Detection and characterization of colonization factor of enterotoxigenic Escherichia coli isolated from adults with diarrhea.
The fimbriate colonization factor antigen (CEA) of Escherichia coli strain H-1047 was isolated and used to prepare anti-CFA antiserum. Enterotoxigenic E. coli (ETEC) isolated from 29 adults with diarrhea acquired in Mexico were examined for CFA by using this serum. Retrospectively, it was found that ETEC possessing the H-10407-type CFA were isolated from 25 (86%) of these diarrhea cases as compared with 2 of 11 (18%) from asymptomatic controls from whom ETEC had been isolated. CFA was found onE. coli of various serotypes, as demonstrated by bacterial agglutination by the anti-CFA serum. Heat treating the cells at 65 degress C for 1 h prevented the agglutination. CFA-positive strains did not react with anti-CFA serum when the cultures were grown at a low incubation temperature (18 degrees C). E. coli isolates identified serologically as CFA positive were shown to adhere to the intestinal villous surfaces of infant rabbits. By the indirect immunofluorescence technique, it was found that adhesion occurred preferentially in the upper 20 cm of the small intestine. Also, the ability or inability of various isolates to adhere to intestinal mucosa in vivo correlated with the presence or absence of fimbriae on the cells when grown in vitro. Agglutinability with anti-CFA serum, fimbriae, and adhesiveness were spontaneously lost by many isolates after laboratory passage in a manner previously described with E. coli H-10407. These observations suggest that the H-10407-type CFA plays a role in the virulence of ETEC possessing this antigen.


Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive rat.
It has recently been proposed that primary mutations in genes involved in fatty acid and lipid metabolism may contribute to the pathogenesis of insulin resistance and dyslipidemia often observed in spontaneous forms of hypertension. In the current study in the spontaneously hypertensive rat (SHR), we mapped and sequenced the gene encoding a key transcription factor known as ADD1 (adipocyte determination and differentiation factor 1) or SREBP-1c (sterol regulatory element binding protein- c) that has recently been identified as a master regulator of genes involved in the hepatic control of lipid and carbohydrate metabolism. We found that (1) the gene for ADD1/SREBP-1c maps to a region of rat Chromosome 10 previously reported to contain a quantitative trait locus involved in the regulation of hepatic cholesterol levels and (2) the SHR harbors a valine-to-methionine substitution in the COOH terminal portion of the ADD1/SREBP-1 protein that is not present in 44 other strains of laboratory rats. These findings, together with previous studies showing that transgenic expression of SREBP-1 isoforms has major effects on hepatic fatty acid and cholesterol biosynthesis, suggest that naturally occurring variation in the gene encoding the SREBP-1 isoforms might contribute to inherited variation in lipid metabolism in the SHR versus other strains of rats. These results should serve to motivate future transfection studies of the effect of the SHR mutant on SREBP-1 expression and activation in vitro, as well as the development of congenic and transgenic strains of SHR to investigate the effects of different variants of SREBP-1 on carbohydrate and lipid metabolism in vivo.


Structure of (+-)-threo-9,10,16-trihydroxypalmitic acid.
9,10,16-Trihydroxyhexadecanoic acid, C16H32O5, Mr = 304.4, triclinic, P1, a = 4.871 (1), b = 8.801 (1), c = 21.121 (2) alpha = 89.54 (1), beta = 84.88 (2), gamma = 76.35 (2) degrees, V = 876.14 (4) A3, Z = 2, Dx = 1.154 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 0.26 cm-1, F(000) = 336, T = 295 K. Final R = 0.055 for 1556 reflections with I greater than or equal to 3 sigma(I). The 16 C atoms form an all-trans zigzag chain. Each molecule is linked to seven neighboring molecules via eight possible hydrogen bonds with O...O distances varying from 2.591 (6) to 2.673 (3) A. Each carboxyl group is potentially hydrogen-bonded to the carboxyl and C16-OH groups of other molecules with O...O distances of 2.591 (6) and 2.644 (4) A. The conformation around the C9-C10 bond is gauche with an O3-C9-C10-O4 torsion angle of 66.4 (5) degrees.


[Interrelations of cellular and humoral immune response and different doses of sheep erythrocytes in mice].
In experiments on CBA and C57BL/6 mice the generation of antibody-forming cells respectively either in the popliteal lymph nodes or spleen as well as a rate of delayed type hypersensitivity response (DTHR) on the background of subcutaneous (into foot) or intraperitoneal injection of different doses of sheep erythrocytes (from 10(4) to 10(8)) have been studied. In so doing two types of immune response can be isolated on the dependence upon the sensitivity threshold to antigen of DTHR and humoral immunity. Thus in C57BL/6 mice the antigen threshold for DTHR is of one time (in intraperitoneal immunization) or of a two times (in subcutaneous) lower order than for antibody response. In CBA line mice under subcutaneous immunization there can be seen quite an opposite picture while intraperitoneal immunization causes exact correlation of antigen threshold for cellular and humoral immune response.


Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer.
Borderline resectable pancreatic cancers are technically amenable to surgical resection, but are associated with increased risk of locoregional recurrence. Patients with these tumours may be treated with neoadjuvant therapy in an attempt to improve margin-negative resection rates. The University of Cincinnati Pancreatic Cancer Database was retrospectively reviewed. Borderline resectable disease was defined by the following radiographic criteria: (i) short segment occlusion of the superior mesenteric vein (SMV), portal vein (PV) or SMV/PV confluence; (ii) short segment hepatic artery encasement, or (iii) superior mesenteric artery/coeliac artery abutment of <180 degrees. Patients with resectable disease who had questionable metastatic disease or poor performance status were also included. Twenty-nine patients met the criteria. Of these, 26 underwent a full course of neoadjuvant therapy. Twelve (46%) underwent surgical resection and 14 had tumour progression or were deemed unresectable at laparotomy. The most common neoadjuvant therapy regimen was gemcitabine-based chemotherapy alone (58%). Of those undergoing surgery, 67% had margin-negative (R0) resections and 42% required venous resection. Median survival was 15.5 months for unresected patients and 23.3 months for resected patients. Borderline resectable pancreatic tumours can be treated neoadjuvantly, resulting in margin-negative resection and survival rates similar to those in initially resectable disease.


Regional variations in microstructural properties of vertebral trabeculae with aging.
The aim of this study was to identify regional variations in the three-dimensional microstructure of vertebral cancellous bones, and their relative differences with respect to aging. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadaver donors in two age groups, three aged 62 years and three aged 69 years; (n=45, each). In each vertebral body, five trabecular columns, each of 8x8x25 mm3, were cut from the anterior, posterior, central, right, and left regions. These columns were scanned, using high-resolution micro-computed tomography (microCT), three times, to obtain superior, middle, and inferior layers. Fifteen regions were obtained for each vertebral body. For all 90 trabecular specimens the bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), as well as the three radii of the mean intercept length (MIL) ellipsoid (H1, H2, and H3) were determined. Regional variations in different transverse layers and vertical columns within and between the two age groups were then analyzed. The results showed significant differences in BV/TV, Tb.N, DA, and H2/H3 between the two age groups. The BV/TV and Tb.N were decreased, while the anisotropic parameters were increased significantly with age, increasing from age 62 to 69. Change in Tb.Th was not statistically significant, although the average was slightly smaller in the 69-year group. Each microstructural parameter followed its own pattern of regional variation within each group, suggesting both mechanical and age-related adaptation. This is the first study that has provided microstructural data of the vertebral body in a Chinese sample. These data may help us to gain more insight into the mechanism of the occurrence of lumbar osteoporosis and the related regional fracture risks, and may provide a reference for better enhancement of fracture repair.


Identification of Bodies by Unique Serial Numbers on Implanted Medical Devices.
Visual identification is the most common identification method used by medical examiners but is not always possible. Alternative methods include X-ray, fingerprint, or DNA comparison, but these methods require additional resources. Comparison of serial numbers on implanted medical devices is a rapid and definitive method of identification. To assess the practicality of using this method, we reviewed 608 consecutive forensic autopsies performed at a regional medical examiner office. Of these, 56 cases required an alternative method of identification due to decomposition (n = 35), gunshot wound (n = 9), blunt trauma (n = 6), or charring (n = 6). Of these 56 cases, eight (14.3%) were known to have an implanted medical device. Of these eight cases, five (63%) could be positively identified by comparing serial numbers. If an implanted medical device is known to be present, and medical records are available, identification by medical device serial number should be a first-line method.


The effects of isoflurane minimum alveolar concentration on withdrawal reflex activity evoked by repeated transcutaneous electrical stimulation in ponies.
The aim of this study was to quantify the effects of isoflurane at approximately the minimum alveolar concentration (peri-MAC) on the temporal summation (TS) of reflex activity in ponies. TS was evoked by repeated electrical stimulations applied at 5 Hz for 2 s on the digital nerve of the left forelimb of seven ponies. Surface electromyographic activity was recorded from the deltoid and common digital extensor muscles. TS thresholds and amplitude of response to stimulations of increasing intensities were assessed during anaesthesia at 0.85, 0.95 and 1.05 times the individual MAC, and after anaesthesia in standing animals. Under isoflurane anaesthesia, TS thresholds increased significantly in a concentration-dependent fashion and at each isoflurane MAC, the responses increased significantly for increasing stimulation intensities. A concentration-dependent depression of evoked reflexes with a reduction in the slopes of the stimulus-response function was observed for both muscles. The results demonstrated that with this model it is possible to describe and quantify the effects of anaesthetics on spinal sensory-motor processing in ponies.


