. The effluent with water was extracted with ethyl acetate and the oxoacids were quantitatively converted into their trimethylsilyl derivatives for detection by gas chromatography-mass spectrometry. Good quality control data were obtained through precision and accuracy tests. Analytical recoveries (53.5-99.8%) were quantitative for a wide variety of oxoacids. This method was used for the measurement of 18 oxoacids in the urine of healthy volunteers.


Rapid detection of H146-like goose calicivirus using real-time RT-PCR with a Taqman minor groove binder probe.
H146-like goose-origin calicivirus (H146-like GCV) is a novel Caliciviridae family member in the Sanovirus genus that was associated with gosling growth retardation syndrome growth retardation syndrome complicated by visceral urate deposition. However, there is no accurate and high throughput real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) available for the rapid and highly sensitive identification of H146-like GCV. In this study, a pair of specific primers and a TaqMan minor groove binder (MGB) probe were designed based on a conserved region in the nonstructural (NS) gene sequence. The TaqMan-MGB probe-based one-step qRT-PCR assay was capable of detecting quite low number of targeting nucleic acid as low as 5.07 copies/μL and had excellent intra-assay and inter-assay repeatability with the coefficient of variation (CV) value from 0.558% to 1.293%. The assay was highly specific for H146-like GCV, without cross-reactions with other non-targeted goose-origin viruses, and 62 suspicious tissue samples infected with H146-like GCV from different regions of Fujian Province were used in this study to verify the feasibility and effectiveness of this assay in clinical diagnosis. The results indicated that our assay for the diagnosis and quantification of H146-like GCV was highly sensitive and specific, and should provide a reliable real-time tool for epidemiological and pathogenetic study of H146-like GCV infection, enabling researchers to better understand the epidemiology and clinical presentation of this disease.


Quantitative analysis of cereulide, the emetic toxin of Bacillus cereus, produced under various conditions.
This paper describes a quantitative and sensitive chemical assay for cereulide, the heat-stable emetic toxin produced by Bacillus cereus. The methods previously available for measuring cereulide are bioassays that give a toxicity titer, but not an accurate concentration. The dose of cereulide causing illness in humans is therefore not known, and thus safety limits for cereulide cannot be indicated. We developed a quantitative and sensitive chemical assay for cereulide based on high-performance liquid chromatography (HPLC) connected to ion trap mass spectrometry. This chemical assay and a bioassay based on boar sperm motility inhibition were calibrated with purified cereulide and with valinomycin, a structurally similar cyclic depsipeptide. The boar spermatozoan motility assay and chemical assay gave uniform results over a wide range of cereulide concentrations, ranging from 0.02 to 230 microg ml(-1). The detection limit for cereulide and valinomycin by HPLC-mass spectrometry was 10 pg per injection. The combined chemical and biological assays were used to define conditions and concentrations of cereulide formation by B. cereus strains F4810/72, NC7401, and F5881. Cereulide production commenced at the end of logarithmic growth, but was independent of sporulation. Production of cereulide was enhanced by incubation with shaking compared to static conditions. The three emetic B. cereus strains accumulated 80 to 166 microg of cereulide g(-1) (wet weight) when grown on solid medium. Strain NC7401 accumulated up to 25 microg of cereulide ml(-1) in liquid medium at room temperature (21 +/- 1 degrees C) in 1 to 3 days, during the stationary growth phase when cell density was 2 x 10(8) to 6 x 10(8) CFU ml(-1). Cereulide production at temperatures at and below 8 degrees C or at 40 degrees C was minimal.


Assessment of aortic root dimensions in patients with suspected Marfan syndrome: intraindividual comparison of contrast-enhanced and non-contrast magnetic resonance angiography with echocardiography.
Our purpose was to evaluate intraindividually the performance of contrast-enhanced magnetic resonance angiography (MRA) and non-contrast MRA for aortic root diameter measurements and to compare the results with routinely performed echocardiography in patients with suspected Marfan syndrome. Aortic roots were examined prospectively in 51 consecutive patients with suspected Marfan syndrome by using contrast-enhanced MRA and non-contrast MRA at 1.5 T. Two readers independently measured aortic root diameters at the annulus, sinuses of Valsalva and sinutubular junction in both data sets and compared results with echocardiographic data. Intraclass correlation coefficient, Pearson correlation coefficient, Bland-Altman, and two-sided t-test were used to assess agreement between observers and methods. 38 (74.5%) of the 51 patients (25 female, 26 male; mean age 37.1 ± 13.7 years) had Marfan syndrome. Both, contrast-enhanced MRA and non-contrast MRA measurements of the sinuses of Valsalva revealed a strong correlation with echocardiography (r=0.850 and r=0.893, respectively). Intraclass correlation was markedly better for non-enhanced MRA (r=0.904) when compared to contrast-enhanced MRA (r=0.690). Image quality (p<0.001) as well as interobserver agreement (p<0.0042) of measurements of the sinuses of Valsalva was significantly better for non-enhanced MRA than for contrast-enhanced MRA. Non-contrast MRA was more reliable and more valid than contrast-enhanced MRA for assessment of aortic root dimensions in patients with suspected Marfan syndrome. Therefore contrast agents can be omitted for establishing the diagnosis of aortic involvement in Marfan syndrome.


Nurses' Perspectives on the Process of Attaining Baby-Friendly Designation.
The Baby-Friendly Hospital Initiative is a global initiative that aims to protect, promote, and support breastfeeding. This study explores and describes the process of attaining Baby-Friendly designation from nurses' perspectives. A purposive sampling design was used to recruit registered nurse participants in a large, safety-net, tertiary care facility. Data were collected via semistructured interviews and were analyzed using descriptive interpretative analysis. The following themes were revealed: Resistance, Culture, Investment in the Journey, Teamwork, and Source of Pride. Results indicate that comfortable yet antiquated practices led to fear of change and resistance. Initial culture shock was mediated by a successful education model, powerful experiences, and positive outcomes.


