Clinical Efficacy Evaluation of Ultrasound-Guided C2 Dorsal Root Nerve Pulsed Radiofrequency Combined with Stellate Ganglion Block in the Treatment of Cervicogenic Headache: A Retrospective Cohort Study.
To explore the therapeutic effect of C2 dorsal root ganglion pulsed radiofrequency (PRF) combined with stellate ganglion block (SGB) in patients with cervicogenic headache (CEH). We retrospectively reviewed 90 patients diagnosed with CEH who were admitted to our hospital between May 2019 and May 2022. All patients were divided into three groups (n = 30 each) according to the actual treatment method used: ultrasound-guided SGB, ultrasound-guided C2 dorsal root ganglion PRF treatment, and ultrasound-guided C2 dorsal root ganglion PRF combined with SGB treatment. Patients' pain intensity, sleep, and mood changes were assessed by statistically analyzing their pain visual analog scale (VAS), Pittsburgh Sleep Quality Inventory (PSQI), and short-form McGill Pain Questionnaire affective item scores before and after treatment. The post-treatment VAS, PSQI, and McGill scores were significantly decreased in all patients (P < 0.05), and all three scores in ultrasound-guided C2 dorsal root ganglion PRF combined with SGB were lower than those in ultrasound-guided SGB alone and ultrasound-guided C2 dorsal root ganglion PRF alone (P < 0.05). The use of ultrasound-guided C2 dorsal root ganglion PRF combined with SGB in patients with CHE is effective in alleviating pain and improving sleep, and deserves to be replicated in the clinic.


Effects of light on melatonin production.
A study was carried out to determine the intensity of light necessary to suppress melatonin. Ten normal subjects were exposed to four light intensities of 1000, 1500, 2000, and 2500 lux for 2 hr on different occasions, and melatonin levels were measured during exposure. All light intensities suppressed melatonin significantly, but none do daytime levels, with 2500 lux appearing to be the most "potent."


A broad range of organophosphate tri- and di-esters in house dust from Adelaide, South Australia: Concentrations, compositions, and human exposure risks.
This study aimed to investigate the occurrences of a suite of thirty-one organophosphate tri-esters (tri-OPEs) and six di-esters (di-OPEs) in house dust collected from Adelaide, South Australia. The results demonstrate ubiquitous presence of most OPEs in Adelaide house dust, with median concentration of 40,200 and 5260 ng/g dry weight for ∑tri-OPEs and ∑di-OPEs, respectively. A number of emerging OPEs with chemical structures resembling that of triphenyl phosphate (TPHP), including bisphenol A bis(diphenyl phosphate) (BPA-BDPP), cresyl diphenyl phosphate (CDP), isodecyl diphenyl phosphate (IDDPP), resorcinol-bis(diphenyl)- phosphate (RDP), as well as a suite of isopropylated or tert-butylated triarylphosphate ester isomers (ITPs or TBPPs), were frequently detected with combined levels surpassing that of TPHP. The investigated di-OPEs, predominated by DPHP, consisted of approximately 13% of the ∑tri-OPEs concentrations. Median concentration ratios of diphenyl phosphate (DPHP) and bis(2-ethylhexyl) phosphate (BEHP) to their respective tri-OPEs [i.e., TPHP and tris(2-ethylhexyl) phosphate (TEHP)] were determined to be 1.8 and 2.0, respectively, indicating possible commercial applications for these two di-OPEs. The estimated human intakes of dust-associated OPEs via dust ingestion and dermal contact were much lower than the reference doses. However, the risks of human exposure to OEPs may be complicated by quickly expanding family of OPEs containing various analogues and isomers as well as additional exposure pathways. Therefore, elucidation of human exposure to OPEs and associated risks requires extensive efforts in analytical, environmental, toxicological, and epidemiological investigations.


Socioeconomic differences and persistent segregation of Italian territories during COVID-19 pandemic.
Lockdowns implemented to address the COVID-19 pandemic have disrupted human mobility flows around the globe to an unprecedented extent and with economic consequences which are unevenly distributed across territories, firms and individuals. Here we study socioeconomic determinants of mobility disruption during both the lockdown and the recovery phases in Italy. For this purpose, we analyze a massive data set on Italian mobility from February to October 2020 and we combine it with detailed data on pre-existing local socioeconomic features of Italian administrative units. Using a set of unsupervised and supervised learning techniques, we reliably show that the least and the most affected areas persistently belong to two different clusters. Notably, the former cluster features significantly higher income per capita and lower income inequality than the latter. This distinction persists once the lockdown is lifted. The least affected areas display a swift (V-shaped) recovery in mobility patterns, while poorer, most affected areas experience a much slower (U-shaped) recovery: as of October 2020, their mobility was still significantly lower than pre-lockdown levels. These results are then detailed and confirmed with a quantile regression analysis. Our findings show that economic segregation has, thus, strengthened during the pandemic.


Adherence to active play and electronic media guidelines in preschool children: gender and parental education considerations.
The primary purpose of the present study was to examine adherence to current active play and electronic media use guidelines in a sample of US preschool-aged children and to examine whether differences occurred across gender and parental education. 164 parents completed an on-line survey to estimate preschool children's active play and sedentary behaviors. For weekdays, 50% of the sample met the active play guideline with this increasing to 65% during the weekend. With respect to electronic media use, 90% of the sample met guidelines during the week, with the percentage meeting guidelines dropping to 78% during the weekend. A greater percentage of preschool children from high parental education families (83.4 ± 3.3) met electronic media use guidelines on the weekends, compared to preschool children from low parental education families (59.4 ± 8.1) (p = 0.002). Our findings indicate that a substantial portion of preschool children are not meeting active play guidelines and that adherence to active play and electronic media use guidelines may be influenced by parental education.


Significance of genital mycoplasmas in pelvic inflammatory disease: innocent bystander!
Our objective was to determine the role of Mycoplasma hominis and Ureaplasma urealyticum in pelvic inflammatory disease (PID). The clinical and microbiologic variables in 114 patients with a clinical diagnosis of PID were compared prospectively according to the isolation of M. hominis and U. urealyticum from their endometrial cavities. The groups were epidemiologically well matched. Clinical parameters such as temperature, leukocyte count, erythrocyte count, and C-reactive protein on admission and length of hospital stay were similar in the patients, regardless of their mycoplasma status. A significant percentage of the patients either continued or started to harbor genital mycoplasmas after the resolution of PID without any significant clinical sequelae. The presence of genital mycoplasmas does not change the clinical presentation and course of PID. Both M. hominis and U. urealyticum can persist or colonize the endometrium after complete recovery from PID. Therefore, the genital mycoplasmas do not seem to have a dominant pathogenic role in PID.


Sequential morphological change of Chiari malformation type II following surgical repair of myelomeningocele.
To document long-term morphological changes of Chiari type II malformation (CM-II) following closure of spina bifida manifesta (SBM). We retrospectively evaluated postnatal magnetic resonance images of the CM-II and posterior fossa (PF) in 28 consecutive cases. We measured changes in vertebral level and length of the cerebellar peg (CP), cerebrospinal fluid (CSF) spaces anterior and posterior to the cerebrospinal junction, PF area, and the anteroposterior diameters of the foramen magnum (FM) and C1 vertebra. We examined the morphological differences between the cases with and without ventriculoperitoneal (VP) shunting and derived predicted means by nonlinear mixed-effect modeling. At birth, there were significant differences in CP length, PF area, and FM and C1 diameters between those who underwent VP shunting and those who did not. In cases with a CP below C1, VP shunting was required in every case but one. In those with visible CSF space at birth, VP shunts were not required. In 17 of 18 cases with a CP below C1, the vertebral level ascended by mean two vertebral levels (range 0-5 levels) within 4-6 months of delivery. In the remaining case, slowly progressive hydrocephalus and delayed CP descent required VP shunting at 8 months. Predicted mean CP length and FM and C1 diameters were greater in those who underwent VP shunting, but there was no difference in predicted mean PF area. The morphology of CM-II and the presence of hydrocephalus influence each other in children who have undergone postnatal SBM repair.


Efficiency of 3D-Ordered Macroporous La0.6Sr0.4Co0.2Fe0.8O3 as an Electrocatalyst for Aprotic Li-O2 Batteries.
Li-O2 batteries (LOBs) with an extremely high theoretical energy density have been reported to be the most promising candidates for future electric storage systems. Porous catalysts can be beneficial for LOBs. Herein, 3D-ordered macroporous La0.6Sr0.4Co0.2Fe0.8O3 perovskite oxides (3D-LSCF) are applied as cathode catalysts in LOBs. With a high Brunauer-Emmett-Teller surface area (21.8 m2 g-1) and unique honeycomb-like macroporous structure, the 3D-LSCF catalysts possess a much higher efficiency than La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) nanoparticles. The unique 3D-ordered macropores play a significant role in the product deposition as well as oxygen and electrolyte transmission, which are crucial for the discharge-charge processes of LOBs.


Estimation of the number of binding sites for a murine monoclonal anti-Lub on human erythrocytes.
The number of Lub antigen sites on the human erythrocyte membrane, as recognised by the murine monoclonal antibody BRIC-108, has been determined. The number of antibody molecules bound per cell on one example of cells of the phenotype Lu(a-b-) with recessive inheritance was an average of around 200 in replicate determinations, which probably represents non-specific antibody binding. A similar number of antibody molecules to this bound to trypsin- or pronase-treated normal cells or cells of the Lu(a-b-) phenotype associated with the inheritance of the X-borne gene, XS2. The number of binding sites on three examples of cells of the phenotype Lu(a-b-) with dominant inheritance was from 440 to 690. A variation in the number of binding sites per cell from 1,640 to 4,070 was found in five individuals with the phenotype Lu(a-b+) and from 850 to 1,820 in four individuals with the phenotype Lu(a+b+). Four individuals with the Lu(a+b-) phenotype had an average of 480 binding sites per cell. The Lub antigen therefore appears to a have low-site density and a variable level of expression on the erythrocyte surface.


The effect of tick-borne fever on metabolism and renal clearance of sulfadimidine in goats.
The tick-borne fever (TBF) model was used to study the effect of fever on the metabolism of sulfadimidine in goats. During TBF the elimination half-lives were prolonged, and the renal clearance values of sulfadimidine and the majority of its metabolites were markedly diminished compared with those in the uninfected state. During TBF the steady-state levels of the hydroxy metabolites were markedly increased. TBF reduced the extent of hydroxymethylation of the pyrimidine side chain; TBF did not affect acetylation of sulfadimidine. In one goat a progressive accumulation of the metabolites was noticed.