An overview of the response of bacteria to beta-lactam antibiotics.
A great variety exists in the ways bacteria respond to beta-lactam antibiotics. The responses of gram-positive cocci and gram-negative bacilli are fundamentally different, and beta-lactam antibiotics vary widely in their ability to penetrate to the target proteins, to bind to those proteins, and to withstand hydrolysis by enzymes that the organism may possess. Continuous turbidimetric monitoring offers a simple means by which the response of bacterial cultures can be followed in undisturbed test conditions. Microscopy of the cultures permits the turbidimetric record to be related to morphologic changes elicited by the antibiotic. Such studies reveal that cephalosporins can often evoke a transient response in bacteria that are completely unaffected by penicillins; beta-lactamase inhibitors appear to be more effective when they build on such a partial response.


The source of plasma dihydrotestosterone in man.
The source of plasma dihydrotestosterone (DHT) (17beta-hydroxy-5alpha-androstan-3-one) in humans has been investigated by infusing two potential peripheral precursors, testosterone (T) and androstenedione (A). Metabolic clearance rates (MCR), conversion ratios (CR), transfer constants (rho), and blood production rates (P(B)) were calculated. Plasma testosterone and dihydrotestosterone were measured by competitive binding techniques. The MCR(DHT) was 652 +/-35 (SD) liters/day in five males and 314 +/-63 (SD) liters/day in four adult females. In each individual, the MCR(DHT) was significantly lower than MCR(T) as predicted by testosterone-binding protein affinity studies. The P(B) (DHT) was 302 +/-65 (SD) mug/day in males and 56 +/-26 mug/day in females. Testosterone and androstenedione are precursors (prehormones) for plasma dihydrotestosterone. The conversion ratio CR(BB) (T-DHT), calculated as the ratio of counts per minute per liter of plasma of product to precursor after infusion of labeled precursor, was 5.6 +/-0.6 (SD)% (six subjects) in the male and 3.5 +/-0.4 (SD)% (four subjects) in the female. CR(BB) (A-DHT) after androstenedione infusion to three female subjects averaged 9.2%. No dihydrotestosterone back conversion was detected (< 0.2%). The transfer constants were [rho]BB(T-DHT), 3.9 +/-1.0% (male) and 1.7 +/-0.6% (female), and [rho]BB(A-DHT) average was 13.3% in three female subjects. Using either plasma testosterone and dihydrotestosterone values from our subjects and mean androstenedione values as reported in the literature, approximate contributions can be calculated. Testosterone conversion accounts for at least 70% of plasma DHT in the male, but less than 20% in the normal female. Androstenedione appears to be a major prehormone of plasma dihydrotestosterone accounting for at least two-thirds plasma dihydrotestosterone by peripheral conversion in adult females. In three normal women undergoing tubal ligation, there was an unimpressive gradient between ovarian vein and peripheral plasma dihydrotestosterone. It is suggested that dihydrotestosterone in the blood does not arise from direct secretion but may reflect events occurring in peripheral androgen target tissues.


Is there a link between treatments with exogenous corticosteroids and dog behaviour problems?
Possible side effects of exogenous corticosteroids have been described in both humans and laboratory animals, with recent studies highlighting this issue in dogs. In this paper the behaviour of 345 dogs drawn from the caseload of a behaviour clinic based in the north of Italy between February 2012 and November 2014 were analysed. Possible relationships between dogs that received treatment with corticosteroids versus dogs that received treatment with drugs other than corticosteroids and positive or negative affective states, aggression towards people, other behaviour problems apart from aggression, occurrence of severe bites, and prescription of psychoactive drugs were initially assessed using a Pearson's chi-squared test. Regression analysis was then performed in order to evaluate the best predictors of the investigated items. The goal of this retrospective survey was to investigate possible relationships between the affective states associated with the behavioural complaint of dogs and their previous history of treatment with corticosteroids. Results showed that a history of corticosteroid treatment was a significant predictor of a range of behaviour problems associated with negative affective state, but this result may be confounded by age-related effects.


An unusual case of cutaneous vasculitis.
We report an unusual case of a patient with clinical and histological features of cutaneous vasculitis. CASE PICTURE: A middle-aged Chinese male presented with livedo reticularis and digital gangrene without visceral involvement. Skin biopsy showed features suggestive of cutaneous vasculitis. Repeated testing for anticardiolipin antibody was negative. He was treated with two courses of intravenous prostacyclin and pulsed with one course of intravenous methylprednisolone. He was also put on oral prednisolone, pentoxifylline, aspirin, nifedipine and colchicine in addition to symptomatic therapy. There was gradual improvement of his toe discolouration and relief of pain. This is an interesting case of cutaneous vasculitis, which has features of polyarteritis nodosa and the antiphospholipid syndrome, who responded well to intravenous prostacyclin, steroids, pentoxifylline, aspirin, nifedipine and colchicine.


Human immunodeficiency virus type 1 induces apoptosis in CD4(+) but not in CD8(+) T cells in ex vivo-infected human lymphoid tissue.
Progression of human immunodeficiency virus (HIV) disease is associated with massive death of CD4(+) T cells along with death and/or dysfunction of CD8(+) T cells. In vivo, both HIV infection per se and host factors may contribute to the death and/or dysfunction of CD4(+) and CD8(+) T cells. Progression of HIV disease is often characterized by a switch from R5 to X4 HIV type 1 (HIV-1) variants. In human lymphoid tissues ex vivo, it was shown that HIV infection is sufficient for CD4(+) T-cell depletion. Here we address the question of whether infection of human lymphoid tissue ex vivo with prototypic R5 or X4 HIV variants also depletes or impairs CD8(+) T cells. We report that whereas productive infection of lymphoid tissue ex vivo with R5 and X4 HIV-1 isolates induced apoptosis in CD4(+) T cells, neither viral isolate induced apoptosis in CD8(+) T cells. Moreover, in both infected and control tissues we found similar numbers of CD8(+) T cells and similar production of cytokines by these cells in response to phorbol myristate acetate or anti-CD3-anti-CD28 stimulation. Thus, whereas HIV-1 infection per se in human lymphoid tissue is sufficient to trigger apoptosis in CD4(+) T cells, the death of CD8(+) T cells apparently requires additional factors.


A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I.
Risk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS). This study sought to analyze the usefulness of electrocardiographic parameters as markers of sudden cardiac death (SCD) in BrS. This study analyzed data from 347 consecutive patients (78.4% male; mean age 45 ± 13.1 years) with spontaneous type 1 BrS by ECG parameters but with no history of cardiac arrest (including 91.1% asymptomatic at presentation, 5.2% with a history of atrial fibrillation [AF], and 4% with a history of arrhythmic syncope). Electrocardiographic characteristics at the first clinic visit were analyzed to predict ventricular fibrillation (VF)/SCD during follow-up. During the follow-up (48 ± 38 months), 276 (79.5%) patients remained asymptomatic, 39 (11.2%) developed syncope, and 32 (9.2%) developed VF/SCD. Patients who developed VF/SCD had a lower prevalence of SCN5A gene mutations (p = 0.009) and a higher prevalence of positive electrophysiological study results (p < 0.0001), a family history of SCD (p = 0.03), and AF (p < 0.0001). The most powerful marker for VF/SCD was a significant S-wave (≥0.1 mV and/or ≥40 ms) in lead I. In the multivariate analysis, the duration of S-wave in lead I ≥40 ms (hazard ratio: 39.1) and AF (hazard ratio: 3.7) were independent predictors of VF/SCD during follow-up. Electroanatomic mapping in 12 patients showed an endocardial activation time significantly longer in patients with an S-wave in lead I, mostly because of a significant delay in the anterolateral right ventricular outflow tract. The presence of a wide and/or large S-wave in lead I was a powerful predictor of life-threatening ventricular arrhythmias in patients with BrS and no history of cardiac arrest at presentation. However, the prognostic value of a significant S-wave in lead I should be confirmed by larger studies and by an independent confirmation cohort of healthy subjects.


Translation and linguistic validation of the Swedish version of Orthotics and Prosthetics Users' Survey.
There is an increasing need for outcome measures in the orthotic and prosthetic field and specifically a lack of outcome measures in Swedish. The Orthotics and Prosthetics Users' Survey (OPUS) was developed in the USA for assessment of the outcome of orthotic and prosthetic interventions, and could potentially also be used for shoe insoles and orthopaedic shoes. The aims of this study were to translate OPUS into Swedish and test the translated version's linguistic validity in a Swedish context. The Orthotic and Prosthetic Users' Survey was translated into Swedish and back-translated into English, following a modified version of the World Health Organization guidelines. After revision of the Swedish version, 39 Swedish clients (12 men, 27 women) answered the OPUS questionnaires and were systematically debriefed afterwards. Most items were understood correctly by the respondents, but some words and expressions had to be changed to avoid misunderstandings or unintended interpretations. The resulting Swedish version of OPUS, OPUS-Swe, showed acceptable linguistic validity and has potential for use in both clinical practice and scientific settings. Nevertheless, before OPUS-Swe can be fully implemented, its psychometric properties need to be evaluated.


Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO(2).
There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease. We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE(-/-)) mice exposed to TiO(2). ApoE(-/-) mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO2 (fTiO2, 288 nm), photocatalytic 92/8 anatase/rutile TiO(2) (pTiO(2), 12 nm), or rutile nano TiO(2) (nTiO(2), 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO(2) (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO(2)-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs). The exposure to nTiO(2) was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE(-/-) mice exposed to fine and photocatalytic TiO(2) had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO(2). Repeated exposure to nanosized TiO(2) particles was associated with modest plaque progression in ApoE(-/-) mice. There were no associations between the pulmonary TiO(2) exposure and inflammation or vasodilatory dysfunction.