Management of ileus and small-bowel obstruction following benign gynecologic surgery.
To describe practice preferences for the diagnosis and management of ileus and small-bowel obstruction (SBO) following benign gynecologic surgery. A secondary descriptive analysis was performed on data from a multicenter case-control study of patients who underwent gynecologic surgery and subsequently developed ileus or SBO. Information was collected regarding interventions such as type of imaging ordered for diagnosis, diet alterations, antiemetic administration, and need for reoperation. In total, 144 cases were identified. Abdominal X-ray was the most common imaging modality, occurring in 54 (37.5%) cases. Sixty-nine (65.1%) of the 106 women who underwent imaging were given definitive radiologic diagnoses of either ileus (50 [72.5%]) or SBO (19 [27.5%]); 57.9% (n=11) of the SBO diagnoses and 90.0% (n=45) of the ileus diagnoses were managed conservatively. Eighteen (12.5%) patients underwent reoperation for bowel obstruction. There were no significant differences in rate of reoperation between cases involving the use of single antiemetics and those involving the use of multiple antiemetics (P=0.18), or between diet statuses on postoperative day 1 (P=0.08). Most study centers initially performed an abdominal X-ray for diagnostic purposes. The majority used a multimodal treatment approach. None of the management options decreased the likelihood of reoperation.


Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis.
The present study aimed to investigate whether dexmedetomidine (Dex) exerts cardioprotection effect through inhibiting ferroptosis. Myocardial ischemia/reperfusion injury (MIRI) was induced in Sprague-Dawley rats in Langendorff preparation. The hemodynamic parameters were recorded. Triphenyltetrazolium chloride (TTC) staining was used to determine infarct size. In the in vitro study, the model of hypoxia/reoxygenation (HR) was established in H9c2 cells. Cell viability and apoptosis were detected using cell counting kit 8 (CCK-8), and AV/PI dual staining respectively. Lipid peroxidation as measured by the fluorescence of the fatty acid analog C11-BODIPY581/591 probe and intracellular ferrous iron levels were measured by fluorescence of Phen Green SK (PGSK) probe, whereas immunofluorescence and transmission electron microscopy were also used to examine ferroptosis. Protein levels were investigated by Western blot. The interactions of AMPK/GSK-3β signaling with Nrf2 were also assessed through AMPK inhibition and GSK-3β overexpression. Our findings indicated that Dex significantly alleviated myocardial infarction, improved heart function, and decreased HR-induced accumulation of Fe2+ and lipid peroxidation in cardiomyocytes. Dex significantly increased the expression levels of Nrf2, SLC7A11, and GPX4. However, inhibition of Nrf2 by ML385 blunted the protective effect of Dex in HR-treated H9c2 cells. Inhibition of AMPK with a specific inhibitor or siRNA decreased the expression levels of phosphorylation of GSK-3β and Nrf2 induced by Dex. Overexpression of GSK-3β resulted in lower levels of nuclear Nrf2, whereas depression of GSK-3β enhanced expressions of nuclear Nrf2. In conclusion, Dex protects hearts against MIRI-induced ferroptosis via activation of Nrf2 through AMPK/GSK-3β signaling pathway.


Listening rate and comprehension as a function of preference for and exposure to time-altered speech.
We conducted experiments on the effects of brief prior exposure to time-altered speech on preferred listening rate and the rate listeners would select when asked to listen to speech as fast as possible with good compression (induced listening rate). In Exp. 1, 48 participants were exposed either to normal rate speech or to speech compressed to twice-normal rate. Brief exposure to twice-normal rate speech led to a faster induced listening rate than exposure to normal rate speech. In Exp. 2, 31 participants were briefly exposed to normal rate speech, speech compressed to twice-normal rate, or speech expanded to half-normal rate. The faster the rate of the exposure speech, the faster the induced rate. Speech compressed to twice-normal rate led to a faster induced listening rate than exposure to speech expanded to half-normal rate. Normal rate speech was intermediate between twice-normal and half-normal rate and did not differ significantly from them. Induced listening rate was a linear combination of listening rate preference and recent forced exposure to time-altered speech.


Endoscopic nasal surgery for mucocele and pyogenic mucocele of turbinate: Three case reports.
Cases of turbinate mucocele or pyogenic mucocele are extremely rare. During nasal endoscopy, turbinate hypertrophy can be detected in patients with turbinate or pyogenic mucocele. However, in many instances, differentiating between turbinate hypertrophy and turbinate mucocele is difficult. Radiological examinations, such as computed tomography (CT) or magnetic resonance imaging (MRI), are essential for the accurate diagnosis of turbinate mucocele. Herein, we report three cases of mucocele or pyogenic mucocele of turbinate, including their clinical presentation, imaging findings, and treatments, to help rhinologists understand this condition better. Three cases of turbinate and pyogenic mucocele were encountered in our hospital. In all patients, nasal obstruction and headache were the most common symptoms, and physical examination revealed hypertrophic turbinates. On CT scan, mucocele appeared as non-enhancing, homogeneous, hypodense, well-defined, rounded, and expansile lesions. Meanwhile, MRI clearly illustrated the cystic nature of the lesion on T2 sequences. Two patients with inferior turbinate mucocele underwent mucocele lining removal, while the patient with pyogenic mucocele underwent endoscopic middle turbinate marsupialization. The patients were followed up on the first, third, sixth month, and 1 year after discharge, and no complaints of headache and nasal congestion were reported during this period. In conclusion, both CT and MRI are helpful in the diagnosis of turbinate or pyogenic mucocele. Additionally, endoscopic nasal surgery is considered to be the most effective treatment method.