[The immune system in Kawasaki disease. Study of the 1st case of the disease found in Italy in an adult subject].
The authors report the results of immunological investigations performed on a patient affected by Kawasaki disease. The study was performed on the first case of this disease observed in Italy in an adult. The immunological findings are discussed in view of the recent reports of the international literature.


Characterization of a C3-like cDNA in a coral: phylogenetic implications.
C3, C4, and C5 are thiolester-containing proteins (TEPs) of vertebrate complement. The identification of the molecular origin of the TEP family, and more specifically the ancestor protein of complement components C3, C4, and C5, remains a fundamental question. The prevailing paradigm suggests that duplication and divergence of these proteins occurred after the deuterostome split in phylogeny. It is believed that the ancestor of thiolester-containing complement proteins was alpha-2-macroglobulin (A2M)-like, a noncomplement-related protein. Here we describe a C3-like cDNA from a gorgonian coral, Swiftia exserta. This study provides evidence for the origins of a complement-related C3-like gene in the Precambrian period, predating both protostomes and deuterostomes. Furthermore, one may speculate that complement-like opsonic reactions were evolving at the earliest stages of metazoan evolution. This calls for a reassessment of the present concepts concerning the origins and evolution of TEPs.


Extracellular matrix assembly of cell-derived and plasma-derived fibronectins by substrate-attached fibroblasts.
Using a previously described model system for the incorporation of plasma fibronectin into the extracellular matrix (McKeown-Longo, P.J. and Mosher, D.F., 1985. J. Cell Biol., 100:364-374), we compared the binding of cell-derived and plasma-derived fibronectins to human fibroblast cell layers. Binding was measured in time course experiments using metabolically labeled cell-derived, iodinated cell-derived, and iodinated plasma-derived fibronectins. The kinetics of matrix assembly of cell- and plasma-derived fibronectins were the same. Competitive binding curves using intact fibronectin or the 70-kD amino-terminal fragment of fibronectin suggested that cell surface binding sites have equal affinity for cell- and plasma-derived fibronectins. Iodinated fibronectins did not bind to isolated matrices containing collagen type I, fibronectin, and thrombospondin. These results suggest that fibroblasts do not distinguish between cell-derived and plasma-derived fibronectins when assembling exogenous fibronectin into extracellular matrix.


Cell types involved in replication and distribution of human cytomegalovirus.
As the number of patients suffering from severe HCMV infections has steadily increased, there is a growing need to understand the molecular mechanisms by which the virus causes disease. The factors that control infection at one time and the events leading to virus multiplication at another time are only beginning to be understood. The interaction of HCMV with different host cells is one key for elucidating these processes. Through modern techniques, much has been learned about the biology of HCMV infections in culture systems. In addition to endothelial cells, epithelial cells, and smooth muscle cells, fibroblasts are one cell population preferentially infected in solid tissues in vivo. From these sites of multiplication, the virus may be carried by peripheral monocytes and circulating endothelial cells to reach distant sites of the body. This would explain the multiorgan involvement in acute HCMV infection and the modes of viral transmission. From what has been learned mainly from human fibroblast culture systems, future studies will focus on how HCMV regulates the expression of its putative 200 genes in different host cells at different stages of cell differentiation and activation to result in viral latency and pathogenesis.


Characterization of Rare Variants in MC4R in African American and Latino Children With Severe Early-Onset Obesity.
Mutations in melanocortin receptor (MC4R) are the most common cause of monogenic obesity in children of European ancestry, but little is known about their prevalence in children from the minority populations in the United States. This study aims to identify the prevalence of MC4R mutations in children with severe early-onset obesity of African American or Latino ancestry. Participants were recruited from the weight management clinics at two hospitals and from the institutional biobank at a third hospital. Sequencing of the MC4R gene was performed by whole exome or Sanger sequencing. Functional testing was performed to establish the surface expression of the receptor and cAMP response to its cognate ligand α-melanocyte-stimulating hormone. Three hundred twelve children (1 to 18 years old, 50% girls) with body mass index (BMI) >120% of 95th percentile of Centers for Disease Control and Prevention 2000 growth charts at an age <6 years, with no known pathological cause of obesity, were enrolled. Eight rare MC4R mutations (2.6%) were identified in this study [R7S, F202L (n = 2), M215I, G252D, V253I, I269N, and F284I], three of which were not previously reported (G252D, F284I, and R7S). The pathogenicity of selected variants was confirmed by prior literature reports or functional testing. There was no significant difference in the BMI or height trajectories of children with or without MC4R mutations in this cohort. Although the prevalence of MC4R mutations in this cohort was similar to that reported for obese children of European ancestry, some of the variants were novel.


A retrospective database analysis of neuropathic pain and oral antidiabetic medication use and adherence among Texas adults with type 2 diabetes enrolled in Medicaid.
Adherence to oral antidiabetic (OAD) medications is essential in achieving glycemic control and slowing the progression of diabeties-related complications such as neuropathic pain. OAD medication adherence has been suboptimal and adding neuropathic pain medications may negatively affect adherence. However, little is known about adherence to neuropathic pain medications by patients with diabetes and how this may be related to OAD medication adherence. The objectives of our study were to: (1) describe painful diabetic peripheral neuropathy (PDPN) and OAD medication use, (2) determine if PDPN medication adherence differs among individual PDPN medications (ie, tricyclic antidepressants, gabapentin, pregabalin, and duloxetine); and (3) determine if PDPN medication adherence is related to post-index OAD medication adherence while controlling for covariates. This retrospective prescription claims database study included continuously enrolled Texas Medicaid beneficiaries who were adult (aged 30-64 years) prescribed OAD (pre- and post-index) and PDPN (post-index) medications. Data were extracted from June 1, 2003 to October 31, 2009. The main study outcome was post-index OAD medication adherence. Primary independent variables included PDPN medication adherence and PDPN medication type. Demographic and medication use characteristics served as covariates. Adherence was measured both continuously and dichotomously (80% cut-off) using medication possession ratio (MPR). The sample's (n = 4277) overall mean MPR (SD) for PDPN medications was 75.4% (23.9%). Mean MPR differed significantly among individual PDPN medications (P < 0.0001) and was highest for duloxetine (85.6% [18.2%]) and lowest for pregabalin (69.4% [24.9%]). Overall mean MPR (SD) for OAD medications decreased significantly (P < 0.0001) from 73.0% (24.3%) in the pre-index period to 64.5% (25.6%) in the post-index period. After controlling for covariates, nonadherers (ie, MPR <80%) to PDPN medications, compared with adherers (ie, MPR ≥80%), were significantly less likely to be adherent to OAD medications in the post-index period (odds ratio = 0.626; 95% CI, 0.545-0.719). Overall, these data suggest that mean adherence to both PDPN and OAD medications was suboptimal (MPR <80%). Patients who were adherent to PDPN medications were more adherent to OAD medications in the post-index period, but OAD medication adherence was independent of the type of PDPN medication used. OAD adherence decreased from pre- to post-index (ie, when patients were prescribed PDPN medications), which may indicate an opportunity for practitioners to emphasize the importance of OAD adherence in reducing the progression to neuropathy.


Predictive factors for the efficacy of abiraterone acetate therapy in high-risk metastatic hormone-sensitive prostate cancer patients.
There is a discrepancy in the efficacy of abiraterone acetate for overall survival (OS) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to identify predictive factors for the efficacy of abiraterone acetate for OS in high-risk mHSPC patients by analyzing them over a longer observation period. Five hundred high-risk mHSPC patients were retrospectively identified at our hospital and affiliated hospitals in the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2022. Two hundred patients were treated with abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) combined with androgen deprivation therapy (ADT). A total of 300 patients were treated with bicalutamide (80 mg/day) in combination with ADT. OS was not significantly different between the two treatments in the overall cohort (p = 0.1643). In the subgroup without Gleason pattern 5 at the primary lesion, OS was significantly better in patients treated with abiraterone acetate than in those treated with bicalutamide (p = 0.0192). In the subgroup with Gleason pattern 5 at the primary lesion, no significant difference was found between the two treatments (p = 0.1799). Univariate and multivariate analyses in the subgroup without Gleason pattern 5 at the primary lesion suggested that abiraterone therapy may be an important and independent predictor of OS in high-risk mHSPC patients. The presence of Gleason pattern 5 at the primary lesion may be a predictor for high-risk mHSPC patients who could benefit from abiraterone acetate treatment.


Chitosan-based mussel-inspired hydrogel for rapid self-healing and high adhesion of tissue adhesion and wound dressings.
The hydrogel wound dressing with self-healing and adhesive property can provide better protection to the wound and prolong the service life of the material. Inspired by mussels, a high-adhesion, injectable, self-healing and antibacterial hydrogel was designed in this study. The lysine (Lys) and the catechol compound 3,4-dihydroxyphenylacetic acid (DOPAC) were grafted onto chitosan (CS). The presence of catechol group endows the hydrogel strong adhesion and antioxidation. In the experiment of wound healing in vitro, the hydrogel can adhere to the wound surface and promote wound heal. In addition, it has been proved the hydrogel has good antibacterial properties against S. aureus and E. coli. The treatment of CLD hydrogel, the degree of wound inflammation was significantly alleviated. The levels of TNF-α, IL-1β, IL-6 and TGF-β1 were reduced from 39.8379 %, 31.6768 %, 32.1015 % and 38.4911 % to 18.5931 %, 12.2275 %, 13.0524 % and 16.9959 %, respectively. And the levels of PDGFD and CD31 were increased from 35.6054 %, 21.7394 % to 51.8555 %, 43.9326 %, respectively. These results indicated that the CLD hydrogel has a good ability to promote angiogenesis, thickening of skin and epithelial structures.