Clinical and in vivo confocal microscopic features of neuropathic corneal pain.
To describe clinical and in vivo confocal microscopy (IVCM) features of neuropathic corneal pain (NCP) without clinically visible signs. Prospective, observational study of 27 eyes of 14 patients who had continuous severe ocular pain for one or more years, with minimal or no ocular surface signs and were non-responsive to topical lubricants, steroids and/or ciclosporin. All patients were evaluated using Ocular Surface Disease Index, Oxford grading scale, Schirmer test 1, Cochet Bonnet esthesiometry and response to topical anaesthesia. Central and paracentral regions of the cornea of patients and seven healthy controls were studied by IVCM. Corneal epithelial thickness and sub-basal nerve density were measured in patients and controls. Four patients responded to topical anaesthesia (responsive group (RG)), indicating peripheral NCP while 10 patients did not show any improvement (non-responsive group (NRG)), indicating central NCP. Schirmer-1 test was within normal limits in the RG but significantly greater in the NRG (p<0.001). None of the other clinical parameters nor corneal epithelial thickness were statistically significantly different. The sub-basal nerve density was significantly reduced (p<0.008) in patients compared with controls. Stroma of all patients demonstrated activated keratocytes and spindle, lateral and stump microneuromas. There was a statistically significant greater number of microneuromas (p<0.0001) and activated keratocytes in RG compared with NRG. NCP without visible clinical signs does not represent typical dry eye disease. Distinct signs demonstrated on IVCM suggest that peripheral NCP, which responds to topical anaesthesia, and central NCP, which does not, are separate entities.


Fungal-fungal cocultivation leads to widespread secondary metabolite alteration requiring the partial loss-of-function VeA1 protein.
Microbial communication has attracted notable attention as an indicator of microbial interactions that lead to marked alterations of secondary metabolites (SMs) in varied environments. However, the mechanisms responsible for SM regulation are not fully understood, especially in fungal-fungal interactions. Here, cocultivation of an endophytic fungus Epicoccum dendrobii with the model fungus Aspergillus nidulans and several other filamentous fungi triggered widespread alteration of SMs. Multiple silent biosynthetic gene clusters in A. nidulans were activated by transcriptome and metabolome analysis. Unprecedentedly, gene deletion and replacement proved that a partial loss-of-function VeA1 protein, but not VeA, was associated with the widespread SM changes in both A. nidulans and A. fumigatus during cocultivation. VeA1 regulation required the transcription factor SclB and the velvet complex members LaeA and VelB for producing aspernidines as representative formation of SMs in A. nidulans. This study provides new insights into the mechanism that trigger metabolic changes during fungal-fungal interactions.


Predictors of response and disease course in patients with inflammatory bowel disease treated with biological therapy-the Danish IBD Biobank Project: protocol for a multicentre prospective cohort study.
Inflammatory bowel diseases (IBDs) are chronic diseases of unknown cause characterised by a progressive and unpredictable disease course. In the last decade, biological treatment has become a cornerstone in the treatment of IBD. However, one-in-three-to-four patients do not respond to first-line biological agents and another third of patients see their response diminish over time. This highlights an unmet need for optimising the use of biologicals and the prediction of treatment response. Considering the multifaceted nature of IBD, we hypothesise that multiomics profiling of sequential samples from single patients could facilitate the discovery of predictive biomarkers of response to biological therapy and disease course. This is a multicentre prospective cohort study which will enrol 840 biological-naïve patients with IBD who initiate biological therapy in a 3-year period. Primary outcomes are the occurrence of primary non-response (evaluated at weeks 14-16) and loss of response (evaluated during entire follow-up in patients who obtain partial or full response after induction period). Each patient will be followed up for their clinical data for at least 1 year or till the end of study period (up to 4 years). Blood and stool samples will be collected sequentially during the first year of biological treatment. Intestinal tissue will be sampled after 1 year of treatment and whenever an endoscopy is performed. Samples will undergo transcriptomic, proteomic and microbial DNA analyses. Omics data will be integrated with clinical data to identify a panel of predictive biomarkers of response to biological therapy and disease behaviour in patients with IBD. Ethical approval has been obtained from the Danish Ethics Committee (H-18064178). Inclusion is ongoing at three study centres and will be initiated in two additional centres. Both positive and negative study results will be disseminated through peer-reviewed journals according to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, as well as presented at international conferences.


LncRNA CDKN2B-AS1 promotes the progression of ovarian cancer by miR-143-3p/SMAD3 axis and predicts a poor prognosis.
Long noncoding RNAs (LncRNAs) show great potential as the therapeutic targets attributing to their implication in the progression of various human cancers, including ovarian cancer (OC). Here, we aimed to explore the biological function of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in OC and its mechanism of action. The abundances of CDKN2B-AS1, miR-143-3p, and SMAD3 mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8) was performed to analyze cell proliferation. Cell apoptosis was assessed by flow cytometry and western blot analyses. Transwell assay was utilized to analyze cell migration and invasion abilities. Tumor xenograft was performed to confirm the role of CDKN2B-AS1 in ovarian tumor growth in vivo. The protein level of SMAD3 was examined by western blot assay. The interaction between CDKN2B-AS1 and miR-143-3p, or miR-143-3p and SMAD3 was demonstrated by bioinformatic, luciferase reporter, qRT-PCR and western blot analyses. CDKN2B-AS1 was upregulated in OC and correlated with clinicopathologic features. The knockdown of CDKN2B-AS1 hampered the development of OC, as reflected by the suppression of cell proliferation, migration, and invasion, and the enhancement of cell apoptosis, whereas the effects could be rescued by the overexpression of SMAD3. The absence of CDKN2B-AS1 blocked tumor growth in vivo. CDKN2B-AS1 served as a molecular sponge for miR-143-3p, leading to the derepression of miR-143-3p target SMAD3, which eventually triggered the progression of OC. In conclusion, CDKN2B-AS1 promoted tumor growth, invasion, and migration of OC by regulation of miR-143-3p/SMAD3 axis, hinting that CDKN2B-AS1 might be a potential biomarker for OC diagnosis and treatment.


Gonococcal cervicitis is associated with reduced systemic CD8+ T cell responses in human immunodeficiency virus type 1-infected and exposed, uninfected sex workers.
Neisseria gonorrhoeae cervicitis and human immunodeficiency virus (HIV) type 1 frequently coinfect core transmitter populations, such as female sex workers. Gonococcal cervicitis is associated with increased viral shedding and plasma viremia in HIV-1-infected women and increased HIV-1 susceptibility in uninfected women. We studied the influence of gonococcal cervicitis on CD8(+) interferon (IFN)-gamma responses to HIV-1 and cytomegalovirus (CMV) epitopes in HIV-1-infected and in highly-exposed, persistently seronegative (HEPS) female sex workers. In HIV-1-infected women, gonococcal cervicitis was associated with reduced IFN-gamma responses in bulk CD8(+) lymphocyte populations, and intracellular cytokine staining, combined with class I major histocompatibility complex (MHC)-peptide tetramer studies, demonstrated reduced IFN-gamma production by HIV-1 epitope-specific CD8(+) lymphocytes. In HEPS sex workers, cervicitis was associated with the transient loss of systemic HIV-1-specific CD8(+) responses and with reduced function of CMV-specific CD8(+) lymphocytes. Impaired function of virus-specific CD8(+) lymphocytes may partly explain the deleterious effects of gonococcal cervicitis on HIV-1 immune control and susceptibility.


[The relationship between the effect of atenolol on the baroreceptor reflex and its hypotensive action in hypertension patients].
A study was made of the influence of atenolol on the sinocarotid and cardiopulmonary baroreceptor reflexes (BR) in patients with essential hypertension. Sinocarotid mechanoreceptors were activated by means of a cervical decompression pressure chamber. The cardiopulmonary BR was tested by changing venous return with the aid of local decompression of the lower limbs. The changes in the hemodynamic parameters were estimated by continuous recording of the mean arterial pressure (AP), tetrapolar rheography, direct manometry arterial pressure (AP), tetrapolar rheography, direct manometry (right atrium), and venous occlusion plethysmography. The drug hypotensive effect was shown to be related to modulation of the sinocarotid BR. It has been demonstrated that there is no relationship between atenolol suppression of the vasoconstrictor cardiopulmonary BR and the drug ability for AP reduction.


Does being on TB treatment predict a higher burden of problems and concerns among HIV outpatients in Kenya? a cross-sectional self-report study.
Tuberculosis illness is associated with uncertain outcomes, and has high prevalence among people living with HIV. The new World Health Organization's End TB strategy specifies person-centred symptom management and psychosocial support alongside treatment within its pillars and components. There is a paucity of research to inform an effective care response in Kenya in terms of self-reported outcomes. We aimed to measure the three day period intensity of problems and concerns (physical, psychological, social and spiritual), and identify predictors of problems and concerns, among HIV patients attending outpatient care. We conducted a cross-sectional self-report quantitative study among adult (aged at least 18 years) patients with confirmed HIV diagnosis, and aware of their diagnosis and attending HIV outpatient care in Kenya. Multi-dimensional palliative care problems and concerns were collected using African Palliative Outcome Scale (APOS). Ordinal logistic regression assessed the association of multi-dimensional problems and concerns controlling for demographic variables (age, gender, education and wealth) and clinical variables (WHO clinical stage, HIV treatment status, TB treatment status, and CD4 count). We recruited N = 400 participants. N = 61 (15.64%) were on TB treatment. The items with worst score responses were help and advice to plan for the future (52.5%), ability to share feelings (46.25%), at peace (30.75%) pain (27%) and life worthwhile (18.75%). TB treatment status was associated with lower (worse) score for APOS total score (odds ratio .59, 95% CI .36 to .99; P = 0.046) and factor 3(existential and spiritual wellbeing: .55, .32 to .92; p = 0.023). Interestingly higher CD4 count was predictive of lower (worse) factor 3 outcomes (existential and spiritual wellbeing: .84, 95% CI 73 to .97; p = 0.014). This study informs the new WHO End TB policy with novel data on specific clinical needs. This calls for holistic symptom assessment, person-centred care and holistic management to respond positively to the End TB strategy.