[Medical responsibility].
Blood transfusion is a medical act, which follows the dictates of important rules in medical responsability. The following presentation will mention the legal responsibility of the practitioner throughout the transfusion process: first, giving the patient complete and precise information and geting his full consent; then, writing the appropriate prescription; finally, balancing the benefice and risk of therapy and using reglementation to avoid the practitioner's responsibility to be put at risks.


Anakinra Treatment in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysms: A Phase I/IIa Trial.
To determine the safety, pharmacokinetics, and immunomodulatory effects of 2-6 weeks of anakinra therapy in patients with acute Kawasaki disease with a coronary artery aneurysm (CAA). We performed a Phase I/IIa dose-escalation study of anakinra (2-11 mg/kg/day) in 22 patients with acute Kawasaki disease with CAA. We measured interleukin (IL)-1RA concentrations after the first dose and trough levels up to study week 6. Markers of inflammation and coronary artery z-scores were assessed pretreatment and at 48 hours, 2 weeks, and 6 weeks after initiation of therapy. Up to 6 weeks of anakinra (up to 11 mg/kg/day) was safe and well tolerated by the 22 participants (median age, 1.1 years), with no serious adverse events attributable to the study drug. All participants were treated with intravenous immunoglobulin (IVIG), and 20 also received infliximab (10 mg/kg) before initiation of anakinra. Serum levels of IL-6, IL-8, and tumor necrosis factor α decreased similarly in patients with Kawasaki disease treated with IVIG, infliximab, and anakinra compared with age- and sex-matched patients with Kawasaki disease treated only with IVIG and infliximab. Anakinra clearance increased with illness day at diagnosis. Simulations demonstrated that more frequent intravenous (IV) dosing may result in more sustained concentrations without significantly increasing the peak concentration compared with subcutaneous (SC) dosing. Both IV and SC anakinra are safe in infants and children with acute Kawasaki disease and CAA. IV dosing every 8-12 hours during the acute hospitalization of patients with Kawasaki disease may result in a sustained concentration while avoiding frequent SC injections. The efficacy of a short course of IV therapy during hospitalization should be studied. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT02179853.


Nonprolapsing atrial myxoma; clinical, echocardiographic, and angiographic correlations.
The auscultatory features typical of myxoma were absent in a patient with nonprolapsing left atrial myxoma. Angiocardiographic and echocardiographic findings including B-mode cross-sectional scanning are presented.


Lingo-1 shRNA and Notch signaling inhibitor DAPT promote differentiation of neural stem/progenitor cells into neurons.
Determination of the exogenous factors that regulate differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes is an important step in the clinical therapy of spinal cord injury (SCI). The Notch pathway inhibits the differentiation of neural stem/progenitor cells and Lingo-1 is a strong negative regulator for myelination and axon growth. While Lingo-1 shRNA and N-[N-(3, 5-difluorophenacetyl)-1-alanyl]-S-Phenylglycinet-butylester (DAPT), a Notch pathway inhibitor, have been used separately to help repair SCI, the results have been unsatisfactory. Here we investigated and elucidated the preliminary mechanism for the effect of Lingo-1 shRNA and DAPT on neural stem/progenitor cells differentiation. We found that neural stem/progenitor cells from E14 rat embryos expressed Nestin, Sox-2 and Lingo-1, and we optimized the transduction of neural stem/progenitor cells using lentiviral vectors encoding Lingo-1 shRNA. The addition of DAPT decreased the expression of Notch intracellular domain (NICD) as well as the downstream genes Hes1 and Hes5. Expression of NeuN, CNPase and GFAP in DAPT treated cells and expression of NeuN in Lingo-1 shRNA treated cells confirmed differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes. These results revealed that while Lingo-1 shRNA and Notch signaling inhibitor DAPT both promoted differentiation of neural stem cells into neurons, only DAPT was capable of driving neural stem/progenitor cells differentiation into oligodendrocytes and astrocytes. Since we were able to show that both Lingo-1 shRNA and DAPT could drive neural stem/progenitor cells differentiation, our data might aid the development of more effective SCI therapies using Lingo-1 shRNA and DAPT.


Review of Lot Quality Assurance Sampling, Methodology and its Application in Public Health.
Rapid collection of data is of utmost importance in monitoring and evaluation of activities of public health importance. Among others techniques, 30 by 7 cluster sampling and Lot quality assurance sampling(LQAS) methods have been described in literature for this purpose. However, LQAS is often sparingly used in most settings, undermining its importance as a effective epidemiological tool in public health practice. To some extent LQAS is inadequately understood and even less emphasized method, especially in the postgraduate teaching and training. In this paper we aim to explain the use, method and application of LQAS in public health settings as well as discuss common pitfalls to avoid while planning and drawing inferences based on data collected through LQAS.


Physical, textural and sensory characteristics of legume-based gluten-free muffin enriched with waxy rice flour.
Physical, textural, and sensory characteristics of the gluten-free muffins made of mungbean and cowpea flours enriched with waxy rice flour were investigated. Amylose content and pasting viscosity of legume-waxy rice flour blend (1:1) were lower than that of wheat flour. The number and area of gas cells of muffin containing legume flour was lower than that of control muffin with wheat flour. Legume-based muffins had low lightness value due to the presence of color components. Weight of the muffins containing legume was higher than that of control muffin, but their height and volume were lower than control. Legume-based muffins had greater crude ash and protein contents than control. Compared with control, muffin containing legume flour had significantly higher hardness and gumminess. In sensory evaluation, overall acceptance of muffin containing Okdang cultivar of cowpea was the highest among legume-based muffins, which was comparable to control muffin.