Associations of Gait Disorders and Recurrent Falls in Older People: A Prospective Population-Based Study.
Recurrent falls represent a major source of serious adverse health outcomes in the general older population. Gait impairment has been linked to recurrent falls, but there are only limited long-term data on this association. The objective of the study was to investigate the association of gait disorders (GDs) and gait tests with future falls in an existing longitudinal population-based cohort. The study was performed in participants of the Bruneck Study cohort 2010 aged 60-97 years, with prospective 5-year follow-up. At baseline, participants underwent a clinical gait assessment (to determine neurological and non-neurological GDs according to an established classification) and were also evaluated by quantitative and semiquantitative gait tests (Hauser Index, Tinetti balance and gait test, and gait speed). Logistic regression analysis adjusted for age and sex was used to determine the relationship of baseline variables with incident recurrent falls at 5-year follow-up. Of 328 included participants, 22 (6.7%) reported recurrent falls at follow-up. Baseline presence of GDs was associated with recurrent falls at follow-up (odds ratio [OR] 4.2; 95% confidence interval [CI] 1.6-11.1; p = 0.004), and this effect was largely driven by neurological GDs (OR 5.5; 95% CI 1.7-17.4; p = 0.004). All 3 simple gait tests were predictive for incident falls (Hauser Index, p = 0.002; Tinetti test, p = 0.006; and gait speed, p < 0.001). Clinical assessment of GDs and gait tests both had independent significant predictive value for recurrent falls over a 5-year follow-up period. This highlights the potential of such assessments for early fall risk screening and timely implementation of fall-preventive measures.


Correlates of sex initiation among school going adolescents in Pune, India.
To identify the correlates of sex initiation among school going adolescents in Pune, India. A study among 910 school going adolescents was conducted in five schools and one junior college in and around Pune, Maharashtra (India) between 2003-2006. Case control analysis (n = 205) was performed among 41 cases who reported ever having sex and 164 controls matched for gender, location and type of school. Correlates of sex initiation were identified using conditional logistic regression. Adolescents studying in vernacular schools, accessing pornography and having unfriendly relationship with parents had higher likelihood of sex initiation. Adolescents who reported sexual abuse, Sexually Transmitted Diseases (STDs) symptoms, smoking habit and those who had not read scientific literature on reproductive and sexual health were more likely to have initiated sex early. In the multivariate model, unfriendly relationship with parents and reported symptoms of STDs were found to be independently associated with 'early initiation of sex' among school going adolescents in this study. Premarital sexual activity, both consensual and non-consensual, was reported indicating a need for school based adolescent reproductive and sexual health education (ARSHE) programs in Maharashtra, India. The program in India should focus on specialized interventions for young adolescents. Routine health check-ups and probing on symptoms of STDs, non-consensual sex and other risky practices should be implemented in schools.


Objective consequentialism and the plurality of chances.
I claim that objective consequentialism (OC) faces a problem stemming from the existence in some situations of a plurality of chances relevant to the outcomes of an agent's acts. I suggest that this phenomenon bears structural resemblance to the well-known Reference Class problem. I outline a few ways in which one could attempt to deal with the issue, suggesting that it is the higher-level chance that should be employed by OC.


Meta multi-task nuclei segmentation with fewer training samples.
Cells/nuclei deliver massive information of microenvironment. An automatic nuclei segmentation approach can reduce pathologists' workload and allow precise of the microenvironment for biological and clinical researches. Existing deep learning models have achieved outstanding performance under the supervision of a large amount of labeled data. However, when data from the unseen domain comes, we still have to prepare a certain degree of manual annotations for training for each domain. Unfortunately, obtaining histopathological annotations is extremely difficult. It is high expertise-dependent and time-consuming. In this paper, we attempt to build a generalized nuclei segmentation model with less data dependency and more generalizability. To this end, we propose a meta multi-task learning (Meta-MTL) model for nuclei segmentation which requires fewer training samples. A model-agnostic meta-learning is applied as the outer optimization algorithm for the segmentation model. We introduce a contour-aware multi-task learning model as the inner model. A feature fusion and interaction block (FFIB) is proposed to allow feature communication across both tasks. Extensive experiments prove that our proposed Meta-MTL model can improve the model generalization and obtain a comparable performance with state-of-the-art models with fewer training samples. Our model can also perform fast adaptation on the unseen domain with only a few manual annotations. Code is available at https://github.com/ChuHan89/Meta-MTL4NucleiSegmentation.


Acute retinopathy following pancreatic head resection for chronic pancreatitis: a rare, severe complication.
Chronic pancreatitis is a pancreatic disorder affecting endocrine and exocrine pancreatic functions with a variety of mainly abdominal symptoms. We report the rare complication of acute retinopathy with visual loss following pancreatic head resection due to chronic pancreatitis. Acute retinal dysfunction is a rare severe complication of acute and chronic pancreatitis. Early recognition and therapy are of utmost importance in restoring normal visual acuity and avoiding irreversible damage.


Double-blind, multicenter controlled trial comparing topical dimethyl sulfoxide and normal saline for treatment of hand ulcers in patients with systemic sclerosis.
A prospective, randomized, double-blind trial compared topical therapy with 0.85% normal saline, 2% dimethyl sulfoxide (DMSO), and 70% DMSO for treatment of digital ulcers in 84 patients with systemic sclerosis. There were no statistically significant differences among the 3 treatment groups in the improvement in the total number of open ulcers, total surface area of open ulcers, average surface area per open ulcer, number of infected ulcers, number of inflamed ulcers, or patient pain assessment. While some patients improved during the study, improvement could not be attributed to a specific treatment. Over one-quarter of the patients treated with 70% DMSO were withdrawn for significant skin toxicity.


Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis.
Synaptic vesicle proteins 2 (SV2) are neuronal vesicles membrane glycoproteins that appear as important targets in the treatment of partial and generalized epilepsies. Therefore, we analysed the expression of SV2 isoforms in the hippocampus of patients with temporal lobe epilepsy (TLE). SV2A, SV2B and SV2C immunostaining and QuantiGene branched DNA assay were performed on biopsies from 31 consecutive TLE patients with mesial temporal sclerosis (MTS) and compared with 10 autopsy controls. SV2 expression was further compared with Timm's staining, and synaptophysin, Zinc transporter 3 (ZnT3), dynorphin, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter (VGAT) expression. In TLE patients, SV2A and SV2B expression was decreased in areas of synaptic loss. SV2C, which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS1A and mossy fibre sprouting but not in cases with other types of MTS. SV2C staining was located in the inner molecular layer of the dentate gyrus and colocalized with dynorphin, ZnT3 and VGLUT1, suggesting selective expression in presynaptic glutamatergic Zn(2+) -rich terminals of abnormal sprouting fibres. SV2 expression patterns correlated with histological subtypes of MTS, but not with clinical features or therapeutic regimens in this patient cohort. In classical MTS1A, the expression of SV2 isoforms is altered with a marked decrease of SV2A and SV2B paralleling synaptic loss and a selective increase of SV2C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV2C-specific strategies.


Responses of anterior hypothalamic-preoptic thermosensitive neurons to locally applied capsaicin.
The effects of local application of capsaicin on the activity of single thermosensitive neurons in the anterior hypothalamic-preoptic area were studied in the urethane-anesthetized rat. Local injection of capsaicin through a cannula to the vicinity of the neurons increased the activity in 15 of 28 warm-units, decreased the activity in 2 of 4 cold-units and had no effect on 5 of 10 thermally-insensitive units. Electrophoretic application of capsaicin with the use of multibarrelled microelectrodes excited 16 of 27 warm-units, inhibited 12 of 17 cold-units and had no effect on 35 of 60 thermally-insensitive units. Progressive decreases in the responsiveness of the neurons to both capsaicin and the hypothalamic temperature were observed with repeated applications of capsaicin. Many neurons ceased firing after showing excitatory or inhibitory responses to single or repeated applications of capsaicin either by local injection or electrophoretic application. The results may explain the acute thermolytic response, as well as the subsequent decrease in responsiveness to the injection of capsaicin into the anterior hypothalamic-preoptic area, on the basis of changes in the activity of thermosensitive neurons in the anterior hypothalamic-preoptic area.


Preliminary Study of Australian Pinot Noir Wines by Colour and Volatile Analyses, and the Pivot© Profile Method Using Wine Professionals.
The aim of this preliminary study was to identify potential colour components, volatile and sensory attributes that could discriminate Pinot noir wines from five Australian winegrowing regions (Adelaide Hills, Yarra Valley, Mornington Peninsula, Northern and Southern Tasmania). The sensory analysis consisted of the Pivot© Profile method that was performed by wine professionals. A headspace solid-phase microextraction-gas chromatography-mass spectrometry method was used to quantify multiple volatile compounds, while the Modified Somers method was used for colour characterisation. Analysis of data suggested ethyl decanoate, ethyl 2-methylpropanoate, ethyl 2-methylbutanoate, in addition to decanoic acid as important contributors to the discrimination between regions. Similarly, wine hue, chemical age indices, total anthocyanin, and (%) non-bleachable pigment also discriminated wines between regions. The sensory analysis showed that wines from Mornington Peninsula were associated with the 'red fruits' aroma, 'acidic', and 'astringency' palate descriptors, while those from Adelaide Hills were associated with the 'brown' colour attribute. This study indicates regionality is a strong driver of aroma typicity of wine.


Improving management of type 2 diabetes, hypertension and dyslipidaemia in the Caribbean: a systematic review of intervention studies.
To evaluate published interventions aimed at improving the management of type 2 diabetes, hypertension and dyslipidaemia in the Caribbean. We conducted a systematic review of four databases in accordance with PRISMA guidelines. Inclusion criteria were conducted in the Caribbean among adults ≥ 18 years who had type 2 diabetes, hypertension or dyslipidaemia; controlled trials, interventions, or comparative studies with pre-post designs and reported on at least one of the clinical outcomes of interest. Seventeen studies met the criteria for inclusion. The majority were conducted in Cuba and Trinidad and Tobago, and 35% were conducted over 10 years ago. Samples were small and largely consisted of older adult females and patients with type 2 diabetes. Four of eight (50%) studies that reported on HbA1c, 5 of 12 (42%) that reported on blood pressure and 2 of 7 (29%) that reported on body mass index observed significant improvements. Study heterogeneity precluded our ability to conduct a meta-analysis. The overall quality of evidence based on GRADE criteria was low for all outcomes assessed. There is insufficient evidence on interventions to address type 2 diabetes, hypertension and dyslipidaemia in the Caribbean.