Effects of combining constraint-induced movement therapy and action-observation training on upper limb kinematics in children with unilateral cerebral palsy: a randomized controlled trial.
Modified constraint-induced movement therapy (mCIMT) improves upper limb (UL) motor execution in unilateral cerebral palsy (uCP). As these children also show motor planning deficits, action-observation training (AOT) might be of additional value. Here, we investigated the combined value of AOT to mCIMT on UL kinematics in children with uCP in a randomized controlled trial. Thirty-six children with uCP completed an UL kinematic and clinical evaluation after participating in a 9-day mCIMT camp wearing a splint for 6 h/day. The experimental group (mCIMT + AOT, n = 20) received 15 h of AOT, i.e. video-observation and execution of unimanual tasks. The control group (mCIMT + placebo, n = 16) watched biological-motion free videos and executed the same tasks. We examined changes in motor control (movement duration, peak velocity, time-to-peak velocity, and trajectory straightness) and kinematic movement patterns (using Statistical Parametric Mapping) during the execution of three unimanual, relevant tasks before the intervention, after and at 6 months follow-up. Adding AOT to mCIMT mainly affected movement duration during reaching, whereas little benefit is seen on UL movement patterns. mCIMT, with or without AOT, improved peak velocity and trajectory straightness, and proximal movement patterns. Clinical and kinematic improvements are poorly related. Although there seem to be limited benefits of AOT to CIMT on UL kinematics, our results support the inclusion of kinematics to capture changes in motor control and movement patterns of the proximal joints.


REM sleep latency and neurocognitive dysfunction in schizophrenia.
Cognitive deficits-the hallmark of schizophrenic deterioration-still remain elusive as far as their pathophysiology is concerned. Various neurotransmitter systems have been implicated to explain these deficits. Abnormalities in cholinergic neurotransmission in the brain are one of the postulations; acetylcholine has also been postulated to regulate rapid eye movement (REM) sleep, especially REM latency. Thus, REM latency in patients with schizophrenia might provide a non-invasive window to look into the cholinergic functions of the brain. To study REM sleep measures and neurocognitive function in schizophrenia, and the changes occurring in these parameters following pharmacological treatment. Thirty subjects (15 with schizophrenia and 15 normal non-relative controls) were evaluated in this study. Most patients with schizophrenia had prominent negative symptoms and deficits in the performance in neurocognitive tests battery. They were treated with antipsychotics for a variable period of time and post-treatment evaluation was done using the same battery of neurocognitive tests and polysomnography. Patients were either drug-naïve or kept drug-free for at least two weeks both at baseline as well as at the post-treatment stage. A positive correlation between the severity of negative symptoms and neurocognitive deficits (especially on the Wisconsin Card Sorting), and a negative correlation between these two parameters and REM latency was observed. It can be hypothesized that the acetylcholine deficit model of dementia cannot be applied to schizophrenic dementia, rather a hypercholinergic state results. This state warrants anticholinergic medication as a treatment option for negative symptoms of schizophrenia.


Seeing white: a critical exploration of occupational therapy with Indigenous Australian people.
This paper aims to critique current occupational therapy practice and theory using Indigenous Australian people as a case example. Critical race theory will be used to help question the privileged position of an occupational therapist from a dominant Westernized culture. In-depth interviews were conducted with 15 (eight female and seven male) Indigenous Australian young people about their perspectives of health and physical activity. In addition, the Kawa model was used as an alternative data-collection tool and detailed field notes and researcher reflections were used as data sources. Preliminary analysis of data is used to illustrate the ways in which critical race theory can inform occupational therapy practitioners and researchers about the ways Indigenous Australian young people view their health. Methodological dilemmas are also discussed. The paper is based on preliminary findings and further analysis needs to continue. Cross-cultural research is inherently complex but can offer those from the dominant culture valuable insights into their taken-for-granted assumptions. Further use of critical race theory may prove useful as the occupational therapy profession continues to evolve its understanding of cultural safety.


Effect of individual or combined ablation of the nuclear groups of the lamina terminalis on water drinking in sheep.
The subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), and median preoptic nucleus (MnPO) were ablated either individually or in various combinations, and the effects on drinking induced by either intravenous infusion of hypertonic 4 M NaCl (1.3 ml/min for 30 min) or water deprivation for 48 h were studied. Ablation of either the OVLT or SFO alone did not affect drinking in response to intravenous 4 M NaCl, although combined ablation of these two circumventricular organs substantially reduced but did not abolish such drinking. Ablation of the MnPO or MnPO and SFO together also substantially reduced, but did not abolish, drinking in response to intravenous hypertonic NaCl. Only near-total destruction of the lamina terminalis (OVLT, MnPO, and part or all of the SFO) abolished acute osmotically induced drinking. The large lesions also reduced drinking after water deprivation, whereas none of the other lesions significantly affected such drinking. None of these lesions altered feeding. The results show that all parts of the lamina terminalis play a role in the drinking induced by acute increases in plasma tonicity. The lamina terminalis appears to play a less crucial role in the drinking response after water deprivation than for the drinking response to acute intravenous infusion of hypertonic saline.


Xylocandin: a new complex of antifungal peptides. II. Structural studies and chemical modifications.
Xylocandins A1, A2, B1, B2, C1, C2, D1 and D2 are new antifungal peptides isolated from Pseudomonas cepacia ATCC 39277. The molecular weights of the xylocandins were determined by fast atom bombardment mass spectrometry (A1 m/z 1,215; A2 1,199; B1 1,229; B2 1,213; C1 1,097; C2 1,081; D1 1,083; D2 1,067). Each xylocandin is a cyclic peptide containing glycine, serine, asparagine (1-3 residues), beta-hydroxytyrosine, and an unusual amino acid with the formula C18H37NO5. Additionally A1, A2, D1 and D2 contain 2,4-diaminobutyric acid; A1, B1, C1 and D1 contain erythro-beta-hydroxyasparagine; and A1, A2, B1 and B2 contain xylose. For each xylocandin pair, an erythro-beta-hydroxyasparagine residue in the first component of the pair is thus replaced by an asparagine in the second component, accounting for the 16 dalton mass difference for each pair. Chemical modification of A1 and A2 at the diaminobutyric acid and beta-hydroxytyrosine residues was used to probe structural requirements for activity.


Altered reward expectancy in individuals with recent methamphetamine dependence.
Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence. Participants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. METH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes. METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.


Characterization of vaginal & rectal colonization with multiple serotypes of group B streptococci using multiple colony picks.
There is paucity of information on vaginal and rectal colonization with multiple serotypes of group B streptococci (GBS). As part of an ongoing cohort study evaluating the natural history of vaginal and rectal colonization by GBS, the colonization with multiple serotypes was studied in 102 non-pregnant women aged 18-30 yr. Up to ten separate colony picks of beta-haemolytic streptococci (total 1515 isolates) were selected from vaginal and rectal primary culture plates. The colonies were identified as GBS, and their capsular polysaccharides (CPS) serotypes determined using monospecific rabbit antisera for types Ia-VIII by double immunodiffusion in agarose (DID). A colony dot immunoblot (DB) assay, using monospecific rabbit antisera to purified type polysaccharides conjugated to tetanus toxoid, was developed to serotype efficiently the multiple colony picks of GBS. The CPS serotype distribution, examining only the 177 "a" or first colony picks from the 102 patients, was 30.5 per cent for Ia; 28.2 per cent for type III; 15.3 per cent for type II; and 13.6 per cent for type V. Only 2.8 per cent were nontypeable. Eighty of the 102 patients (78.4%) were colonized with only one serotype; 20 (19.6%) had two serotypes and two patients (2%) had three serotypes in their vaginal and/or rectal paired cultures. Overall, 91.9 per cent of the culture sites colonized with one to three CPS types (from the total number of colonies picked) were identified with a minimum of three colony picks. In 75 patients with vaginal/rectal pairs the GBS serotype concordance of only the "a" colony was 89.3 per cent and concordance decreased to 80 per cent when the serotype concordance of the total colony picks was analyzed. In conclusion, there was a relatively high prevalence of serotype nonconcordance in this population, and 21.6 per cent of patients had multiple GBS serotypes.


A unipolarly located, cell-surface-associated agglutinin, RapA, belongs to a family of Rhizobium-adhering proteins (Rap) in Rhizobium leguminosarum bv. trifolii.
The phage-display cloning technique was used to find rhizobial proteins that bind to receptors located on the bacterial cell surface. The aim was to clone the gene(s) encoding rhicadhesin, a universal rhizobial adhesion protein, and/or other cell-surface-binding proteins. Four such Rhizobium-adhering proteins (Rap) were revealed in Rhizobium leguminosarum bv. trifolii strain R200. The binding is mediated by homologous Ra domains in these proteins. One member of the Rap protein family, named RapA1, is a secreted calcium-binding protein, which are also properties expected for rhicadhesin. However, the size of the protein (24 kDa instead of 14 kDa) and its distribution among different rhizobia (present in only Rhizobium leguminosarum biovars and R. etli instead of all members of Rhizobiaceae argue against RapA1 being rhicadhesin. Protein RapA1 consists of two homologous Ra domains and agglutinates R200 cells by binding to specific receptors located at one cell pole during exponential growth. Expression of these cell-surface receptors was detected only in rhizobia that produce the RapA proteins. The authors propose that the homologous Ra domains, found to be present also in other proteins with different structure, represent lectin domains, which confer upon these proteins the ability to recognize their cognate carbohydrate structures.


A mutation in Drosophila simulans that lengthens the circadian period of locomotor activity.
The length of the Thr-Gly repeat within the period gene of Drosophilids, coevolves with its immediate flanking region to maintain the temperature compensation of the fly circadian clock. In Drosophila simulans, balancing selection appears to maintain a polymorphism in this region, with three repeat lengths carrying 23, 24 or 25 Thr-Gly pairs, each in complete linkage disequilibrium with a distinctive flanking region amino acid moiety. We wondered whether separating a specific length repeat from its associated flanking haplotype might have functional implications for the circadian clock. We fortuitously discovered a population of flies collected in Kenya, in which a chimeric Thr-Gly haplotype was segregating that carried the (Thr-Gly)24 repeat, but the flanking region of a (Thr-Gly)23 allele. One of the five isofemale lines that carried this 'mutant' Thr-Gly sequence showed a dramatically long and temperature-sensitive free-running circadian period. This phenotype was mapped to the X chromosome, close to the D. simulans per gene, but there was also a significant effect of a modifying autosomal locus or loci. It seems remarkable that such a mutant phenotype should be discovered in a screen of chimeric Thr-Gly regions.