Associations of peptic ulcer and gastric cancer with other diseases in US veterans.
The purpose of this study was to examine, through the database of the Department of Veterans Affairs, the joint occurrence of different diseases in individual patients. Patients with a diagnosis of gastric cancer, gastric ulcer, or duodenal ulcer were extracted from the 1987 through 1990 computer files. A random sample of patients from each annual file served as a control population. All previous discharges of each case or control patient between 1970 and 1990 were searched for the occurrence of hypertensive diseases or chronic diseases of the joints, lungs, pancreas, and liver. The relative frequencies of such diagnoses in case and control patients were compared by multivariate logistic regression. Gastric ulcer and duodenal ulcer, but not gastric cancer, were significantly associated with chronic diseases of the joints, lungs, pancreas, and liver. None of the three diagnoses showed any significant association with hypertensive diseases. These relationships may reflect the influence of nonsteroidal anti-inflammatory drugs, smoking, and alcohol. They stress the importance of environmental risk factors other than Helicobacter pylori in terms of damage to the upper gastrointestinal mucosa.


Cancer pain and alcohol self-medication.
Cancer survivors are at increased risk of pain due to their either cancer and/or treatments. Substances like alcohol may be used to self-medicate cancer pain; however, these substances pose their own health risks that may be more pronounced for cancer survivors. We used cross-sectional data from the Behavioral Risk Factor Surveillance System (BRFSS) 2012-2019 to quantify the association between cancer pain and alcohol use. We used negative binomial regression, with interaction terms added to examine variations across age, sex, and race. We also examined whether alcohol use relates to cancer pain control status. Cancer survivors with cancer pain were more likely to be younger, female, Black, and to have been diagnosed with breast cancer. Cancer pain was associated with lower alcohol consumption (incidence rate ratio (IRR): 0.88, confidence interval (CI): 0.77, 0.99). This association was primarily among people 65 and older, women, and white and Hispanic people. Cancer pain control status was not related to alcohol use. Lower alcohol use among cancer survivors with pain has many possible explanations, including several alternative pain management strategies or a decrease in social engagement. Our findings of racial and gender disparities in cancer pain are consistent with the broader evidence on disparities in pain. Cancer pain management for marginalized groups should be improved. Healthcare providers should screen cancer survivors for both pain and substance use, to prevent unhealthy self-medication behaviors.


Flexible Biomanufacturing Processes that Address the Needs of the Future.
: As the age of the blockbuster drug recedes, the business model for the biopharmaceutical industry is evolving at an ever-increasing pace. The personalization of medicine, the emergence of biosimilars and biobetters, and the need to provide vaccines globally are just some of the factors forcing biomanufacturers to rethink how future manufacturing capability is implemented. One thing is clear: the traditional manufacturing strategy of constructing large-scale, purpose-built, capital-intensive facilities will no longer meet the industry's emerging production and economic requirements. Therefore, the authors of this chapter describe the new approach for designing and implementing flexible production processes for monoclonal antibodies and focus on the points to consider as well as the lessons learned from past experience in engineering such systems. A conceptual integrated design is presented that can be used as a blueprint for next-generation biomanufacturing facilities. In addition, this chapter discusses the benefits of the new approach with respect to flexibility, cost, and schedule. The concept presented here can be applied to other biopharmaceutical manufacturing processes and facilities, including-but not limited to-vaccine manufacturing, multiproduct and/or multiprocess capability, clinical manufacturing, and so on.


Early Stroke Risk after Transient Ischemic Attack in Patients without Large-Artery Disease or Atrial Fibrillation.
Patients with transient ischemic attack (TIA) without large-artery disease (LAD) or atrial fibrillation (AF) on admission may be at higher risk of stroke than previously thought. The aim of this study was to investigate early stroke risk and its predictors in such patients. We studied 410 TIA patients admitted to our institute within 48 hours of onset. Urgent etiological workup revealed that 210 patients had neither symptomatic LAD nor AF. The outcome measure was the stroke occurrence within 7 days after admission. Stroke occurred within 7 days in 15 patients, 7.1% of patients without LAD or AF and 6.5% of those with LAD or AF, showing no statistical difference between the 2 groups. Twelve of the 15 patients were diagnosed with small-vessel disease as the stroke etiology. In multivariable regression analysis, motor lacunar symptoms (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.4-41.1), high systolic blood pressure on admission of 183 mm Hg or greater (OR, 15.3; 95% CI, 3.8-80.2), and positive diffusion-weighted imaging findings (OR, 6.1; 95% CI, 1.6-28.1) were independent predictors for the stroke occurrence within 7 days in patients without LAD or AF. TIA patients should be cautiously managed, even when neither LAD nor AF are identified by urgent workup. Clinical findings as motor lacunar symptom or high admission blood pressure, besides diffusion-weighted imaging findings, may be helpful to predict early stroke in such patients.


Psychopharmacology and pharmacokinetics.
The overall physiologic changes associated with aging lead to changes in both pharmacokinetic and pharmacodynamic actions of many medications. This, in turn, leads to changes in the impact that a wide variety of medications have on older adults when compared to younger, healthy individuals. These pharmacokinetic and pharmacodynamic variations can cause either lesser or greater than expected responses to medication. Knowledge of the physiologic changes that are expected to occur in the elderly can help to identify medications that may require dose adjustments or that should be avoided, due to increased risk in this population. As a general principle, medications should be started at lower doses in the elderly with slow titration schedules to reduce the risk of adverse effects.