Lipocalin-2 regulates the expression of interferon-stimulated genes and the susceptibility of prostate cancer cells to oncolytic virus infection.
Lipocalin-2 (LCN2) performs pleiotropic and tumor context-dependent functions in cancers of diverse etiologies. In prostate cancer (PCa) cells, LCN2 regulates distinct phenotypic features, including cytoskeleton organization and expression of inflammation mediators. Oncolytic virotherapy uses oncolytic viruses (OVs) to kill cancer cells and induce anti-tumor immunity. A main source of specificity of OVs towards tumor cells stems from cancer-induced defects in interferon (IFN)-based cell autonomous immune responses. However, the molecular underpinnings of such defects in PCa cells are only partially understood. Moreover, LCN2 effects on IFN responses of PCa cells and their susceptibility to OVs are unknown. To examine these issues, we queried gene expression databases for genes coexpressed with LCN2, revealing co-expression of IFN-stimulated genes (ISGs) and LCN2. Analysis of human PCa cells revealed correlated expression of LCN2 and subsets of IFNs and ISGs. CRISPR/Cas9-mediated stable knockout of LCN2 in PC3 cells or transient overexpression of LCN2 in LNCaP cells revealed LCN2-mediated regulation of IFNE (and IFNL1) expression, activation of JAK/STAT pathway, and expression of selected ISGs. Accordingly, and dependent on a functional JAK/STAT pathway, LCN2 reduced the susceptibility of PCa cells to infection with the IFN-sensitive OV, EHDV-TAU. In PC3 cells, LCN2 knockout increased phosphorylation of eukaryotic initiation factor 2α (p-eIF2α). Inhibition of PKR-like ER kinase (PERK) in PC3-LCN2-KO cells reduced p-eIF2α while increasing constitutive IFNE expression, phosphorylation of STAT1, and ISG expression; and decreasing EHDV-TAU infection. Together, these data propose that LCN2 regulates PCa susceptibility to OVs through attenuation of PERK activity and increased IFN and ISG expression.


Exploring novel diabetes surveillance methods: a comparison of administrative, laboratory and pharmacy data case definitions using THIN.
The objective of this study was to identify patients with diabetes in a comprehensive primary care electronic medical records database using a number of different case definitions (clinical, pharmacy, laboratory definitions and a combination thereof) and understand the differences in patient populations being captured by each definition. Data for this population-based retrospective cohort study was obtained from The Health Information Network (THIN). THIN is a longitudinal, primary care medical records database of over 9 million patients in UK. Primary outcome was a diagnosis of diabetes, defined by the presence of a diabetes read code, or an abnormal laboratory result, or a prescription for an Oral Anti-diabetic drug or insulin. A 2-year washout period was applied prior to the index of diabetes to avoid inclusion of prevalent cases for each case definition. This study demonstrated that different case definitions of diabetes identify different sub-populations of patients. When the cohorts were observed based on any measure of central tendency, each of the cohorts were reasonably comparable to each other. However, the distribution of each of the cohorts when grouped by age categories and sex, reveal differences. For example, using pharmacy case definition results in a bimodal distribution among women, one between 1-19 year and 35-39 age categories, and then again between 60-64 and 85 years-however, the histogram becomes more normally distributed when metformin was removed from the case definition. Our results suggest that clinical, pharmacy, laboratory case definitions identify different sub-populations and using multiple case definitions is likely required to optimally identify the entire diabetes population within THIN. Our study also suggests that age and sex of patients may affect the indexing of diabetes in THIN and is critical to better understand these variations.


State of the art percutaneous intervention for the treatment of valvular heart disease: a review of the current technologies and ongoing research in the field of percutaneous valve replacement and repair.
Technical developments in valvular intervention culminated in the first percutaneous valve replacement in the pulmonary position (2000) followed by replacement in the aortic position (2002). More recently, with the proven feasibility of percutaneous mitral valve repair, interventional cardiologists and cardiothoracic surgeons have begun to develop a new subspecialty dedicated to the percutaneous treatment of valvular disease. This review describes the clinical status of the current field, the applicability and limitations of new technologies, and the upcoming devices that will soon reach Phase I clinical trials.


Acute and chronic pulse-width thresholds in solid versus porous tip electrodes.
Sixty-one patients given programmable pacemakers at initial implantation have been followed for a mean of 18 months (3-42) with non-invasive measurements of myocardial pulse-width threshold. Fifty of the patients had CPI 0505/0522 (Microlith-P/Microthin-PI) pacemakers with either Cordis 322-462 8 mm2 ball tip (n=12), Cordis 322-620 17.5 mm2 (n=23), or CPI 4116 porous tip electrodes (stimulation area 7.5 mm2 and sensing area 50 mm2) (n=15). Eleven patients had Medtronic 5985 (Spectrax-SX) pacemakers with either Medtronic 6907-R 8 mm2 ring tip (n=7), 6907 11 mm2 (n=3) or 6917 myocardial electrodes (area 12 mm2) (n=1). At acute implant, the ball tip and porous tip electrodes had the lowest stimulation thresholds, but the differences were only statistically significant in comparison with the 17.5 mm2 electrode (p less than 0.01). Chronically there were no significant differences between the various electrodes (p greater than 0.1), but the ball tip electrode tended to give best long-term results, and the porous tip electrode the poorest. Thirty-eight of the 61 patients (62.3%) had chronic pulse-width thresholds of 0.1 ms or less at approximately equal to 5 V output, indicating that pulse-width programming is a useful way to conserve battery energy. However, at some stage of the study, six of the patients (9.8%) had a pulse-width threshold of 0.5 ms or more. Pulse width should therefore not be set too narrow in standard nonprogrammable pacemakers.


[Modalities of transition of diabetic adolescents from pediatrics to the adult care in the Paris-Ile-de-France region: an appeal to cooperative work for improving quality of care. Paris-Ile-de-France Section of DESG (Diabetes Education Study Group) in French language].
The purpose of this study was to evaluate the conditions in which diabetic adolescents are transferred from pediatric to adult health care, and to record the opinions of the physicians about this issue. A questionnaire-based study was performed among all the pediatricians in the hospital setting and all the diabetologists from the Paris-Ile-de-France area. Questionnaires from 50 pediatricians and 51 diabetologists were completed (response rate: 68%). 1) Not enough information was transmitted: a quarter of the diabetologists were visiting for the first time without any information on the adolescent, and only half the pediatricians received feedback information from the internists after the first visit. And yet, when considered, it was important to be kept informed after the first visit and the following ones. 2) Medical relationships were poor: more than three out of four pediatricians and diabetologists had none or very few professional meetings, and two thirds of them were not aware of the way the others were working. 3) Eighty percent of pediatricians and diabetologists considered that the transfer of diabetic adolescents had to be organised in order to keep the coherence of medical follow-up, to minimise the psychological effects of the transition, and to avoid a complete break in the patient follow-up. 4) The expectations of the pediatricians were: the validation of their previous follow-up through the feedback information from diabetologists and the continuity of the medical follow-up; those of the diabetologists were: to gain the patient's confidence and to master the patient's previous history, in order to provide a better follow-up. 5) According to the opinion of both pediatricians and diabetologists, the main errors to avoid were, by the paediatricians, to miss the time and the preparation of the transfer and, by the diabetologists, to denigrate the previous pediatric management and to change the insulin regimen immediately. This study demonstrates a lack of communication between physicians of pediatric and adult health care centres. But it also underlines their recognition of the importance of the transition's stakes and their common motivations in order to improve it.


Antimicrobial potential of unstressed and heat stressed Allium sativum.
Garlic (Allium sativum) is generally known to be of medicinal value, possessing potentials that include antimicrobial activity, but are often consumed in foods after subjection to cooking heat. The antimicrobial potential of heat stressed garlic may become decreased or lost when cooked, making its medicinal benefit unavailable to consumers. The potential of uncooked and cooked extracts from garlic imported to Jamaica, to inhibit the growth of eight microbes of clinical significance was investigated. Aqueous extracts of fresh garlic of 15 g/100 ml (fw), and dried and pulverized garlic cloves of 12.5 g/100 ml, 25 g/100 ml, 50 g/100 ml, and 100 g/100 ml (dw), were tested for inhibition of microbial growth. Extracts were tested uncooked, and cooked by boiling for 5, 10, and 15 min respectively. Of all the microbes studied, C. albicans incurred the largest zone of inhibition (57.7 ± 0.6 mm at the 100 g/100 ml of the dried extract, F(3, 8) = 51.778, p < 0.001, ω2 = 0.93). Cooking of garlic extracts resulted in statistically significant decreases in zones of inhibition of microbes, as evident in the linear regression and one-way ANOVA analyses, and/or complete loss of microbial inhibition. C. albicans was the most inhibited microbe, followed by E. coli, and Salmonella sp., respectively. The use of uncooked garlic may be the best route for obtaining the greatest antimicrobial potential of garlic against susceptible bacteria and fungi because cooking heat stress resulted in the decrease and complete loss of the antimicrobial potentials of the garlic.


Label-free detection of cupric ions and histidine-tagged proteins using single poly(pyrrole)-NTA chelator conducting polymer nanotube chemiresistive sensor.
Novel chemical and biological sensors based on a single poly(pyrrole)-NTA chelator nanotube for sensitive, selective, rapid and real-time detection of histidine-tagged protein and cupric ions are reported. NTA groups on the nanotube surface provided a simple mechanism for metal ion sensing via the high-affinity interaction between NTA and the subsequent detection of histidine-tagged protein through the coordination with metal chelated nanotube. Poly(pyrrole)-NTA chelator nanotubes of 190 nm outside diameter, 35 nm wall thickness and 30 microm long were synthesized by electrochemical polymerization of pyrrole-NTA inside a 200 nm diameter alumina template and assembled as a chemoresistive device by bottom-up contact geometry on a pair of parallel gold electrodes with a gap distance of 3 microm. The chemoresistive sensors based on single poly(pyrrole)-NTA chelator nanotube exhibited detection as low as one-hundredth attomolar (0.6 ppt) cupric ions and 1 ng/ml of penta-histidine tagged syntaxin protein.


Guarding the genome: electrostatic repulsion of water by DNA suppresses a potent nuclease activity of topoisomerase IB.
Type IB topoisomerases cleave and rejoin DNA strands through a stable covalent DNA-(3'-phosphotyrosyl)-enzyme intermediate. The stability of the intermediate is a two-edged sword; it preserves genome integrity during supercoil relaxation, but it also reinforces the toxicity of drugs and lesions that interfere with the DNA rejoining step. Here, we identify a key determinant of the stability of the complex by showing that introduction of an Sp or Rp methylphosphonate linkage at the cleavage site transforms topoisomerase IB into a potent endonuclease. The nuclease reaction entails formation and surprisingly rapid hydrolysis of a covalent enzyme-DNA methylphosphonate intermediate. The approximately 30,000-fold acceleration in the rate of hydrolysis of a methylphosphonate versus phosphodiester suggests that repulsion of water by the DNA phosphate anion suppresses the latent nuclease function of topoisomerase IB. These findings expose an Achilles' heel of topoisomerases as guardians of the genome, and they have broad implications for understanding enzymatic phosphoryl transfer.