The genomic basis of adaptation to high-altitude habitats in the eastern honey bee (Apis cerana).
The eastern honey bee (Apis cerana) is of central importance for agriculture in Asia. It has adapted to a wide variety of environmental conditions across its native range in southern and eastern Asia, which includes high-altitude regions. eastern honey bees inhabiting mountains differ morphologically from neighbouring lowland populations and may also exhibit differences in physiology and behaviour. We compared the genomes of 60 eastern honey bees collected from high and low altitudes in Yunnan and Gansu provinces, China, to infer their evolutionary history and to identify candidate genes that may underlie adaptation to high altitude. Using a combination of FST -based statistics, long-range haplotype tests and population branch statistics, we identified several regions of the genome that appear to have been under positive selection. These candidate regions were strongly enriched for coding sequences and had high haplotype homozygosity and increased divergence specifically in highland bee populations, suggesting they have been subjected to recent selection in high-altitude habitats. Candidate loci in these genomic regions included genes related to reproduction and feeding behaviour in honey bees. Functional investigation of these candidate loci is necessary to fully understand the mechanisms of adaptation to high-altitude habitats in the eastern honey bee.


Protein-Targeting Drug Discovery.
Protein-driven biological processes play a fundamental role in biomedicine because they are related to pathologies of enormous social impact, such as cancer, neuropathies, and viral diseases, including the one at the origin of the recent COVID-19 pandemic [...].


Mitogen-activated protein kinases with distinct requirements for Ste5 scaffolding influence signaling specificity in Saccharomyces cerevisiae.
Scaffold proteins are believed to enhance specificity in cell signaling when different pathways share common components. The prototype scaffold Ste5 binds to multiple components of the Saccharomyces cerevisiae mating pheromone response pathway, thereby conducting the mating signal to the Fus3 mitogen-activated protein kinase (MAPK). Some of the kinases that Ste5 binds to, however, are also shared with other pathways. Thus, it has been presumed that Ste5 prevents its bound kinases from transgressing into other pathways and protects them from intrusions from those pathways. Here we found that Fus3MAPK required Ste5 scaffolding to receive legitimate signals from the mating pathway as well as misdirected signals leaking from other pathways. Furthermore, increasing the cellular concentration of active Ste5 enhanced the channeling of inappropriate stimuli to Fus3. This aberrant signal crossover resulted in the erroneous induction of cell cycle arrest and mating. In contrast to Fus3, the Kss1 MAPK did not require Ste5 scaffolding to receive either authentic or leaking signals. Furthermore, the Ste11 kinase, once activated via Ste5, was able to signal to Kss1 independently of Ste5 scaffolding. These results argue that Ste5 does not act as a barrier that actively prevents signal crossover to Fus3 and that Ste5 may not effectively sequester its activated kinases away from other pathways. Rather, we suggest that specificity in this network is promoted by the selective activation of Ste5 and the distinct requirements of the MAPKs for Ste5 scaffolding.


Parents, friends and immigrant youths' academic engagement: A mediation analysis.
Parents and friends can help facilitate the academic engagement of newcomer immigrant youth during the early post-migration years. Using an accelerated longitudinal design and the integrative risk and resilience framework, we examined how parent home involvement and friendships were directly and indirectly associated with the development of newcomer immigrant youths' academic engagement. We used data from three waves (Years 3-5) of the Longitudinal Immigrant Student Adaptation study where a culturally diverse group of immigrant youth (N = 354, ages 10-17, MtimeinUS = 3.98 years, SD = 1.39) in the United States reported on their perceptions of parent home involvement (educational values and communication) and friendship (educational values and academic support) in Year 3 and on their academic engagement (behavioural and emotional) across 3 years. Findings showed high-stable behavioural and emotional engagement and direct positive associations between perceptions of parent home involvement and initial levels of behavioural and emotional engagement and between perceptions of friend educational values and initial levels of emotional engagement. Additionally, perceptions of parents' educational values indirectly contributed to initial levels of emotional engagement through positive associations with perceptions of friends' educational values. These findings can inform family-school partnerships and school-interventions targeting newcomer immigrant youths' engagement.


A high-resolution comparative radiation hybrid map of ovine chromosomal regions that are homologous to human chromosome 6 (HSA6).
In this study, we constructed high-resolution radiation hybrid (RH) and comparative maps of ovine chromosomes or chromosomal segments that are homologous to human chromosome 6 (HSA6). A total of 251 markers were successfully genotyped across the recently developed USUoRH5000 whole-genome panel; 208 of these markers were assigned to five RH linkage groups distributed on three ovine chromosomes (OAR8, 9 and 20). The RH maps have good correspondence with previous chromosome painting data, although a small centromeric region on OAR9 that is homologous to HSA6 had not been previously detected using human chromosome paints on ovine chromosomal spreads. High percentages of the ovine markers were identified as orthologues in the bovine (86.3%), dog (85.8%), horse (69.3%) and human (88.7%) genomes. These maps contribute to investigations in mammalian chromosome evolution and the search for economic trait loci in sheep.


Effective communication of public health guidance to emergency department clinicians in the setting of emerging incidents: a qualitative study and framework.
Evidence to inform communication between emergency department clinicians and public health agencies is limited. In the context of diverse, emerging public health incidents, communication is urgent, as emergency department clinicians must implement recommendations to protect themselves and the public. The objectives of this study were to: explore current practices, barriers and facilitators at the local level for communicating public health guidance to emergency department clinicians in emerging public health incidents; and develop a framework that promotes effective communication of public health guidance to clinicians during emerging incidents. A qualitative study was conducted using semi-structured interviews with 26 key informants from emergency departments and public health agencies in Ontario, Canada. Data were analyzed inductively and the analytic approach was guided by concepts of complexity theory. Emergent themes corresponded to challenges and strategies for effective communication of public health guidance. Important challenges related to the coordination of communication across institutions and jurisdictions, and differences in work environments across sectors. Strategies for effective communication were identified as the development of partnerships and collaboration, attention to specific methods of communication used, and the importance of roles and relationship-building prior to an emerging public health incident. Following descriptive analysis, a framework was developed that consists of the following elements: 1) Anticipate; 2) Invest in building relationships and networks; 3) Establish liaison roles and redundancy; 4) Active communication; 5) Consider and respond to the target audience; 6) Leverage networks for coordination; and 7) Acknowledge and address uncertainty. The qualities inherent in local relationships cut across framework elements. This research indicates that relationships are central to effective communication between public health agencies and emergency department clinicians at the local level. Our framework which is grounded in qualitative evidence focuses on strategies to promote effective communication in the emerging public health incident setting and may be useful in informing practice.


Diffusion driven optofluidic dye lasers encapsulated into polymer chips.
Lab-on-a-chip systems made of polymers are promising for the integration of active optical elements, enabling e.g. on-chip excitation of fluorescent markers or spectroscopy. In this work we present diffusion operation of tunable optofluidic dye lasers in a polymer foil. We demonstrate that these first order distributed feedback lasers can be operated for more than 90 min at a pulse repetition rate of 2 Hz without fluidic pumping. Ultra-high output pulse energies of more than 10 μJ and laser thresholds of 2 μJ are achieved for resonator lengths of 3 mm. By introducing comparatively large on-chip dye solution reservoirs, the required exchange of dye molecules is accomplished solely by diffusion. Polymer chips the size of a microscope cover slip (18 × 18 mm(2)) were fabricated in batches on a wafer using a commercially available polymer (TOPAS(®) Cyclic Olefin Copolymer). Thermal imprinting of micro- and nanoscale structures into 100 μm foils simultaneously defines photonic resonators, liquid-core waveguides, and fluidic reservoirs. Subsequently, the fluidic structures are sealed with another 220 μm foil by thermal bonding. Tunability of laser output wavelengths over a spectral range of 24 nm on a single chip is accomplished by varying the laser grating period in steps of 2 nm. Low-cost manufacturing suitable for mass production, wide laser tunability, ultra-high output pulse energies, and long operation times without external fluidic pumping make these on-chip lasers suitable for a wide range of lab-on-a-chip applications, e.g. on-chip spectroscopy, biosensing, excitation of fluorescent markers, or surface enhanced Raman spectroscopy (SERS).


Management of Low-Risk Thyroid Cancers: Is Active Surveillance a Valid Option? A Systematic Review of the Literature.
Thyroid cancer is the most common endocrine malignancy, representing 2.9% of all new cancers in the United States. It has an excellent prognosis, with a five-year relative survival rate of 98.3%.Differentiated Thyroid Carcinomas (DTCs) are the most diagnosed thyroid tumors and are characterized by a slow growth rate and indolent course. For years, the only approach to treatment was thyroidectomy. Active surveillance (AS) has recently emerged as an alternative approach; it involves regular observation aimed at recognizing the minority of patients who will clinically progress and would likely benefit from rescue surgery. To better clarify the indications for active surveillance for low-risk thyroid cancers, we reviewed the current management of low-risk DTCs with a systematic search performed according to a PRISMA flowchart in electronic databases (PubMed, Web of Science, Scopus, and EMBASE) for studies published before May 2021. Fourteen publications were included for final analysis, with a total number of 4830 patients under AS. A total of 451/4830 (9.4%) patients experienced an increase in maximum diameter by >3 mm; 609/4830 (12.6%) patients underwent delayed surgery after AS; metastatic spread to cervical lymph nodes was present in 88/4213 (2.1%) patients; 4/3589 (0.1%) patients had metastatic disease outside of cervical lymph nodes. Finally, no subject had a documented mortality due to thyroid cancer during AS. Currently, the American Thyroid Association guidelines do not support AS as the first-line treatment in patients with PMC; however, they consider AS to be an effective alternative, particularly in patients with high surgical risk or poor life expectancy due to comorbid conditions. Thus, AS could be an alternative to immediate surgery for patients with very-low-risk tumors showing no cytologic evidence of aggressive disease, for high-risk surgical candidates, for those with concurrent comorbidities requiring urgent intervention, and for patients with a relatively short life expectancy.