The organization of the mouse satellite DNA at centromeres.
The mouse genome contains a major and a minor satellite DNA family of repetitive DNA sequences. The use of 5-azacytidine has allowed us to demonstrate that these satellite DNAs are organized in two separate domains at the centromeres of mouse chromosomes. The minor satellite is closer to the short arms of the acrocentric chromosomes than the major satellite. The major satellite is farther away, flanking the minor satellite and adjacent to the euchromatic long arm of each mouse chromosome. At the level of resolution afforded by the in situ hybridization technique it would appear that the organization of the centromeric domain of the mouse is similar to that in man. That is, both contain two repetitive DNA sequence families arranged in major blocks.


Hospital remains in inner city by moving to recycled factory.
An urban hospital that needed an up-to-date physical plant renovated and moved into a nearby foundry building. By remaining in its inner-city neighborhood, the hospital continues its programs to help solve socioeconomic problems that affect the community's health and well-being and that may help stimulate the community's recovery from urban blight.


Assessing Telomerase Activities in Mammalian Cells Using the Quantitative PCR-Based Telomeric Repeat Amplification Protocol (qTRAP).
Telomerase expression and activity appear elevated in >80% of human cancers. The activity of the telomerase may serve as a diagnostic marker for malignancy, and an indicator of the proliferative potential of somatic and stem cells. The telomeric repeat amplification protocol (TRAP) is a sensitive and accurate PCR-based assay for telomerase detection and measurement. Here, we describe a quantitative PCR-based TRAP assay (qTRAP) that is more convenient and amenable to high-throughput applications compared to traditional gel-based TRAP assays. qTRAP can not only facilitate drug screening processes for compounds that regulate telomerase activities but also enable the measurement of total telomerase activities of cultured cells or clinical specimens; the latter should prove particularly valuable to investigators of malignancies and diseases that are associated with telomerase and telomere dysfunction.


Experimental validation of methods for the measurement of coronary sinus blood flow in man.
The measurement accuracy of clinically applicable methods for blood flow measurement in coronary sinus -- continuous local thermodilution (LTD), differential pressure (DP), ultrasonic Doppler (US) and the electromagnetic flow measurement method (EMF) -- was examined in 15 anaesthetized closed chest dogs with left ventricle weights between 150 and 200 g. The LTD, DP, US and the EMF were examined in each experiment in the two following arrangements. 1. In coronary sinus -- left jugular vein by-pass: This arrangement allowed four reference methods for measurement of coronary sinus blood flow (CBF). 2. In "clinical" position, without by-pass, which allowed two reference methods for CBF measurements. The results on the measurement accuracy of the LTD, DP and US are, depending on the measurement arrangement, contradictory. In the by-pass arrangement 1 there was observed a good agreement of the LTD, DP and US CBF values with the reference values. In the "clinical" position, without by-pass 2 the measurement accuracy of LTD was not sufficient for exact measurement of CBF and derived parameters. The examined velocity tip flow probes (US, DP) gave no correlation with the reference methods. US and DP are even for semiquantitative estimation of CBF unsuitable. The EMF tip flow probe was for the CBF measurement unsuitable, because of disturbance by the electrical activity of myocardium.


Cancer of the prostate: is there a need for aggressive treatment?
Adenocarcinoma of the prostate constitutes 18% of all cancers in men, and is a major cause of neoplastic death second only to carcinoma of lungs and large bowel. In spite of the high incidence of the disease, there is still disagreement as to the right treatment. In our study we reviewed 101 patients in stages T0b, T1 + T2, T3 (N0M0) who were treated by nonradical prostatectomy and no other treatment. The follow-up of these patients was 58 months. The actuarial 5- and 10-year survival according to stage was respectively: 91.30 and 64.62% in stage T0b; 60.61 and 34.11% in stage T1 + T2, and 41.67% in stage T3. Survival rates resembled those quoted in the literature. Our results justify a less aggressive approach to carcinoma of the prostate.


What are the sensitivity and specificity of endoscopic photographs in determining completion of colonoscopy? Results from an online questionnaire.
There is no consensus as to the optimal method for documenting colonoscopy completion. For endoscopic photographs to be useful for documentation, reviewers must be able to distinguish between photographs taken from incomplete and complete colonoscopy. The primary aim of this study was to calculate the diagnostic specificity and sensitivity of a pair of photographs in confirming complete colonoscopy. The secondary aim was to assess current methods of documenting colonoscopy completion. Eighty pairs of photographs were taken from completed colonoscopies. Two photographs, including at least one view of the ileo-caecal valve, were taken of caecal landmarks and/or the terminal ileum. Colonoscopy completion was independently validated using video clips. Twenty pairs of photographs were also taken from another colonic site that could potentially be misinterpreted as the caecum, for example, hepatic flexure. Using an online questionnaire 34 experienced endoscopists were asked about their own methods of colonoscopy documentation. Thirty-two of these reviewers then assessed the 100 photographic pairs, blinded to their origin, and were asked 'Taking both photographs into account, are you convinced that complete colonoscopy has been performed?' Fifty-six percent of endoscopists did not routinely use any objective method of documentation although 38% frequently used some photographs for documentation. Using a pair of endoscopic photographs to document colonoscopy completion has a sensitivity of 51.4% (confidence intervals: 49.5-53.3%) and a specificity of 89.2% (confidence intervals: 86.8-91.6%). Both the sensitivity and the specificity of a pair of endoscopic photographs are too low to be used for reliably documenting colonoscopy completion.