Evaluation of nasopharyngeal microbial flora and antibiogram and its relation to otitis media with effusion.
Acute otitis media and otitis media with effusion (OME) are the main causes of hearing impairment in children which require proper treatment, mainly antibiotic therapy. Patients whom were appropriate candidates for adenoidectomy were divided into two groups regarding the presence of middle ear effusion. Adenoid tissue specimens were cultured in both groups and the bacterial flora and anti-microbial resistance pattern were determined. 72 patients were studied, 42 % had OME while 58 % did not. The following bacteria were isolated and cultured from both groups with no meaningful difference in prevalence: Streptococcus viridans (p = 0.265), Staphylococcus aureus (p = 0.72), H. influenza (p = 0.806), Entrococcus. spp (0.391), Streptococcus pneumonia (p = 0.391), nonhemolytic Streptococcus (p = 0.230). Bacterial sensitivity was similar for Amoxicillin-clavulanate (p = 0.935), Amoxicillin (p = 0.935), Cephalexin (p = 0.806), Cefixime (p = 0.391) and Azithromycin in both groups. The two groups showed no meaningful difference considering the bacterial flora of nasopharynx and their sensitivity. Bacteria in both groups were sensitive to Amoxicillin and Amoxicillin-clavulanate and resistant to Azithromycin, Cefixime and Cephalexin.


Adenosine induces mesangial cell contraction by an A1-type receptor.
Adenosine is known to decrease renal blood flow and glomerular filtration rate. We have tested the hypothesis that adenosine exerts contractile effects on mesangial cells. Furthermore, we have studied, using selective agonists and antagonists for adenosine, which kind of adenosine receptor, A1 or A2, is mainly implicated in this response. We also investigated whether calcium is involved in adenosine-induced mesangial cell contraction. Rat cultured mesangial cells were exposed to adenosine (10(-7) to 10(-3) M) and the contraction was measured as changes in planar cell surface area (PCSA). Adenosine induced a time- and dose-dependent reduction of PCSA. This reduction in PCSA was prevented by incubation with the A1 blocker PD116,948 but not with the A2 blocker PD115,199. Adenosine-5'-ethylcarboxamide (NECA), an A2 agonist, did not induce significant changes in PCSA whereas N6-S-1-methyl-2-phenylethyl adenosine (S-PIA), an A1 agonist, induced a dose-dependent decrease in PCSA. Adenosine-induced mesangial contraction was prevented by verapamil or by incubation in a calcium-free medium. These results suggest that adenosine induces a specific contraction of cultured rat mesangial cells that seems to be mediated by its binding to the adenosine A1-type receptor. This contraction seems to be dependent on the influx of extracellular calcium.


Excitonic photoluminescence in semiconductor quantum wells: plasma versus excitons.
Time-resolved photoluminescence spectra after nonresonant excitation show a distinct 1s resonance, independent of the existence of bound excitons. A microscopic analysis identifies exciton and electron-hole plasma contributions. For low temperatures and low densities, the excitonic emission is extremely sensitive to details of the electron-hole-pair population making it possible to identify even minute fractions of optically active excitons.


Characterization of regulatory T cells in patients with dermatomyositis.
The purpose of this study was to characterize regulatory T cells (T(reg)) in skin lesions and peripheral blood from patients with dermatomyositis (DM) and to determine the serum levels of regulatory cytokines in the disease. In skin biopsy specimens from patients with DM, immunohistochemistry was performed for CD4(+), CD25(+), forkhead/winged helix transcription factor (FoxP3)(+), transforming growth factor (TGF)-β(+) and interleukin (IL)-10(+) cells. Additionally, we defined the number of T(reg) subpopulations in peripheral blood by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RO, CD95, CCR4 and CLA. The levels of TGF-β and IL-10 were also determined in serum samples from patients with DM by enzyme-linked immunosorbent assays. Controls included patients with cutaneous lupus erythematosus, psoriasis and atopic dermatitis (AD) as well as healthy donors. The frequency of FoxP3(+) cells was significantly reduced in skin lesions from patients with DM (p < 0.001) compared to psoriasis and AD. Moreover, the number of cells positive for TGF-β was lower in DM than in psoriasis and AD, while IL-10(+) cells were significantly reduced only compared to psoriasis. The number of CD4(+)CD25(++)FoxP3(+) T(reg) in the peripheral blood of patients with DM was significantly reduced compared to healthy controls (p < 0.05), whereas other cell populations showed no significant differences. Finally, TGF-β and IL-10 serum levels were significantly lower in patients with DM compared to healthy controls (p < 0.05). These data suggest that the depletion of T(reg) and their main effector cytokines in the skin and the serum of patients with DM may be an important factor in the pathogenesis of the disease.


Promoter- and strain-selective enhancement of gene expression in a mouse skeletal muscle by a polymer excipient Pluronic P85.
Amphiphilic triblock copolymers of ethylene oxide and propylene oxide (Pluronic) significantly enhanced expression of plasmid DNA in the skeletal muscle. In the presence of Pluronic P85 (P85) high levels of expression of a reporter gene (luciferase) were sustained for at least 40 days and the area under the gene expression curve increased by at least 10 times compared to the DNA alone. The effect of Pluronic depended on the strain of the mouse and the type of the promoter used. Thus, P85 enhanced luciferase expression by 17 to 19-fold in immunocompetent C57Bl/6 and Balb/c mice, while no enhancement was observed with athymic Balb/c nu/nu mice. Furthermore, P85 activated the expression of luciferase gene driven by CMV promoter, NFkappaB and p53 response elements. There was much less or no effect on the gene driven by SV40 promoter or AP1 and CRE response elements. Overall, the promoter selectivity suggested that Pluronic induced transcriptional activation of gene expression by activating the p53 and NFkappaB signaling pathways. In addition Pluronic increased the number of DNA copies and thus affected initial stages of gene transfer in a promoter selective manner.


Relationship of serum levels and dietary intake of isoflavone, and the novel bacterium Slackia sp. strain NATTS with the risk of prostate cancer: a case-control study among Japanese men.
Isoflavones may play a role in the prevention of hormone-related cancers. Equol is an isoflavone metabolized from daidzein in the presence of certain intestinal bacteria. Slackia sp. strain NATTS, a newly identified equol-producing bacterium, was recently isolated from human feces in Japan. We investigated the association of serum levels and dietary intake of isoflavones and Slackia sp. strain NATTS with the risk of prostate cancer in a case-control study among Japanese men. Fifty-six patients with newly diagnosed prostate cancer and 56 hospital controls were enrolled in this study. Isoflavones were assessed by measurement of serum levels and administration of a food frequency questionnaire. Slackia sp. strain NATTS in feces was also measured. The odds ratios (ORs) and 95 % confidence intervals (CIs) for prostate cancer were then determined using a logistic regression model. The adjusted ORs for prostate cancer in comparison with the highest to lowest categories were 0.06 (95 % CI 0.02-0.24) for serum genistein, 0.18 (95 % CI 0.06-0.52) for daidzein, 0.16 (95 % CI 0.06-0.46) for glycitein, 0.52 (95 % CI 0.22-1.22) for equol, 0.86 (95 % CI 0.30-2.48) for dietary genistein, and 0.80 (95 % CI 0.28-2.28) for dietary daidzein. The adjusted OR for prostate cancer in comparison with values above versus below the median was 0.95 (95 % CI 0.42-2.16) for Slackia sp. strain NATTS. Our study findings suggest that high serum levels of genistein, daidzein, and glycitein are significantly associated with a decreased risk of prostate cancer among Japanese men.


A comparative study on proteomics between LNCap and DU145 cells by quantitative detection and SELDI analysis.
The differences in intracellular and extracellular protein expressions between human prostate cancer lines LNCap and DU145 were examined. The proteins of the two cell lines were extracted and condensed by using protein extraction kits. And the intracellular and extracellular proteins were quantitatively detected on a micro-plate reader by using bicinchoninic acid (BCA) method. The proteins in cell culture fluid were qualitatively assayed by SELDI-TOF-MS. The results showed that the intracellular protein contents of LNCap cells were extremely higher than those of DU145 cells. After serum-free culture, both intracellular and extracellular protein contents of LNCap and DU145 were decreased to some extent. And the intracellular proteins were decreased by 5% in LNCap and by 36% in DU145 respectively, while the extracellular proteins were decreased by 89% in LNCap and 96% in DU145 respectively. SELDI assay revealed that there were 5 marker proteins in LNCap and 6 in DU145. Although both LNCap and DU145 cell lines originated from human prostate cancer, they had some differences in protein expression.


Exploring various modulation-sideband recoupling conditions of SHA+ sequence at fast MAS.
We explore modulation-sideband recoupling conditions of the (13)C-(13)C Second-order Hamiltonian among Analogous nuclei plus pulse sequence (SHA+), and found that this sequence can be used in two different recoupling regimes. The first regime, νR>Δνiso(max), is recommended for broad-band recoupling to avoid any rotational resonance broadening. In this regime, the spinning speed should be only slightly larger than Δνiso(max), to obtain the best transfer efficiency. The second regime, νR<Δνiso(max), can be used to observe long-range constraints with lower spinning speed, which increases the transfer efficiency, and may allow using bigger rotors to increase the S/N ratio.


The safety and usefulness of endoscopy for evaluation of the graft and anastomosis early after esophagectomy and reconstruction.
Although rare, graft ischemia and necrosis after esophagectomy is a devastating complication. The aim of this study was to review our experience with early endoscopy for evaluation of the graft and anastomosis after esophagectomy and reconstruction. From a population of 479 patients who underwent esophagectomy during the years 1996-2003, we identified 102 patients who had endoscopy within 21 days of operation. Endoscopy was performed a median of 9 days after operation. Graft ischemia, anastomotic leak, or both were found in 63 of the 102 patients. Reoperation was necessary in 27% of these patients, including graft removal in nine patients. In 39 patients, endoscopy demonstrated a healthy graft; only one of these patients (2.6%) required reoperation. No patient with ischemia judged insufficient to warrant graft removal on initial endoscopy subsequently lost their graft. There were no complications or anastomotic injuries associated with early endoscopy. Endoscopy early after esophagectomy is safe and provides accurate and reliable identification of graft ischemia that can be used to guide the treatment of these patients.