Platelet von Willebrand's antigen II: active release by aggregating agents and a marker of platelet release reaction in vivo.
von Willebrand's antigen II (vW AgII), a plasma and platelet antigen immunologically and biochemically distinct from factor-VIII-related antigen (VIIIR:Ag), is decreased in von Willebrand's disease. vW AgII is released from platelets during aggregation and clotting. The release of platelet vW AgII was studied in washed platelets following aggregation by thrombin, collagen, and adenosine diphosphate (ADP). Total platelet vW AgII was 3.39 U/10(9) platelets. Thrombin and collagen yielded release of 85% and 86% of platelet vW AgII, respectively, at the highest concentrations. Release of platelet vW AgII was correlated with the release of 5-hydroxytryptamine (5HT). Release of vW AgII by collagen and thrombin was inhibited by metabolic inhibitors. In addition, collagen release of vW AgII was inhibited by aspirin. In clinical syndromes associated with intravascular platelet destruction, marked elevations of plasma vW AgII were noted. Thus, vW AgII is released by a metabolically active process from platelets during aggregation. In addition, vW AgII appears to be a marker of intravascular platelet destruction.


Modifier 22 for acetabular fractures in morbidly obese patients: does it affect reimbursement?
Modifier 22 in the American Medical Association's Current Procedural Terminology (CPT®) book is a billing code for professional fees used to reflect an increased amount of skill, time, and work required to complete a procedure. There is little disagreement that using this code in the setting of surgery for acetabulum fractures in the obese patient is appropriate; however, to our knowledge, the degree to which payers value this additional level of complexity has not been determined. We asked whether (1) the use of Modifier 22 increased reimbursements in morbidly obese patients and (2) there was any difference between private insurance and governmental payer sources in treatment of Modifier 22. Over a 4-year period, we requested immediate adjudication with payers when using Modifier 22 for morbidly obese patients with acetabular fractures. We provided payers with evidence of the increased time and effort required in treating this population. Reimbursements were calculated for morbidly obese and nonmorbidly obese patients. Of the 346 patients we reviewed, 57 had additional CPT® codes or modifiers appended to their charges and were excluded, leaving 289 patients. Thirty (10%) were morbidly obese and were billed with Modifier 22. Fifty-three (18%) were insured by our largest private insurer and 69 (24%) by governmental programs (Medicare/Medicaid). Eight privately insured patients (15%) and seven governmentally insured patients (10%) were morbidly obese and were billed with Modifier 22. For our primary question, we compared reimbursement rates between patients with and without Modifier 22 for obesity within the 289 patients. We then performed the same comparison for the 53 privately insured patients and the 69 governmentally insured patients. Overall, there was no change in mean reimbursement when using Modifier 22 in morbidly obese patients, compared to nonmorbidly obese patients (USD 2126 versus USD 2149, p < 0.94). There was also no difference in mean reimbursements with Modifier 22 in either the privately insured patients (USD 3445 versus USD 2929, p = 0.16) or the governmentally insured patients (USD 1367 versus USD 1224, p=0.83). Despite educating payers on the increased complexity and time needed to deal with morbidly obese patients with acetabular fractures, we have not seen an increased reimbursement in this challenging patient population. This could be a disincentive for many centers to treat these challenging injuries. Further efforts are needed to convince government payer sources to increase compensation in these situations. Level IV, economic and decision analyses. See Instructions for Authors for a complete description of levels of evidence.


COMPARISON OF CORNEAL WETTING PROPERTIES OF DIFFERENT DISPERSIVE OPHTHALMIC VISCOSURGICAL DEVICES: An Optical Coherence Tomography Study.
To compare corneal wetting performances of different dispersive ophthalmic viscosurgical devices. Three different types of dispersive ophthalmic viscosurgical devices, hydroxypropyl methylcellulose %2 (HPMC), sodium hyaluronate %3-sodium chondroitin sulphate %4 (HACS), and sodium hyaluronate %3 (HA), were applied on corneal surfaces of 10 healthy volunteer subjects repeatedly at 3 different time points. Corneal wetting properties of the ophthalmic viscosurgical devices were compared qualitatively and quantitatively by anterior segment optical coherence tomography for 30 minutes. Sodium hyaluronate 3% and HACS applications had a higher mean precorneal ophthalmic viscosurgical device thickness than HPMC application at all time points (seventh minute HPMC: 105.2 ± 25.3 μm, HA: 561.4 ± 115.8 μm, HACS: 481.2 ± 55 μm, P < 0.001). All HPMC applications were terminated by the 12th minute because of insufficient corneal wetting. Mean survival estimate time was significantly shortest for HPMC (11.5 ± 0.5 minutes, P < 0.001) and longest for HA (29.7 ± 0.28 minutes). It was slightly shorter for HACS (26.9 ± 0.87 minutes, P = 0.007) than the HA application. Sodium hyaluronate 3% and HACS provide superior corneal covering compared with HPMC with an effect that can be maintained up to 30 minutes. They may be an effective option for corneal wetting during long vitreoretinal surgeries with longer duration of effect and fever number of applications.


Minocycline delayed photoreceptor death in rds mice through iNOS-dependent mechanism.
To elucidate the role of activated microglia and nitric oxide (NO) in photoreceptor apoptosis in rds mice, and to investigate the effect of minocycline treatment on rds mice. Photoreceptor apoptosis in rds mice was detected by terminal dUTP transferase nick end labeling (TUNEL). Retinal microglial cells were identified by CD11b antibody. The mRNA expression of inducible nitric oxide synthase (iNOS) and chemokines were examined by reverse transcription polymerase chain reaction (RT-PCR) assay. The protein expression of iNOS was examined by immunohistochemistry and Western blotting analysis. The rds mice were treated intra-peritoneally from the second postnatal day (P2) with minocycline. Accompanying photoreceptor degeneration in rds mice, microglia were activated and immigrated from inner retinal layer (IRL) to outer nuclear layer (ONL), and the expression of iNOS was up-regulated. Minocycline treatment reduced the iNOS expression and decreased the initial photoreceptor apoptosis, but did not provide long term ameliorative effect on the photoreceptor cell loss of rds mice. NO played a major role in the initial photoreceptor apoptosis in rds mice. The migration of activated microglia to the ONL contributed to the subsequent photoreceptor cell death; minocycline treatment ameliorated the photoreceptor apoptosis in rds mice, and this protective effect was partly through iNOS-suppressive mechanism.


Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents.
Scrapie-associated fibrils (SAF) were isolated and purified from animals infected with three different scrapie agents: ME7 and 139A in mice, and 263K in hamsters. Mouse ME7 and 139A SAF differed from hamster 263K SAF in morphology, sedimentation rate and protein composition. SAF from the three scrapie agents were distinguishable from each other by their sensitivity to proteinase K digestion. SAF copurified with infectivity in both the hamster and mouse systems. SAF appear to be a unique class of structures which are related but specific for each individual scrapie agent. These properties may correlate with the biological and pathological differences seen among these agents.


Observations of binary population biofilms.
Biofilm research has focused on studies of undefined mixed microbial populations and, more recently, on investigations of monopopulation biofilms. In the first case, the biofilm is considered a homogeneous mass, ignoring the properties of individual species. The second case concentrates on the properties and processes of one microbial species in the biofilm. This article describes biofilm experiments conducted with monopopulations of Klebsiella pneumoniae and Pseudomonas aeruginosa and with binary populations of K. pneumoniae and P. aeruginosa. Process rates and stoichiometric coefficients were determined for the monopopulation and for the binary population biofilms and evaluated in light of the species distribution in the latter. Results indicate that neither the specific cellular product formation rate nor the glucose-oxygen stoichiometric ratio of K. pneumoniae or P. aeruginosa in the binary biofilm is affected by the presence of the other species. Consequently, species interaction was not observed. Although the specific cellular growth rate of K. pneumoniae is five times that of P. aeruginosa, the former species did not dominate the microbial population in the biofilm. Possible reasons for this unexpected behavior are discussed.


Potential lncRNA diagnostic biomarkers for early gastric cancer.
Long noncoding RNAs (lncRNAs) serve important functions in many crucial biological processes; however, the effects of lncRNAs in early gastric cancer (EGC) are not entirely clear. The present study aimed to demonstrate the potential of lncRNAs to be used as biomarkers in EGC. Reverse transcription‑quantitative polymerase chain reaction was used to measure the expression levels of lncRNAs, including X inactive‑specific transcript (XIST), Yiya, brain cytoplasmic RNA 1 (BCYRN1), ribosomal RNA processing 1B (RRP1B), KCNQ1 opposite transcript 1 (KCNQ1OT1) and testes development related 1 (TDRG1), in EGC tissues compared with normal adjacent tissues (NATs). XIST, BCYRN1, RRP1B and TDRG1 were identified as differentially expressed in EGC tissues compared with NATs. The specificity and sensitivity of XIST, BCYRN1, RRP1B and TDRG1 were determined by receiver operating characteristic curve analysis. In addition, RRP1B expression was revealed to be significantly correlated with distal metastasis (P=0.020) and tumor‑node‑metastasis staging (P=0.018), and TDRG1 expression was significantly correlated with lymph node metastasis (P=0.001). Furthermore, BCYRN1, RRP1B and TDRG1 expression levels were compared between EGC tissues and plasma, and the results indicated that there were significant positive correlations of XIST, BCYRN1, RRP1B and TDRG1 expression levels between the EGC tissues and plasma. Therefore, the present study suggested that XIST, BCYRN1, RRP1B and TDRG1 may be served as potential diagnostic biomarkers for EGC.