Stem cell mobilization and harvesting by leukapheresis alters systemic cytokine levels in patients with multiple myeloma.
Stem cell mobilization and harvesting by peripheral blood leukapheresis in patients with myeloma can alter plasma levels of certain cytokines. In the present study, we investigated the effects of these interventions on a larger group of cytokines. Plasma cytokine levels were determined in 15 patients with myeloma who were undergoing peripheral blood stem cell harvesting, and we compared the patients with healthy donors who were undergoing platelet apheresis. Several cytokines showed altered levels in patients with myeloma when examined after chemotherapy plus granulocyte colony-stimulating factor-induced stem cell mobilization. The most striking effect was increased levels of several CCL (CCL2/3/4) and CXCL (CXCL5/8/10/11) chemokines as well as increased thrombopoietin, interleukin 1 receptor antagonist, interleukin-4, granulocyte colony-stimulating factor and hepatocyte growth factor. Stem cell harvesting by apheresis altered the plasma levels of several mediators (CD40 ligand, interleukin 1 receptor antagonist, CCL5 and CXCL5/8/10/11). Apheresis in patients with myeloma had divergent effects on these chemokine levels, although they were all still significantly higher than for healthy individuals. Thrombapheresis in healthy individuals had only minor effects on plasma cytokine levels. Stem cell graft supernatants showed high levels of several cytokines, especially CCL and CXCL chemokines. Analyses of chemokine profiles in pre-apheresis plasma and graft supernatants suggested that such profiling can be used to detect prognostically relevant differences between patients. Our results demonstrate that patients with myeloma have an altered cytokine network during stem cell mobilization, and the network is further altered during stem cell harvesting by leukapheresis. These treatment- or procedure-induced alterations involve several mediators known to affect myeloma cell proliferation, migration and survival.


Factors related to the provision of home-based end-of-life care among home-care nursing, home help, and care management agencies in Japan.
To promote home death, it is necessary to clarify the institutional barriers to conducting end-of-life (EOL) care and consider strategies to deal with this process. This study aims to clarify institution-related factors associated with the provision of home-based EOL care cases, and to compare them among three different types of home-care agencies. We administered a cross-sectional survey throughout Japan to investigate the number and characteristics of EOL cases of home-care nursing (HN), home-help (HH) and care management (CM) agencies. Bivariate and multivariate analyses were performed for each type of agency to examine factors related to the provision of EOL care. 378 HN agencies, 274 HH agencies, and 452 CM agencies responded to the distributed questionnaire. HN agencies had on average 2.1 (SD = 4.0; range 0-60) home-based EOL cases in the last 3 months, while HH agencies had 0.9 (SD = 1.3; range 0-7) and CM agencies had 1.5 (SD = 2.2; range 0-18) in the last 6 months. In a multivariable analysis of HN agencies, a large number of staff (OR: 1.52; p < 0.001) and a large number of collaborating CM agencies (OR: 1.08; p = 0.008) were positively associated with the provision of EOL care; in HH agencies, accepting EOL clients in the agency (OR: 3.29; p < 0.001) was positively associated with the provision of EOL care; in CM agencies, the number of staff (OR: 1.21; p = 0.037), the number of collaborating HH agencies (OR: 1.07; p = 0.032), and whether home-care nurses and home helpers visit clients together (OR: 1.89; p = 0.007) were positively associated with the provision of EOL care. The agency's size and the inter-agency collaborative system seemed most important among HN agencies and CM agencies, while institutional preparedness for EOL was most important for HH agencies. These findings represent important new information for targeting different effective strategies in the promotion of home-based EOL care, depending on the agency type.


"I don't want to take buprenorphine for the rest of my life": Acceptance and Commitment Therapy for a Client Struggling to Reduce Low-Dose Buprenorphine (a Hermeneutic Single-Case Efficacy Design).
The misuse of substances is often maintained by both physical and psychological factors. Opioid-substitution medications manage physical aspects of addiction; however, difficulties with emotional regulation and avoidance perpetuate continued substance misuse. In the UK, individuals who misuse substances are often excluded from mental health services, meaning these underlying difficulties are not addressed. Acceptance and Commitment Therapy (ACT) seeks to reduce emotional avoidance. A hermeneutic single-case efficacy design was used to evaluate the effects of ACT within drugs and alcohol service. Quantitative and qualitative data was critically analysed to understand factors involved in identified changes. Analysis recognised the client progressed towards two of three of their goals, related to motivation and anxiety. Their psychological flexibility also increased. ACT processes played a key role in this; however, the therapeutic relationship and psychopharmacological factors were also noted. Study limitations and clinical and research implications are discussed.


Susceptibility of different cell lines to infection with bovine respiratory syncytial virus.
The growth of bovine respiratory syncytial virus (BRSV) was evaluated in six different cell lines. Chicken embryo related cells (CER), a chicken embryo fibroblast/baby hamster kidney hybrid and bovine CRIB cells (a bovine viral diarrhea virus-resistant clone of MDBK cells) showed to be the most appropriate for virus multiplication. Both cells provided infectious virus titres of up to 10(5.5) 50% tissue culture infective doses per 100 microl (TCID(50)/100 microl). One-step growth curves revealed no significant differences in the growth of BRSV in these two cell lines. Furthermore, they proved to be susceptible to infection with three different BRSV strains. It was concluded that both CER and CRIB cells may be used for laboratory multiplication of BRSV with optimal results.