The role of practice and automaticity in temporal and nontemporal dual-task performance.
Research on time and attention shows that a nontemporal task may interfere with a concurrent timing task by making time judgments shorter, more variable, and/or more inaccurate compared to timing-only conditions. Brown (1998, Psychological Research, 61, 71-81) counteracted the interference effect by giving subjects automaticity training on a nontemporal task to reduce the amount of processing resources the task required. Such practice attenuated interference in timing. Two new experiments were designed to replicate and extend the previous findings. Subjects generated a series of 5-s temporal productions under single-task (timing only) and dual-task (timing plus nontemporal task) conditions. The nontemporal tasks were pursuit rotor tracking (Experiment 1), and mirror-reversed reading (Experiment 2). We employed a pretest-practice-posttest paradigm, with the practice sessions devoted to performance of the nontemporal task. Pretest-posttest comparisons showed that practice reduced interference in timing in both experiments. Dual-task probe trials were given during the practice sessions to trace the time course of the improvement in timing. The results showed that interference in timing was reduced with even small amounts of practice. The findings support the idea that timing is very sensitive to changes in the allocation of attentional resources.


C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor.
Cord factor, also called trehalose-6,6'-dimycolate (TDM), is a potent mycobacterial adjuvant. We herein report that the C-type lectin MCL (also called Clec4d) is a TDM receptor that is likely to arise from gene duplication of Mincle (also called Clec4e). Mincle is known to be an inducible receptor recognizing TDM, whereas MCL was constitutively expressed in myeloid cells. To examine the contribution of MCL in response to TDM adjuvant, we generated MCL-deficient mice. TDM promoted innate immune responses, such as granuloma formation, which was severely impaired in MCL-deficient mice. TDM-induced acquired immune responses, such as experimental autoimmune encephalomyelitis (EAE), was almost completely dependent on MCL, but not Mincle. Furthermore, by generating Clec4e(gfp) reporter mice, we found that MCL was also crucial for driving Mincle induction upon TDM stimulation. These results suggest that MCL is an FcRγ-coupled activating receptor that mediates the adjuvanticity of TDM.


Cost-free education as a new variable of mixed financing policies in Chilean higher education and its impact on student trajectory and social mobility.
This research aimed to analyze the effects of mixed financing policies from the incorporation of cost-free education in Chilean higher education in the processes of student access and retention (trajectory) and social mobility. Two methods were applied to achieve this aim: monographic research and longitudinal comparative statistical analysis between 2016 and 2021. Different databases were analyzed to evaluate coverage, retention, and social mobility rates. The research used multivariate techniques and the Gini index to measure social mobility. The results showed the transformations that Chilean higher education has experienced in increasing financing, demand, and coverage rates, especially in vulnerable quintiles. The current financing system has positively impacted social mobility and the trajectory of students from the poorest quintiles. This study seeks to contribute to the reflection on the urgency of implementing effective public policies for social progress, safeguarding quality assurance indicators in education as an accurate way of developing a country.


Microseismic records classification using capsule network with limited training samples in underground mining.
The identification of suspicious microseismic events is the first crucial step in microseismic data processing. Existing automatic classification methods are based on the training of a large data set, which is challenging to apply in mines without a long-term manual data processing. In this paper, we present a method to automatically classify microseismic records with limited samples in underground mines based on capsule networks (CapsNet). We divide each microseismic record into 33 frames, then extract 21 commonly used features in time and frequency from each frame. Consequently, a 21 × 33 feature matrix is utilized as the input of CapsNet. On this basis, we use different sizes of training sets to train the classification models separately. The trained model is tested using the same test set containing 3,200 microseismic records and compared to convolutional neural networks (CNN) and traditional machine learning methods. Results show that the accuracy of our proposed method is 99.2% with limited training samples. It is superior to CNN and traditional machine learning methods in terms of Accuracy, Precision, Recall, F1-Measure, and reliability.


Abrupt RNA changes precede the first cell division during the differentiation of Trypanosoma brucei bloodstream forms into procyclic forms in vitro.
We have monitored the timing of DNA and RNA synthesis during the synchronous differentiation of Trypanosoma brucei bloodstream forms into procyclic forms in vitro. Both are triggered after a lag period of 4 h and reach a first peak after 9 h. The division of the kinetoplast precedes that of the nucleus by about 4 h. The first cell divisions are observed after 10 h, and the cell number is doubled after 20 h. The total RNA content per cell increases sharply between 4 and 10 h, then progressively decreases as cell division progresses. The increase in RNA content cannot be due solely to accumulation of rRNA since it is also observed for mRNAs such as actin. The VSG mRNA has almost disappeared within 2 h, while the procyclin mRNA accumulates soon after the triggering of differentiation, with a strong peak between 4 and 6 h. At this moment, the amount of procyclin mRNA per cell is at least 20-fold higher than in established procyclic culture forms. The loss of the VSG and the appearance of procyclic-specific proteins essentially occur before the first cell division. These observations contrast with the progressive transition observed when monomorphic slender forms are induced to transform under the same conditions.


Transmitter sensitivities in oval neurons from rat brainstem cultures.
Using cultures of dissociated neurons from the lower brainstem of 14-15-day-old rat embryos, we studied a specific relation between neuronal activities of small-sized oval neurons and their sensitivities to various transmitter substances. Oval neurons were characterized by non-effective responses to acetylcholine and a facilitatory response to both leucine- and methionine-enkephalin.


Cardiovascular health metrics in low and middle-income countries: A scoping review.
In 2010 the American Heart Association defined the concept of ideal cardiovascular health to renew the focus on primordial prevention for cardiovascular disease. Evidence primarily from high-income countries suggests ideal CVH prevalence is low and decreases with age, with vulnerable populations differentially affected. We aimed to identify and characterize the evidence relevant to CVH metrics in low- and middle-income countries (LMICs). We followed the Joanna Briggs Institute guideline for the conduct of this scoping review. We searched MEDLINE, Embase, LILACS and study registers from inception to 14 March 2022. We included cross-sectional and cohort studies in populations representing a geographically-defined unit (urban or rural) in LMICs, and with data on CVH metrics i.e. all health or clinical factors (cholesterol, blood pressure, glycemia and body mass index) and at least one health behavior (smoking, diet or physical activity). We report findings following the PRISMA-Scr extension for scoping reviews. We included 251 studies; 85% were cross-sectional. Most studies (70.9%) came from just ten countries. Only 6.8% included children younger than 12 years old. Only 34.7% reported seven metrics; 25.1%, six. Health behaviors were mostly self-reported; 45.0% of studies assessed diet, 58.6% physical activity, and 90.0% smoking status. We identified a substantial and heterogeneous body of research presenting CVH metrics in LMICs. Few studies assessed all components of CVH, especially in children and in low-income settings. This review will facilitate the design of future studies to bridge the evidence gap. This scoping review protocol was previously registered on OSF: https://osf.io/sajnh.


Effect of the inadequacy of antibiotic therapy in the Emergency Department on hospital stays.
The main objective of the study was to determine the frequency of patients receiving inappropriate empiric antibiotic therapy and to assess the impact in terms of increase length of hospital stay, 30-day re-admissions, and 30-day mortality. An observational retrospective cohort study was conducted over a one-month period that included all patients hospitalised from an Emergency Department (ED) due to infection. Demographic variables, comorbidity, multi-resistance risk factors, site of infection, microbiological findings, and antibiotic prescribed in ED were collected. Outcomes were length of hospital stay, 30-day re-admissions, and 30-day mortality. A total of 376 patients were included, with a mean age of 71.1 (SD 21) years. The most frequent causes were respiratory (45.7%) and urine (23.9%) infections. The number of patients with length of stay over the median (≥9 days) was 165 (46.1%), with re-admissions 74 (19.7%), and mortality at 30 days 44 (11.7%). There was inappropriate antibiotic treatment in 42 (11.2%) cases. After adjusting for demographic data, comorbidity, risk factors for multidrug resistant organism, presence of sepsis criteria in ED, and site of infection, inappropriate treatment was associated with an extended length of hospital stay (OR 2.22; 95% CI; 1.07-4.60; P=.032), but did not to an increase in mortality (P=.271) or re-admission (P=.784) at 30 days. The inappropriate empirical antibiotic therapy in patients admitted from the ED leads to an extended hospital stay, but did not increase mortality or readmission.


Comparison of deformation by stereophotogrammetry of various kinds of major connectors in maxillary Kennedy Class I removable partial dentures.
Major connectors must be rigid to perform their functions with maximum efficacy. This study investigated the deformation of four major connectors for maxillary Kennedy Class I removable partial dentures. The designs were palatal plate, U-shaped plate, palatal strap, and anteroposterior bar. The deformation properties of major connectors were comparatively analyzed by two methods. In the photogrammetric part, a stereometric camera, Avipan-100 glass films, and an analytic apparatus were used. A computerized hydraulic machine was programmed to load the eight test dentures at 4-Hz frequency under a vertical load of 100 kg and a maximum of 300,000 cycles. The fluorescence penetrant liquid inspection test was used to detect the surface microcracks. The anteroposterior bar showed the least deformation. The other connectors, ranked in increasing order for the amount of deformation, were the U-shaped plate, the palatal strap, and the palatal plate. There were no microcracks in the U-shaped plate and the anteroposterior bar designs. Anteroposterior bar major connectors showed the least deformation among the maxillary major connector types tested. Microscopic cracks were seen in major connectors showing the highest degree of deformation and located at the depth of the hard palate.


Sperm motion in a microfluidic fertilization device.
Microfluidics has shown promise as a new platform for assisted reproduction. To assess the potential of microfluidics for fertilization, we studied sperm and fluid motion in microchannels to better understand the flow characteristics in a microfluidic device, how sperm interacted with this flow, and how sperm-oocyte attachment occurs in the device. There is a threshold fluid velocity where sperm transition from traveling with the fluid to a regime in which the sperm can move independently of the flow. A significant population of sperm remained in the inlet well area. Based on the lack of progressive forward movement, it was presumed that these sperm may have defects. Also of extreme interest was the tendency of sperm to travel along surface contours. These observations provide an improved understanding of sperm motion in microchannels and provide a basis for improved device designs that take advantage of the sperm/flow and sperm/geometry interactions.