Taxonomic study of the genera Halogeometricum and Halosarcina: transfer of Halosarcina limi and Halosarcina pallida to the genus Halogeometricum as Halogeometricum limi comb. nov. and Halogeometricum pallidum comb. nov., respectively.
Members of the haloarchaeal genera Halosarcina and Halogeometricum (family Halobacteriaceae) are closely related to each other and show 96.6-98 % 16S rRNA gene sequence similarity. This is higher than the accepted threshold value (95 %) to separate two genera, and a taxonomic study using a polyphasic approach of all four members of the two genera was conducted to clarify their relationships. Polar lipid profiles indicated that Halogeometricum rufum RO1-4(T), Halosarcina pallida BZ256(T) and Halosarcina limi RO1-6(T) are related more to each other than to Halogeometricum borinquense CGMCC 1.6168(T). Phylogenetic analyses using the sequences of three different genes (16S rRNA gene, rpoB' and EF-2) strongly supported the monophyly of these four species, showing that they formed a distinct clade, separate from the related genera Halopelagius, Halobellus, Haloquadratum, Haloferax and Halogranum. The results indicate that the four species should be assigned to the same genus, and it is proposed that Halosarcina pallida and Halosarcina limi be transferred to the genus Halogeometricum as Halogeometricum pallidum comb. nov. (type strain, BZ256(T) = KCTC 4017(T) = JCM 14848(T)) and Halogeometricum limi comb. nov. (type strain, RO1-6(T) = CGMCC 1.8711(T) = JCM 16054(T)).


The diagnostic value of pleural biopsy in bronchopulmonary carcinoma.
The diagnosis of bronchopulmonary carcinoma was either corroborated or arrived at in 13 out of a total of 26 cases by pleural biopsy. Taken as a whole, pleural biopsy is inferior to repeated examination of the pleural exudate for neoplastic cells. In individual observations, however, the former can be found positive at a time when neither the pleural fluid nor any other material provide a diagnostic clue. In an instance of primary pleural growth (mesothelioma) its nature was recognizable in the pleural biopsy material. Pleural biopsy can correctly lead to the diagnostic exclusion of growth in favour of tuberculosis. Pleural biopsy can be suggestive of the rheumatic aetiology of changes.A pleural biopsy positive for carcinoma can be obtained on both sides. All stages, from early submesothelial deposition of individual neoplastic cells to the dense infiltration of the subserous connective and fat tissue, were observed.


A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease.
A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up. A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results. We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights. The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; p<0.001), and time to metastasis, HR/20 units=2.75 (95% CI 1.63-4.63; p<0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p<0.001). No patient with low- or intermediate-risk disease and a GPS of<20 developed metastases or PCD (n=31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS+CAPRA; p<0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance. GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease. Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease.


Epidemiology and clinical findings of colorectal carcinoma in two tertiary care hospitals in Benghazi, Libya.
The aim is to determine the pattern of patients with colorectal cancer (CRC) seen in two tertiary hospitals in Benghazi, Libya. The cohort includes all patients of CRC who were presented between January 2007 and December 2009 to the Oncology Department, Aljomhoria Hospital and 7(th) October Hospital, Benghazi. Patient's age, gender, clinical presentation, location of cancer involvement, and histopathologic diagnosis were reviewed. Tumor staging was carried out according to Astler Coller modification of Duke's system, dividing it into stage A to C depending upon the extent of local involvement and regional node spread. Stage D was added to account for distant metastasis in accordance with Turnbull modification. A total of 152 patients with CRC were included, 84 males (55%) and 68 females (45%) with a male to female ratio of 1.2:1.0. The mean age was 57.4 ± 12.92 years (range 21-87 years). 18 (11.8%) patients were below 40 years of age. The most common presenting symptoms were rectal bleeding and abdominal pain and were together present in 71% of the patients. The majority (67.8%) of tumors arise from rectum and sigmoid colon. More than one-third of the patients had poorly differentiated adenocarcinoma. Sixty patients (39.5%) presented in stage D, whereas 30.9% (47/152) and 29.6% (45/152) of patients were in stage B and stage C, respectively. None of the patients had stage A at presentation. The radiological evaluation showed presence of liver metastasis in 14 patients (9.2%) and pulmonary metastasis in two patients (1.3%). Anemia was found in 56 patients (36.8%). It was more common in females (P = 0.01) and in the right sided tumors (66.7%) than left sided tumors (29.5%) (P = 0.001). The majority of CRC patients in Benghazi were diagnosed in locally advanced or metastatic stage. In order to achieve early detection of CRC, a comprehensive cancer education program and screening of high risk population for CRC should be considered in this part of Libya.


Yellow Fever Outbreak in Eastern Senegal, 2020-2021.
Yellow fever virus remains a major threat in low resource countries in South America and Africa despite the existence of an effective vaccine. In Senegal and particularly in the eastern part of the country, periodic sylvatic circulation has been demonstrated with varying degrees of impact on populations in perpetual renewal. We report an outbreak that occurred from October 2020 to February 2021 in eastern Senegal, notified and managed through the synergistic effort yellow fever national surveillance implemented by the Senegalese Ministry of Health in collaboration with the World Health Organization, the countrywide 4S network set up by the Ministry of Health, the Institut Pasteur de Dakar, and the surveillance of arboviruses and hemorrhagic fever viruses in human and vector populations implemented since mid 2020 in eastern Senegal. Virological analyses highlighted the implication of sylvatic mosquito species in virus transmission. Genomic analysis showed a close relationship between the circulating strain in eastern Senegal, 2020, and another one from the West African lineage previously detected and sequenced two years ago from an unvaccinated Dutch traveler who visited the Gambia and Senegal before developing signs after returning to Europe. Moreover, genome analysis identified a 6-nucleotide deletion in the variable domain of the 3'UTR with potential impact on the biology of the viral strain that merits further investigations. Integrated surveillance of yellow fever virus but also of other arboviruses of public health interest is crucial in an ecosystem such as eastern Senegal.


Assessment of HIV/AIDS comprehensive correct knowledge among Sudanese university: a cross-sectional analytic study 2014.
Comprehensive correct HIV/AIDS knowledge (CCAK) is defined as correctly identify the two major ways of preventing the sexual transmission of HIV, and reject the most common misconceptions about HIV transmission. There are limited studies on this topic in Sudan. In this study we investigated the Comprehensive correct HIV/AIDS knowledge among Universities students. A cross-sectional analytic study was conducted among 556 students from two universities in 2014. Data were collected by using the self-administered pre-tested structured questionnaire. Chi-square was used for testing the significance and P. Value of ≥ 0.05 is considered as statistically significant. The majority (97.1%) of study subjects have heard about a disease called HIV/AIDS, while only 28.6% of them knew anyone who is infected with AIDS in the local community. Minority (13.8%) of students had CCAK however, males showed a better level of CCAK than females (OR = 2.77) with high significant statistical differences (P. Value = 0.001). Poor rate of CCAK among university students is noticed, especially among females. Almost half of students did not know preventive measures of HIV, nearly two thirds had misconception, about one third did not know the mode of transmission of HIV.


The curvature of sensitometric curves for Kodak XV-2 film irradiated with photon and electron beams.
Sensitometric curves of Kodak XV-2 film, obtained in a time period of ten years with various types of equipment, have been analyzed both for photon and electron beams. The sensitometric slope in the dataset varies more than a factor of 2, which is attributed mainly to variations in developer conditions. In the literature, the single hit equation has been proposed as a model for the sensitometric curve, as with the parameters of the sensitivity and maximum optical density. In this work, the single hit equation has been translated into a polynomial like function as with the parameters of the sensitometric slope and curvature. The model has been applied to fit the sensitometric data. If the dataset is fitted for each single sensitometric curve separately, a large variation is observed for both fit parameters. When sensitometric curves are fitted simultaneously it appears that all curves can be fitted adequately with a sensitometric curvature that is related to the sensitometric slope. When fitting each curve separately, apparently measurement uncertainty hides this relation. This relation appears to be dependent only on the type of densitometer used. No significant differences between beam energies or beam modalities are observed. Using the intrinsic relation between slope and curvature in fitting sensitometric data, e.g., for pretreatment verification of intensity-modulated radiotherapy, will increase the accuracy of the sensitometric curve. A calibration at a single dose point, together with a predetermined densitometer-dependent parameter ODmax will be adequate to find the actual relation between optical density and dose.


Term-tissue specific models for prediction of gene ontology biological processes using transcriptional profiles of aging in drosophila melanogaster.
Predictive classification on the base of gene expression profiles appeared recently as an attractive strategy for identifying the biological functions of genes. Gene Ontology (GO) provides a valuable source of knowledge for model training and validation. The increasing collection of microarray data represents a valuable source for generating functional hypotheses of uncharacterized genes. This study focused on using support vector machines (SVM) to predict GO biological processes from individual or multiple-tissue transcriptional profiles of aging in Drosophila melanogaster. Ten-fold cross validation was implemented to evaluate the prediction. One-tail Fisher's exact test was conducted on each cross validation and multiple testing was addressed using BH FDR procedure. The results showed that, of the 148 pursued GO biological processes, fifteen terms each had at least one model with FDR-adjusted p-value (Adj.p) <0.05 and six had the values between 0.05 and 0.25. Furthermore, all these models had the prediction sensitivity (SN) over 30% and specificity (SP) over 80%. We proposed the concept of term-tissue specific models indicating the fact that the major part of the optimized prediction models was trained from individual tissue data. Furthermore, we observed that the memberships of the genes involved in all the three pursued children biological processes on mitochondrial electron transport could be predicted from the transcriptional profiles of aging (Adj.p < 0.01). This finding may be important in biology because the genes of mitochondria play a critical role in the longevity of C. elegans and D. melanogaster.