Zinc chloride affects chondrogenesis via VEGF signaling.
Insulin mimetics, including zinc containing compounds, have previously been shown to influence chondrogenesis as it relates to healing of fractures in various preclinical models. However, the mechanism by which these compounds drive chondrogenic differentiation is yet undefined. Here, via next-generation sequencing (NGS) and in vitro functional validation, we show that Zinc Chloride (ZnCl2) induces expression of both chondrogenic genes (Sox9, Runx1, collagen) as well as genes associated with VEGF-mediated signal transduction, including VEGF receptors 1 and 2 and their ligands; VEGF-A and VEGF-B. Noticeably, although insulin was able to also induce expression of these pro-angiogenic and pro-chondrogenic genes, the impact of insulin on expression of VEGF receptor and ligand genes was marginal when compared to that of ZnCl2. Furthermore, while the VEGFR antagonist, Axitinib, was able to attenuate the pro-chondrogenic effects of both insulin and ZnCl2; a reduction in gene and protein expression was most profoundly observed when the antagonist was applied to cells treated with ZnCl2. Taken together, these data suggest an important role for the VEGF-mediated signal transduction pathways in the positive effects observed when applying zinc-based compounds as adjuvants for chondrogenesis-mediated fracture healing. In this regard, further mechanistic evaluation of ZnCl2 and other zinc-containing insulin mimetics may support rational design of therapies targeted for disease indications associated with impaired fracture healing.


Rescue therapy with an albuvirtide-based antiretroviral regimen in an HIV-infected child with multidrug resistance and multiple opportunistic infections: a case report.
Managing multidrug-resistant (MDR) HIV infections in children is particularly challenging due to the lack of experience with new drugs in the pediatric setting. Second-line albuvirtide (ABT) with an optimized antiretroviral background therapy was approved for adults and adolescents after first-line treatment failure. This paper describes the treatment outcomes and adverse effects of an ABT-based dual-active antiretroviral treatment regimen in a child with MDR HIV strains. A 13 year-old Chinese female patient infected with MDR HIV strains showed a decrease in viral load (from 4.48 log10 to 1.73 log10) and an increase in CD4 + T cells (from 15 to 308 cells/µl) after 12 months of treatment with an ABT-based antiretroviral regimen. The child showed no relevant drug-related adverse reactions. The case reported here could suggest that an ABT-based antiretroviral therapy might be beneficial and without relevant toxicity in children with MDR HIV. Infectiologists specializing in managing HIV should be prepared to manage an increasing number of children with MDR HIV. ABT might be a new treatment option for MDR HIV infection in children.


Management of neonatal abstinence syndrome from opioids.
Most infants at risk for neonatal abstinence syndrome have opioid plus another drug exposure; polypharmacy is the rule rather than the exception. Scales for evaluation of neonatal abstinence syndrome are primarily based for opioid withdrawal. A standard protocol to treat neonatal abstinence syndrome has not been developed. Institute nonpharmacologic strategies for all neonates at risk. The American Academy of Pediatrics recommends mechanism-directed therapy (treat opioid withdrawal with an opioid) as the first-line therapy. Second-line medications are currently under evaluation.


Symptoms associated with malignancy of peripheral nerve sheath tumours: a retrospective study of 69 patients with neurofibromatosis 1.
Neurofibromatosis 1 (NF1) is a common genetic disorder with variable clinical manifestations and an unpredictable course. Plexiform neurofibromas are common complications of NF1. Their malignant transformation is the main cause of mortality in adult patients with NF1. To identify clinical factors associated with malignant transformation of plexiform neurofibromas. Using the database of our neurofibromatosis clinic we included in a retrospective study all patients with NF1 having at least one peripheral nerve sheath tumour for which they underwent surgery or surgical biopsy. Predictive values for malignant transformation of three clinical symptoms, i.e. pain, enlargement of mass and neurological symptoms, were evaluated in association with histological parameters. Of 69 patients studied, 48 had at least one plexiform neurofibroma and 21 had a malignant peripheral nerve sheath tumour. Only enlargement of the tumour had high negative and positive predictive values for malignant transformation: 0.92 and 0.95, respectively. In multivariate analysis, tumour enlargement was independently associated with malignant transformation (odds ratio 167.8, 95% confidence interval 14.0-2012.1). From a practical point of view, pain, neurological deficit and enlargement of a pre-existing peripheral nerve sheath tumour in NF1 must lead to deep surgical biopsy to rule out malignant transformation.


A university system-wide qualitative investigation into student physical activity promotion conducted on college campuses.
This study aimed to examine college student physical activity promotion. A cross-sectional approach to qualitative research was used. Southeastern state university system. Fourteen of 15 (93%) universities recruited were included in this study; 22 university employees participated in a semistructured interview. Nonprobabilistic purposive and snowball sampling strategies were used to recruit individuals who were likely to be engaged in physical activity promotion efforts on their respective campuses. Thematic analyses lead to the identification of emerging themes that were coded and analyzed using NVivo software. Themes informed three main areas: key personnel responsible for promoting physical activity to students, actual physical activity promotion efforts implemented, and factors that influence student physical activity promotion. Results suggest that ecological approaches to promote physical activity on college campuses are underused, the targeting of mediators of physical activity in college students is limited, and values held by university administration influence campus physical activity promotion. Findings support recommendations for future research and practice. Practitioners should attempt to implement social ecological approaches that target scientifically established mediators of physical activity in college students. Replication of this study is needed to compare these findings with other types of universities, and to investigate the relationship between promotion activities (type and exposure) and physical activity behaviors of college students.