Effect of lecithin and MgCO3 as additives on the enzymatic activity of carbonic anhydrase encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres.
A model enzyme, carbonic anhydrase, was encapsulated and released from poly(lactide-co-glycolide) (PLGA) microspheres (1-3 microm) made by a novel phase inversion technique. Lecithin was used as a surfactant in the encapsulation process and was incorporated in either the organic phase, aqueous phase, both phases, or not at all. Additional microspheres were also made with lecithin incorporated in the aqueous phase and a basic salt, MgCO3, in the polymeric phase. Released carbonic anhydrase, protein extracted from microspheres, or enzyme incubated with lecithin and PLGA were analyzed via HPLC and activity assay to determine the effect of these additives on protein integrity and activity. Lecithin in the aqueous phase appeared to increase the fraction of enzyme in monomeric form as well as its activity for both extracted protein and released protein as compared to the other formulations without MgCO3. Incubation of enzyme with PLGA degradation products indicated that the acidic environment within the microspheres aids in the irreversible inactivation of the encapsulated protein. Addition of MgCO3 further increased the amount of monomer in both the extracted and released protein by decreasing the amount of acid-induced cleavage and noncovalent aggregation, but still greatly decreased the activity of the enzyme.


Urinary apolipoprotein M could be used as a biomarker of acute renal injury: an ischemia-reperfusion injury model of kidney in rat.
It has been well documented that apolipoprotein M (apoM) is principally expressed in hepatocytes as well as renal tubular epithelial cells. The importance of apoM in the kidney is unknown. In the present study we examined urinary any apoM after short-term ischemia-reperfusion injury (IRI) of kidney in a rat model. The kidneys of 11 male Sprague-Dawley rats were rendered ischemic for 45 minutes followed by different intervals of reperfusion. Serum and urine apoM concentrations were determined using a dot-blot analysis with specific rabbit anti-human apoM antibodies that cross-react with rat apoM. Serum concentrations of blood urea nitrogen (BUN) and creatinine (Cr) were determined using standard clinical automated analyses. BUN was significantly elevated after 45 minutes of ischemia followed by 24 hours of reperfusion; serum Cr concentrations were also significantly increased at 6 and 24 hours of reperfusion. Interestingly, similar to BUN and Cr, serum apoM concentrations were significantly increased after ischemia for 45 minutes alone and after 2 hours of reperfusion. Urinary apoM concentrations were obviously increased after 2 h as well as 6 hours of reperfusion. apoM showed characteristics of an acute-phase reactive protein; its occurrence in urine may be considered to be a biomarker of acute renal injury.


Spatiotemporal control of Cindr at ring canals during incomplete cytokinesis in the Drosophila male germline.
During male and female gametogenesis in species ranging from insects to mammals, germ cell cyst formation by incomplete cytokinesis involves the stabilization of cleavage furrows and the formation of stable intercellular bridges called ring canals. Accurate regulation of incomplete cytokinesis is required for both female and male fertility in Drosophila melanogaster. Nevertheless, the molecular mechanisms controlling complete versus incomplete cytokinesis are largely unknown. Here, we show that the scaffold protein Cindr is a novel component of both mitotic and meiotic ring canals during Drosophila spermatogenesis. Strikingly, unlike other male germline ring canal components, including Anillin and Pavarotti, Cindr and contractile ring F-actin dissociate from mitotic ring canals and translocate to the fusome upon completion of the mitotic germ cell divisions. We provide evidence that the loss of Cindr from mitotic ring canals is coordinated by signals that mediate the transition from germ cell mitosis to differentiation. Interestingly, Cindr loss from ring canals coincides with completion of the mitotic germ cell divisions in both Drosophila females and males, thus marking a common step of gametogenesis. We also show that Cindr co-localizes with Anillin at mitotic and meiotic ring canals and is recruited to the contractile ring by Anillin during male germ cell meiotic cytokinesis. Taken together, our analyses reveal a key step of incomplete cytokinesis at the endpoint of the mitotic germ cell divisions in D. melanogaster.


Enhancing the magnetic response on polycrystalline nanoframes through mechanical deformation.
The mechanical and magnetic properties of polycrystalline nanoframes were investigated using atomistic molecular dynamics and micromagnetic simulations. The magneto-mechanical response of Fe hollow-like nanocubes was addressed by uniaxial compression carried out by nanoindentation. Our results show that the deformation of a nanoframe is dominated at lower strains by the compression of the nanostructure due to filament bending. This leads to the nanoframe twisting perpendicular to the indentation direction for larger indentation depths. Bending and twisting reduce stress concentration and, at the same time, increase coercivity. This unexpected increase of the coercivity occurs because the mechanical deformation changes the cubic shape of the nanoframe, which in turn drives the system to more stable magnetic states. A coercivity increase of almost 100 mT is found for strains close to 0.03, which are within the elastic regime of the Fe nanoframe. Coercivity then decreases at larger strains. However, in all cases, the coercivity is higher than for the undeformed nanoframe. These results can help in the design of new magnetic devices where mechanical deformation can be used as a primary tool to tailor the magnetic response on nanoscale solids.


Perceptual asymmetry for chimeric stimuli in children with early unilateral brain damage.
The present study used a chimeric stimuli task to assess the magnitude of the left-hemispace bias in children with congenital unilateral brain damage (n = 46) as compared to typically developing matched controls (n = 46). As would be expected, controls exhibited a significant left-hemispace bias. In the presence of left hemisphere (LH) damage, the left-hemispace preference was found to be present, but attenuated, whereas right hemisphere (RH) damage resulted in a less lateralized process. Examination of lesion severity revealed that large lesions in the RH were associated with a reversal of the typical left-hemispace bias, while small lesions resulted in a left bias approximating that of controls. In contrast, the left-hemispace preference in children with LH damage was similar across lesion size. We conclude that damage to either hemisphere early in brain development may alter hemispheric preference for processing of nonverbal stimuli, and that at least in the case of RH damage, alteration of the normal perceptual asymmetry may depend on the interaction between lesion side and severity.


Exclusion of the SCN2B gene as candidate for CMT4B.
Charcot-Marie-Tooth disease type 4B (CMT4B) is a demyelinating autosomal recessive motor and sensory neuropathy characterised by focally folded myelin sheaths in the peripheral nerve. The CMT4B gene has been localised by homozygosity mapping and haplotype sharing in the 11q23 region. A cDNA encoding for the beta 2 subunit of the human brain sodium channel, SCN2B, has been recently assigned to the same chromosomal interval by FISH. The SCN2B gene has been considered a good candidate for CMT4B on the basis of protein homology, chromosomal localisation, and putative biological function of the coded product. In this paper, we report the genomic structure of the SCN2B gene consisting of 4 exons and 3 introns spanning a region of approximately 12 Kb. In addition, a search for mutations in patients affected with CMT4B as well as a refined physical localisation excludes SCN2B as the CMT4B gene.


Reconfigurable networking for coordinated multi-agent sensing and communications.
An implementation of a neurally-inspired system comprised of multiple mobile sensor-effector agents is described. Each agent has features of a complex neural network that is able to communicate and adjust its behavior depending upon a variety of parameters, including changes in the environment and the behavior of other agents. The system as a whole spatiotemporally reconfigures itself to perform coordinated behaviors not obtainable with single agents. Transient clustering of agents into functional subsystems to perform specific tasks generates a "system of systems" architecture. The interesting findings of this dynamic platform show that (a) the formation and dissolution of functional subsystems is a local phenomenon without the need for global control and (b) minimal intermittent communication among the agents can yield large-scale, coordinated, goal-driven behavior under a wide range of conditions.


Rapid differentiation of Ralstonia solanacearum avirulent and virulent strains by cell fractioning of an isolate using high performance liquid chromatography.
Ralstonia solanacearum is one of the most destructive plant bacterial pathogens worldwide. The population dynamics and genetic stability are important issues, especially when an avirulent strain is used for biocontrol. In this study, we developed a rapid method to differentiate the virulent and avirulent strains of R. solanacearum and to predict the biocontrol efficiency of an avirulent strain using high performance liquid chromatography (HPLC). Three chromatographic peaks P1, P2 and P3 were observed on the HPLC spectra among 68 avirulent and 28 virulent R. solanacearum strains. Based on the HPLC peaks, 96 strains total were assigned to three categories. For avirulent strains, the intense peak is P1, while for virulent strains, P3 is the majority. Based on the HLPC spectra of R. solanacearum strains, a chromatography titer index (CTI) was established as CTIi = Si/(S1+S2+S3) × 100% (i represents an individual HPLC peak; S1, S2 and S3 represent peak areas of P1, P2 and P3, respectively). The avirulent strains had high values of CTI1 ranging from 63.6 to 100.0%, while the virulent strains displayed high values of CTI3 ranging from 90.2 to 100.0%. Biological inoculation studies of 68 avirulent strains revealed that the biocontrol efficacy was the best when CTI1 = 100%. The purity and genetic stability of R. solanacearum strains were confirmed in the P1 fraction of avirulent strain FJAT-1957 and P3 fraction of virulent strain FJAT-1925 after 30 generations of consecutive subculture. These results confirmed that fractioning by HPLC and their deduced CTI can be used for rapid and efficient evaluation and prediction of an isolate of R. solanacearum. To the best of our knowledge, this is the first report that HPLC fractioning can be used for rapid differentiation of virulent and avirulent strains of R. solanacearum.


[Analysis of medical workers suffered from SARS].
To investigate the prevalence of SARS infection in medical workers and the efficacy of isolation precautions in the hospital. A retrospective analysis was employed to study the prevalence of SARS infection in medical workers who contacted with SARS patients directly. The data were analyzed with EPI statistic soft ware. From March 15th, 2003 to May 18th, 2003, 224 patients with clinical confirmed SARS and 72 patients with clinical suspected SARS were presented in our hospital. The principle and system of the isolation precautions were established and implemented in our hospital. Seven hundreds and twenty medical workers including doctors, nurses and nurse-assistants were involved in the medical care of patients with SARS. Eighteen out of the 720 (2.43%) medical workers were infected with SARS, most of them were from the department of emergency, and the majority of infected medical workers were nurse-assistants. After the isolation precautions in hospital were established, the spreading of SARS in medical stuffs declined dramatically. The medical workers infected with SARS were 7.20% of SARS patients presented or hospitalized in our hospital. The infection rate was significantly lower than that of the average rate in our country. The isolation precautions taken in our hospital was effective.