Therapeutic Breast Reconstruction Using Gene Therapy-Delivered IFNγ Immunotherapy.
After mastectomy, breast reconstruction is increasingly performed using autologous tissue with the aim of improving quality of life. During this procedure, autologous tissue is excised, relocated, and reattached using microvascular anastomoses at the site of the extirpated breast. The period during which the tissue is ex vivo may allow genetic modification without any systemic exposure to the vector. Could such access permit delivery of therapeutic agents using the tissue flap as a vehicle? Such delivery may be more targeted and oncologically efficient than systemic therapy, and avoid systemic complications. The cytokine IFNγ has antitumor effects, and systemic toxicity could be circumvented by localized delivery of the IFNγ gene via gene therapy to autologous tissue used for breast reconstruction, which then releases IFNγ and exerts antitumor effects. In a rat model of loco-regional recurrence (LRR) with MADB-106-Luc and MAD-MB-231-Luc breast cancer cells, autologous tissue was transduced ex vivo with an adeno-associated viral vector encoding IFNγ. The "Therapeutic Reconstruction" released IFNγ at the LRR site and eliminated cancer cells, significantly decreased tumor burden, and increased survival compared with sham reconstruction (P <0.05). Mechanistically, localized IFNγ immunotherapy stimulated M1 macrophages to target cancer cells within the regional confines of the modified tumor environment. This concept of "Therapeutic Breast Reconstruction" using ex vivo gene therapy of autologous tissue offers a new application for immunotherapy in breast cancer with a dual therapeutic effect of both reconstructing the ablative defect and delivering local adjuvant immunotherapy.


Successful psychotherapy for psychogenic seizures in men.
This qualitative study examined factors contributing to the development and successful treatment of psychogenic non-epileptic seizures (PNES), in civilian men. In-depth interviews were conducted with therapist-client dyads comprising two male clients who had been successfully treated for PNES and their therapists. A theory-building case study approach provided evidence that those factors known to contribute to PNES and other somatoform symptoms in females and in males engaged in war also contributed to these symptoms in these two civilian males. In addition, PNES in these civilian males occurred in contexts where masculine identity was developmentally curtailed and socially constrained. Successful treatments occurred in long-term therapeutic relationships that sanctioned verbal expression of strong emotion and provided the attunement necessary for development of a robust masculine identity. These findings have implications for the funding of therapy, and training of therapists.


Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI.
Calf blood flow was measured simultaneously in healthy human subjects (n = 7) during cuff inflation and deflation using near-infrared diffuse correlation spectroscopy (DCS) and arterial spin labeled perfusion MRI (ASL-MRI). The DCS and ASL-MRI data exhibited highly correlated absolute and relative dynamic flow responses in each individual (p < 0.001). Peak flow variations during hyperemia were also significantly correlated, though more for relative (p = 0.003) than absolute (p = 0.016) flow. Repeated measurement variation was less than 8% for both modalities. The results provide much needed quantitative blood flow validation of the diffuse optical correlation method in humans.


Enhanced organic pollutant removal influenced by activated-ferric-sludge.
The primary goal of this study was to compare the pollutant removal efficiency of the reactivated activated-ferric-sludge (AFS) with that of the activated sludge (AS). Most tested organic pollutants were preferably removed by reactivated AFS. The optimal reactivated conditions for AFS were a reactivation time of 3 h, pH of 5-9, AFS dose of 5 g/L and dissolved oxygen of 2-6 mg/L. The results revealed a positive correlation between microbial activity and the removal efficiency of organic pollutants, with a higher microbial activity being associated with a better removal efficiency of organic pollutants. Additionally, variations in extracellular polymeric substances were found to be crucial to the microbial activity and adsorption capacity of reactivated AFS. After reactivation, reactivated AFS was superior to AS for the removal ofmost pollutants. Finally, the mechanism of AFS reactivation was investigated. Overall, the results of the present study demonstrate that reactivated AFS has the potential for widespread application in the removal of organic pollutants during the wastewater treatment process.


Psychosocial and Computer-Assisted Intervention for College Students with Autism Spectrum Disorder: Preliminary Support for Feasibility.
The number of young adults with Autism Spectrum Disorders (ASD) enrolled in higher education institutions has steadily increased over the last decade. Despite this, there has been little research on how to most effectively support this growing population. The current study presents data from a pilot trial of two novel intervention programs developed for college students with ASD. In this small randomized controlled trial, college students with ASD (n = 8) were assigned to one of two new programs - either an intervention based on a virtual reality-Brain-Computer Interface for ASD (BCI-ASD) or a psychosocial intervention, the College and Living Success (CLS) program. Preliminary evidence supports the feasibility and acceptability of both programs, although behavioral outcomes were inconsistent across participants and interventions. Results indicate that expanded research on psychosocial and computer-assisted intervention approaches for this population is warranted, given the preliminary support found in this pilot study.


Polymeric nucleic acid vehicles exploit active interorganelle trafficking mechanisms.
Materials that self-assemble with nucleic acids into nanocomplexes (e.g. polyplexes) are widely used in many fundamental biological and biomedical experiments. However, understanding the intracellular transport mechanisms of these vehicles remains a major hurdle in their effective usage. Here, we investigate two polycation models, Glycofect (which slowly degrades via hydrolysis) and linear polyethyleneimine (PEI) (which does not rapidly hydrolyze), to determine the impact of polymeric structure on intracellular trafficking. Cells transfected using Glycofect underwent increasing transgene expression over the course of 40 h and remained benign over the course of 7 days. Transgene expression in cells transfected with PEI peaked at 16 h post-transfection and resulted in less than 10% survival after 7 days. While saccharide-containing Glycofect has a higher buffering capacity than PEI, polyplexes created with Glycofect demonstrate more sustained endosomal release, possibly suggesting an additional or alternative delivery mechanism to the classical "proton sponge mechanism". PEI appeared to promote release of DNA from acidic organelles more than Glycofect. Immunofluorescence images indicate that both Glycofect and linear PEI traffic oligodeoxynucleotides to the Golgi and endoplasmic reticulum, which may be a route towards nuclear delivery. However, Glycofect polyplexes demonstrated higher co-localization with the ER than PEI polyplexes, and co-localization experiments indicate the retrograde transport of polyplexes via COP I vesicles from the Golgi to the ER. We conclude that slow release and unique trafficking behaviors of Glycofect polyplexes may be due to the presence of saccharide units and the degradable nature of the polymer, allowing more efficacious and benign delivery.


Medication adherence, ethnicity, and the influence of multiple psychosocial and financial barriers.
Medication adherence is critical for patients with bipolar disorder to avoid symptom exacerbation and diminished quality of life. Most analyses consider adherence barriers individually rather than conjointly, while neglecting potential ethnic differences. 435 patients in the Continuous Improvement for Veterans in Care--Mood Disorders study reported multiple financial and psychosocial factors influencing adherence. Logistic regression modeled adherence as a function of perceived barriers, including cost burden, access, binge drinking, poor therapeutic alliance, and medication beliefs. Nearly half the cohort experienced adherence difficulty, averaging 2.8 barriers, with minority veterans reporting lower adherence than white patients, particularly financial burden and treatment access. Total barriers were significantly associated with worse adherence (OR = 1.24 per barrier), notably poor medication beliefs, binge drinking, and difficulty accessing psychiatric specialists (ORs of 2.41, 1.95 and 1.73, respectively). Veterans with bipolar disorder experience numerous adherence barriers, with certain obstacles proving especially pernicious. Fortunately tailored clinical interventions can improve adherence, particularly by addressing modifiable risk factors.


Effect of Heart Rate Reserve on Prefrontal Cortical Activation While Dual-Task Walking in Older Adults.
Hypertension is considered a risk factor for cardiovascular health and non-amnestic cognitive impairment in older adults. While heart rate reserve (HRR) has been shown to be a risk factor for hypertension, how impaired HRR in older adults can lead to cognitive impairment is still unclear. The objective of this study was to examine the effects of HRR on prefrontal cortical (PFC) activation under varying dual-task demands in older adults. Twenty-eight older adults (50-82 years of age) were included in this study and divided into higher (n = 14) and lower (n = 14) HRR groups. Participants engaged in the cognitive task which was the Modified Stroop Color Word Test (MSCWT) on a self-paced treadmill while walking. Participants with higher HRR demonstrated increased PFC activation in comparison to lower HRR, even after controlling for covariates in analysis. Furthermore, as cognitive task difficulty increased (from neutral to congruent to incongruent to switching), PFC activation increased. In addition, there was a significant interaction between tasks and HRR group, with older adults with higher HRR demonstrating increases in PFC activation, faster gait speed, and increased accuracy, relative to those with lower HRR, when going from neutral to switching tasks. These results provide evidence of a relationship between HRR and prefrontal cortical activation and cognitive and physical performance, suggesting that HRR may serve as a biomarker for cognitive health of an older adult with or without cardiovascular risk.


Counter-propagating parametric interaction with phonon-polaritons in periodically poled KTiOPO4.
Strongly enhanced backward stimulated polariton scattering (BSPS) is demonstrated in periodically-poled KTiOPO4 (KTP) crystals with a high power-conversion efficiency up to 70%. We study the physical mechanism of such counter-propagating parametric interaction with phonon-polaritons in χ(2) modulated structures. BSPS is a three-wave mixing that is distinguished from backward stimulated Raman scattering (BSRS), while a strong absorption at large polariton wave-vectors can still make BSPS display certain characteristics of BSRS such as self-compression of the Stokes pulse. We also compare BSPS with counter-propagating parametric oscillation in the near- and mid-infrared range, providing an estimation of the fabrication error margin to expect the outcome of their competition in the same device.