Consumer products and fall-related injuries in seniors.
To conduct an environmental scan to identify the scope of literature on consumer products and injuries in seniors and to fill in some of the information gaps by exploring the relationship between assistive devices (AD) and fall-related injuries. The environmental scan included primary literature identified in Medline and EMBASE databases and grey literature was identified in Google and consumer product safety sites in the US, Canada, the UK, and Australia.Weighted logistic regression was then used to examine the relationship between socio-demographic factors, frailty indicators, and AD use at the time of the fall, and the type of health services utilized and psychological consequences of the fall based on data from the 2008-2009 Canadian Community Health Survey on Healthy Aging. The majority of the articles on consumer products and injuries reported secondary database sources and did not directly link the consumer product's influence on a given injury. We found AD use at the time of a fall was associated with hospitalization, worry about re-injury, and limiting one's activities due to this worry, even after adjustment for socio-demographic variables. When frailty variables were included in the model, however, AD use was no longer statistically significant. This study provides preliminary information on the relationship between AD use and fall-related outcomes. However, the current data are not sufficient to draw specific conclusions. More detailed questions regarding AD use for the entire population and additional questions regarding the contribution of the AD to the injury will help to provide a richer understanding of this relationship.


Porous Silicon Fabry-Pérot Interferometer for N-Acetyl-β-d-Glucosaminidase Biomarker Monitoring.
Bovine mastitis (BM) is a prominent inflammatory disease affecting the dairy industry worldwide, originated by pathogenic agent invasion onto the mammary gland. Early detection of new BM cases is of high importance for infection control within the herd. Conventional analytical techniques lack the ability to detect BM-predicting biomarkers, used as analytical indicators for health status evaluation, in real time or outside the laboratory boundaries. Herein, we describe a biosensing platform for label-free detection and identification of BM onset through targeting N-acetyl-β-d-glucosaminidase (NAGase) for potential evidence-based therapy. The lysosomal activity in dissimilar milk qualities was monitored by a gelatin-functionalized porous Si Fabry-Pérot interferometer, while estimating the biochemical reaction precipitating products within the nanostructure. The optical response was proportional to the inherent NAGase concentration found in real milk samples, influenced by two dominant BM causative pathogens (i.e., Escherichia coli and Streptococcus dysgalactiae) at various somatic cell counts. Quantitative analysis of NAGase levels within the entire inflammatory spectrum (healthy, subclinical, and clinical BM) was obtained within the range of 1.0-4.2 μM/min (enzymatic activity per volume unit), while presenting a detection limit of 0.51 μM/min. The optical performances correspond with standardized biochemical activity assay in dissimilar milk qualities. Overall, the presented sensing concept exhibits the potential of BM-predicting biomarker detection using a simple and portable experimental setup for convenient early biodiagnostics and health status evaluation.


Metastatic thyroid carcinoma: an unusual presentation.
A case is described in which the presentation of symmetrical thyroid lesions combined with their unusual site and histological appearance served initially to mask the underlying thyroid neoplasm.


Lipid carriers in the synthesis of high-mannose glycoproteins in algae.
Particulate preparations from the chlorophyta Prototheca zopfii catalyze the incorporation of mannose and N-acetylglucosamine into glycolipids. These had been characterized as lipid monophosphate mannose, lipid pyrophosphate N,N'-diacetylchitobiose and various lipid-linked oligosaccharides containing two N-acetylglucosamine residues plus a variable number of mannose residues. The lipid moiety has the properties expected for dolichyl phosphate. The oligosacchride-linked lipids serve as precursors for the formation of a polymer sensible to pronase digestion. The oligosaccharide is linked by N-glycosidic linkage to an asparagine residue. In longer incubation periods, a polymer insensitive to pronase hydrolysis, but precipitable by copper salts such as cell wall mannans is formed. Polymer formation is inhibited by 1 mM bacitracin. The reactions leading to the formation of the mannoprotein were found associated to the rough endoplasmic reticulum. The synthesis of mannans was found to occur in the Golgi vesicles.


Return to sports after glenoid reconstruction using an implant-free iliac crest bone graft.
The purpose of this study was to evaluate sports ability and the rate of return to sports after implant-free iliac bone graft for recurrent, anterior shoulder instability and anterior glenoid bone loss. Subgroups of younger and older patients and patients who had previous arthroscopic Bankart surgery and those who did not have such surgery before implant-free iliac bone graft were formed and compared. We retrospectively analyzed 34 patients; 14 patients had previous arthroscopic Bankart surgery, and 20 patients did not have the surgery; The median age at the time of iliac bone graft was 35.3 years (range, 23 to 75), 17 patients were over the age of 35, and 17 patients were under the age of 35. The mean follow-up was 40 months (range: 25 to 56). All the 34 patients were engaged in pre- and post-operative sport, which represents a return to sport rate of 100%. Although the number of sport disciplines decreased significantly from 6 before the operation to 4.8 after the operation (p=0.002), the number of sports sessions per week did not change significantly, and the duration per session did not change significantly. More than two-thirds of all patients returned to sports within 6 months. Overall, 41% of patients changed sport disciplines, 15% of whom cited shoulder-related causes; however, all patients returned to the same sport level. Overall and within the subgroups, the return to sport rate after implant-free iliac bone grafting was high, with a high sense of well-being. The number of sport disciplines decreased significantly and more than one-third of the patients changed disciplines, of which 15% percent changed due to shoulder-related causes. The sport level remained equal, and no other parameters changed significantly compared with the time before the onset of restrictive shoulder symptoms.


The development of the male genitourinary system: III. The formation of the spongiose and glandar urethra.
It is generally agreed that the urethral plate disintegrates, resulting in the urethral groove. This is subsequently transformed into the urethra by fusion of the urethral folds, which flank its sides. Recently, the existence of such a groove and folds has been denied and this challenge to the long accepted existence of such folds is significant since hypospadias is considered to result from failure of their fusion. The present studies indicate that mesodermal fold formation and its subsequent subepithelial fusion across the midline plays an essential role in urethral tube formation. Disruption of this process readily explains common congenital abnormalities of the urethra.