The effect of liposomal size on the targeted delivery of doxorubicin to Integrin αvβ3-expressing tumor endothelial cells.
Size of the liposomes (LPs) specially governs its biodistribution. In this study, LPs were developed with controlled sizes, where variation in LP size dictates the ligand-receptor interaction, cellular internalization and its distribution within the tumor microenvironment. The therapeutic efficacies of doxorubicin (DOX)-loaded RGD modified small size (~100 nm in diameter, dnm) and large size (~300 dnm) PEGylated LPs (RGD-PEG-LPs) were compared to that of Doxil (a clinically used DOX-loaded PEG-LP, ~100 dnm) in DOX resistant OSRC-2 (Renal cell carcinoma, RCC) tumor xenografts. Doxil, which accumulated in tumor tissue via the enhanced permeability and retention (EPR) effect, failed to suppress tumor growth. Small size RGD-PEG-LP, that targets the tumor endothelial cells (TECs) and extravasates to tumor cells, failed to provide anti-tumor effect. Large size RGD-PEG-LP preferentially targets the TECs via minimization of the EPR effect, and significantly reduced the tumor growth, which was exerted through its strong anti-angiogenic activity on the tumor vasculature rather than having a direct effect on DOX resistant RCC. The prepared large size RGD-PEG-LP that targets the TECs via interacting with Integrin αvβ3, is a potentially effective and alternate therapeutic strategy for the treatment of DOX resistant tumor cells by utilizing DOX, in cases where Doxil is ineffective.


Comparison of serum metabolomics in women with breast Cancer Prior to Chemotherapy and at 1 year: cardiometabolic implications.
Early-stage breast cancer (BC) is the second most common malignancy in women, worldwide. Early-detection and treatment advances have led to 5-year survival rates of 90% for early-stage breast cancer. However, the long-term morbidity of breast cancer remains high, with a majority of survivors facing increased risk of cardiometabolic conditions as well as secondary cancers. In particular, African American women with breast cancer experience higher morbidity and mortality than other women. Metabolomics is the comprehensive study of metabolites in biological samples to elucidate the role of monosaccharides, amino acids, and their respective metabolic pathways. Although some studies have found differential metabolites in women with breast cancer compared to normal controls, there has been little study of women with breast cancer across time and the active treatment trajectory. This study examines and compares the serum metabolomic profile of women with BC, prior to initial chemotherapy and at 1 year after inception of chemotherapy. This study examined serum metabolites through a secondary analysis of a longitudinal parent study (EPIGEN) of women diagnosed with early-stage BC. Participants were evaluated across 5 time points: prior to their receipt of chemotherapy (T1), at the time of their 4th chemotherapy treatment (T2), 6 months after the initiation of chemotherapy (T3), one year after the initiation of chemotherapy (T4) and two years after the initiation of chemotherapy (T5). This analysis focused on the metabolomic data from 70 participants from T1 to T4. Using ultra high-pressure liquid chromatography high resolution mass spectrometry (UHPLC-HRMS), we performed Friedman Rank Sum Test followed by Nemenyi post-hoc pairwise tests to identify which metabolite levels differed between time points, focusing on metabolites with a Benjamini-Hochberg false discovery rate (FDR) from the overall Friedman test < 0.05 and then specifically examined the p-values from the T1 vs. T4 pairwise comparison. The untargeted serum metabolomics yielded a total of 2,395 metabolites identified on the basis of the accurate mass and MS/MS fragmentation, 1,264 of which were significant after Friedman's test (FDR < 0.05). The analysis then focused on the levels of 124 metabolites from the T1 vs. T4 post-hoc comparison that had a combined FDR < 0.05 and fold change (FC) > 2.0. Metabolite set enrichment analysis (MSEA) as part of Metaboanalyst 3.0 was performed to identify pathways that were significantly altered. The known metabolites identified from the functional analysis were used to evaluate the up and down regulated pathways. The 40metabolites from the Functional Analysis were mainly attributed to amino acids (specifically lysine regulation), fatty acids (particularly unsaturated) and steroid hormone synthesis (lysophosphatidic acid). There were multiple significant changes in the serum metabolomic profile of women with breast cancer at one-year post inception of chemotherapy compared to pre-chemotherapy, most notably associated with lysine degradation, branched-chain amino acid synthesis, linoleic acid metabolism, tyrosine metabolism and biosynthesis of unsaturated fatty acids as the top 5 metabolic pathways. Some of these changes could be associated with metabolic perturbations that are consistent with heightened risk of cardiometabolic morbidity. Our results provide new insights into the mechanisms underlying potential heightened cardiovascular health risks in this population.


Selenium nanoparticles based on Amphipterygium glaucum extract with antibacterial, antioxidant, and plant biostimulant properties.
In recent years, crop production has expanded due to the variety of commercially available species. This increase in production has led to global competition and the search for biostimulant products that improve crop quality and yield. At the same time, agricultural products that protect against diseases caused by phytopathogenic microorganisms are needed. Thus, the green synthesis of selenium nanoparticles (SeNPs) is a proposal for achieving these needs. In this research, SeNPs were synthesized from methanolic extract of Amphipterygium glaucum leaves, and chemically and biologically characterized. The characterization of SeNPs was conducted by ultraviolet-visible spectrophotometry (UV-Vis), scanning electron microscopy (SEM), electron microscopy transmission (TEM), Dynamic Light Scattering (DLS), energy dispersion X-ray spectroscopy (EDX), and infrared spectrophotometry (FTIR) techniques. SeNPs with an average size of 40-60 nm and spherical and needle-shaped morphologies were obtained. The antibacterial activity of SeNPs against Serratia marcescens, Enterobacter cloacae, and Alcaligenes faecalis was evaluated. The results indicate that the methanolic extracts of A. glaucum and SeNPs presented a high antioxidant activity. The biostimulant effect of SeNPs (10, 20, 50, and 100 µM) was evaluated in vinca (Catharanthus roseus), and calendula (Calendula officinalis) plants under greenhouse conditions, and they improved growth parameters such as the height, the fresh and dry weight of roots, stems, and leaves; and the number of flowers of vinca and calendula. The antibacterial, antioxidant, and biostimulant properties of SeNPs synthesized from A. glaucum extract demonstrated in this study support their use as a promising tool in crop production.


Upregulation of cyclin T1/CDK9 complexes during T cell activation.
Cyclin T1 has been identified recently as a regulatory subunit of CDK9 and as a component of the transcription elongation factor P-TEFb. Cyclin T1/CDK9 complexes phosphorylate the carboxy terminal domain (CTD) of RNA polymerase II (RNAP II) in vitro. Here we report that the levels of cyclin T1 are dramatically upregulated by two independent signaling pathways triggered respectively by PMA and PHA in primary human peripheral blood lymphocytes (PBLs). Activation of these two pathways in tandem is sufficient for PBLs to enter and progress through the cell cycle. However, the expression of cyclin T1 is not growth and/or cell cycle regulated in other cell types, indicating that regulation of cyclin T1 expression is dependent on tissue-specific signaling pathways. Upregulation of cyclin T1 in stimulated PBLs results in induction of the CTD kinase activity of the cyclin T1/CDK9 complex, which in turn correlates directly with phosphorylation of RNAP II in vivo, linking for the first time activation of the cyclin T1/ CDK9 pair with phosphorylation of RNAP II in vivo. In addition, we report here that endogenous CDK9 and cyclin T1 complexes associate with HIV-1 generated Tat in relevant cells and under physiological conditions (HIV-1 infected T cells). This, together with our results showing that HIV-1 replication in stimulated PBLs correlates with the levels of cyclin T1 protein and associated CTD kinase activity, suggests that the cyclin T1/CDK9 pair is one of the HIV-1 required host cellular cofactors generated during T cell activation.


Posterior pelvic floor compartment disorders.
Posterior pelvic floor compartment disorders generally refer to functional anorectal disturbances that by definition are symptom-based rather than anatomical defect-based and have a significant impact on quality of life. Symptoms attributed to the posterior compartment are often non-specific and associated with structural, neuromuscular and functional defects giving rise to symptoms of prolapse, pelvic pressure, faecal incontinence, stool trapping and constipation. They may range from mild to incapacitating and occur in varying combinations. While symptoms of constipation and incontinence may conceptually represent the opposing extremes of normal anorectal function, the dynamic interrelationships between the different pathophysiological mechanisms involved in the development of these disorders suggest a more complex explanation. Faecal continence and defecation are dependent on several neurological and anatomical factors that involve coordinated physiological processes, including intestinal transit and absorption, colonic transit, rectal compliance, anorectal sensation and continence mechanism. However, it is well recognized that pelvic floor symptoms originating from one compartment do not imply absent pathology in another compartment. Furthermore, symptoms associated with one disorder (such as constipation related to functional obstructed defecation) can be causative in the sequential development of other pelvic floor disorders, such as a urogenital prolapse syndrome, that may further exacerbate symptoms. In addition, it has been found that treatment that corrects one problem may improve, worsen or even predispose to other symptoms from another compartment. Consequently, while the concept of global pelvic floor dysfunction has emerged, the traditional single speciality referral and evaluation of pelvic floor problems continues to foster potentially segregated management strategies that can overlook the relevance of concomitant symptomatology. The evaluation and treatment of posterior pelvic compartment disorders needs to assume an individualized but multidisciplinary therapeutic approach. Given the variation in surgical approaches described to correct anatomical integrity of posterior pelvic compartment deficits, the consensus on optimal management has yet to be achieved. Therefore, it is critical that outcome measures following surgery are clearly defined. Treatment is to a great extent dictated to by functional severity and the impact that symptoms have on quality of life. Long-term follow-up should ensure that the potential for complications is minimized and satisfactory bowel, bladder and sexual function is maintained.


From older to younger generations: Intergenerational transmission of health-related roles in families with Huntington's disease.
Older generations play relevant roles in the well-being of younger generations, namely by influencing their health management. Literature regarding the influence in families affected by highly incapacitating hereditary diseases, such as Huntington's disease (HD), however, is scarce. This study addresses the intergenerational flow of health-related roles, from older to younger generations in families with HD, that is, who plays what roles towards whom while considering age, gender, kinship and genetic status in both generations. This qualitative exploratory study adopted the critical incidents technique, applied through semi-structured interviews. Ten participants reported 189 critical incidents. Thematic analysis was applied to transcript data from the interviews to glean common themes. The main findings suggested two main roles performed by older generations: "shaping awareness" and "influencing management". The intergenerational flow involved mainly women, in contiguous generations (usually mother-to-daughter); it was more frequent from either older non-biological or affected relatives aged ≥60 years towards younger members aged 20-29 years, who were still at-risk or non-carriers. Older generations are relevant influencers in the health management of their younger relatives and they create illness-related legacies. The results are relevant for healthcare services and professionals, as they bring further insight into how older relatives may be involved in genetic counselling, as well as insight into the provision of psychological support to affected families.